MELANOMA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Melanoma: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84031-8 1. Melanoma-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on melanoma. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MELANOMA .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Melanoma...................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 76 CHAPTER 2. NUTRITION AND MELANOMA .................................................................................. 123 Overview.................................................................................................................................... 123 Finding Nutrition Studies on Melanoma .................................................................................. 123 Federal Resources on Nutrition ................................................................................................. 131 Additional Web Resources ......................................................................................................... 132 CHAPTER 3. ALTERNATIVE MEDICINE AND MELANOMA ............................................................ 133 Overview.................................................................................................................................... 133 National Center for Complementary and Alternative Medicine................................................ 133 Additional Web Resources ......................................................................................................... 163 General References ..................................................................................................................... 167 CHAPTER 4. DISSERTATIONS ON MELANOMA .............................................................................. 169 Overview.................................................................................................................................... 169 Dissertations on Melanoma ....................................................................................................... 169 Keeping Current ........................................................................................................................ 171 CHAPTER 5. CLINICAL TRIALS AND MELANOMA ........................................................................ 173 Overview.................................................................................................................................... 173 Recent Trials on Melanoma ....................................................................................................... 173 Keeping Current on Clinical Trials ........................................................................................... 197 CHAPTER 6. PATENTS ON MELANOMA ........................................................................................ 199 Overview.................................................................................................................................... 199 Patents on Melanoma ................................................................................................................ 199 Patent Applications on Melanoma............................................................................................. 228 Keeping Current ........................................................................................................................ 264 CHAPTER 7. BOOKS ON MELANOMA ............................................................................................ 265 Overview.................................................................................................................................... 265 Book Summaries: Federal Agencies............................................................................................ 265 Book Summaries: Online Booksellers......................................................................................... 266 The National Library of Medicine Book Index ........................................................................... 271 Chapters on Melanoma .............................................................................................................. 272 CHAPTER 8. MULTIMEDIA ON MELANOMA ................................................................................. 273 Overview.................................................................................................................................... 273 Video Recordings ....................................................................................................................... 273 Bibliography: Multimedia on Melanoma ................................................................................... 274 CHAPTER 9. PERIODICALS AND NEWS ON MELANOMA .............................................................. 277 Overview.................................................................................................................................... 277 News Services and Press Releases.............................................................................................. 277 Newsletter Articles .................................................................................................................... 282 Academic Periodicals covering Melanoma................................................................................. 282 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 283 Overview.................................................................................................................................... 283 U.S. Pharmacopeia..................................................................................................................... 283 Commercial Databases ............................................................................................................... 284 Researching Orphan Drugs ....................................................................................................... 285 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 291
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Overview.................................................................................................................................... 291 NIH Guidelines.......................................................................................................................... 291 NIH Databases........................................................................................................................... 293 Other Commercial Databases..................................................................................................... 295 The Genome Project and Melanoma .......................................................................................... 295 APPENDIX B. PATIENT RESOURCES ............................................................................................... 301 Overview.................................................................................................................................... 301 Patient Guideline Sources.......................................................................................................... 301 Finding Associations.................................................................................................................. 310 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 313 Overview.................................................................................................................................... 313 Preparation................................................................................................................................. 313 Finding a Local Medical Library................................................................................................ 313 Medical Libraries in the U.S. and Canada ................................................................................. 313 ONLINE GLOSSARIES................................................................................................................ 319 Online Dictionary Directories ................................................................................................... 321 MELANOMA DICTIONARY...................................................................................................... 323 INDEX .............................................................................................................................................. 415
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with melanoma is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about melanoma, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to melanoma, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on melanoma. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to melanoma, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on melanoma. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON MELANOMA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on melanoma.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and melanoma, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “melanoma” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Amelanotic Melanoma of the Palate: Report of Case Source: Journal of Oral and Maxillofacial Surgery. 59(5): 580-583. May 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: Malignant melanoma arises primarily in the skin and represents the leading cause of death from cutaneous malignancy in the United States. Fewer than 1 percent of all reported primary melanomas arise in the oral cavity. The cutaneous form of this lesion normally is highly visible, with irregular borders and dark pigmentation. Rarely, melanoma may present without clinically evident pigmentation (coloration). Termed amelanotic melanoma, these lesions tend to have a worse prognosis because of delayed recognition and subsequent treatment. This article reports a case of amelanotic
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melanoma of the palate. A 68 year old Caucasian female presented with a 2 centimeter nodular lesion on the right soft palate found on routine dental examination. The patient's medical history was significant for a stroke, which resulted in left hemiplegia. She had lost all her teeth from periodontal disease; she had been wearing complete upper and lower dentures for the preceding 15 years. After diagnosis, surgical excision (removal) was performed. The patient did well postoperatively and has undergone successful prosthetic rehabilitation. The surgical margins were clear of disease, and the patient remains disease free at 1 year. The authors note that because oral cavity melanomas are extremely rare, it is difficult to determine the optimum method of staging, prognosis, and treatment. 3 figures. 17 references. •
Spontaneous Regression of Cutaneous Melanoma with Subsequent Metastasis Source: Journal of Oral and Maxillofacial Surgery. 60(5): 588-591. May 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: There has been a four-fold increase in the incidence of cutaneous malignant melanoma during the past 25 years. However, the ratio of expected deaths from melanoma to new melanoma cases has actually decreased steadily during this time period, largely as a result of increased public awareness leading to earlier diagnosis and treatment. The relationship between malignant melanoma and melanocytic nevi (pigmented skin blemishes, present at birth) is well recognized; more than 80 percent of patients with melanoma reported a change in a preexisting nevus as the initial sign of their disease. This article presents the case of a patient with an apparent spontaneous regression of a presumed malignant melanoma that arose from a longstanding cutaneous melanocytic nevus followed by the development of a regional lymph node metastasis (spread of the cancer). The authors describe the patient's multimodal therapy with wide surgical excision of the gross lesion, noting that this offers the most favorable opportunity for locoregional control and, therefore, prolonged disease-free survival. 6 figures. 16 references.
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Oral Melanoma: Diagnosis and Treatment Source: Seminars in Cutaneous Medicine and Surgery. 16(4): 320-322. December 1997. Summary: This article reviews the diagnosis and treatment of oral melanoma. The author notes that melanoma of the mouth is rare, most commonly occurring on the upper jaw of patients older than 50 years. Because of a frequent delay in diagnosis (the oral cavity is often neglected during the physical examination, and pain is often nonexistent), the tumors are often diagnosed after they are deeper than the average cutaneous melanoma. Hence, the prognosis tends to be poor. The 5-year survival rate is 15 to 38 percent. Surgery is the mainstay of treatment, but often it is difficult because of anatomic restraints. Although melanoma is classically not radiosensitive, occasional patients have had a good response to radiation therapy, sometimes with temporary palliation. Other treatment modalities are similar to those used for cutaneous melanoma. Immunotherapy, including interferon, has been used. Chemotherapy has a low response rate. The author reiterates that, as with the skin, early diagnosis of oral melanoma is important. 4 figures. 13 references. (AA-M).
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Melanoma: A Strategy For Detection And Treatment Source: Patient Care. 30(11):126-28, 30, 34-36, 41-42, 45, 48, 53; June 1995.
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Summary: This journal article examines the diagnosis and treatment options of skin cancer, including the types of drugs available, identification tips, and patient counseling. The authors discuss the difficulties in identifying suspicious growths on the skin; when an autopsy is needed; monitoring when a biopsy is inconclusive; prognostic indicators in cases of positive biopsies; the clinical staging examination; and available courses of action such as surgery, adjuvant therapy, palliative therapy, and experimental treatments. Concluding comments address long-term follow-up and patient counseling. 11 references, 2 figures, 3 tables. •
Pigment Clues Guide Melanoma Risk Diagnosis Source: Skin and Allergy News. 28(9):22; September 1997. Summary: This journal article for health professionals reports on the use of epiluminescence microscopy (ELM) for determining whether an equivocal lesion is melanoma. If a lesion seen with ELM has a pigment network with a fishnet or honeycomb pattern it is most likely melanocytic. In addition, other features that suggest a high, medium, or low risk of melanoma are identified.
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Preventing Mortality in Cutaneous Melanoma Source: Patient Care. 33(9): 34-36,39-40,43-44,46,49,56-58,60. May 15, 1999. Summary: This journal article provides health professionals with information on detecting early cutaneous melanomas. It addresses screening issues, describes the features of suspicious lesions, and presents methods of treating melanoma. The main early detection tools are screening by physicians and skin self-examination by patients. Although many medical organizations do not recommend routine screening for skin cancer, the American Academy of Dermatology, the American Cancer Society, the National Institutes of Health, and the Skin Cancer Foundation do recommend skin examination or annual screening. The risk level of a particular patient is an important factor in the decision to screen for melanoma. The most effective skin examination is comprehensive, and some experts recommend dermatologic photography as a supplement to total skin examination in high-risk patients. Tools that can help diagnose a suspicious lesion include optimal illumination, side-lighting, a hand lens, and a Wood's lamp. The types of melanoma are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral-lentiginous melanoma. A biopsy is needed for all lesions meeting the ABCD (asymmetry, borders, color, diameter) criteria for melanoma. The histopathology report will indicate whether the lesion is benign or malignant. Treatment consists of surgical excision. Other treatments include chemotherapy for patients who have metastatic disease, liquid nitrogen cryosurgery, radiation therapy, and Mohs' micrographic surgery. Experimental therapies include melanoma vaccines and isolated limb perfusion. Involvement of regional lymph nodes is the most significant prognostic risk factor, followed by primary tumor thickness. The frequency of follow-up and the laboratory studies that should be obtained at each followup visit depend on the stage of disease and the risk of recurrence. Patient education is important in increasing the chances of early detection. 8 figures, 2 tables, and 11 references.
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How to Diagnose Malignant Melanoma Source: Nurse Practitioner. 27(2): 26-27,31-35. February 2002. Summary: This journal article, a continuing nursing education activity, provides nurse practitioners with information on diagnosing malignant melanoma. The incidence of
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malignant melanoma has increased dramatically in recent decades. Malignant melanoma can either begin de novo or develop in association with a preexisting nevus. Although curable if caught early, malignant melanoma often presents a diagnostic challenge. Clinicians can use various methods, both old and new, to evaluate melanoma, including the ABCD method, total body photography, skin surface microscopy, and machine vision. The ABCD method involves evaluating a lesion for asymmetry, border, color variegation, and diameter. Benign nevi tend to be round and symmetric; have smooth, regular borders; be homogeneously colored; and be less than 6 millimeters in diameter. However, melanomas are often asymmetric; have irregular, uneven, and ragged edges; have multiple colors and various hues of light and dark brown, black, red, blue, or gray; and be larger than 6 millimeters in diameter. The inaccuracy of the ABCD method has prompted clinicians to use other modalities such as total body photography for high risk patients. Although potentially more accurate than the ABCD method, total body photography is still based on clinical visual inspection. In contrast, skin surface microscopy, also known as dermoscopy or epiluminescence microscopy, uses a handheld instrument to provide a 10 times illuminated view of the skin surface. This technique bridges clinical experience with histopathology. Learning dermoscopy requires understanding color, structures, and borders. Although skin surface microscopy improves diagnostic accuracy, it is labor intensive with a fairly high learning curve. Machine vision is a promising diagnostic tool that is being studied in various countries. This technique uses an electronic digital dermatoscopic camera to acquire and process images. A computer then segments the image, separating the boundaries of the pigmented lesion from the surrounding skin. The article discusses practice implications. 16 figures and 27 references. (AA-M).
Federally Funded Research on Melanoma The U.S. Government supports a variety of research studies relating to melanoma. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to melanoma. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore melanoma. The following is typical of the type of information found when searching the CRISP database for melanoma: •
Project Title: A MOUSE MODEL FOR UV-INDUCED JUNCTIONAL MELANOMA Principal Investigator & Institution: Noonan, Frances P.; Professor; Immunology; George Washington University 2121 I St Nw Washington, Dc 20052
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Cutaneous malignant melanoma (CMM), already notorious for its highly aggressive behavior and its recalcitrance to currently available therapeutics is one of the the fastest increasing cancers in the USA. Recent studies have provided compelling evidence for a significant underlying genetic basis for CMM, as well as an initiating role for sunlight exposure in its etiology. The functional relationship, however, between genes and environment in the pathogenesis of melanoma is virtually unknown. Until now, research on this deadly disease has been badly hampered by the lack of an animal model which adequately recapitulates human disease. We have developed a new transgenic mouse model for UV-induced melanoma which, for the first time, shows an etiology, histopathology and molecular pathogenesis remarkably similar to human CMM. In this proposal, we seek to characterize and further validate this model which shows great promise for melanoma investigations. Preliminary data to date have demonstrated that a single neonatal burning dose of UV exposure is necessary and sufficient to induce highly penetrant cutaneous melanoma, arising in apposition to epidermal elements with a junctional morphology and a molecular pathogenetic profile remarkably reminiscent of human melanoma. Specifically, the UV responsiveness and waveband dependence of this model will be established, the role of critical genetic alterations in the tumor suppressor loci Ink4a and p53 occurring in early lesions and in malignant tumors will be investigated using an in vivo genetic approach, and we propose to establish if UV-induced immune alterations play a fundamental role in the early pathogenesis of disease in this model. We anticipate that these studies will provide the major basis for development of this system for application in the design of preventive strategies and therapeutic interventions and for further investigations of the fundamental biology of cutaneous malignant melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AN INTELLIGENT MELANOMA DIAGNOSTIC TRAINING SYSTEM Principal Investigator & Institution: Crowley, Rebecca S.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 21-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This project will determine whether the welldescribed paradigm of the model-tracing Intelligent Tutoring System can be adapted to create a multimedia, knowledge-based, medical training system. We propose to develop the Melanoma Diagnostic Training System, a virtual-slide based tutor for pathology residents. The system is designed to provide instruction in detection, classification, and reporting of Malignant Melanoma and other melanocytic skin lesions. Melanocytic lesions are a difficult area of histologic cancer diagnosis. False negative and false positive diagnoses of Melanoma can result in significant morbidity and mortality, and are among the most commonly litigated pathology case types. New advances in treatment of Melanoma have placed an increasing responsibility on the pathologist to identify and report on a range of histologic prognostic indicators. We propose to develop a diagnostic training system in this domain using the paradigm of the Intelligent Tutoring Systems (ITS). ITS are computer-based systems that provide individualized instruction by incorporating models of expert performance and dynamically building a unique student model for each user. ITS can be highly effective in systems that simulate real-world tasks, enabling students to work through case-based scenarios as the ITS offers guidance, points out errors and organizes the curriculum to address the needs of that individual learner. As part of the project, we will develop a library of whole-slide digital images of melanocytic lesions and melanoma, each with a
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gold-standard diagnosis. System development will be accompanied by a controlled, randomized laboratory evaluation in which we will examine the effect of the system on accuracy of detection, classification, and reporting using pre-test and post-test methods. In the final year of the project, we will deploy the system across multiple sites in the Pennsylvania Cancer Alliance Bioinformaties Consortium, and evaluate acceptance and use of the system using surveys, interviews, and log-file analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF BREAST/MELANOMA MULTIPLE PRIMARY CANCERS Principal Investigator & Institution: Gerrero, Michelle Renee.; Pediatrics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The proposed project is centered on cancer susceptibility gene discovery. This project is based on the hypothesis that a subset of individuals with multiple primary cancers has an underlying susceptibility gene mutation that is common to all tumors in that individual. Earlier studies using population-based tumor registries have demonstrated an increased risk of melanoma as a second malignancy in women diagnosed with breast cancer. Conversely, an increased risk of breast cancer has been demonstrated in women who have been previously diagnosed with melanoma. This bi-directional increased risk of a second malignancy deserves further attention and is suggestive of a common mechanism as the etiology of these two tumors. To this end, we intend to define and characterize a population of women who have been diagnosed with both breast cancer and melanoma. Outside of defined syndromes, little had been documented regarding multiple primary cancers. What data exist strongly support the hypothesis that women with multiple primary cancers are more likely to harbor germline susceptibility alleles than those with a single malignancy. We hypothesize that women with the multiple primary cancers, breast and melanoma, represent a clinically significant variation in disease phenotype for one of the known candidate genes. We will screen this population for germline and somatic mutations in genes known to be involved in cancer predisposition or progression. In addition, we will use array-based comparative genomic hybridization (aCGH) to identify the critical genetic changes that are necessary to transform normal melanocytes or breast epithelium into cells with malignant potential. A DNA-based microarray platform using bacterial artificial chromosomes (BACs) containing human genomic DNA representative of the entire genome at 1-2 Mb intervals, will be utilized to define regions of chromosomal gain and loss using DNA from breast and melanoma tumors both from a single individual as well as versus matched sporadic tumors. The overall objective of this proposal is the identification of additional cancer susceptibility genes, which will enable the study of the genes themselves and advance our understanding of the etiology of breast cancer and malignant melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANCHOR MODIFIED PEPTIDES FOR IMMUNIZATION IN MELANOMA Principal Investigator & Institution: Linette, Gerald P.; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 29-SEP-1999; Project End 31-JAN-2003
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Summary: Recent experimental evidence suggests that therapeutic immunization for certain malignancies is a realistic approach. Pre-clinical models based upon immunization of tumor-bearing hosts with antigen-pulsed dendritic cells (DC) demonstrate that regression of established tumors can be induced. Tumor regression is dependent upon an intact immune system and is mediated by antigen specific CD8+ T lymphocytes. This proposal is built upon the premise that delivery of an immunogenic peptide vaccine with subsequent intensive immunologic monitoring is required to optimally elicit an effective T cell response capable of eradicating residual tumor. Compelling evidence suggests that immunogenicity correlates with peptide binding affinity for molecules encoded by the major histocompatibility complex. The principal goal of this study is to create better, more immunogenic vaccines for melanoma by designing peptide antigens modified in crucial (anchor) residues that affect binding affinity for HLA class I molecules. Melanoma antigen gp100 and Mart-1 anchor modified peptides will be used with DC in clinical immunization trials designed to optimize the in vivo generation of antigen specific CD8+ cytotoxic T lymphocytes. Immunologic, pathologic, as well as radiologic endpoints will be used to judge the efficacy of each peptide. Newer methodologies such as T cell receptor beta chain repertoire analysis and four color flow cytometry will be incorporated into vaccine trials for melanoma to allow more precise monitoring. Immunogenicity of selected peptides will be validated using HLA transgenic mice. The specific aims of this application are: 1) to create anchor modified peptides of the gp100 melanoma antigen restricted by HLAA2; 2) to identify HLA-B7 restricted epitopes of gp100 and Mart-1; 3) to develop better strategies to characterize human T cell activation and recruitment after DC vaccination. The issues addressed in this application are designed to provide a more detailed understanding of the relationship between cellular immunity, tumor regression, and clinical response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOGENIC FACTORS ASSOCIATED WITH UVEAL MELANOMA Principal Investigator & Institution: Polans, Arthur S.; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-MAY-2003 Summary: Uveal melanoma is the most prevalent primary ocular tumor found in adults. The annual incidence of uveal melanoma is equivalent to the number of new cases of retinitis pigmentosa. The genetic alterations underlying the disease are unknown, and there are few prognostic indicators that can be observed clinically, contributing to enucleation as a principal method of treatment. Unfortunately, events leading to systemic metastases may have occured by the time the ocular symptoms are recognized, and death due to hepatic disease and other complications usually ensues. Clearly, improved methods are needed for the early detection and treatment of the disease. The current application focuses on the contributions of angiogenic growth factors and inhibitors to the progression of the disease. We hypothesize that the malignant and metastatic properties of such tumors depend on the simultaneous expression of multiple angiogenic factors, specifically Cyr61, Tissue Factor, and VEGF. Further, the balance between the expression of these growth factors and inhibitors determines the quiescent period prior to detectable metastases. Specific Aims include: 1. Verify the expression of Cyr61, Tissue Factor and VEGF in primary ocular melanoma using both archival specimens and fresh biopsies of tumor tissue. Methods of detection will include immunohistochemistry, Northern blot hybridization, RT-PCR, and in situ hybridization. Expression will be correlated with vascular density. 2. Assess the importance of Cyr61,
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Tissue Factor and VEGF during growth of the primary tumor and its metastases using an animal model. Transfected cell lines of uveal melanoma with varying levels of expression of these three genes will be transplanted into the anterior chambers of nude mice, and the growth of the primary ocular tumors, the extent of hepatic lesions, and the vascular density at both sites will be measured. 3. Determine the cellular localization of Cyr61, Tissue Factor and VEGF using a combination of immunocytochemical methods and cellular fractionation. 4. Identify additional angiogenic growth factors (angiopoietin-1) and inhibitors (angiostatin and endostatin) associated with uveal melanoma by RT_PCR, immunoblotting and Northern blot hybridization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA
ANTI-GD3
NKT
CELLS
AS
EFFECTOR
CELLS
AGAINST
Principal Investigator & Institution: Chapman, Paul B.; Associate Attending Physician; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): GD3 ganglioside is expressed on neuroectodermal tissue and on tumors such as melanoma, sarcoma, and small-cell lung cancer. Antibodies against GD3 can shrink melanoma in rodents and patients. In clinical trials designed to immunize patients against GD3 in the adjuvant setting, we saw surprisingly low relapse rates that did not correlate with induction of anti-GD3 antibodies. Since GD3 is not presented by MHC class I or class II, we considered the alternative possibility that immunization might induce a NKT response against GD3. We have induced CD1restricted NKT cells against GD3 in mice and in this project; we propose to characterize further the anti-GD3 murine NKT cell response. Specific Aim 1 - Define the T cell receptor usage, cytokine profile, and specificity of mouse CD1-restricted NKT cells against GD3. Most murine CD1-restricted NKT cells described to date recognize glycolipids derived from bacteria or invertebrates. Much less is known about CD1restricted NKT cells that recognize self-glycolipids expressed on mammalian cells. Specific Aim 2 - Characterize how GD3 is loaded on to mouse CD1. In the human system, some CD1-restricted glycolipid antigens require internalization and loading in acidified late endosomes; other CD1-restricted glycolipids are loaded in post-Golgi vesicles not requiring acidification. Little is known about how self gangliosides are loaded on to CD1 although in the human system there is some evidence that GM1 ganglioside does not even require internalization to be presented. Using the mouse system, we will characterize how GD3 is loaded on to mouse CD1 assessing requirements for internalization, acidification of endosomes and Golgi function. We plan to map the intracellular processing pathway using confocal immunomicroscopy. Specific Aim 3 -Test the hypothesis that mouse NKT cells against GD3 can mediate antitumor effects in an antigen-specific manner. CD1-restricted NKT cells activated by alpha-galactosylceramide (from marine invertebrates) can mediate antitumor effects in a manner that does not appear to be antigen-specific. It is not known if CD1-restricted NKT cells specific for an antigen expressed on tumor cells can have anti-tumor effects. We will test the ability of CD1-restricted NKT cells against GD3 to lyse GD3+ mouse melanoma in vitro and to reject GD3+ mouse tumors in vivo. This will provide initial support for an immunotherapeutic approach based on antigen-specific NKT cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATYPICAL NEVI IN MELANOMA--A CASE-CONTROL STUDY Principal Investigator & Institution: Titus-Ernstoff, Linda T.; Associate Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-JAN-2002 Summary: Despite substantial interest in atypical nevi as melanoma risk factors and precursors, little is known about risk factors for these lesions, or their role in melanoma etiology. Previous case-control studies that have assessed atypical nevi as melanoma risk factors were small and/or clinic based. Similarly, only a few small, clinic-based studies have examined risk factors for atypical nevi. Our primary aims are to 1) conduct a large, population-based, case-control study of nonfamilial melanoma to evaluate atypical nevi, benign nevi, sun sensitivity, and solar exposure as risk factors, and 2) conduct a large, population-based evaluation of risk factors for atypical nevi. In separate analyses, we will explore risk factors associated with melanoma subgroups based on a) presence or absence of atypical nevi, and b) tumor histologic type. As a tertiary aim, we propose a validation substudy that will evaluate whether subjects can accurately selfdiagnose atypical nevi. At least 535 cases of melanoma, ascertained through the NH State Cancer Registry, will be enrolled over a five year study period. We will enroll 800 population controls identified from drivers' license lists (age 65 or less), and medicare beneficiary lists (age greater than 65). Consenting subjects will complete a telephone interview, conduct skin self-examination, and participate in a dermatologist-conducted skin examination. Based on the dermatology examination, all subjects will be classified as "with" or "without" atypical nevi. Our statistical approach will include two primary case-control analyses to evaluate 1) risk factors for melanoma, and 2) risk factors for atypical nevi. In addition, we will conduct separate case-control comparisons to explore risk factors for specific melanoma subsets. Our approach will elucidate the etiology of melanoma, and identify risk factors for atypical nevi. Finally, we will evaluate subjects' ability to self-screen for atypical nevi by comparing the results of self-examination to the results of the dermatologist examination. The ability to self-diagnose atypical nevi has important implications for melanoma prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTOLOGOUS HAPTEN MODIFIED VACCINE FOR HUMAN CANCER Principal Investigator & Institution: Berd, David A.; Professor of Medicine; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 01-MAY-1985; Project End 31-MAR-2003 Summary: We have developed a novel approach to immunotherapy of human cancer: autologous tumor cells modified with the hapten, dinitrophenyl (DNP). Administration of DNP-vaccine to patients with metastatic melanoma induces a unique response - the development of inflammation in metastatic masses. Histologically, this response is characterized by infiltration of activated T cells that are predominantly CD8+. Moreover, molecular analysis of the T cell receptor (TCR) structures within metastases indicates that the T cell infiltration consists, at least in part, of novel T cell clones not found in pre-treatment metastases. Occasionally, administration of DNP-vaccine results in regression of established metastases; small lung metastases are most likely to respond. Moreover, administration of DNP-vaccine to melanoma patients with bulky regional node metastases following lymphadenectomy results in a remarkably high
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relapse-free (about 45 percent) and overall (about 58 percent) survival at five years. Now we propose to extend the work in the following directions: 1)Determine whether comparable immunological and clinical results can be obtain with a second tumor type adenocarcinoma of the ovary. Preliminary experiments suggest that patients with stage III ovarian cancer develop delayed-type hypersensitivity (DTH) to autologous tumor cells following administration of DNP-vaccine. We will expand these studies to determine whether the positive immunological response is associated with tumor regression and/or prolonged survival. 2)Determine whether modification with a second hapten, sulfanilic acid, further augments the immunogenicity of melanoma cells. The use of a second hapten, one that modifies peptide residues that are different from those modified by DNP, is based on extensive animal data. We will test the immunogenicity of tumor cells modified with sulfanilic acid and with a combination of DNP and sulfanilic acid. 3)Determine whether haptenized cell membranes can substitute for intact melanoma cells as test materials and immunogen. The substitution of haptenized cell membranes for intact cells has theoretical and practical advantages. We will prepare cell membranes from hapten-modified tumor cells and test their ability to elicit DTH and to immunize patients against intact cells. 4)Characterize the T cell repertoire of lymphocytes infiltrating metastases following hapten-modified vaccine. We will build on the data obtained during the last grant period showing that the lymphocytic infiltration induced by the vaccine represents clonal T cell expansion. Using established molecular techniques, we will characterize the TCR structures found in inflamed and/or regressing metastases. This work may lead to the development of reagents useful in identifying the target antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BILIVERDIN IN MELANOMA CELL DIFFERENTIATION Principal Investigator & Institution: Falchuk, Kenneth H.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: We reported that biliverdin is required for formation of eyes, brain, spinal cord and other dorsal organs in amphibia. Beyond that mandatory requirement for embryogenesis, we found that biliverdin is a pleiotropic molecule capable of altering the phenotypes of a number of cancer cells to a more differentiated state. An early and common behavior caused by biliverdin is an arrest of proliferation in six cancer cells (melanoma, colon adenocarcinoma, liposarcoma, thyroid carcinoma, T and B cell lymphomas). In colon adenocarcinoma, the c Myc oncogene disapp9ears within two days of incubating with 5 x 10-7 M biliverdin. Concurrently, biliverdin slows their G1 to S transition. Subsequently, two differentiation markers, CEA and alkaline phosphatase, are up-regulated. These findings suggest that biliverdin reverses the phenotypic consequences of APC and beta catenin mutations characteristic of colon adenocarcinoma. Central to the current proposal are the documented findings that, like in colon adenocarcinoma, melanoma cells characteristically exhibit mutations in the same signaling system including GSK3beta phosphorylation sites of beta catenin and/or abnormally expressing high amounts of beta catenin itself. These mutations and overexpression lead to an increase in stable cytoplasmic beta catenin and enhanced transcription of beta catenin/Tef/Lef oncogenes, such as c Myc. The common alterations in beta catenin signaling found in colon cancer and melanoma cells calls for examination of the possibility that the dermatological malignancy also may be responsive to the effects of biliverdin and be directed along a differentiation pathway. In favor of this premise is a) our finding that biliverdin arrests cell division if SJ NEK 24 melanoma cell
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and b) literature reports that 12-o-tetra decanoyl phorbol 13 acetate (TPA), a molecule that up-regulates heme oxygenase 1 (HO 1) in cancer cells and, therefore, must lead to an increase in biliverdin content of these cells, also inhibits proliferation of melanoma cells. Consequently, we propose to examine the effect of biliverdin on SK MEL 24 phenotype focusing on oncogene molecules transcriptionally regulated by the beta catenin signaling system (Aim 1) and on beta catenin itself and GSK3beta, the enzyme responsible for its phosphorylation and degradation (Aim 2). These two aims will be examined by incubating the SK MEL 24 cells with biliverdin. If the results are positive, we will examined these same molecules in SK MEL 24 cells induced to synthesize biliverdin in response to phenylarsine oxide, a known activator of heme oxygenase 1 (Aim 3). Positive results will demonstrate that melanoma cells can be made to undergo differentiation and open the door to possible novel therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL LUMPHOCYTES
BASED
TUMOR
VACCINES
TARGETING
CD4+
T
Principal Investigator & Institution: Ostrand-Rosenberg, Suzanne O.; Professor; Biological Sciences; University of Maryland Balt Co Campus Baltimore, Md 21250 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: We are developing vaccine strategies for inducing immunity to ocular melanoma, the most common malignancy of the eye. Although primary tumor can be treated, 50% of patients develop metastatic disease for which there is no successful therapy. We hypothesize that the generation of tumor-specific, long-term immunity may be a useful therapy for established primary and metastatic disease. During the past 8 years we have developed a unique immunization therapy using genetically modified tumor cell-based vaccines for enhancing antigen presentation of tumor antigens. Our strategy focuses on activating tumor-specific CD4+ T helper lymphocytes. CD4+ T cells are particularly important in anti- tumor immunity because they provide the requisite "help" for optimal CD8+ activity, and because they are critical for long-term memory. We have shown in 3 mouse models that tumor cells transfected with syngeneic MHC class II, CD80 and superantigen genes are potent immunotherapeutic agents. Given the promising animal results, we would like to test our approaches in patients. The animal studies used autologous tumor cells for the "base" vaccine. Autologous human tumor material, however, is not always available, and customization for individual patients is neither cost effective nor feasible. As an alternative approach we will use established human ocular melanoma tumor cell lines as the "base" vaccine. We believe that optimal vaccine efficacy can be achieved if we understand the mechanism by which the vaccines stimulate anti- tumor immunity. We will, therefore, not only assess vaccine efficacy, but also test several hypothesis on which the vaccine strategy is based by performing the following Specific Aims: 1) Identify human ocular melanoma cell lines are the "base" lines for the vaccine, and transfect them with CD80, HLA-DR, and superantigen genes. 2) Determine the ability of the transfectants to stimulate tumor-specific HLA-DR restricted CD4+ T cell responses. 3) Determine if the stage or extent of disease affects patients' ability to respond to the vaccine. 4) Determine if individuals with tumor are "tolerant" to their tumor antigens and hence less likely to respond; and 5) Determine if the vaccines function as antigen presenting cells for tumor-encoded endogenously synthesized antigens. Completion of these studies will provide the framework for conducting a clinical trial, and will provide mechanistic information for further improvement of the vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION OF TUMOR SPECIFIC T CELLS IN MELANOMA Principal Investigator & Institution: Lee, Peter P.; Assistant Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) The goal of this proposal is to study in detail the biological properties of T cells specific for tumor-associated antigens (TAAs) that arise either de novo (Aim 1) or postvaccination (Aim 2) in patients with melanoma. Using powerful and novel tools such as peptide/MHC tetramers and 10-color FACS analysis, we will assess the expression of up to 45 surface and intracellular markers, cytokine expression, and functional status of TAA-specific T cells isolated directly from melanoma patients. We will also determine the gene expression profiles of such cells (Aim 3) to elucidate the molecular differences between functional and dysfunctional TAA-specific T cell populations. By correlating these data with the clinical state of the patient from which each population is isolated and the eventual clinical outcome, we hope to understand why TAA-specific T cells are protective in some patients but not in others. Lastly, we will dissect the factors which mediate T cell dysfunction in cancer by testing various individual and combinations of immunomodulatory agents to induce or reverse T cell dysfunction (Aim 4). Together, these data should lead to a better understanding of the biology of the T cell response to melanoma, and may lead to improvements in current cancer immunotherapy approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMO AND CYTOKINE IMMUNOTHERAPY IN HIGH RISK MELANOMA Principal Investigator & Institution: Atkins, Michael; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: Cytokine-based therapy has shown considerable promise in melanoma, producing high-quality responses and freedom from relapse in some patients with Stage IV or high-risk Stage III disease. Interferon alpha, FDA approved in 1996, is able to prevent relapse in up to 1/3 of patients with high-risk melanoma, with high-dose IL-2, FDA approval in 1998, produces durable responses in a 6-10% of patients with distant metastases. Efforts to improve upon these approaches have to date been unsuccessful. Perhaps the most promising approach involves combinations of IL-2 and IFN with chemotherapy, so called biochemotherapy. We developed a concurrent biochemotherapy regimen (cisplatin, vinblastine, DTIC, IL-2 and IFN) that produces tumor responses in about 45-50% of patients with metastatic melanoma and is sufficiently tolerable and practical to allow for testing in a Cooperative Group setting. This regimen in currently being explored in two large phase II Intergroup trials: a) E3695 that compares the concurrent biochemotherapy regimen with CVD chemotherapy in patients with Stage IV disease and b) SOOO8 that compares 3 cycles of biochemotherapy to a year of the standard high dose IFN in patients with stage III disease. In this project, patients treated on these two trials, as well those treated at DF/HCC institutions on similar treatments, will be asked to provide serial samples of blood, tumor and lymph node tissue. This material will be analyzed in a variety of ways to determine the mechanisms of responses and resistance to cytokine-based and cytotoxic therapy. Evidence of generation of specific immunity directed against melanoma antigens will be assessed using tetramer and ELISPOT analyses against
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defined melanoma peptide antigens and autologous tumor cells. Results will then by correlated with tumor response, therapy and disease status. The memory and homing properties of tetramer reactive cells will be explored using multi-parameter flow cytometry in order to determine the characteristics of T cells that best correlate with long acting immunity to melanoma antigens. In addition, T cell receptor signaling properties of peripheral blood T cells will be examined for evidence of tumor based immune dysfunction and the results correlated with treatment, disease status, and effects of therapy. Finally, melanoma tissues will be examined for the presence of various recently discovered factors associated with resistance to apoptosis (STAT1 and 2, STAT 3, Flip, Apaf-1 etc) and the findings will be correlated with treatment, treatment results and disease status. Taken together, this ambitious evaluation, should fully define the capabilities and limitations of existing therapies for advanced melanoma and, as such, will pave the way for the application of new treatments, perhaps in combination with the most promising of these standard approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOPREVENTION IN AN INDUCIBLE MOUSE MELANOMA MODEL Principal Investigator & Institution: Spanjaard, Remco A.; Associate Professor; Otolaryn & Head & Neck Surgery; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The number of cases of malignant cutaneous melanoma has been rising at an alarming rate over the last decades, at about 4% per year, and it has been estimated that up to 1 in 80 Americans will develop melanoma. Despite years of research, there are no viable treatment modalities for advanced melanoma, and mortality rates remain exceptionally high. This saddening fact emphasizes the urgent need for new effective drugs, not only to treat existing tumors, but also to inhibit occurrence of second primary cancers after convential treatment modalities, or prevent further transformation of premalignant cells in high-risk patients. This application aims to address these issues by assessing the chemopreventive activity of a promising selection of drugs in a novel, inducible murine melanoma model. This uniquely suitable model is the only one to allow synchronization of the onset of development of cutaneous melanoma on a genetic background, which accurately mimics that of human disease. By adding doxycyclin (Dox) to the drinking water, expression of H-RASV12G is induced in melanocytes on a p16INK4A-ARF null background. This cooperativity then results in development of largely non-metastatic, cutaneous melanomas in 25% of mice with an average latency of 60 26 days. The mouse model itself has already been thoroughly analyzed in terms of tumor pathology, which closely resembles that of human disease, and the essential role for H-Ras in maintaining tumor growth. However, these mice have never been used to develop new chemoprevention protocols. We will test the efficacy of the following drugs: suberohydroxamic acid (SHA), celecoxib, retinoic acid (RA) and lovastatin. These drugs were selected because they i) are non-toxic (except for RA, but 13-cisRA provides a less toxic clinical alternative), ii) are widely used already, iii) affect different biochemical pathways, iv) have shown promise as chemopreventive agents in other studies, and v) have shown potential to enhance each other's activity when combined. Our working hypothesis is that these drugs will inhibit tumor growth to some degree, but that the combination of at least some of these drugs will inhibit proliferation of premalignant melanoma cells to a much larger extent than any drug alone can achieve, without
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significantly increasing toxicity. We propose to induce 4-week old animals drugs, and determine chemopreventive antitumor efficacy by monitoring size, number and location of skin tumors. Specific Aim I proposes to establish an optimal chemoprevention drug protocol to suppress tumor development. Specific Aim II proposes to establish expression of key cell cycle regulatory genes in control, drug-responsive and nonresponsive transgenic tumors to determine whether expression is associated with tumor growth and responsiveness to therapy. The results of these experiments in this inducible melanoma model will allow us to assess whether our protocol should be considered for use in phase I trials in high risk patients, which is the long term goal of this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLASSIFICATION OF AMBIGUOUS MELANOCYTIC TUMORS Principal Investigator & Institution: Bastian, Boris C.; Assistant Clinical Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant) While current histopathological criteria permit classifying the majority of melanocytic tumors as either benign nevi or melanoma, welldocumented uncertainty exists in a significant number of cases. Misclassification results in inappropriate over- or under-treatment of patients. Our recent work using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) on primary tumors has shown that the pattern of genomic aberrations differs significantly between clearly identifiable melanoma and benign nevi. The vast majority of primary melanomas have multiple chromosomal aberrations, whereas the vast majority of nevi do not have any. The few benign nevi that do have aberrations typically have a very restricted set, which does not occur in melanoma. This project will determine if a similar genomic analysis would help distinguish between benign and malignant lesions that are ambiguous by current histopathological criteria, and if those morphological criteria can be improved. In this project we will use two separate cohorts of histologically ambiguous melanocytic tumors that have extensive follow-up in order to systematically screen for genomic and histopathological markers that can predict outcome. The first cohort will serve as a training set and the second as a test set for validation. Cases will be contributed by a panel of internationally recognized pathologists with great expertise in melanocytic tumors. The genomic analysis will take advantage of array-based CGH. This technology has recently been developed in our laboratories and provides a resolution of approximately 1 megabase across the human genome. This technique can be performed with small amounts of DNA extracted from routinely fixed archival tissue from primary tumors. First, we will use array CGH on the training set to screen for genomic aberrations that distinguish metastasizing and nonmetastasizing cases and the expert panel will use these same tumors to develop improved morphological classification criteria. The genetic and morphological criteria will be built into classification rules using the training set. The vies that work best on the training set will be validated on the independent set of tumors. Finally, we will implement the genomic rule in form of hybridization probes for a few specific loci and develop a FISH-based test. The long-term goals of this project are to find genetic and morphological criteria that can classify melanocytic tumors that are low ambiguous and to develop a prototype clinical test for this purpose. Such a test would be of significant clinical relevance, as it would help to identify patients who need additional treatment, and prevent others from getting inappropriately aggressive treatment. In addition, this
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project will provide a detailed view of the aberrations found in melanocytic tumors, their prevalence and prognostic relevance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL RELEVANCE OF MICROMETASTASES IN MELANOMA Principal Investigator & Institution: Ghossein, Ronald A.; Professor; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: The candidate is a diagnostic surgical pathologist whose immediate research goals are the detection and molecular characterization of circulating tumor cells (CTC) and micrometastases in solid tumors, especially in malignant melanoma (MM). His long term goals are the 1) development of these molecular tests into clinically relevant prognostic markers and 2) an in depth analysis of the mechanisms of metastases in solid tumors. Memorial Sloan-Kettering Cancer Center has the clinical and laboratory facilities appropriate for the development of junior faculty members into independent researchers, and for the conduct of this type of research. There is a need for better prognostic markers in advanced MM. The objectives of this proposal are to assess the prognostic significance of CTC and bone marrow (BM) micrometastases in patients with advanced melanoma (i.e patients with melanoma >4mm thickness, with lymph node or distant metastases). Blood and BM from 250 patients with advanced melanoma who were rendered surgically free of disease will be tested for CTC and micrometastases using reverse transcriptase po1yrnerase chain reaction (RT PCR) for the presence of tyrosinase, MART1/Melan-A and GAGE mRNAs. The test data will be correlated with outcome and other clinico-pathologic parameters - The investigators will also study the variation in blood RT PCR results in relation to serial sampling and its prognostic significance. The expression of these markers will be also studied in the primary tumors and metastatic tissue deposits by immunohistochemistry and RT PCR. This latter tissue data will be correlated with the RT PCR tests for CTC and BM micrometastases in order to study how these markers are modified during the metastatic process. This will increase our understanding of the metastatic process in MM, and provide new prognostic markers aimed at better stratifying and therefore more accurately treat MM patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COARSE MELANIN IN HUMAN MELANOMA Principal Investigator & Institution: Pawelek, John M.; Senior Research Scientist; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: A clinical feature of primary cutaneous melanoma is variegate pigmentation, yet little is known of its cellular basis. Clark (1977) observed melanoma cells with "melanin deposited in a coarsely granular fashion, commonly seen in vertical phase melanomas". The purpose of this study was to investigate these coarse melanin structures and their potential role in melanoma progression. Archival biopsies of primary and metastatic melanomas were surveyed for coarse melanin-containing melanoma cells and characterized through immunohistochemistry. In 14 of 18 cases of primary vertical phase tumors, coarse melanin structures were found in hypermelanotic areas in both melanoma cells and melanophages. The structures had a characteristic glycosylation pattern of beta 1-6 branched N-glycans, detected by staining with the lectin LPHA. They also stained with HMB45 and anti-CD63 (phagolysosomal membrane
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component. Thus, coarse melanin was associated with phagolysosomal membrane component). Thus, coarse melanin was associated with phagolysosomal vesicles having melanosomal components. Further, similar vesicles were detected in non-melanized melanomas, staining positively for LPHA, HMB45, and CD63, yet lacking melanin. Since betaI-6 branched N-glycans are highly correlated with metastasis, and are indicators of poor prognosis in breast and colon carcinomas, the possibility is raised that these LPHA-staining melanoma cells may be involved in metastatic progression. Consistent with this, an initial survey of archival melanoma metastases revealed an abundance of cells with coarse melanin vesicles. The purpose of this study is to expand our initial observations to a larger cohort of primary and metastatic melanomas, matched from individual patients, to determine the prevalence and distribution of such vesicles in melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF EYE MELANOMA METASTASIS Principal Investigator & Institution: Grossniklaus, Hans E.; Professor; Ophthalmology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 05-MAR-2001; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term goals of this research are to identify compounds that may be used in human trials to prevent and control eye melanoma metastasis. Despite advances in the treatment of primary ocular melanoma, there been no decrease in the mortality rate of this disease. In humans, ocular melanoma often spreads to the liver as micrometastases that have the potential to grow into vascularized metastases and lead to death. There is evidence that downregulation of the natural killer (NK) response is associated with an increase in micrometastases, and upregulation with immunotherapeutic agents such as interferon (IFN) decrease the number of micrometastases. Additionally, there is evidence that primary ocular melanoma produces angiostatin, an anti-angiogenic compound that suppresses growth of micrometastases into vascularized metastases. The objective of this proposal is to test the mechanisms of immunotherapeutic and anti-angiogenic/anti-melanoma invasion agents in a murine model of ocular melanoma that spreads to the liver and causes micrometastases that potentially grow into metastases. Intramuscular (IM) injections of IFN alpha-2b wil1 be given prior to enucleation and subcutaneous (SC) injections of angiostatin will be given just after enucleation of the eyes that contain melanoma. The IFN will eliminate micrometastases by enhancing the host NK response. Both the IFN and angiostatin will prevent the progression of micrometastases into metastases by antiangiogenesis. Angiostatin will prevent metastases by an anti-melanoma invasion effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--IMMUNE MONITORING Principal Investigator & Institution: Mier, James W.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The Immunologic Monitoring Laboratory (IML) will serve three of the five primary projects and two of the developmental projects of this SPORE application. This laboratory has two primary responsibilities: 1) It will perform the majority of assays proposed to assess the effects of treatment (e.g. with dendritic cell vaccines, biochemotherapy) on the number, phenotype, and function of melanoma antigenspecific T cells isolated from serial blood specimens, lymph nodes, and tumor biopsies.
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These assays will consist primarily of peptide- and tumor cell-based ELISPOT analyses, tetramer analyses, as well as assays of cytolytic activity, cytokine induction and proliferation. 2.) The IML will also be responsible for the studies proposed to evaluate the homing characteristics of cutaneous T cell lymphoma (CTCL) cells (Project 3) and those of lymphocytes obtained from the blood, lymph nodes, or tumor tissues of melanoma patients (Projects 4 and 5). These assays consist of extensive multi-parameter flow cytometry studies of adhesion molecule and chemokine receptor expression. The laboratory studies conducted by the IML will determine the extent to which various immune-based therapies immunize patients against melanoma antigens and the extent to which the results of surrogate assays of specific immune responses correlate with treatment outcome and other clinical parameters. They will also provide a great deal of new information about the chemokine receptors and adhesion molecules expressed by CTCL cells and by the PBL and TIL of patients undergoing immunotherapy for melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENDRITIC CELL-BASED GENETIC IMMUNOTHERAPY FOR MELANOMA Principal Investigator & Institution: Economou, James S.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JAN-1999; Project End 31-JAN-2007 Summary: (provided by applicant): This is a competitive renewal for ROI CA79976 "Dendritic cell-based genetic immunotherapy for melanoma" in which we request support for years 05-08. Our accomplishments in the previous funding period include: 1. defining the immunological events taking place in a murine melanoma model using dendritic cell (DC) engineered with a defined tumor antigen MART-1, 2. completing a phase l/II clinical trial in melanoma patients receiving MART-1/27-35 peptide pulsed DC and 3. opening a gene therapy trial using adenovirus (AdV) MART-1-transduced DC. Based on this progress, we propose to continue our translational studies of genetic immunotherapy of human melanoma centered around three specific aims. Aim 1: Genetic Immunotherapy in a CDS-Deficient Environment. We have made the remarkable and original observations that CD8 or Class I knock out mice immunized with AdVMART1-transduced DC have superior levels of protection to B16 melanoma than wild type (wt) mice. Since wt mice depleted of CD8 cells are unable to generate protective immunity, CD8 KO mice have developed a compensatory mechanism from generating robust tumor immunity to DC vaccination. We present preliminary evidence that this antitumor immunity is mediated by collaboration between effector cells of the innate (NK-like) and adaptive (CD4) arms of the immune systems. We propose to characterize the underlying mechanism. Aim 2: The Biology of Class I and Class IIRestricted T Cell Responses in AdVMART1/DC Immunized Patients with Melanoma. This clinical trial, in which patients with stage IV MART-1-positive melanoma are immunized with AdVMART1/DC, provides a unique opportunity to define immunological events triggered by genetic immunization to a defined "self" tumor antigen. Only two epitopes have been described for this small protein-HLA-A2.1restricted MART-1/27-35 and HLA-DK4 restricted MART-1/51-73. Using ELISPOT and tetramer assays for this class I and II epitopes, we will quantitate, isolate and study MART-1-reactive CD8 and CD4 T cell in immunized patients. We will also study the role of determinant spreading and cross-presentation in clinical response, the biology of DC used for vaccination and the possible participation of innate (NK) immunity in DCbased immunotherapy. Aim 3: CTLA4 Blockade in Clinical Dendritic Cell-Based
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Immunotherapy. DC-based immunotherapy generates occasional but dramatic clinical antitumor responses. We have closely studied one subject in whom the administration of MART-1/DC vaccines was followed by a CTLA4 blocking antibody. Immunological analysis suggests that the antitumor immune response initiated by the DC vaccines was maintained by CTLA4 blockade. To test this hypothesis, we have designed a phase II randomized trial with the primary goal of detecting the effect of MART-1/27-35/DC + CTLA4 blockade on the frequency of melanoma antigen-specific activated T cells using ELISPOT assays. This trial will provide insight in the autoregulatory mechanisms that govern the activity of DC-based immunotherapy. In summary, we propose to continue our translational program in genetic immunotherapy with an emphasis on immune mechanism and clinical hypothesis-testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENDRITIC CELL-BASED VACCINES IN STAGE IV MELANOMA PATIENTS Principal Investigator & Institution: Nickoloff, Brian J.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2006 Summary: The purpose is to perform carefully controlled vaccine-based trials to determine the optimal therapeutic approach by which tumor reactive T lymphocytes can be safely and efficiently generated for treatment of advanced melanoma patients, coupled with alternative methods of immunological monitoring that move beyond changes in the blood to detailed cellular and molecular tissue-based analyses. Since melanoma will be diagnosed in 43,000 new patients annually, and 7,300 deaths result from melanoma, new treatment approaches are indicated because melanoma generally progresses despite conventional chemotherapy and radiation. A promising approach for melanoma involves immunotherapy in which the patient's immuno system is stimulated to generate effective anti-tumor responses. The primary antigen presenting cell used in these trials are dendritic cells (DCs) pulsed with autologous tumor-cell lysate containing T-cell stimulatory tumor cell-derived antigens. Incentives for this immunotherapy approach include the capacity of appropriately selected DCs to stimulate both CD4+ as well as CD8+ effector T cells. Our therapeutic strategy is designed to by-pass several known methods by which melanoma cells normally thwart the immune system. Thus, we will expand both immature and mature DCs ex-vivo (using CD40L) apart from the systemic immunosuppressive factors produced by melanoma cells, and create lysates from autologous tumor cells. Studies are designed to identify immunological in-vivo activity in blood, and at various tissue sites for mature versus immature DCs, and the preferred method of vaccination, to generate the highest number of cytotoxic T cells and positive clinical responses. Since many Stage IV patients will not respond to treatment with complete remissions, focus will be directed at methods to monitor and explore the mechanistic basis by which tumor cells escape the activated immune response following vaccination. Specific protocols include an initial randomized Phase I study of 24 patients to compare immature DCs versus mature DCs loaded with tumor lysate-containing antigens injected intradermally, followed by a randomized Phase II clinical trial of 40 patients using the best DC (immature vs. mature) and comparing intradermal versus intranodal routes of delivery. Immunological monitoring of patients will include a comparison of traditional blood-derived markers versus assays performed on cells with serial gene profiling of samples derived from sequential fine needle aspirates of metastatic melanoma lesions before and after vaccination, as well as normal lymph nodes and the sentinel node draining from
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vaccination sites. The vaccination site itself will also be examined in the phase I trial comparing the local tissue response to mature versus immature DCs. Taken together the guiding tenant of this grant is that we can best mimic the physiological protective immune pathway by carefully isolating specific types of DCs and exposing them ex-vivo to appropriate tumor antigens, followed by re-infusing them in a manner that takes advantage of the immunological potency of DCs, with concommitant avoidance or bypassing local and systemic immunosuppressive or immune-escape mechanisms created by melanoma cells. In this way greater understanding and better treatment protocols and immunological monitoring strategies will be developed for patients undergoing vaccination to eliminate metastatic melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETECTION OF METASTASIS ASSOCIATED ANTIGENS IN MELANOMA Principal Investigator & Institution: Hamby, Carl V.; Microbiology and Immunology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 1999; Project Start 06-APR-1999; Project End 31-MAR-2004 Summary: (adapted from the investigator's abstract) The major cause of mortality in patients with malignant melanoma is metastatic dissemination of primary tumors. Currently, there are no highly specific cellular markers for evaluating the metastatic potential of primary melanoma tumors. The long-term goals of this project are to discover diagnostic markers for the early detection of metastatic disease in patients with melanoma and to evaluate these markers as prognostic indicators for the clinical course of disease. To identify these molecules we proposed to use a phage display library of human single-chain variable fragment (scFv) antibodies. The library contains >108 different scFv antibody specificities, which they expect is sufficiently diverse to contain scFv antibodies recognizing metastasis-associated antigens. They will utilize a panning procedure to select a subset of scFv antibodies that bind to a line of cultured human melanoma tumor cells, which are highly metastatic in nude mice. From this subset they will remove scFv antibodies that can bind to an autologous subline of weakly metastatic human melanoma tumor cells. The scFv that remain will be screened for reactivity against tissue samples of primary tumor and metastatic lesions obtained from melanoma patients. They expect to discover scFv antibodies that specifically recognize metastasis-associated antigens in human melanoma lesions. These scFv antibodies will be used for the development of early diagnostic markers and prognostic indicators of metastatic dissemination of human melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELANOMA
DIRECT
COMPARISON
DENDRITIC
CELL
VACCINES
IN
Principal Investigator & Institution: Halusa, Frank; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: Melanoma is a lethal malignancy that is poorly responsive to conventional treatments, but it is potentially an immunoresponsive disease. Several approaches to melanoma immunotherapy have demonstrated the feasibility of eliciting RT cell responses to melanoma- associated antigens. In this proposal we focus on the use of dendritic cells (DC) to induce anti-tumor immunity in patients with advanced melanoma. Because of the manner in which they process protein, express co-stimulatory
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Melanoma
molecules, and elaborate cytokines that support the development of cytolytic T lymphocyte (CTL) responses, DC are uniquely capable of antigen presentation. They appear to be ideal vehicles for delivery of antigen in tumor vaccination strategies. However, the optimum strategy for antigen delivery has not been determined. Our laboratories have in parallel studied two methodologies for antigen delivery: peptide pulsing of DC with melanoma antigen-derived peptide epitopes, and production of cell fusions between DC and tumor cells. We carried out pre-clinical studies on DC production and function. In doing so, we demonstrated our ability to reliably produce DC in high yields by culturing PBMCs obtained via leukapheresis. Phenotypic and functional analyses showed that these cells express a profile of cell-surface markers characteristic of DC. Concurrently we utilized DC to verify that specific substitutions of the gp100 280 epitope result in peptides that bind to HLA-A2 with higher affinity than the native epitope. Based on these studies, w4e are carrying out a phase I, dose escalation trial of peptide- pulsed DC therapy. To date we have shown that this approach is safe. Immunogenicity of vaccination has been documented by the production of CTL specific for the immunizing antigen, and clinical responses have been observed. We also studied the production of DC/tumor fusions. Pre- clinical data demonstrated our ability to generate heterokaryons from DC and breast, ovary, renal cell and melanoma tumors. Such hybridomas express both DC-derived co-stimulatory molecules and tumor-associated antigens and reproducibly stimulate the production of anti-tumor T cell immunity in vitro. We are conducting a phase I trial and preliminary have demonstrated that clinical administration of DC/tumor fusion is safe. DC/fusions also elicit T cell anti-tumor immunity, documented by enhanced interferon secretion in response to stimulation by tumor. Based on these pre-clinical and phase I clinical data, we propose to translate these findings into a phase II, randomized clinical study. Patients will be recruited to both approaches using uniform eligibility criteria at our four institutions. The primary endpoint of the study is the comparison of immunologic data obtained from the approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DORMANCY VERSUS PROGRESSION OF HUMAN PRIMARY MELANOMA Principal Investigator & Institution: Kerbel, Robert S.; Director; Sunnybrook & Women's Coll Hlth Scis Ctr Health Sciences Centre Toronto, Timing: Fiscal Year 2001; Project Start 01-JUN-1992; Project End 31-DEC-2002 Summary: (adapted from the investigator's abstract) The majority of primary cutaneous melanomas go through a prolonged period of dormant growth before acquiring malignant properties. Unlike most other primary tumors, however, this dormancy stage is visible in melanomas, subdermal/orthotopic injection of human melanoma cell lines, obtained from different stages of disease progression, into nude mice. Thus, whereas almost all advanced stage primary or metastatic-derived cell lines give rise to progressively small slow-growing, plaque-like lesions -- similar to radial growth phase (RGP) or thin vertical growth phase (VGP) tumors in humans. Using various methods, e.g. retroviral insertional mutagenesis or gene transfection, this applicant has recently succeeded in isolating tumorigenic variants from a number of such early-stage primary melanomas. These cell lines present an outstanding opportunity to study the basis of pre-malignant melanoma dormancy and the reasons for its termination. First, (based on their recent results), they believe there are three major interconnected factors which govern primary melanoma dormancy. These are: (i) sensitivity to inhibitory controls mediated by several cytokines, including IL-6; (ii) a deficient capacity of melanoma cells
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to survive in a multicellular growth context; (iii) a deficient ability to induce angiogenesis; Second, overcoming these 'defects' results in acquisition of overt malignant growth characteristics. Third, genetic alterations thought to be involved in the progression of melanomas, such as loss of p21WAF1 or p16INK4, do so by affecting several, or all three phenotypes simultaneously (i.e., cell proliferation, survival, and angiogenesis). Examination of these hypotheses comprise the three specific aims of the research program. The proposed research will shed new light on what is probably the most crucial stage of melanoma progression, but which, thus far, has received little experimental scrutiny because of the lack of appropriate experimental models. It may also serve as a model for factors influencing premalignant-primary tumor dormancy in other types of cancer where access to early-stage lesional material is severely limited, or non-existent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ECM MATRIX, PROTEASE AND MELANOMA PROLIFERATION Principal Investigator & Institution: Declerck, Yves A.; Vice President Research, and Director Re; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2003; Project Start 10-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The extracellular matrix (ECM) is a microenvironmental factor that controls cell function. The central theme of this grant proposal is the investigation of the mechanisms by which the ECM controls tumor cell proliferation and how they are affected by proteolytic degradation. We postulate that modification of the ECM by proteases, and in particular matrix metalloproteinases (MMPs), alters the contact between tumor cells and matrix proteins, which subsequently influences the expression of proteins controlling the cell cycle, to favor cell proliferation. In support of this concept we have published observations demonstrating that upon contact with intact fibrillar type I collagen, human M24met melanoma cells are growth arrested at the GI/S interphase and that this arrest involves a specific up-regulation of the cell cyclin dependent kinase inhibitor p27KIP1 (Henriet et al., PNAS, 97:10026-10031, 2000). We have now obtained evidence that up-regulation of p27KIP1 is the consequence of a down-regulation of the S phase kinase associated protein 2 (Skp2) that binds p27KIP1 to ubiquitin conjugase and targets it for degradation by proteasomes. We discovered that down-regulation of Skp2 is dependent on protein kinase Cd (PKCd) activity and have obtained preliminary evidence suggesting that this ECM-dependent regulatory pathway is functional in other melanoma and non-melanoma tumor cell lines. In contrast, in the presence of denatured, non-fibrillar collagen (gelatin), p27KIP1 is down-regulated, cells spread, the focal adhesion kinase protein p125 FAK is phosphorylated, and cells enter into cell cycle. On the basis of these observations, we hypothesize that proteolytic degradation of fibrillar collagen by melanoma cells is necessary to down-regulate p27KIP1, establish functional focal adhesions, and enter the cell cycle, and that preventing collagen deg radation will inhibit cell growth in a p27KIP1/Skp2 dependent manner. Our proposal has 4 specific aims. In the first specific aim we will explore the signaling pathway by which contact with fibrillar collagen activates PKCd and down-regulates Skp2, and obtain proof that p27 and Skp2 are the main regulators downstream of PKCd. In a second specific aim, we will explore the signaling pathway by which contact with denatured and proteolyzed collagen promotes cell proliferation and will determine the role of RhoA, p27KIP1 and Skp2 in this pathway. In the third specific aim, we will examine how proteolytic modification of fibrillar collagen by MMPs changes the environment from growth inhibitory to growth permissive. In a fourth specific aim we will validate our observations in a murine model
24
Melanoma
of melanoma growth and in human melanoma tumor specimens. This information will lead to a better understanding of the role of matrix degrading proteases such as MMPs in cancer, which will be important in the design of better clinical trials involving MMP inhibitors in cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCEMENT OF IMMUNOGENICITY OF HUMAN MELANOMA VACCINE Principal Investigator & Institution: Hsueh, Eddy C.; John Wayne Cancer Institute 2200 Santa Monica Blvd Santa Monica, Ca 90404 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: Our group has demonstrated the clinical promise of a whole-cell vaccine composed of irradiated but viable melanoma cells from three human melanoma cell lines (M10, M24, and M101). Because melanoma cells also can express receptors for cytokines currently used in invitro expansion and activation of dendritic cells, we hypothesized that the efficacy of a human whole-cell melanoma vaccine could be significantly increased by using these cytokines to upregulate vaccine expression of costimulatory molecules. This study's objective is to demonstrate the induction of significant immune responses in patients receiving a cytokine- modified M24 whole-cell vaccine for treatment of regional or distant metastatic melanoma. There are three specific aims: 1. To determine whether certain cytokines such as interleukin 4, granuloctye macrophage-colony stimulating factor, and tumor necrosis factor-alpha can upregulate expression of multiple costimulatory molecules (CD54, CD58, CD80, and CD86) on human melanoma cells. 2. To determine how the coexpression of multiple costimulatory molecules and tumor antigens on melanoma cells affects the activation of T cells, the induction of autologous tumor-specific cellular cytotoxicity, and induction of specific cytotoxic T cells against MAGE1, MAGE3, and tyrosinase peptide epitopes. 3. To determine if administration of a cytokine- modified melanoma cell vaccine can induce significant immunological responses, specifically delayed-type hypersensitivity, cellular cytotoxicity, and complement-dependent cytotoxicity, in HLA haplotypematched melanoma patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EVOLUTION OF ANTIMETASTATIC ENZYME Principal Investigator & Institution: Smider, Vaughn V.; Integrigen, Inc. 42 Digital Dr, Ste 6 Novato, Ca 94949 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-DEC-2003 Summary: (provided by applicant): Cancer is a devastating disease with few cures. Most treatments rely on damaging cellular DNA or disrupting the cell cycle in tumor cells. Metastatic melanoma is especially devastating, as it is often rapidly fatal due to its relative resistance to conventional chemo and radiation therapy. However, a novel pathway involved in tumorigenesis and metastasis in melanoma and other cancers is activated by the amino acid tyrosine. Remarkably, tumor invasion and metastases are suppressed by depletion of tyrosine in melanoma cell lines, as well as mouse models. Tyrosine depletion can be accomplished by dietary restriction or through catabolism by the enzyme tyrosine phenol-lyase (TPL). The activity of TPL as measured by Km is low, requiring large amounts of the enzyme for further animal investigation or eventual human therapy. "DNA shuffling" is one method capable of evolving enhanced proteins through a DNA homology based process. This method, however, is not applicable to
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TPL because its structural homologs are not similar at the DNA level. IntegriGen is developing a method to non-homologously "shuffle" genes. This method will be applied to TPL in order to enhance its function as measured by Km. Thus, this project has two applications: 1) to evolve a novel TPL variant which has enhanced activity, that can subsequently be evaluated as an anti-cancer therapeutic, and 2) to establish a new method to non-homologously "shuffle" genes as a molecular evolution technology applicable in general to protein engineering. PROPOSED COMMERCIAL APPLICATIONS: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GANGLIOSIDE GD2 AS TARGET FOR IMMUNOTHERAPY IN MELANOMA Principal Investigator & Institution: Foon, Kenneth A.; Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-AUG-1996; Project End 31-AUG-2007 Summary: (Provided by applicant) The objective of this proposal is to apply the antiidiotype (Id) vaccine approach for the therapy of stage III (resected node positive) melanoma patients. Disialoganglioside GD2 is expressed at high density on melanoma cells and will be used as a target for immunotherapy. We have generated a murine monoclonal anti-Id antibody 1A7 (TriGem) which functionally mimics GD2 and acts as a surrogate protein antigen for the ganglioside. In pre-clinical studies, active immunization of mice, rabbits and monkeys with TriGem induced polyclonal IgG antiGD2 responses and TriGemspecific T cell proliferative responses suggesting the generation of CD4+ T cell help. In previous clinical trials, we have demonstrated that patients with advanced metastatic melanoma and patients with high risk melanoma in the postsurgical adjuvant setting generated active immune responses against GD2 following immunization with TriGem. We demonstrated a predominantly IgG polyclonal humoral immune response with specific binding to purified GD2 and GD2 positive cells that mediated antibody-dependent cellular cytotoxicity (ADCC). The vaccinated patients also demonstrated in vitro T cell proliferative responses in the presence of TriGem. Median survival was 16+ months for 47 patients with advanced disease. Eighty-two percent of 69 patients with stage III disease are alive at a median follow up of 2 years. Twenty-five of the 69 patients with stage III disease were treated with high dose interferon Alfa-2b (HDI) plus TriGem. Immune responses were equivalent or superior to TriGem alone and 96 percent are alive and 80 percent are disease free. Toxicity of TriGem was limited to local reactions at the site of injection with occasional mild fevers. In this project, we will conduct a randomized Phase III clinical trial in which 294 patients with node positive local regional melanoma will be stratified by nodal status (IIIA vs IIIB vs IIIC) and then randomized to treatment with either HDI or HDI plus TriGem. The patients will be observed for immune responses and for clinical outcome. We will continue to test the hypothesis that elicitation of a strong immunologic response will eradicate the residual tumor cells, prevent the dissemination of metastatic disease, and prolong survival in high risk patients in the post-surgical adjuvant setting. To achieve this goal, we have proposed four specific aims. The primaryobjective of this clinical study is to compare the effect of HDI versus HDI plus TriGem on relapse free survival. The secondary objective is to compare the effect on overall survival. The third objective is correlation of the quantitative IgG anti-GD2 response with relapse free and overall survival. The fourth is to monitor toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC EPIDERMIOLOGY OF MELANOMA Principal Investigator & Institution: Elder, David E.; Professor of Pathology and Laboratory Me; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The Melanoma Genetics Consortium, comprising groups with diverse expertise from the USA, Europe and Australia, was established in 1997 to facilitate research into: -- the identification and characterisation of melanoma susceptibility genes, and -- the interactions of the effects of these genes with each other, and with relevant environmental exposures -chiefly solar ultraviolet (UV) radiation - in melanoma tumorigenesis. These goals will only be achieved by conducting sufficiently large studies of genetically diverse populations experiencing a range of environmental exposures: objectives beyond the capacity of any single group. The current proposal is specifically motivated by the Consortium's success, over a short period of time, in: -rapidly integrating information from the large number of multiple-case melanoma kindreds ascertained by its individual groups and initiating comparative penetrance and linkage studies, and -- successfully initiating new collaborative projects to map and identify melanoma predisposition genes over the past two years, which have identified significant new candidate loci for melanoma susceptibility genes. The general objectives of this proposal are: -- to maximise the epidemiological and genetic information derived from multiple-case melanoma kindreds ascertained by the Consortium in three continents Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOME WIDE APPROACH TO MELANOMA CLASSIFICATION Principal Investigator & Institution: Flotte, Thomas; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The incidence of malignant melanoma is increasing worldwide at rates that have been reported to be between 3 and 7 percent. In the United States, the incidence of melanoma is rising faster than any other malignancy. The overall goal of this project is to evaluate whether gene expression profiling can provide additional diagnostic and prognostic information for patients with malignant melanoma. Despite decades of attempts to identify clinical and histological features that would be useful in predicting which lesions were going to metastasize, only limited success can be claimed. The measured thickness (the Breslow measurement) and the presence or absence of ulceration are the strongest predictors of outcome for localized disease. The identification of patients with a high risk of metastasis is important for the surgical management of the patient as well as to determine which patients should be admitted to clinical trials of adjuvant agents as these become available. A comprehensive knowledge of the genes expressed by melanoma may be helpful in management of these patients. The specific aims are as follows: 1. To use genome-wide gene expression using microarray technology of human metastatic melanoma and congenital nevi in tissue specimens to identify candidates for accurate prognostication of melanoma patients with localized disease (Stages I and II). 2. Develop in situ hybridization assays for the candidate genes identified in Specific Aim 1. The assays will be validated both on from the tissues used in Specific Aim 1 as well as specimens from additional patients. 3. In situ hybridization will be utilized to examine tissue sections of primary melanomas. The pattern of involvement of the primary tumors will be
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correlated with clinical outcome. The results will be correlated with known prognostic factors to determine if the information provides additional prognostic information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGHLY DIFFERENTIATED TISSUE CULTURE MODELS OF MELANOMA Principal Investigator & Institution: Klausner, Mitchell; Mattek Corporation 200 Homer Ave Ashland, Ma 01721 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAR-2003 Summary: (provided by applicant): With the exception of lung cancer in women, the incidence of cutaneous melanoma (CM) is increasing faster than any other cancer. Current estimates are that one of every 75 individuals in the US will contract CM during his or her lifetime. The various stages of melanoma have been well described, however, to devise improved treatments allowing patients to lead longer and more productive lives, a better understanding of progression of CM is needed. The purpose of this proposal is to produce highly differentiated, tissue culture models of the various stages of CM progression. During Phase I, cell lines from the various disease states of CM will be expanded in monolayer culture and characterized. Using a serum free culture system, these cells will be incorporated into an organotypic, full thickness skin model to produce tissue reconstructs which parallel the various stages of CM in vivo. The tissues will be characterized in terms of morphology, tumor progression, and adhesion receptors. Finally, reproducibility of the tissue models will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IDENTIFICATION OF MELANOMA PREDISPOSITION LOCI Principal Investigator & Institution: Cannon Albright, Lisa A.; Professor; Medical Informatics; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Previous investigation of Utah melanoma pedigrees resulted in the identification of the only major melanoma predisposition gene yet identified, cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) (Cannon Albright et al., 1992; Cannon Albright et al., 1994; Kamb et al. 1994). However, only 20-40% of melanoma high-risk pedigrees have a p16 mutation, suggesting that additional melanoma predisposition genes exist. This is also supported by the existence of studied informative melanoma pedigrees that do not have mutations in the coding region of the p16 gene nor demonstrate linkage to the p16 locus on chromosome 9p21. The goal of this project is to identify additional melanoma predisposition genes through the genotypic characterization of Utah high-risk melanoma pedigrees which do not appear to be due to p16, ARF, or CDK4. This investigation will utilize resources that are unique to the University of Utah to identify non-p16 melanoma predisposition genes. These resources include 1) the Utah Population Database (UPDB), which permits identification and recruitment of numerous, extended high-risk melanoma pedigrees and facilitated investigation of the original Utah high-risk pedigree collection used to identify p16 and 2) a highly focused Familial Melanoma Research Clinic (FMRC) that is devoted to the clinical examination and molecular characterization of at-risk relatives in high-risk melanoma pedigrees. We will identify and sample high-risk melanoma pedigrees, perform a genomic search on the pedigrees with no indication of 9p involvement, and fine map any predisposition regions identified. Identification of melanoma predisposition genes will ultimately increase our ability to appropriately screen high-
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Melanoma
risk patients, and will suggest additional molecular pathways that may serve as targets for the diagnosis and treatment of melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMAGING MALIGNANT MELANOMA WITH RADIOLABELED ALPHA-MSH PEPTIDE ANALOGS Principal Investigator & Institution: Quinn, Thomas P.; Assistant Professor; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (Revised Abstract) (provided by applicant): This application outlines a research effort to develop and evaluate radiolabeled peptides for malignant melanoma imaging. Malignant melanoma is a serious public health problem due to an increase in its incidence and resistance to conventional chemotherapeutics and external beam radiation therapy. Early detection is critical for proper therapeutic management. There is a clear need to develop new and efficacious imaging and therapeutic agents. Our laboratory has developed a new class of metal-cyclized peptide (CCMSH) that target the a-MSH receptor present on melanoma cells. The CCMSH peptides will be radiolabeled with 99mTc, 111In for SPECT and 64Cu for PET imaging of melanoma in murine and human melanoma mouse models. Mice bearing solid tumors and metastatic melanoma in the lungs will be imaged at various times during the course of their disease to determine the detection sensitivity and specificity of the radiolabeled peptides. Micro SPECT and micro PET imaging studies will also be compared to determine the optimal combination of peptide, radionuclide and detection modality for melanoma imaging. The CCMSH imaging agents are envisioned to be part of a matched pair strategy for melanoma imaging and therapy in which the same melanoma targeting vector (CCMSH) can be radiolabeled with radioisotopes that possess imaging or therapeutic properties. We also plan to employ bacteriophage (phage) display technology to discover new melanoma targeting vectors. The random peptide libraries, displaying 5150 peptides per particle, will be selected in human melanoma bearing mice for tumor targeting peptides. In vivo selection strategy should closely simulate the complex targeting environment an imaging agent encounters thus allowing us to select superior melanoma avid phage. We propose to use the tumor avid phage particles themselves as targeting agents in a pretarget approach. The tumor avid phage will be conjugated with <10 copies of Neutravidin per particle. Neutravidin phage will be injected into tumor bearing mice and allowed to localize to the tumor or clear the body over a period of day(s). Indium-111 labeled DTPA-biotin will be injected intravenously and the animals will be imaged over a period of several hours. Pretarget phage imaging will allow us to take advantage of the power of in vivo selection with polyvalent peptide display while not suffering the partitioning consequences of a large radiolabeled molecule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNITY TO MELANOMA VIA DENDRITIC CELLS Principal Investigator & Institution: Steinman, Ralph M.; Professor & Senior Physician; Lab/Cell Physiol & Immunology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: Human tumor immunology has been advanced by the identification of antigens and the corresponding tumor specific lymphocytes, particularly killer and helper T cells. This program will exploit the dendritic cell [DC] to enhance presentation of melanoma antigens to T cells, primarily in humans but also in mouse models. Our
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MHC class I and II products on DCs can be charged with an array of tumor antigens by feeding apoptotic and necrotic cells; 3] antigen-bearing DCs can be charged with an array of tumor antigens by feeding apoptotic and necrotic cells; 3] antigen-bearing DCs can rapidly boost the human immune system in situ. Therefore an integrated program in Dallas and New York can begin to actively immune system in situ. Therefore an integrated program in Dallas and New York can begin to active immunize patients to melanoma antigens, concomitant with laboratory studies to learn to enhance DC processing of tumor antigens, to evaluate the roles of distinct DC subsets and maturation states, and to observe DC function in tumors and lymph nodes in situ. This program emphasizes melanoma, because tumor-specific T cells are known for mice and humans, and it is now evident that DCs an present in vitro melanoma antigens derived from apoptotic cells. Documentation of tumor-specific immunity in humans has become more accessible with quantitative assays that are in place and include: binding of MHC tetramers, production of ELISPOTS, and recall assays to elicit specific killer T cells. The program will include dual center randomized trials. In the first we will compare two types of DC in eliciting immunity to melanoma peptides, and look for speaking of the immune response to other antigens, as an index of cross presentation in vivo. In the second, we will compare DCs loaded with peptides vs. dying tumor cells in expanding tumor specific CD4 and CD8 T cells. Shared ongoing core facilities for administration, DC production, and immune monitoring will energize and standardize interactions. Together, we hypothesize that DCs, nature's adjuvant, will enhance immunity to tumor antigens so that the clinical consequences for cancer vaccination and therapy can be pursued. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNODERMATOLOGICAL THERAPY OF SKIN CANCER Principal Investigator & Institution: Elmets, Craig A.; Professor and Chair; Dermatology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 06-JAN-1999; Project End 31-DEC-2003 Summary: Non-melanoma (basal cell and cutaneous squamous cell carcinomas) skin cancer and melanoma are common human malignancies whose growth is controlled at least in part by T-lymphocyte mediate immune responses. There is great interest in developing new modalities which will enhance and exploit this host defense mechanism for therapeutic benefit. We have observed that cutaneous squamous cell carcinomas and melanomas exhibit a profound reduction in tumor growth when treated with the bacterial super- antigen Staphylococcal enterotoxin B (SEB). The response is immunologic in nature and is highly specific for malignant tissue, both in vivo and in vitro. SEB may thus have great potential as a immunodermatologic therapy for skin cancer. In this proposal, we plan to investigate the hypothesis that the bacterial superantigen SEB causes selective destruction of non- melanoma and melanoma skin cancers by serving as a ligand between the tumor cell and cytotoxic T-lymphocytes. We will more fully assess the immunodermatologic potential of SEB as a therapy for skin cancer by studying the range of cutaneous tumors responsive to SEB immunodermatologic therapy. We will also assess the efficacy of mutants SEB as therapeutic agents in skin cancer in order to identify those regions of the molecule most important at causing regression of skin cancers. Studies will be performed to evaluate whether inhibition of tumor cell growth by SEB and T-cells is cytotoxic in nature. Experiments will be conducted to identify the molecule on cutaneous squamous cell carcinomas to which SEB binds that allows it to inhibit the growth of cutaneous tumors. We will be particularly interested in determining whether SEB binding to major histocompatibility
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complex class I and class II molecules plays a role in the response. Because SEB limits the growth of malignant cells, but has little effect on keratinocytes from which these tumors are derived, we will investigate whether this is due to differential binding on SEB to tumor cells versus normal keratinocytes, differences in the expression of the adhesion molecule ICAM-1 on these two cell types, or to differences in the Fas pathway in normal versus malignant keratinocytes. Finally, experiments will be performed to precisely define the characteristics of the T-cell most effective at causing SEB-induced regression of cutaneous tumors. The ultimate goal of this proposal is to generate new knowledge that can be used to develop new and better strategies for the control of nonmelanoma and melanoma skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGICAL METASTASES
MODULATION
OF
OCULAR
TUMOR
Principal Investigator & Institution: Niederkorn, Jerry Y.; Professor; Ophthalmology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 31-DEC-2006 Summary: (From the Applicant's Abstract): Uveal melanoma is the most common and malignant intraocular tumor in adults. Metastases appear in 19 percent to 35 percent of patients within 5 years of diagnosis of uveal melanoma. The liver is the primary organ for the development of metastases and up to 95 percent of the patients who die from uveal melanoma, have liver metastases. Although the treatment of primary uveal melanoma has improved substantially over the past two decades, there have been no significant advances in the management of metastases and as such, the five year survival time for uveal melanoma patients has not changed in over 25 years. Regretably, there still remains no effective treatment for uveal melanoma metastases. This Research Plan will address three specific aims relating to the immunobiology and therapy of liver metastases, the leading cause of morbidity and mortality in uveal melanoma patients. The proposed studies consider three hypotheses. The first hypothesis proposes that a component of the innate immune system, the natural killer (NK) cell repertoire, is instrumental in controlling metastases arising from intraocular melanomas. A corollary of this hypothesis is that successful uveal melanoma metastases employ a variety of escape mechanisms to thwart NK cell-mediated immune surveillance. The second hypothesis predicts that therapeutic strategies that stimulate NK activity will overcome the NK escape mechanisms of uveal melanomas and will culminate in reduced liver metastases and improved host survival. The third hypothesis predicts that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be effectively used to treat uveal melanoma liver metastases. The specific aims for this project are: 1) Evaluate and characterize NK cell escape mechanisms employed by uveal melanoma cells; 2) evaluate NK cell-based immunotherapy; and 3) evaluate tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL)based therapy. These studies will utilize a wellcharacterized mouse model that recapitulates the human counterpart. The long rang goal of this project is to design, develop, and evaluate novel immunotherapeutic modalities for the prevention and treatment of uveal melanoma metastases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOTHERAPY OF MELANOMA WITH DENDRITIC-TUMOR HYBRIDS Principal Investigator & Institution: Shu, Suyu C.; Director; John Wayne Cancer Institute 2200 Santa Monica Blvd Santa Monica, Ca 90404
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Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): In the John Wayne Cancer Institute, active immunotherapy of melanoma by allogeneic tumor cell (PMCV) vaccination has shown enhanced survival of patients who developed an immune response but only a fraction demonstrates the regression of established metastases. Alternatively, the therapeutic efficacy may be improved if isolated tumorimmune T cells are transferred to the tumorbearing host. We have identified that lymph nodes draining tumor vaccines contain T lymphocytes specifically sensitized to the tumor, but those cells require in vitro activation to differentiate into functional cells. We have designed a clinical protocol to treat patients with metastatic melanoma with such T cells. Although responses were observed in some patients, the majority did not seem to benefit. A theoretically attractive improvement for both active and adoptive immunotherapy will rely on targeted vaccine designs. To induce antigen (Ag)- specific immune responses, host Ag presenting cells (APC) play a pivotal role. Among various APC, dendritic cells (DC) seem to be most potent for eliciting T cell responses. The use of DC for stimulating antitumor immunity has been achieved by pulsing DC with peptides, protein, tumor lysates or RNA derived from neoplastic cells. A new approach is the generation of DCtumor fusion hybrids. Because of technical difficulties, attempts have been made to fuse cells by exposing them to electric fields. Recently, a clinical trial treating patients with metastatic renal cancer with electrofusion of allogeneic DC and autologous tumor cells demonstrated a high response rate (7/17). Fused hybrids should have the ability to elicit both MHC class I- and II-restricted responses by processing and presenting both known and undefined Ag. With this approach, it may be the technique rather than conceptual aspects that limit its transfer to clinic. In animal studies, we have demonstrated that a high fusion efficiency (~35%) by electrofusion. Using PMCV, preliminary results showed at least a 10% fusion rate. In this project, we propose to carry out Phase I/Ii clinical trials and address important questions regarding the biological and immunological functions of autologous DC-allogeneic tumor hybrids generated by electrofusions. The specific aims are: 1) To optimize electrofusion of autologous DC and allogeneic melanoma PMCV cells; 2) To characterize the functions of fused cells for Ag processing and presentation as well as MHC restriction; 3) To conduct Phase I/II clinical trials of immunotherapy of melanoma; 4) To analyze humoral and cellular immune responses of patients undergoing immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING RISK ASSESSMENT FOR MELANOMA Principal Investigator & Institution: Colditz, Graham A.; Professor of Medicine and Epidemiology; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The overarching goals of this Project are (1) to utilize our epidemiological understanding of cutaneous melanoma in order to create clinical and population risk estimation and risk stratification and (2) to translate these modeling approaches into patient care in an active clinical setting We will explore different risk modeling approaches to better inform primary and secondary prevention strategies. This will lead t stratification for prevention trials, including chemoprevention when agents become available for clinical applications. Extensive epidemiological data from the Nurses' Health Study (121,700 women followed from 1976 to 2000), Health Professionals Followup Study (52,000 men followed from 1986 to 2000), and Nurses' Health Study II (116,000 women followed from 1989 to 2001) provide a rich resource on risk factors and the incidence of melanoma in over 230,000 women and 50,000 men. None of these cohorts
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has funding to evaluate melanoma risk. Given the unique size and scope of these cohorts, we will examine the ability of risk models to classify individuals with regard to risk of melanoma, and we will evaluate if such a classification of risk can be clinically useful in determining primary prevention strategies and in directing the level of screening surveillance. Based on the above, our specific aims are as follows. We will construct statistical models for melanoma risk, incorporating traditional epidemiological risk factors to stratify population subgroups based on risk We will construct separate models for women (combining data from the HS and NHS II cohorts) and women. We will construct separate models for women (combining data from the NHS and NHS II cohorts) and men. We will evaluate the models with respect to both goodness of fit (i.e., predicting incidence in subgroups) and discriminatory accuracy at the individual level, and will evaluate the additional discriminatory accuracy gained by including additional risk factors, including genetic markers. Using results from Aims 1 and 2 above, we will evaluate the potential public health effectiveness, in terms of reduction in disease burden, associated with various high-risk and population-based primary and secondary prevention strategies. Using results from Aims 1 and 2 above, we will test the hypothesis the individual risk awareness will lead to risk-minimizing behaviors. We will perform these studies at the adult general dermatology clinics affiliated with Harvard Medical School Department of Dermatology (i.e. Massachusetts General Hospital, Brigham and Women's Hospital, Beth Israel Deaconess Hospital). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INCREASING EFFECTS OF INTERFERONS FOR MELANOMA Principal Investigator & Institution: Borden, Ernest C.; Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 07-JAN-2002; Project End 31-DEC-2005 Summary: New therapies to eliminate melanoma must be identified both for the highrisk patient after surgery and for metastatic disease. Interferons (IFNs) have therapeutic activity in both clinical settings but little expansion has occurred in understanding of mechanisms underlying clinical effectiveness in melanoma -- or indeed other malignancies. Underlying clinical antitumor effects must be the potent and pleiotropic gene modulatory effects that occur at a transcriptional level. Utilizing oligonucleotide array analysis, over 100 genes that are induced by IFNs in a melanoma cell line have been identified. On an equimolar basis these genes are induced to a substantially greater extent by IFN-beta than by IFN-alpha2. Based upon the hypothesis that the antitumor effects of IFNs in melanoma may result from direct effects on tumor cells, apoptosis, an understudied effect of IFNs, is a focus of our studies. Induction of apoptosis, coupled with array studies, led to the protein TRAIL (TNF-Related Apoptosis Inducing Ligand) as a mechanism that in part accounts for melanoma cell death. In sensitive melanoma cell lines, IFN-beta, but not IFN-alpha2, induces caspase dependent apoptosis that was associated with TRAIL. Resistant melanoma cell lines are characterized by lack of proliferative inhibition or apoptosis induction by either IFN- alpha2 or IFN-beta and lack of TRAIL induction. The data further suggest that apoptosis induction is negatively influenced by NFkappaB (Nuclear Factor kappa B) activation by TRAIL. With a goal of understanding of IFNs as antitumor cytokines and using melanoma as a model, our working hypothesis is that genes and functional mechanisms, yet to be identified, contribute substantially to the antitumor effects of IFNs. Our estimates based upon genome size suggest that greater than 500 interferon- stimulated genes (ISGs) remain to be identified. The goals of the proposal are: 1) By assessment of sensitive and resistant melanomas to identify new genes that may contribute to mediating apoptosis response
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and resistance in response to IFNs, 2) To define and confirm functional effects of the newly identified ISG, TRAIL, on IFN-induced apoptosis, 3) To determine how NFkappaB or other induced anti-apoptotic pathways influence actions of IFNs and TRAIL, and 4) As an effective inducer of of apoptosis in mice and of TRAIL, to conduct a Phase II trial of IFN-beta to identify disease response in metastatic melanoma. The data should contribute to understanding of IFNs effects in melanoma but also other neoplasms and to a beginning understanding of the therapeutic potential of TRAIL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF MELANOMA METASTASIS BY ERISTOSTATIN Principal Investigator & Institution: Mclane, Mary Ann A.; Assistant Professor of Clinical Laborato; Medical Technology; University of Delaware Newark, De 19716 Timing: Fiscal Year 2001; Project Start 19-APR-2001; Project End 31-MAR-2003 Summary: Metastasis (i.e. tumor spread) is the major obstacle to cancer cure. The metastatic process consists of many steps. If this cascade of events is interrupted at any step, metastasis will not occur. Malignant melanoma cells interacted with their environment using the same repertoire of molecules (e.g. receptors) found on normal cells surfaces. Since cell-to- cell interactions occur at many pints of the cascade, blockade of receptor(s) on melanoma cells, through which they interact with other cells, represents a rational target for interruption of tumor spread. Eristostatin, am member of the disintegrin family of viper venom proteins, has been found to inhibit melanoma metastasis in vivo using immunodeficient mice. To date, the basis for eristostatin's antimetastatic effect remains unknown. The long term objective of this research is to identify molecular mechanisms by which melanoma metastasis may be inhibited. The specific goal proposed here is to investigate hoe eristostatin inhibits experimental melanoma metastasis by pursuing three specific aims: i) Create a panel of eristostatin mutations designed to alter single amino acid residues along its entire length. ii) Characterize the interactions of eristostatin and its mutants with four melanoma cell lines possessing distinct combinations of well-defined surface receptors. iii) Identify the structural sequence within eristostatin which is most critical for its anti-metastatic ability. Recombinant eristostatin mutations will be created by alanine scanning mutagenesis, and made as bacterial fusion proteins with glutathione-S transferase. These purified mutants will be used in a series of functional assays with four metastatic, human melanoma cell lines. We will identify the specific molecule with which eristostatin interacts on each type pf melanoma cell through crosslinking and immunological techniques. To determine which residue(s) of eristostatin are responsible for its cellular interactions, each mutant will be compared to wild type eristostatin's activity in cellular assays. Those mutants which show the greatest difference in cellular interactions will be used in experimental metastasis assays. After I.V. injection of immonodeficient mice with melanoma cells and mutated eristostatin, mice will be observed for 4 weeks, and then necropsied. Metastatic potential will be assessed by counting lung metastases. Cryosections of how lungs will be evaluated using immunohistochemical stains. Taken together, these studies will provide insights into how one naturally occurring protein possesses the "right fit" to bind melanoma cells and block their metastatic ability. This information will, in turn, lead to a rational design of therapeutic agents which would target these cells and triumph over tumor spread the major obstacle to cancer cure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTRACELLULAR MATURATION
PH
HOMEOSTASIS
AND
TYROSINASE
Principal Investigator & Institution: Trombetta, Eduardo Sergio.; Associate Research Scientist; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: The goal is to examine the role of organellar acidification in tyrosinase (TYR) activation, stabilization and transport through the secretory pathway. Recent findings that the level of pigmentation in melanocytes negatively correlates with acidic intracellular organelles, leading to increasingly more severe inactivation of TYR, its retention in a pre- Golgi compartment and subsequent degradation. Furthermore, we have recently found that some amelanotic melanoma cells have a higher cytosolic PH, which together with a lower organellar PH are reminiscent of the intracellular PH characteristic of tumor cells refractory to chemotherapy. Therefore, it is possible that alterations in intracellular PH homeostasis may cause not only TYRE inactivation in amelanotic melanomas, but may also underlay other phenotypes, such as immunogenicity of melanosome associated proteins, drug resistance, and possibly antiapoptotic mechanisms in melanoma. We will address the role of intracellular PH in TYR biogenesis by the following assays: First, we will determine the subcellular localization of TYR in amelanotic melanoma cells before and after TYR activation with acidification inhibitors. Second, we will measure the PH in the cytosol and in diverse intracellular organelles in melanocytes defective in P-protein, in which a role for organelle PH was implicated. The P-protein is a putative transporter, proposed to be the "guardian" of melanosomal PH, whose dysfunction causes misrouting of TYR to other sites, including the plasma membrane. These studies will test the hypothesis that variable intracellular PH homeostasis is the cause for variability in the levels of pigmentation between these cell types. Specific aim #1: To evaluate the intracellular location of TYR in different cell types and conditions. The steady state subcellular localization of epitope-tagged location of TYR in different cell types and conditions. The steady immunogold electron microscopy and cell fractionation, to understand the mechanism by which intracellular PH affects TYR maturation. Specific aim #2: To visualize the intracellular distribution of chemotherapeutic drugs and acidic compartments in living melanocytes cells. This will provide a comparative overview of the intracellular PH in melanocytes and amelanotic melanomas. This studies will be complemented by those in aim #3. Specific aim #3: To evaluated the pH in the cytosol and selected intracellular organelles in melanocytes defective in P-protein. PH sensitive probes will be targeted to specific intracellular compartments and will be used to specifically determine the PH in the cytosol, endoplasmic reticulum (ER), Golgi and lysosomes/melanosomes. This information will be correlated with TYR activation under different conditions that simultaneously induced alkalization and activation of TYR to determine how inactivation of wild type TYR in melanomas correlate with alterations in intracellular PH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INVOLVEMENT OF MGLUR1 IN MOUSE MELANOMA CELLS Principal Investigator & Institution: Marin, Yari E.; Chemical Biology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Normal neuronal cells express the metabotropic glutamate receptor 1 (mGluR1), a G protein coupled seven transmembrane domain receptor, mGluR1 can be activated by its natural ligand, glutamate, the major
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neurotransmitter in the mammalian central nervous system. Targeted ectopic expression of this receptor to melanocytes transforms the cells in vivo giving rise to melanoma in mice. Studies of the signaling pathways activated by mGluR1 in melanocytes can give insights into mechanisms and molecular markers of melanoma which may be targets for therapeutic approaches. Preliminary data from gene array analysis and DNA-protein binding assays using tumor cell lines derived from these tumor-bearing transgenic mice suggest that the transcription factor nuclear factor kappa B (NF-kappaB) and other genes in this pathway may be involved in the signal transduction events activated by mGluR1. NF-KappaB has been shown to promote the transcription of anti-apoptotic genes, and in many cases it is constitutively activated in tumor cells. We also have preliminary data showing that these tumor cell lines are capable of releasing the natural ligand of mGluR1, glutamate, into the growth media. The aims of these studies are to determine if the release of glutamate by these tumor cells is able to activate mGluR1 and lead to NF-KappaB activation. We will also investigate some of the upstream kinases that may mediate the mGluR1 triggered activation of NF-KappaB in our system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: L1 CAM AND MELANOMA PROGRESSION AND ANGIOGENESIS Principal Investigator & Institution: Montgomery, Anthony M.; Pediatrics; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 31-DEC-2002 Summary: (adapted from the investigator's abstract) The major objective of this proposal is to define the role of the human neural cell adhesion molecule L1-CAM (L1) in the progression and neovascularization of human malignant melanoma. Despite widespread expression of this CAM on malignant melanoma, little is known of its function with respect to tumor progression. Two central hypotheses will be tested. First, that L1 ligation will directly influence tumor progression by affecting melanoma cell aggregation, survival, proliferation and translocation. Second, that L1 will regulate tumor growth and metastasis by inducing tumor neovascularization or angiogenesis. These hypotheses are primarily based on two novel findings presented in this proposal. First, that L1 can function as a heterophilic ligand for alphavbeta3; an integrin closely associated with melanoma progression and second that shet L1 polypeptides can induce a significant angiogenic response. The specific aims are three-fold. First, they will test the hypothesis that as a result of homophilic or heterophilic ligation, L1 will regulate melanoma cell behavior central to tumorigenicity, including adhesion, migration, survival, and proliferation. This will be assessed by using purified native L1 and defined recombinant L1 fragments. These fragments will allow a determination of those molecular domains or regions that are important for specific tumor cell responses. Second, the focus will be on defining L1- mediated interactions that will influence tumor progression or metastasis in the host, including homotypic melanoma interaction and heterotypic interactions with vascular cells and extracellular matrix (ECM). The consequences of L1 shedding will also be investigated with emphasis on inhibition of melanoma aggregation and modification of ECM to promote attachment and migration. Third, they will determine the role of L1 in melanoma neovascularization or angiogenesis. In this regard, they will first substantiate the hypothesis that L1 shed by melanoma cells can induce a significant angiogenic response and will, therefore, potentiate tumor growth and hematogenous metastasis. As a further objective of this aim, an attempt will be made to define the mechanism by which L1 induces an angiogenic response. Among other possibilities tested, it will be determined whether L1 is angiogenic by virtue of its ability to interact with the integrin alphavbeta3 expressed
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Melanoma
on host vasculature. Finally, they will further assess the significance of a preliminary observation reported in this proposal that describes the expression of L1 on angiogenic vessels. Achieving the objectives of this proposal should significantly further the understanding of the role of the L1 cell-adhesion molecule in the progression of highly metastatic neural crest derived tumors; a role that to date has remained largely unresolved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAPPING MELANOMA METASTASIS SUPPRESSOR GENE(S) Principal Investigator & Institution: Miele, Mary E.; Medical Technology; University of Delaware Newark, De 19716 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from the investigator's abstract) As metastasis (i.e., tumor spread) is the most life-threatening complication of cancer. Identification of genes that regulate the spread of cancer is of utmost importance to reduce cancer deaths. Malignant melanoma serves as a good in vivo model for study of the metastatic process. Understanding the genetic changes in melanoma cells that are responsible for its metastatic phenotype is crucial for improvements in melanoma treatment and survival, and may relate to other solid tumor types as well. The long-term goal of this research is to identify the gene on chromosome 6 (#6) that regulates metastatic potential in cutaneous malignant melanoma. Transfer of a normal copy of #6 into human melanoma cell lines that form tumors and metastasizes in immunodeficient mice results in suppression of tumor spread (i.e. metastasis) without reducing tumor formation. These data suggest that a metastasis-suppressor gene (MSG) is located on #6. More recently, the location of the MSG has been narrowed to 6q16.3-q23 ( about40Mb) by similar studies using #6 fragment. Presently our laboratory has hybrid cells that contain a transferred #6 deleted at 6q21 ( about4Mb), a region frequently lost in many types of advanced cancers. These cells await evaluation in metastasis assays. Thus, the first specific aim is to narrow the region on #6 that encodes the metastasis-suppressor gene by evaluating hybrid melanoma cell lines with a transferred #6 deleted at 6q21 in metastasis assays. The second specific aim will be to further refine the location of the melanoma suppressor gene by identifying BAC, PAC, and/or YAC clones that span the region located at 6q16.3-q23. Selecting overlapping PACs and BACs that cover the region implicated in metastasis suppression will be introduced into the melanoma cell line. Transfected clones will be monitored for suppression of metastasis in immunodeficient mice, These studies will narrow the region of the MSG to <1Mb, which will facilitate its isolation by a combination of cloning techniques. Identification of this gene will shed light on steps in the metastatic process that can be targeted for therapeutic intervention. Gene therapies or novel agents may be designed to restore regulation of cell growth to metastatic cells. Expression of the MSG might be used as a marker to monitor response or to predict patient outcome. In addition, mutational analysis of the gene may provide diagnostic clues that would aid in selection of appropriate treatment regimens that would improve melanoma survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELANOMA AND ALLELIC VARIATION IN THE MCIR GENE Principal Investigator & Institution: Kanetsky, Peter A.; Assistant Professor; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
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Timing: Fiscal Year 2001; Project Start 06-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Description) One of my academic career goals is to develop molecular and genetic epidemiologic research to identify etiologic factors associated with pigmented lesions, including cutaneous malignant melanoma and multiple primary melanoma (MPM). Determination of susceptibility genes for melanoma can facilitate identification of those at increased risk for disease and may result in increase public and individual efforts of prevention and early detection. The potential impact of these measures is great, as melanoma incidence has reached epidemic proportions and mortality due to melanoma has slowly increased over the past decades. The Preventive Oncology Academic Award will give me an opportunity to become a competent melanoma molecular epidemiologist. To this end, I will advance my academic understanding of melanoma through further education in the basic sciences, molecular biology/epidemiology, genetics, and clinical decision making. Practical experience will be gained through participation in molecular laboratory biology, with a focus on methodologies used in molecular epidemiology. Two research projects are proposed to explore the association of a candidate susceptibility gene and development of melanoma. Mutations in the candidate gene of interest, the melanocortin-1 receptor (MC1R), may affect melanin synthesis, resulting in an increased potential for cellular DNA damage that may lead to melanocytic carcinogenesis. The goals of the first study are i) to determine the number and types of gene variants among persons with MPM and single cutaneous melanoma (SCM), and ii) to test whether these mutations play a role in the subsequent development of MPM. The results will contribute greatly to the epidemiologic literature on candidate susceptibility genes associated with melanoma and will help focus primary and secondary prevention for persons at increased risk for secondary, primary melanomas. The second project evaluates whether allelic variants in the MC1R gene explain the pattern of melanoma in families prone to melanoma. Result from this project may provide valuable insight into the genetic predisposition to melanoma seen in some families, and may lead to more efficient mechanisms of primary prevention and clinical follow-up within these families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA CELL SURFACE PROTEOGLYCANS IN METASTASIS Principal Investigator & Institution: Mc Carthy, James B.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from the investigator's abstract) Melanoma chondroitin sulfate proteoglycan (MCSP), also known as high molecular weight melanoma associated antigen (HMW-MAA) is large, highly antigenic cell surface proteoglycan that is dramatically upregulated in melanoma. MCSP is being actively pursued as a target for melanoma vaccine development due to its restricted expression and antigenic properties. Despite its potential clinical importance, relatively little is known about the role of MCSP in melanoma progression. Previous studies have implicated MCSP in adhesion, motility, or cellular growth control. He presents data to demonstrate that inhibition of MCSP expression by anti-sense oligonucleotides inhibits tumor invasion and growth in soft agar in vitro. He has demonstrated that MCSP functions as an adhesion molecule, in part by enhancing the activity of a4b1 integrin, a mediator of tumor invasion and arrest. In addition, he has identified a novel signaling pathway stimulated by MCSP. Activation of MCSP leads to the rapid association and tyrosine phosphorylation of p130cas, an adapter protein implicated in tumor motility and
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Melanoma
invasion. This signaling pathway also involves the association of MCSP with cdc42, a rho-family GTPase that mediates filopodial formation, cell motility and growth. Furthermore, Ack-1, a tyrosine kinase that associates with active (i.e., GTP bound) cdc42, is required for MCSP induced tyrosine phosphorylation of p130cas. Collectively the data are consistent with a model in which MCSP enhances tumor growth and invasion by sequestering intracellular components of a signaling complex in response to an external stimulus. In this application he will further define that signaling complex and study its importance for melanoma growth, invasion and metastasis. Additionally, although the MCSP sequence is published, it has not previously been cloned. He has recently amplified the full-length coding sequence for MCSP by RT-PCR of human melanoma mRNA and are in the process of expressing it in transfected melanoma cells which lack MCSP. This clone will enable them to examine the structural and functional relationships between MCSP, its extracellular stimuli, and its intracellular signal transduction. He proposes three specific aims: 1. To evaluate the importance of MCSP expression and function in the growth, invasion and metastasis of malignant melanoma cells. 2. To delineate the mechanism of Ack-1 in MCSP induced tyrosine phosphorylation of p130cas and to study this mechanism in the survival, growth and metastasis of malignant melanoma cells. 3. To define functional domains of the MCSP core protein required for signaling and melanoma growth, invasion and metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA CHEMOPREVENTION Principal Investigator & Institution: Dellavalle, Robert P.; Dermatology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The incidence of cutaneous malignant melanoma is rising faster than any other cancer in the US. 1 in 74 Americans will develop melanoma, more than 45,000 cases will be diagnosed, and more than 7,500 Americans will die from melanoma this year. Effective prevention of melanoma will not only save lives, but will also decrease the estimated one billion dollars spent annually treating melanoma in the US. There is currently no recognized chemoprevention for melanoma. Two large, randomized, placebo-controlled clinical trials, the VA-HIT Study utilizing gemfibrozil, and the AFCAPS Study utilizing lovastatin, have each reported an association of lipidlowering medication therapy with statistically significant lower melanoma incidence rates. Lovastatin inhibits melanoma cell growth in tissue culture, and mice Jed lovastatin develop lower lung metastases following tail vein injection with mouse B16 melanoma cells. More recently low concentrations of atorvastatin have been reported to specifically induce apoptosis and inhibit migration of human A375 melanoma cells but not cultured melanocytes. To investigate the unconventional hypothesis that lipidlowering medications might prevent melanoma, a case-control study will be conducted utilizing Veterans Administration (VA) databases to answer the following question: Do persons who have developed cutaneous malignant melanoma have a history of less lipid-lowering medication exposure than persons who are spared the disease? The answer to this question will help determine whether more expensive and labor intensive randomized prospective clinical trials of potentially teratogenic lipid-lowering medications should be initiated in persons at high risk of developing melanoma. Robert Dellavalle, MD, Ph.D., is an Assistant Professor of Dermatology at the University of Colorado Health Sciences Center and a staff dermatologist at the Denver VA medical center He is committed to a career in academic dermatology and public health. His
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current career goals are completing a Masters of Science in Public Health and becoming an independent researcher in skin cancer prevention and control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA CONTROL FOR SIBLING OF MELANOMA PATIENTS Principal Investigator & Institution: Gilchrest, Barbara A.; Professor and Chair; Dermatology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-JAN-2004 Summary: With low cost screening and preventive procedures readily available, no one should die of cutaneous melanoma. Promoting melanoma control for at risk populations through regular skin cancer screening and sun protection practices should counter this modern cancer epidemic. Siblings (and other first-degree relatives) of melanoma patients have a two - eight fold elevated relative risk of developing melanoma themselves but have suboptimal knowledge of their risk and limited practice of screening and prevention measures. To date, no intervention protocols have targeted this high risk sibling group, a population estimated to be up to three-quarters million or more Americans. The investigators propose a randomized trial testing personalized telephone counseling intervention support and screening (PERTCISS) that delivers melanoma risk information to siblings and promotes screening and prevention practices. They propose to intervene at a time of a new diagnosis of melanoma in a family member, capitalizing on this teachable moment to reach siblings. They will randomize 450 adult siblings (New England residents) of newly diagnosed melanoma patients to PERTCISS or standard care (SC). The specific aims are to determine, in siblings, the impact of PERTCISS compared to SC on melanoma screening and prevention practices, as well as the knowledge and attitudes that mediate and motivate these practices. They hypothesize that, compared to those in SC, siblings randomized to PERTCISS will demonstrate: 1) Higher levels of three practices: a) physician skin cancer screening examinations, b) skin self-examination for melanoma, c) sun protection practices; and 2) Higher levels of knowledge about melanoma risk and improved attitudes about early detection and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELANOMA NRAS/BRAF MUTATIONS: A POPULATION-BASED STUDY Principal Investigator & Institution: Thomas, Nancy E.; Dermatology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Melanoma, which is rapidly increasing in incidence, remains a potentially fatal disease with poor medical treatment options and controversial methods of prevention. Because of the increasing burden of this disease and its lethality, improved methods of prevention, early diagnosis and treatment are expected to be of increasing importance. NRAS and BRAF, mediators in the RAS-RAFMEK-ERK-MAP cell signaling pathway, are the most commonly mutated oncogenes thus far described for melanoma. However, despite the identification of these mutations in primary human melanomas, the frequency and mutational spectrum of NRAS and BRAF mutations in melanoma have not been fully characterized and there is a critical gap in the knowledge base regarding the association of these mutations with heterogeneity, precursor lesions, risk, and prognosis in melanoma. The specific aims of this study are to: (1) determine the population-based frequency and mutational
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Melanoma
spectrum of NRAS and BRAF somatic alterations in primary cutaneous invasive melanoma and their associations with histologic subtype and potential precursor lesions, and (2) determine associations between NRAS and BRAF mutational phenotypes and known prognostic indicators and risk factors. For this study, a group of approximately 300 consecutive patients with malignant melanoma in North Carolina in the year 2000 has been assembled. Complete epidemiologic data, pathology, and tumor blocks have been obtained for these patients. NRAS and BRAF somatic mutations will be detected and characterized using the highly sensitive technique of single strand conformational polymorphism (SSCP) analysis combined with direct sequencing of PCR products. The population-based frequency of these mutations will be determined and compared between pathologically distinct subtypes of melanoma (superficial spreading, lentigo maligna, nodular, and acral lentiginous). In melanoma samples associated with a nevus, this component will be analyzed separately for mutations using laser capture microdissection. Mutational phenotype will be associated with subtype, potential precursor lesions, risk factors, and prognostic indicators. The data derived from this study is expected to clarify the role of NRAS and BRAF in the development, progression and heterogeneity of melanoma, ultimately leading to better prevention, classification and treatment. Elucidation of how these mutations might arise in relationship to environmental and hereditary factors should result in more evidence-based recommendations for risk factor avoidance. In addition, understanding how mutations arise in relationship to precursors should provide information regarding which potential precursors should be removed. This study is also expected to lead to identification of new hemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA T CELL DEFINED ANTIGEN IDENTIFICATION Principal Investigator & Institution: Hogan, Kevin T.; Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant) Vaccination with antigenic peptides that stimulate a melanoma-specific cytotoxic T lymphocyte (CTL) response is a promising approach to the treatment of melanoma. The work proposed here is predicated on the hypothesis that T cell-mediated immunotherapy will be most successful when: (i) multiple peptide epitopes derived from different source proteins are presented by the same MHC molecule: and (ii) peptide epitopes are presented on multiple MHC molecules within the same individual. Immunization with peptides derived from multiple source proteins rather than a single source protein should minimize the probability that a gene mutation or deletion will result in immune escape, while targeting peptide epitopes to multiple class I MHC molecules should minimize the likelihood that mutation or loss of a single class I gene will result in immune escape, and at the same time broaden the percentage of the population that can receive treatment. Therefore, the overall objective of the research proposed here is to expand the available repertoire of melanoma-derived peptide antigens, both with respect to their absolute number and the range of MHC molecules on which they can be presented, with the ultimate goal (although beyond the scope of this proposal) of using the peptides as a vaccine for the treatment of melanoma. The specific aims of this research proposal are to: (1) determine if the utility of the known class I MHC-restricted melanoma epitopes can be expanded by first determining if they are naturally processed and presented by other members of the same class I MHC supertype family, and secondly by asking if the complexes are capable of stimulating a
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melanoma-specific CTL response; (2) utilize SRM scanning mass spectrometry to identify new CTL epitopes derived from gp 100, tyrosinase, MART-1, TRP- 1, TRP-2, MC1R, MAGE-3, and MAGE-12; (3) determine the extent to which the gplOO, tyrosinase, MART-l, TRP-1, TRP-2, MC1R, MAGE-3, and MAGE-12 melanoma antigens give rise to HLA-A1, A2, A3, B7, or B8 MHC associated epitopes that can be recognized by melanoma-specific CTL; and (4) identify and characterize novel epitopes recognized by melanoma-specific CTL. The methods employed in this proposal will involve a unique combination of cellular immunology and mass spectrometry which will allow for the identification of antigenic peptides both with and without pre-existing CTL. The successful completion of this research should impact on melanoma therapy by increasing the number of available antigens for vaccination, as well as by increasing the percentage of the population that can avail themselves of this form of treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT AWARD
PATIENT-ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Florell, Scott R.; Dermatology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The goal of this project is to determine the role of p16, a tumor-suppressor gene in the retinoblastoma cell-cycle regulation pathway, in familial melanoma kindreds. Malignant melanoma is the most lethal of the skin cancers, and unlike most malignancies, often affects younger patients in their third and fourth decades. Several risk factors have been associated with melanoma, including sun exposure, genetic predisposition, total number of nevi present on an individual, and characteristics of nevi. The overall proportion of cutaneous melanoma attributable to genetic predisposition is reported to be about 10- 15%, but evaluation of cancer incidence data from the Utah Population Database suggests that the fraction of melanoma occurring in a familial setting may be as high as 30%. The applicant proposes to re-examine members of Utah melanoma kindreds, first studied 15 years ago at the UUSM, that helped establish the presence of a melanoma susceptibility locus on 9p21 and later confirm the association of p16 mutations with familial melanoma. A five-year mentored program is proposed to investigate the global hypothesis that carriage of a germline p16 mutation results in measurable clinical, histologic, and cellular changes that lead to familial susceptibility to melanoma. This program will incorporate both didactic and research training and will be guided by a research oversight committee composed of four established scientists at the UUSM and the Huntsman Cancer Institute. Three specific aims are proposed. First, clinical differences between carriers and non-carriers of a p16 mutation will be examined in the Familial Melanoma Research Clinic (FMRC) at the Huntsman Cancer Institute. Kindred members studied 15 years ago will be re-examined to measure differences in photodamage, number of nevi, size of nevi, characteristics of nevi, and distribution of nevi among p16 carrier and noncarrier kindred members. Second, I will determine whether p16 mutation carriage results in decreased senescence or apoptosis of nevus cells utilizing B-galactosidase levels and TUNEL staining, respectively. Third, I will determine whether nevi and melanomas from p16 mutation carriers have acquired additional mutations that could lead to increased risk of malignant transformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Melanoma
•
Project Title: METABOLIC IMMUNOTARGETING
ENGINEERING
OF
CANCER
FOR
Principal Investigator & Institution: Guo, Zhongwu; Chemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Oncogenic transformations are closely correlated with the change of glycosylation patterns of cell surfaces, and the aberrant carbohydrates expressed on tumors, which are called tumor-associated carbohydrate antigens (TACAs), are important targets for the development of cancer vaccines that can be used for cancer diagnosis and therapy. However, the problem of immunotolerance to TACAs has severely hindered further progress in the area. To solve this problem and to develop new, effective cancer vaccines, this project will exploit a new strategy that is based on modified TACAs and metabolic engineering of cancers. First, a TACA on cancer cells will be metabolically modified by treating them with an artificial derivative of a monosaccharide that can be taken as a precursor by cancer cells to biosynthesize a neoantigen - an artificially modified analog of the TACA. The metabolic engineering of cancer takes the advantage of the remarkable flexibility of carbohydrate biosynthetic machineries. Then, specific monoclonal antibodies (mAbs) will be used to selectively target tumor cells labeled by the neoantigen. The mAbs in return can be prepared with a synthetic vaccine made of the neoantigen. As vaccines made of artificial carbohydrates are potentially more immunogenic than those made of the natural TACAs and the metabolic engineering can specifically mark cancer cells, effective vaccines may be easily composed from modified TACAs and the new strategy will potentially solve the problem of immunotolerance to TACAs. The metabolic modifying targets of this project are sialyl TACAs. Melanoma is employed as the tumor model, and GD3 and GM3 on its cells are the specific targets. The N-modified analogs of mannosamine and sialic acid will be used as the precursors, and the neoantigens expressed on melanoma will then be the N-modified derivatives of GD3 and GM3. The aims of this project are: 1)to find the effective precursors for metabolic engineering of melanoma via studying the bioavailability of various precursors to the enzymes involved in the biosynthesis of sialyl TACAs and to melanoma cells; 2) to find the effective vaccines that can provoke specific immune responses to the neoantigens via studying the conjugates of various Nmodified GD3 and GM3; 3) to illustrate the new strategy through specific immunotargeting of metabolically engineered melanoma. This research will eventually establish a proper combination of the precursor and vaccine. As the overexpression of sialic acid is found in various tumors and sialic acid is a shared feature of many TACAs, the principles established herein may be of wide applicability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROCIRCULATION OF UVEAL MELANOMA Principal Investigator & Institution: Folberg, Robert; Fc Blodi Professor; Pathology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-MAR-2008 Summary: (provided by applicant): Uveal melanomas are both sight and life threatening. Radiation therapy and enucleation are equally limited in preventing metastasis, and there is no effective treatment for metastatic uveal melanoma. There are no lymphatics in uveal melanomas: these tumors spread exclusively by a hematogenous route. The uveal melanoma microcirculation is heterogeneous, including incorporated pre-existing vessels, mosaic vessels, angiogenic vessels, and perfusable extra-vascular
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matrix patterns (EMPs) now regarded as a "fluid conducting meshwork". The presence of looping and interconnected EMPs in primary melanomas is strongly associated with death from metastases: the primary tumors of 88% of patients dying of metastatic uveal melanoma contain EMPs which are also present in all sites of metastatic uveal melanoma. EMPs are generated in vitro by aggressive uveal melanoma cells that are embedded in matrix in the absence of endothelial cells and fibroblasts; non-aggressive melanoma cells do not generate EMPs, regardless of matrix conditions, addition of soluble growth factors and hypoxia. EMPs connect to tumor blood vessels and conduct plasma in animal models and human tissues. Preliminary data indicate that the 3dimensional distribution of perfused EMPs may provide a greater surface area exposure to plasma and therapeutic agents than vessels. We propose in the first specific aim to compare the distribution of plasma in EMPs with blood vessels in an orthotopic animal model and in human tissues using novel 3-dimensional visualization techniques. In the second aim, we take advantage of the fact that EMPs are generated by aggressive uveal melanoma cells only when these cells are embedded in thick matrix. By growing aggressive uveal melanoma cell lines under conditions permissive and not permissive of EMP formation, we can compare differential gene expression regulating EMP formation. By validating expression of these discriminating genes in human primary uveal melanoma tissues with EMPs from patients who have died of metastatic melanoma, and in metastatic uveal melanoma tissues, we can identify novel molecular targets for the treatment of aggressive primary uveal melanomas and their metastases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR EPIDEMIOLOGY OF NON-MELANOMA SKIN CANCER Principal Investigator & Institution: Nelson, Heather H.; Cancer Cell Biology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: Non-melanoma skin cancer is the most prevalent malignancy in the US, resulting in significant morbidity and health-care expense. Epidemiologic investigations have identified exposure to ultraviolet radiation as the primary risk factor for this disease; other environmental exposures that contribute to risk include ionizing radiation, arsenic, polycyclic aromatic hydrocarbons, and chronic immunosuppression. Host factors associated with increased risk for non-melanoma skin cancer include increasing age, male gender, and sun sensitive skin type. Basal cell and squamous cell carcinomas have been shown to contain alterations in the p53 gene, and recent work has identified a gene on chromosome 9q22, ptch, that is hypothesized to be critical in basal cell carcinoma tumorigenesis. These findings, while informative, are derived from relatively small, selected groups of patients and reflects the paucity of population-based molecular epidemiology for this disease. We propose to expand a large, well-established case-control study of non-melanoma skin cancer in New Hampshire to include investigation of genetic susceptibility. The project will focus on genes that potentially modify ultraviolet radiation exposure, including polymorphisms in the glutathione Stransferases (GSTM1, GSTT1, and GSTP1) and the newly identified variants in DNA excision repair genes (ERCC2/XPD, and XPF). In addition, we will collect tumor specimens from cases for characterization of mutations at p53 and 9q22/ptch. We will determine mutation spectra examine associations of mutation with carcinogenic exposures and patient traits, and refine a novel model of skin tumorigenesis. These studies will increase our understanding of host susceptibility to non-melanoma skin
44
Melanoma
cancer and advance current models of skin carcinogenesis through identification of patterns of gene inactivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF MELANOMA INVASIONS Principal Investigator & Institution: Chen, Wen-Tien; Professor; Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-JAN-2004 Summary: The metastatic potential of tumor cells is the most important determinant for the prognosis of neoplastic disease. Among the molecular steps required for successful metastasis are several discrete events that involve the invasion of tumor cells through connective tissue barriers. Cell invasiveness concerns adhesion to and proteolysis of extracellular matrices and basement membranes, as well as cell motility. This proposal focuses on plasma membrane-associated proteases and adhesion molecules of human malignant melanoma cells that are important in mediating the invasiveness and metastatic potential of these cells. Recent work from this laboratory identifies several novel membrane proteases from human malignant melanoma cells, chicken embryonic cells, chicken transformed cells, and chicken embryos. Unique cell surface structures called invadopodia are present on cells expressing the malignant phenotype and have been shown to be involved in the invasiveness of cells. The invadopodia are sites of active tyrosine-phosphorylation, localization of beta1 integrins, and active degradation of the extracellular matrix by membrane proteases. The goals of this proposal are (1) to determine the biochemical nature of membrane proteases by the combined approaches of protease activity assays, cellular localization by monoclonal antibody production, sub-cellular fractionation, inhibitor- and antibody-affinity chromatography, protein biochemistry including microsequencing, and molecular cloning, (2) to determine how membrane proteases interact with other proteases to activate degradation, and their role in the expression of cell invasiveness, (3) to investigate the control mechanisms of cell invasion, particularly focusing on the direct or indirect interaction of membrane proteases with putative motility factors including the laminin A chain peptide, autocrine motility factor, acidic fibroblast growth factor, and interleukin-I during the induction of invadopodia and with the human integrins that localize to invadopodia during the stabilization of invasion-associated membranes, and (4) to determine the expression and localization of protease and adhesion molecules in experimental invasion and metastasis models and human tumors by scanning confocal microscopy and immuno-electron microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR PATHOGENESIS OF MALIGNANT MELANOMA Principal Investigator & Institution: Chin, Lynda; Assitant Professor of Dermatology; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: Genetic basis of malignant melanoma is poorly understood. Progress in our understanding of the pathogenesis of malignant melanoma and in the design of therapeutic modalities has been significantly hampered by the lack of a bona fide animal model. In this proposed study, transgenic and knockout mouse technology will be utilized to construct a mouse model for malignant melanoma. Commonly encountered melanoma-associated genetic lesions will be analyzed in vitro to dissect their molecular functions and their causal roles in disease will be validated in vivo. Specifically, I will
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focus on the differential roles of p15 INK4b, P16INK4a and p19ARF as well as activated H-rasva112 in development of malignant melanoma. My working hypothesis is that loss of both gene products of the INK4a gene, (namely p16INK4a and p19ARF), are important, but not sufficient, in development of malignant melanoma, that p15INK4b does not play a key role in melanoma pathogenesis, and that additional genetic events such as RAS activation may be necessary to achieve full malignant transformation of melanocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METASTASIS
MOLECULAR
REGULATION
OF
HUMAN
MELANOMA
Principal Investigator & Institution: Singh, Rakesh K.; Pathology and Microbiology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: The major goal of our research is to define the mechanism(s) that regulate the process of metastasis, and use this knowledge to design innovative hypothesis-based therapies. Metastasis is a highly selective process that is regulated by multiple interrelated mechanisms whose outcome is dependent upon both the intrinsic properties of tumor cells and the host response. Signals from autocrine or paracrine pathways, alone or in combination, may regulate tumor growth and metastasis with the eventual outcome dependent on a balance of stimulatory and inhibitory factors. Recent data from our laboratory demonstrate that the organ microenvironment can modulate gene expression of growth and angiogenic factors in tumor cells in an organ site specific manner. Our analyses of different human metastatic melanoma cell variants demonstrated a direct correlation between the levels of interleukin-8 (IL-8) mRNA expression and protein secretion with metastatic phenotype in nude mice. Preliminary data from our laboratory and others suggest that IL-8 is an obligate autocrine growth, motility and angiogenic factor for melanoma cells. In this application we propose to test the hypothesis that autocrine production of IL-8 and its receptors and their regulation by organ specific cytokines are important determinant in melanoma growth and metastasis. Three specific aims will be pursued: First, we will determine the functional significance of the autocrine production of IL-8 and its receptors on the expression of cellular phenotypes associated with melanoma growth and metastasis. Second, we will analyze whether the organ microenivronments can differentially modulate the expression of IL-8 and its receptors in metastatic melanoma cells. Third, we will determine whether the expression of IL-8 correlates with the clinical grade of human melanoma tumor specimens. The knowledge gained from this research will extend our basic and clinical understanding of the mechanism(s) regulating the process of melanoma tumor growth and metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODEL OF MALIGNANT MELANOMA Principal Investigator & Institution: Depinho, Ronald A.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: The significance and impact of melanoma as a disease entity can not be understated. Despite the long history of clinical and molecular efforts directed towards this disease, surprisingly little is known about the precise genetic lesions leading to melanoma and even less is known with regard to how these few genetic lesions relate to
46
Melanoma
disease classification or progression. Significant progress on both the basic and clinical fronts could be achieved through the production of an accurate mouse model of malignant melanoma that faithfully reproduces disease progression on the pathological and molecular levels. This proposal attempts to refine and validate further an established mouse model of cutaneous melanoma. To achieve this goal, mice will be engineered to possess several genetic lesions commonly observed in human melanomas, including activated MET, EGF receptors as well as disruption of the p16INK4a, PTEN and possibly Mxi1 genes. Evolving gene expression patterns and genomic changes at various tumor stages will be extensively cataloged as a means of validation. This refined model of melanoma should serve to advance our understanding of melanoma biology as well as to provide a system for melanoma gene discovery. The latter will include a combination of CGH, genome wide LOH, genetic mapping of susceptibility loci and candidate gene mutational analyses. The use of these melanoma mice in preclinical testing are outlined as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTI-EPITOPE MELANOMA PEPTIDE VACCINATION WITH GMCSF Principal Investigator & Institution: Slingluff, Craig L.; Professor of Surgery Chief, Division Of; Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The majority of shared melanoma antigens identified thus far can be divided into two groups; 1) melanocyte differentiation proteins (MDP) and 2) cancer-testis antigens (CTA). Generally, both types of proteins are encoded by non-mutated genes, which lack tumor-specific mutations. Therefore, epitopes derived from these molecules could be useful in a vaccine for a large population of melanoma patients. Interestingly, MDP and CTA are differentially expressed in various stages of melanoma. Generally, the expression of MDA decreases in more metastatic lesions, whereas the expression of CTA increases in metastatic lesions. Thus, metastatic tumors contain a heterogeneous population of cells with respect to protein expression, Based on the emergence of metastases that have lost expression of target antigens vaccines that incorporate single melanoma derived epitopes may be inadequate in generating a complete immune response against the tumor. Ideally, a polyvalent vaccine that incorporates epitopes derived from both groups of antigens should compensate for the differential display of melanomaassociated antigens. Preliminary data from an ongoing vaccine trial at the University of Virginia (UVA-Me139) support the safety and immunogenicity of a vaccine strategy incorporating 12 melanoma peptides. This 12-peptide preparation will be used in the currently proposed study. Granulocyte-macrophage colony stimulating factor (GM-CSF) has been included in our vaccine regimens as a local cytokine adjuvant. The rationale for inclusion of GM-CSF is based on substantial murine and human data, but other studies with Montanide ISA-51 adjuvant alone have been demonstrated immunogenicity in the absence of GMCSF. In the present study, we propose to test the hypothesis that the GMCSF included in this regimen contributes to a heightened cellular immune response compared to vaccination in Montanide ISA-51 adjuvant alone. A second question being addressed in this study is the immunologic consequences of vaccination in more than one injection site. In the following study, we propose a 2-by-2 design to address both questions. The primary goals are to estimate: (1) whether GM-CSF administered locally changes the immunogenicity of vaccination with multiple synthetic melanoma peptides
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in an emulsion with incomplete Freund's adjuvant, (2) whether vaccination at two extremity sites induces different immunogneicty than vaccination at a single site. Secondary goals are to obtain preliminary data on (3) whether booster vaccination every three months may maintain immune responses to a peptide vaccine, and (4) whether celluar immune responses to a 12-peptide vaccine may correlate with clinical outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIMERIC LIGANDS FOR TARGETING OF MELANOMA Principal Investigator & Institution: Gillies, Robert J.; Professor; Biochemistry; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The goal of the proposed work is to develop platform targeting agents for imaging and, eventually, therapy of metastatic melanoma. These agents are heteromultimeric ligands directed against combinations of cell surface receptors or epitopes. Prior work by our team and others has shown that homomultimers of ligands bind with significantly higher affinity compared to their component monomers through a process known as cooperative affinity. The current research extends this observation to the use of heteromultimers. The composition of the multimers will be driven by DNA array and monomer ligand binding data, They will have advantages over agents directed against single epitopes by not relying on a single overexpressed cell surface protein. They will have advantages over other multifunctional agents in that they are produced via convergent synthesis and the multimer will be relatively small. Two hypotheses drive this work. 1) Heteromulfimeric ligands directed against combinations of cell surface proteins will bind with higher affinity and apparent cooperativity compared to individual monomers. 2) Combinations of expressed cell surface proteins can uniquely define individual cell types. The two aims of the proposed work follow these two hypotheses. Aim 1 will use a model system comprised of four well-defined ligand-receptor combinations. This system will be used to determine the optimum linker spacing and rigidity, the optimal avidity of the monomeric units, the in vitro binding curves and the in vivo biodistribution characteristic. Aim 2 will screen the expression patterns of 209 cell surface proteins associated with metastatic melanoma. This screen will use a custom DNA array, which will generate comprehensive data sets to identify potential targets. These data will be used to compare patterns of expression in melanoma cells from established and low passage primary cultures, to libraries ofmRNA from normal human tissues. These will be confirmed by RT-PCR, and by binding assays using bona fide agonists. At the end of Aim 2, the two aims will converge in the design of multimeric ligands that will specifically recognize metastatic melanoma for eventual use in detection, diagnosis and treatment of this terminal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NON-INVASIVE BRESLOW THICKNESS MEASUREMENT FOR MELANOMAS Principal Investigator & Institution: Elbaum, Marek; Electro-Optical Sciences, Inc. 1 Bridge St Irvington, Ny 10533 Timing: Fiscal Year 2001; Project Start 19-APR-2001; Project End 31-JUL-2001 Summary: (Verbatim from the Applicant's Abstract): The aim of the proposed effort is to demonstrate the feasibility of an innovative method for in vivo preoperative evaluation of malignant cutaneous melanoma. This method will analyze images of melanomas in
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Melanoma
the visible and near infrared acquired with a multispectal digital dermoscope, MelaFind(tm), developed by Electro-Optical Sciences, Inc., for automatic detection of cutaneous melanoma. The method will meet the following goals: (1 ) reliable in vivo differentiation of invasive from in situ melanomas; (2) in vivo estimation of Breslow thickness for invasive melanomas with an accuracy not worse than that of the standard histological determination. Breslow thickness is one of the most important predictors of the prognosis of cutaneous melanoma. It is also used to decide on surgical management as well as work-up and follow-up strategies for melanoma patients. Thus the proposed method has the potential to improve the care of melanoma patients and to reduce the cost of health care by reducing the number of re-excisions of the tumor. The feasibility of the method will be demonstrated in Phase I. In Phase II, a software package (MelaMeter) for noninvasive Breslow thickness measurement, will be developed and tested with MelaFind (tm). PROPOSED COMMERCIAL APPLICATION: The proposed product is a practical hand-held and portable instrument that will perform two functions: 1) differentiation between invasive and in situ melanomas and 2) estimation of Breslow thickness. This product has the potential of benefit 100,000 new melanoma patients each year in the U. S. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEOTIDE EXCISION REPAIR IN CUTANEOUS MELANOMA Principal Investigator & Institution: Tsao, Hensin; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The incidence of cutaneous melanoma (CM) has dramatically increased over the past several decades. Like other cancers, melanomas most likely result from an interaction between environmental carcinogens, such as ultraviolet radiation, and genetics. Evidence so far suggests that mutations in growth regulatory genes, such as RAS and INK4alpha, contribute to the development of CM. Less understood, however, is the role of DNA repair in melanoma tumorigenesis. Defects in nucleotide excision repair (NER), as seen in the clinical disorder xeroderma pigmentosum, lead to a greatly exaggerated risk of developing CM. The mechanism, however, underlying this clinical observation is largely uncharacterized. The long-term objective of this project is to understand the role of nucleotide excision repair in the pathogenesis of cutaneous melanoma. Specifically, the proposed studies will evaluate if (1) ongoing NER is critical in restricting spontaneous melanoma tumor growth; (2) novel targets for mutation in addition to RAS and INK4alpha emerge in the absence of NER; (3) loss of INK4alpha disrupts the UV response in NER-deficient cells. To test these hypotheses, the Candidate will use murine models to (I) examine, in vivo, the biological consequence of NER loss on the formation of melanomas and (II) characterize, in vitro the impact of INK4alpha loss on the UV-response in NER-deficient murine embryonic fibroblasts (MEFs). A more thorough understanding of the DNA repair mechanisms could lead to better strategies for prevention and therapy. Dr. Tsao received both his M.D. and Ph.D. from Columbia University. After completing a residency in Dermatology, he returned to the laboratory in order to focus on human melanoma genetics. With the proposed studies, he is taking a dramatic departure from previous studies and immersing himself in mice cancer genetics. Dr. Tsao is an Assistant Professor of Dermatology at Harvard Medical School and an associate physician at the Massachusetts General Hospital Melanoma Center. Dr. Tsao is committed to the study of cutaneous melanoma and the career development activities outlined in this application will allow him to become fully independent.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OCULAR MELANOMA Principal Investigator & Institution: Simpson, E Rand.; Director / Associate Professor; Ontario Cancer Institute 610 University Ave Toronto, Timing: Fiscal Year 2001; Project Start 01-SEP-1986; Project End 31-JAN-2004 Summary: The Collaborative Ocular Melanoma Study is a multicenter, randomized, controlled clinical trial designed to compare the efficacy of enucleation vs. irradiation in the treatment of eyes with choroidal melanoma. Candidates for the study will be newly diagnosed cases with choroidal melanoma in one eye greater than 3 mm in height and up to 18 mm by 8 mm in size and with no evidence of metastatic disease. Informed consent will be obtained from all patients prior to randomization. The outcome of primary interest is death from all causes. Secondary outcomes will include death from cancer, whether metastatic or not, diagnosis of other tumors, and preservation of vision. Complications of irradiation and changes in visual acuity will be documented and monitored carefully throughout follow-up. Standardized clinical and data collection procedures will be employed, and standardized forms will be used in all centers. Central training and certification of all study staff will be required. The study will be conduced in cooperating clinics located throughout the United States. The study will be directed by an Executive Committee consisting of 12 to 15 study investigators and a Steering Committee to deal with day-to-day operational decisions. An independent Data and Safety Monitoring Committee will be responsible for assuring the ethical conduct of the study and for reviewing the accumulating data on a regular basis for evidence of adverse or beneficial effects of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEPTIDE AND APC BASED MELANOMA VACCINE Principal Investigator & Institution: Mukherji, Bijay; Professor of Medicine; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 31-DEC-2002 Summary: The major objective of this proposal is to develop a more effective form of active specific immunization with a vaccine made from synthetic peptides loaded on to dendritic cells in the human melanoma model. We have shown that a peptide and antigen presenting cell-based vaccine can induce a peptide specific and autologous melanoma reactive cytolytic T lymphocyte (CTL) response in melanoma patients. We have observed that in vitro stimulation of PBL from the immunized patients led to the rapid generation of peptide specific CTL, the CTL activities, however, often precipitously declined after repeated stimulation with the development of a Th2 type response. There was preliminary evidence of apoptosis in the process. These suggest that in vivo expansion of antigen specific CTL might also be regulated by a Th2 type response or through activation induced cell death (AICD). Hence, the proposed study will examine the mechanism of the decline of the CTL response with particular reference to the role of the Th2 cells and the role of AICD. Further, we shall test the hypothesis that a more effective peptide/APC-based immunization can be achieved with a number of innovations to the approach (such as by using dendritic cells, higher peptide loading, a different format of immunization consisting of priming and boosters, pretreating with cyclophosphamide to block the Th2 response, and using the type 1 cytokine IL-12 to induce a Th1 response). The study will be carried out with a clinical trial that will include these new approaches coordinated with extensive laboratory evaluations of the
50
Melanoma
biologic response to test whether or not a Th1 type response can be induced, CTL response can be amplified, and memory response can be generated. The trial will be carried out with a vaccine made of DC (cultured in GM-CSF and IL-4) loaded with the HLA-A1 or - A2 determined peptides encoded by the following genes: MAGE-1, MAGE- 3, MART-1/Melan A. Thus, melanoma patients, who are HLA-A1 or HLA-A2 positive and whose melanomas express the above genes, will be primed with the vaccine and then given several boosters with a single low but biologically active dose of Interleukin-12 and a single injection of cyclophosphamide 3 days before immunization. A skin test with the naked peptide will be done after each vaccination and extensive analyses of the host immune responses in the draining lymph nodes, in tumors, and in circulation will be performed to determine whether or not the new approach could induce a Th1 type response and amplify specific CTL response and activate memory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERCEPTION OF GENE-ENVIRONMENT CANCER RISKS IN MELANOMA Principal Investigator & Institution: Hay, Jennifer L.; Instructor; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 08-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The overall goal of this career development application is to launch an independent research program on perception of geneenvironment cancer risks. There is mounting evidence that common genetic polymorphisms can either accentuate or attenuate environmental risks, such as smoking and sun exposure, and that these interactions are a primary etiological pathway to carcinogenesis. In the coming years, it is likely that a growing number of individuals will receive probabilistic information concerning genetic and environmental cancer risk factors. The number of individuals who are affected will exceed those with uncommon, highly penetrant single-gene mutations. Existing research on cancer risk communication targeted to those with single risk factors, such as genetic mutations alone, or lifestyle risk factors alone, do not adequately address the potential challenges and prevention opportunities presented by our increasingly comprehensive understanding of environmental and genetic risk interactions. Gene-environment interactions are implicated in the etiology of a number cancer sites. Melanoma will provide the paradigm for study in this application because of the evidence for gene-environment etiology, rising incidence rates, and promise of behavioral prevention. Given the current absence of identified germ line mutations, studying first-degree relatives of melanoma patients will provide a vehicle in the proposed studies to examine the role of geneenvironment risk perceptions and both skin cancer screening and sun protection behavior. Study I is a qualitative interview study of risk perceptions among first-degree relatives of melanoma patients. Study II is a prospective assessment of risk perceptions, skin cancer screening, and sun protection behaviors among first degree-relatives of recently diagnosed melanoma patients. Through intensive interaction with multidisciplinary colleagues, formal epidemiology coursework, teaching, and research, this career development award will establish my multidisciplinary research skills at the interface of genetic epidemiology and behavioral science, and position me to establish novel theory and measurement strategies for the role of risk perceptions of geneenvironment interactions, and ultimately to develop communication models of geneenvironment cancer risks which will be applicable to other cancer sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--CUTANEOUS ONCOLOGY Principal Investigator & Institution: Johnson, Timothy M.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 31-MAY-2006 Summary: The Cutaneous Oncology Program was initially established as a developmental program and achieved full programmatic status in 1996. Its mission is to utilize knowledge gained from basic, preclinical, and clinical research endeavors to improve the overall care of patients with skin cancer. We believe that understanding the biology of melanoma and non-melanoma skin cancers will drive future innovations in prevention, diagnosis, and treatment. The program now consists of 15 investigators from 9 Departments, with over $3.2 million dollars in annual direct funding for basic and clinical research activities. Basic research efforts are focused on areas that have relevance to all forms of cutaneous neoplasia, including the investigation of molecular, biochemical, cellular, and tissue alterations driving the development and progression of skin cancer. A major new initiative is aimed at developing mouse models of human skin cancer for basic and preclinical studies. The clinical research program has made important advances using innovative, immune-based therapies for melanoma. Given the importance of early detection, additional efforts in melanoma are focused on the development of improved patient-education materials, while other work is aimed at better understanding the psychosocial and behavioral repercussions of being diagnosed with melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POLYVALENT VACCINE IN IL-2+GM-CSF LIPOSOMES FOR MELANOMA Principal Investigator & Institution: Bystryn, Jean-Claude; Professor; Dermatology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 12-SEP-2001; Project End 31-AUG-2005 Summary: Our goal is to develop a potent adjuvant that can strongly, but safely, boost the immunogenicity of cancer vaccines. The proposal is based on recent observations that IL-2 and GM-CSF can individually increase the immunogenicity of vaccines, and that the adjuvant activity of each cytokine is markedly increased by co-encapsulating the cytokine into liposomes together with the vaccine. As each cytokine upregulates vaccine immunogenicity by different mechanisms, the combination of both cytokines should result in a particularly potent adjuvant. To test this hypothesis, we propose to conduct a randomized phase II trial to examine: 1) Whether IL-2+GM-CSF co-encapsulated into liposomes together with a melanoma vaccine can increase vaccine-induced cellular immune responses more strongly than either cytokine alone. Patients with resected AJCC stage III melanoma who are HLA-A2(+) will be randomized to treatment with a polyvalent, shed melanoma antigen vaccine encapsulated into lipsomes together with IL-2 or GM-CSF, or with both cytokines. The magnitude of vaccine-induced CD8+ T cell responses to A-2 restricted peptides derived from MAGE-3, MART-1, gp100, tyrosinase and TRP-2 will be measured by ELISPOT at baseline and at fixed intervals following immunization. 2) Whether IL-2+ GM-CSF lipisomes can enhance vaccine-induced antibody responses more strongly than either cytokine alone: Vaccine-induced antibody responses in the 3 groups of patients will be measured to individual melanoma antigens by Western immunoblotting. 3)The safety of this treatment/ Side effects will be followed by standard procedures. Major strengths of this proposal are that we have already demonstrated that IL-2 liposomes and GM-CSF liposomes are individually
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potent vaccine adjuvants in humans, that we have determined the optimal doses of each cytokine that maximally enhance vaccine-induced immune responses when encapsulated into lipsomes, that we have developed assays that are sufficiently sensitive to measure vaccine-induced CD8+ T cell and antibody responses to individual melanoma antigens, and that the vaccine contains multiple melanoma antigens so that the adjuvant activity of IL-2 + GM-CSF liposomes with different antigens can be evaluated. Successful completion of this work will provide a new method to increase the effectiveness of melanoma vaccines, and may lead to an improved treatment for the primary and secondary prevention of this cancer. More broadly, it may provide a general method of potentiating the immunogenicity of vaccines against other cancers and to infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGNOSTIC MARKERS FOR ASSESSMENT OF TREATMENT EFFICACY OF MELANOMA Principal Investigator & Institution: Hoon, Dave S B.; Director of Molecular Oncology/ Member; John Wayne Cancer Institute 2200 Santa Monica Blvd Santa Monica, Ca 90404 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): One of the major problems in managing malignant melanoma is predicting the course of disease progression after removal of the primary tumor. Our main hypothesis is that molecular markers can be used for analysis of tumors and blood as surrogates to predict disease progression and outcome, and treatment efficacy well in advance of clinicopathological events. Malignant melanoma progression occurs from accumulation of multiple genetic aberrations that result in progressive genetic instability. In order to translate the detection and prognostic value of these changes efficiently, analysis must be conducted on specimens from well-defined retrospective and prospective clinical trials. Validation of the molecular results will allow better disease stratification and management of malignant melanoma. In the previous grant period we developed multimarker RTPCR assays to identify blood prognostic molecular markers (PMMs) and demonstrated that they could be useful as potential surrogates of subclinical disease progression, and to predict disease recurrence. We will continue to develop new informative PMMs for blood in this proposal. Our hypothesis is that quantitative levels of PMMs which include melanomaassociated antigens (MAAs) and cellular physiologic factors influencing tumor progression/metastasis in melanoma tumors can also be used as surrogates of disease outcome and the efficacy of active-specific immunotherapy (vaccine). Our hypothesis is that DNA markers in primary and metastatic melanoma can also be used as PMMs. We have identified several DNA markers that have shown potential clinicopathological utility. In this renewal we will focus on assessing paired primary/metastatic melanomas to develop different types of PMMs to complement the blood RT-PCR assay as correlates to disease progression and outcome, and treatment failure. The Aims of the project are as follows: 1) Development and assessment of new mRNA PMMs for assessing melanoma patients' tumor and blood; 2) Development and assessment of DNA markers in melanoma tumors as prognostic indicators of disease progression and outcome; and 3) Validation of the clinical and pathological utility of RNA and DNA molecular markers in melanomas from patients entered in the multicenter PMCV Phase III clinical trial. The Aims will take advantage of the JWCI's large melanoma patient referral and comprehensive follow up to provide resources to develop and assess PMMs. The Aims will also take advantage of the randomized multicenter vaccine trial's archived and prospectively collected specimens to validate the PMMs. Identification of
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molecular markers for melanoma at different stages of disease progression will allow us to develop an "applicable" molecular progression model to aid in management decisions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA
PROGNOSTIC
MARKERS
FOR
PRIMARY
CUTANEOUS
Principal Investigator & Institution: Pinkel, Daniel D.; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Cutaneous melanoma presents a significant health problem in Western Europe, Australia, and the United States. Americans in the United States currently have approximately a 1 in 75 lifetime risk developing this disease. If melanoma is not excised before it metastasizes the prognosis is poor. Recent evaluation of adjuvant treatments such as interferon alpha indicate the ability to prolong survival in patients with occult metastases, so identification of these patients is highly important. The goal of this proposal is to develop DNA copy number and gene expression markers in the primary tumor that will improve the ability to determine if clinically significant metastasis has occurred by the time of diagnosis. Sentinel lymph node (SLN) biopsy, coupled with several other characteristics of the primary tumor such as thickness and ulceration, are currently the best prognostic indicators. The finding of malignant cells in a sentinel node is a definite sign that the disease has begun to spread. but negative nodes do not guarantee a good outcome. A substantial proportion of all cases of metastatic melanoma come from patients who were SNL- at diagnosis. Thus improving the ability to determine which patients were at elevated risk of progression would have substantial medical benefit. In this project we w ill study primary tumors and corresponding metastases from a cohort of 700 patients that underwent SLN biopsy at UCSF, and an additional set of 100 primary tumors of Acral Lentiginous Melanoma (ALM), to detect DNA copy number changes and gene expression changes that distinguish primary tumors that metastasize from those that do not. Screening for DNA copy aberrations will be performed using array comparative genomic hybridization (array CGH) which has recently been developed in our laboratories. Candidate genes will be identified based on the copy number aberrations, and the prognostic power of the expression levels of these candidates will be evaluated. Using an independent set of tumors from the SLN cohort, we will validate the ability of these markers to: 1) distinguish patients that develop metastases from those that do not, and 2) to distinguish patients with negative sentinel nodes that develop metastases from those with negative nodes that remain disease free. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUALITY OF LIFE--THE COLLABORATIVE OCULAR MELANOMA STUDY Principal Investigator & Institution: Melia, B. M.; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2005 Summary: The Collaborative Ocular Melanoma Study (COMS) is a set of randomized clinical trials sponsored by the National Eye Institute and designed to evaluate the role of radiotherapy in the treatment of choroidal melanoma. The primary COMS trial will determine whether enucleation or radiotherapy without enucleation provides patients
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with the longest remaining lifespan. The two treatment approaches under investigation, enucleation versus radiation therapy, are likely to have different psychological and physiological effects on the patients receiving them. In addition to consideration of any survival difference between treatment approaches, the impact of the treatments on the patient's quality of life will be an important consideration in determining the best form of therapy. The COMS does not currently incorporate measures of the disease impact on quality of life, with the exception of an assessment of visual acuity. The purpose of the proposed study is to address the issues of quality of life and the psychological and physical impact of treatment in patients with choroidal melanoma using the existing framework of the COMS. Specifically, the study will: 1. estimate baseline quality of life and its changes over time in choroidal melanoma patients from enrollment into the COMS, with follow-up for 5 years; 2. compare baseline quality of life and its changes over time in patients randomized to receive radiotherapy versus enucleation; 3. and compare quality of life cross-sectionally according to treatment assignment in patients previously enrolled in the COMS. To achieve these aims, a health-related quality of life instrument, the SF-36 Health Survey, and a visual functioning assessment instrument, the Activities of Daily Vision Scale, will be incorporated into the patient evaluations performed at baseline and during follow-up for the COMS. This study will provide valuable information about the how patients with choroidal melanoma experience the disease and its treatment. Future patients will benefit from these results, which will help them balance the trade-offs between quantity and quality of life related to choice of treatment for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF EXPRESSION OF MGSA/GRO GENES IN MELANOMA Principal Investigator & Institution: Richmond, Ann A.; Professor; Cell and Developmental Biology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-FEB-1993; Project End 31-JAN-2003 Summary: The chemokines, MGSA/GRO and IL-8, are constitutively expressed in melanoma and appear to play a causal role in melanoma tumor progression. Evidence to date points to a transcriptional deregulation of the MGSA/GRO chemokine, partly through an endogenous activation of the transcription factor, NF- kappaB. An immediate upstream regulatory region (IUR) is located adjacent to the NF-kappaB element and in CAT reporter assays, mutation of this element drastically decreases basal transcription. The IUR element, TCGAT, binds three proteins, approximately 100, 40 and 22kD, and the binding of these proteins cannot be eliminated or supershifted in electrophoretic mobility shift assay by antibodies to other potentially relevant transcription factors. Preliminary data point to a potential interaction between the NFkappaB and the novel IUR binding proteins. There are four specific aims for this proposal: 1) to characterize the process by which NF-kappaB is constitutively activated in Hs294T melanoma cells and determine whether NF-kappaB activation contributes to the endogenous transcription of MGSA/GRO in melanoma; 2) to purify, sequence and clone the proteins which bind to the immediate upstream region (IUR) of the MGSA/GROalpha gene enhancer, and to determine if these factors contribute to MGSA deregulation in melanoma; 3) to characterize the prevalence or coordinate deregulation of CXC chemokines in malignant melanoma; and 4) to determine whether overexpression of the mouse homolog of MGSA in normal melanocytes is associated with tumor formation in vivo, a transgenic model will be developed. Expression of the
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mouse homolog of MGSA/GRO, MIP-2, will be directed by the tyrosinase promoter which will result in melanocyte specific expression. We will treat the transgenic mice with chemical carcinogens and uv irradiation to determine how continued expression of these chemokines effects melanocyte response to agents involved in tumor initiation/progression. These experiments should provide important new information about the mechanism by which deregulation of the expression of chemokines chemotactic occurs and this is key to understanding how to suppress these mediators of tumorigenesis and chronic inflammatory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLES OF NITRIC OXIDE AND OXYGEN IN OCULAR MELANOMA Principal Investigator & Institution: Braun, Rodney D.; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: (Adapted from applicant's abstract): Choroidal melanoma is the most common primary ocular cancer among the adult population. It is an important disease, because treatment may destroy vision in the affected eye and the tumor can metastasize. Its treatment is very controversial and is currently the subject of a major NEI clinical trial. Enucleation is a common treatment, but there has only been recent emphasis to develop eye-sparing therapies. Unfortunately, these newer treatments have been only marginally successful in eradicating the tumor while sparing vision. The ultimate goal should be to improve therapy so that safer, more efficacious treatments can be applied sooner in the course of the disease. The ability to treat sooner and more aggressively may ultimately enhance patient survival. Some eye-sparing therapies (e.g., radiation therapy, photodynamic therapy, and immunotherapy) are dependent on oxygen, yet virtually nothing is known about the physiology of this tumor, including mechanisms for blood flow control. In other areas of cancer research, there has been recent interest in the modulation of nitric oxide (NO) to modify tumor blood flow and oxygenation to improve treatment. One major drawback of these strategies, however, is that NO modulators must typically be given systemically, and side effects may limit their clinical application. Since choroidal melanomas are often accessible to treatment using an episcleral approach, the utilization of compounds associated with NO to locally manipulate the microenvironment of this tumor is especially appealing, since systemic treatment can be avoided. The purpose of the proposed study is to test hypotheses relating to the effects of NO on blood flow and oxygenation in human choroidal melanoma growing in the choroid of the athymic rat. The hypotheses to be tested are that (1) NO synthetase (NOS) is expressed in human choroidal melanoma parenchyma and/or vasculature, (2) NO plays a role in regulating microvascular blood flow in human choroidal melanoma and (3) human choroidal melanoma in vivo has areas in which the oxygen tension is low (hypoxia) and the oxygenation of the tumor is dependent on NO availability. The results of these studies could lead to development and testing of new therapies for choroidal melanoma, based upon selective, local delivery of agents which modulate NO availability and modify tumor blood oxygenation, thereby enhancing the effectiveness of treatments directed toward salvage of the affected eye. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SENSITIZATION TO THERMORADIOTHERAPY IN HUMAN XENOGRAFTS Principal Investigator & Institution: Leeper, Dennis B.; Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2007 Summary: Project 1 serves the program by testing the hypothesis that acute acidification by lactic acidosis will enhance thermosensitization and selectively sensitize melanoma xenografts to radiotherapy. Protocols were established for acute acidification to less than or equal too pH3 6.3 and oxygenation of melanoma has uniquely high activity of H+ linked monocarboxylate transporters (MCT, a.k.a. lactate symport) that are the major membrane proton exchange. Although thermosensitization by acidification was demonstrated, radiation must be combined with hyperthermia to achieve local control. Five specific aims will test the hypothesis and investigate mechanisms of melanoma acidification. Aim 1 will investigate inhibition of mitochondrial respiration by metaiobenzylguanidine (MIBG) on melanoma acidification and oxygenation for sensitization to thermoradiotherapy. Variation in glycolytic/respiratory ratio among frozen melanoma biopsy cell suspensions will indicate relative susceptibility to MIBG. Aim 2 will investigate inhibition of the MCT either by alpha-cyano-4-hydroxy-cinnamic acid (CNCn) or by Ionidamine on acidification of melanoma and sensitization to thermoradiotherapy. The activity of the plasma membrane MCT among stored melanoma biopsy cell suspensions will indicate relative susceptibility to CNCn or Ionidamine. Aim 3 will identify the utility of combining MIBG and CNCn as a cocktail to acidify and oxygenate all melanomas. Melanomas with high rates of respiration will be sensitive to MIBG, and those with high rates of glycolysis sensitive to CNCn. In each protocol excess glucose must be combined with inhibitors to fuel lactate production. Two different F2 melanomas xenografts in nude mice will be studied that differ in vascularity, radiation sensitivity and expression of heat shock proteins. Tumor growth delay will be compared with tibial bone marrow toxicity to establish therapeutic gain. Cellular radiation response parameters in vitro will be determined in Project 3. Project 1 provides mice with melanoma xenografts to Project 2, so that together with Core A, biological endpoints can be investigated to predict response of melanomas and normal tissues to treatment pH9, pHi, 23Nai, pO2, oxygen consumption, bioenergetics and blood flow. Aim 4 supports Project 3 to determine the effect of acute acidification on apoptosis and the relationship with hyperthermia-induced upregulation of hsp70 in DB1 xenografts grown up from cell stably transfected with the gene for enhanced green fluorescent protein (egfp) under control of the hsp70 promoter. Aim 5 with Project 3 supports Project 4 to confirm whether nucleolin translocation is a determinant of heat response in vivo by measuring nucleolin movement from the nucleolus into the nucleoplasm in DB-1 xenografts as a function of acidification during hyperthermia. Acute tumor acidification will have the clinical effect of increased tumor temperature with additional benefit from increased tumor oxygenation. These results will help direct a Phase I/II trial conducted by Dr. Douglas Fraker, Univ. of Penn. To demonstrate the effects of acidification of melanoma response to limb perfusion with melphalan at 42 degrees Centigrade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNALING PATHWAYS FOR UV-INDUCED MELANOGENIC RESPONSES Principal Investigator & Institution: Abdel-Malek, Zalfa A.; Research Professor; Dermatology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221
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Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 31-MAR-2008 Summary: (provided by applicant): In human skin, epidermal melanocytes play a crucial role in photoprotection mainly due to their ability to synthesize melanin. Melanocytes have an extremely low proliferative capacity, thus their survival in the epidermis is crucial for cutaneous photoprotection. However, it is becoming clear that the risk for skin cancer is not simply determined by melanin content in the skin, but rather by the ability of the metanocyte to maintain genomic stability in the face of exposure to ultraviolet radiation, to prevent malignant transformation into melanoma. Endothelin-1 (ET-1) and alpha-melanocyte stimulating hormone (alpha-MSH) are two epidermal factors whose synthesis is stimulated by UV exposure. Both factors enable human melanocytes to overcome UV-induced G1 arrest and stimulate melanogenesis. Recently, we demonstrated that ET-1 and apha-MSH increase the survival of UVirradiated melanocytes by inhibiting apoptosis. We found that cultured human melanocytes that express loss-of-function mutations in the melanocortin 1 receptor, the receptor for alpha-MSH, have increased susceptibility to killing by UVR. We attribute this increased sensitivity to UV exposure to extensive DNA damage that overwhelms the repair capacity of those cells, and to inability to fully activate survival pathways. These mutations have been associated with poor tanning ability, and increased risk for melanoma and non-melanoma skin cancers, independently of skin or hair color. We hypothesize that ET- 1 and alpha-MSH promote human melanocyte survival by inhibiting apoptosis and reducing the extent of UVB-induced DNA damage. We propose to investigate the ability of ET-1 and/or a-MSH to limit the extent of UVBinduced DNA damage and/or to enhance the rate of DNA repair. We will also determine the capacity of ET-1 and alpha-MSH to activate the Akt/PKBdependent survival pathway. Activated Akt/PKB is known to inhibit apoptosis by phosphorylating and inactivating its substrates Bad and caspase 9, and by activating NFkB and CREB. Additionally, we plan to elucidate whether the survival effects of ET-1 and/or alphaMSH involve activation of the transcription factor Mitf, which upregulates Bcl2 expression, by modulating the activities of ERK1/2, p38 and JNK/SAPK, and CREB in UVB-irradiated melanocytes. Determining the differences in the ability of melanocytes from different pigmentary phenotypes to respond to survival factors is significant for assessing the magnitude of the cytotoxic and genotoxic effects of UVR in the skin. Also, assessing the differential sensitivity to the survival effects of a-MSH and ET-1 can be used as a reliable marker for determining individual risk to skin cancer, particularly melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLC AND DENDRITIC CELLS IN ANTITUMOR IMMUNITY & THERAPY Principal Investigator & Institution: Mule, James A.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2006 Summary: In order to develop new and more effective immune-based cancer treatments, relevant, small animal models continue to play a necessary role in understanding the underlying biology of such therapies, which are designed to modulate the immune system to recognize a neoplasm as "foreign". We have shown that murine tumor lysatepulsed dendritic cells (TP-DC) can elicit tumor-specific T cell reactivities in vitro and in vivo. This observation has been made in a variety of histologically-distinct murine tumors, including sarcoma, carcinoma, and melanoma. We have further shown that synegeneic hosts can be effectively immunized in vivo to reject aggressive, weakly-
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immunogenic sarcomas, a breast carcinoma, and a poorly-immunologic subline of the B16 melanoma by immunization with TP-DC, which is dependent upon host-derived CD8+ and CD4+ T cells. TP-DC treatments can also result in regression of both established subcutaneous tumor nodules and lung metastases., which can be further enhanced by the systemic administration of IL-2. The experimental studies outlined in this application are designed to continue our preclinical efforts to generate more potent immunization strategies against cancer based on potent antigen-presenting DC. We will now extend our efforts on novel approaches to use TP-DC in the setting of a powerful chemoattractant cytokine, denoted secondary lymphoid tissue chemokine (SLC). The rationale for doing so is based on our recent data demonstrating that SLC is a unique, potent chemokines selective for the recruitment of naive T cells and immature DC. It is our hypothesis that concomitant expression of SLC at the immunization site of TP-DC will result in increased tumor reactivity through elevated levels of host immune cell recruitment and activation. We propose the following Specific Aims: 1. To evaluate the efficacy of SLC to attract T cells and DC to primary immunization sites in vivo; 2. To evaluate the capacity of immunization of tumor-bearing mice with SLC gene-modified TP-DC to mediate a therapeutic anti-tumor response in vivo; 3. To determine the mechanism of tumor response in mice immunized with SLC gene- modified TP-DC; 4. To evaluate the combination of SLC and additional recombinant cytokines to enhance therapeutic efficacy in vivo; and 5. To evaluate the clinical use of SLC in the treatment of patients with advanced melanoma. The range of therapeutic strategies will be tested and compared in settings of minimal and advanced disease states. The overall goal of our research effort will be to develop and optimize a new strategy that combines a chemokine with DC-based vaccine approaches for the treatment of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPORE IN SKIN CANCER Principal Investigator & Institution: Kupper, Thomas S.; Professor and Chair; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: In this proposal, we seek to establish a Specialized Program of Research Excellence (SPORE) in Skin Cancer at Harvard University and Brigham and Women's Hospital, within the newly configured Dana Farber Harvard Cancer Center. The DanaFarber Harvard Cancer Center SPORE includes investigators from Harvard Medical School and School of Public Health, as well as the Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Children's Hospital Medical Center, Dana- Farber Cancer Institute, and the Massachusetts General Hospital. These institutions have come together around the theme of translational research in melanoma and cutaneous oncology Five Projects, five Shared Resources (Cores), a Developmental Program, and a Cancer Development Program are proposed. Project 1 will translate epidemiologic findings into the Development of improved risk models for melanoma; once developed, these will be validated across a large patient population. Project 2 employs the power of whole genome transcriptional profiling with the ultimate goal of improving our ability to diagnose and predict the biological course of primary melanoma. Project 3 tests the hypothesis that cutaneous T cell lymphoma is a malignancy of a population of memory T cells that normally performs immunosurveillance of the skin, and seeks to identify new targets for therapy. Projects 4 and 5 are exciting translational clinical trials. In Project 4, two diametrically different dendritic cell vaccination strategies are directly compared, using novel immunological endpoints. In Project 5, biochemotherapeutic approaches are employed to treat metastatic melanoma. Immunologic monitoring will
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be performed again with the goal of improving therapy for melanoma patients. These five Projects are integrated by five Cores. The Biostatistics Core provides expert consultation to each study while the Tissue and Pathology Core provides controlled and organized access to tissue vital for these projects. An assessment of immunologic endpoints. The Clinical Data Management Core provides a vital service of creating dynamic and flexible databases that integrate Projects across multiple Harvard-affiliated hospitals. Finally, a Development Program features five projects, each of which is a candidate for evolution into a full project is promising translational results are obtained. A Career Development Program, which takes a broad view of the development of the physician scientist over the course of a career, is a centerpiece of this application. An administrative structure is in place that will assure oversight, integration, planning, didactic activities, and most importantly, the growth and evolution into a full project if promising translational results are obtained. A Career Development Program, which takes a broad view of the development of the physician scientist over the course of a career, is a centerpiece of this application. An administrative structure is in place that will assure oversight, integration, planning, didactic activities, and most importantly, the growth and evolution of the SPORE over the next five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUN EXPOSURE RECALL--INSTRUMENT DEVELOPMENT & EVALUATION Principal Investigator & Institution: Marrett, Loraine D.; Cancer Care Ontario 620 University Ave, Ste 1500 Toronto, Timing: Fiscal Year 2001; Project Start 11-AUG-2000; Project End 31-JUL-2003 Summary: (Applicant's Description) This project's long-term objective is to improve data collection on early-life sun exposure in etiologic studies of melanoma and other skin cancers; findings may have implications for epidemiologic studies involving recall of other early-life risk factors like diet and physical exercise. The specific aims are: 1) to develop instruments for adult recall of childhood sun exposure through key informant interviews and collegial pretesting, focus groups, cognitive interviewing and field pretesting; 2) to evaluate the developed instruments, through field testing in young adult melanoma cases and population controls, as to response completeness, test-retest reliability, and the effect of these on odds ratio estimates. The investigators have developed, from existing instruments, a life events calendar to help define stable exposure periods and a draft questionnaire. Further preliminary development through interviews with other investigators and collegial pretesting will be unfunded work. Funding is requested for the focus group, cognitive interview, field pretest and evaluation phases. Focus groups of young melanoma cases and like-aged population controls will be invited to discuss the way they think about and retrieve information concerning early life sun exposure (memory triggers, salient aspects, etc.) and then to review the draft questionnaire and provide feedback for improvements. Analysis of these sessions will result in a revised questionnaire. Small-group cognitive interviews will explore how subjects comprehend and prepare answers to the questions in this revised instrument. Resulting refinements to wording and probes will be pretested in telephone interviews and then field tested in a sample of melanoma cases and population controls, with reinterview at least four months later. Evaluation will focus on item nonresponse and reliability in cases and controls, and the effect of these on odds ratio estimates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TCR-GENE IMMUNOTHERAPY
MODIFIED
T-CELLS
FOR
ADAPTIVE
Principal Investigator & Institution: Van Besien, Koen Walter.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): It has been demonstrated that tumor reactive T-cells can induce tumor regression in patients with metastatic melanoma and some of the target antigens have been identified. Still, the clinical impact of current immunomodulatory approaches by use of cytokines/biologic response modifiers, vaccination or the use of adoptive immunotherapy remains limited. We have recently identified and cloned the T-cell receptor (TCR) of a CD4 Tumor infiltrating lymphocyte with MHC class I restricted recognition and strong affinity for its target, the 368-376 peptide of tyrosinase. The overall aim of this proposal is to develop an adoptive immunotherapy approach using TCR-gene modified PBL. In specific aim 1 we will determine if the retroviral vector encoding the TCR from an HLA-A2 restricted, tryosinase:368-376 reactive T cell clone (TIL 13831) can engineer normal peripheral blood T cells from normal donors and melanoma patients to recognize melanoma cells with high affinity. For this purpose we will use specifically designed retroviral vectors with a SAMEN backbone that are adapted for the transfer of TCR alpha and beta and that in some cases also express the neo(r) gene for G418 selection. In specific aim 2 we will determine the optimal conditions to TCR gene modify human peripheral blood T cells from normal donors and melanoma patients for patient treatment. For this set of experiments, we will use the previously produced A6 and A7 retroviral vectors that carry the low affinity TIL 5 TCR. Using this model, we will optimize methods of transducing and expanding normal PBL. We will evaluate 2 transduction methodologies, spinoculation and retronectin based transduction. We will also optimize methods for in vitro expansion of transduced T-cell populations and study TCR transduction (by RT-PCR) expression (by tetramer staining) as well as functional activity (by Cytokine release and Cr release assay). It is anticipated that methods developed under specific aim 2, will be applicable for cell populations transduced with newer vectors generated under specific aim 1. In specific aim 3 we will determine if TIL 13831 TCR gene modified T cells can be detected and quantified using RTP-CR and competitive RT-PCR. For this purpose specific primere for TIL 13831 will be designed, as well as a clone specific inhibitor. The validity of the test and its accuracy will be extensively evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF CD4+ T CELLS IN MELANOMA IMMUNOTHERAPY Principal Investigator & Institution: Bullock, Timothy N.; Microbiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 11-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The candidate is a recently promoted Research Assistant Professor who has been investigating the use of dendritic cells to activate CD8+ T cell responses against melanoma in the laboratory of Dr. V. Engelhard. As part of a move towards independence, the candidate is developing his own research project that extrapolates from his postdoctoral investigations. It is the candidate's intention to use the Temin Award as a foundation to advance intellectually and scientifically under the mentorship provided by Dr. Engelhard, followed by a successful transition to completely independent research in tumor immunotherapy. The University of Virginia
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provides an ideal environment for this proposal due to the excellence of the basic science faculty and the potential for collaboration with physicians interested in applying immunotherapy in a clinical setting. The research proposal is based on the accumulated data from several groups that suggests that CD4+ T cells play an integral role in directing adaptive immune responses against tumors, by providing activation stimuli for professional antigen presenting cells, cytokine support the generation of effector and memory CD8+ T cells and direct anti-tumoricidal activity. Therefore, vaccination protocols that elicit CD8+ T cell and CD4+ T cell responses against tumors are likely to be more effective than those that target either arm of the adaptive immune response alone. Based on the hypothesis that the generation of CD4+ T cells that can respond specifically to MHC class II-restricted epitopes derived from melanocyte differentiation proteins will enhance the generation of tumor-specific CD8+ T cell responses, and the generation of memory CD8+ T cells against melanoma, we propose to: 1. Identify and compare HLA-DR*0401- restricted peptides derived from tyrosinase that are presented on dendritic cells, melanoma cells, or both. 2. Characterize the CD4+ T cell response to tyrosinase-derived HLA-DR*0401-restricted peptides in DR4/IEd transgenic mice that either do or do not express tyrosinase in the periphery. 3. Define the role of tyrosinasespecific CD4+ T cells and their epitopes in the generation of tyrosinase-specific CD8+ T cells and anti-melanoma responses. The results derived from this proposal are expected to have immediate impact on our understanding of the immune response to peripherally expressed self-antigens t h a t are relevant to melanoma, and the design of immunotherapeutic interventions against melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOPICAL RETINOIDS FOR CHEMOPREVENTION OF MELANOMA Principal Investigator & Institution: Cattaneo, Maurizio V.; Ivrea, Inc. 216 Ricciuti Dr Quincy, Ma 02169 Timing: Fiscal Year 2003; Project Start 01-JUN-2000; Project End 31-MAR-2005 Summary: (provided by applicant): Malignant melanoma's incidence is increasing by 2.7% annually even as most other cancers are experiencing a decline in incidence. The long-term objective of this project is to commercialize a topical formulation containing retinoic acid (ATRA) for subjects with dysplastic nevi at a higher risk of developing malignant melanoma. However, ATRA is highly irritating to the skin. Several topical delivery systems have been shown to reduce ATRA-induced skin irritation. Phase I studies have shown that the biopolymer chitosan acts as a topical delivery system for ATRA. In this Phase II SBIR study we propose to: (1) standardize the topical formulation containing the ATRA/chitosan delivery system according to our IND 60,073, (2) test the long-term toxicity and irritation of the formulation in both rodents and non-rodents species according to FDA 21 CFR, Part 58, (3) determine whether 6 months of topical ATRA/chitosan will result in a significant clinical improvement of dysplastic nevi, and/or a decrease in the dysplasia grade, and/or a change in the expression of proliferation biomarkers, by performing a multicenter controlled clinical trial involving 16 dysplastic nevi subjects using Internet-based randomization, electronic data capture, coordination and monitoring, and pre and post study clinical and histological assessment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTION FACTOR AP2 IN METASTASIS OF MELANOMA Principal Investigator & Institution: Bar-Eli, Menashe; Professor; Surgical Oncology & Cell Biol; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030
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Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-JAN-2003 Summary: (adapted verbatim from investigator's abstract) The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase (VGP) (metastatic phenotype) are not very well defined. Recent work from this laboratory demonstrated that the expression of the cell surface adhesion molecule MCAM/MUC18, which belongs to the immunoglobulin superfamily, directly correlates with the metastatic potential of human melanoma cells. While none of the MCAM/MUC18-negative cell lines examined have been found to be metastatic, transfection of such cells with MCAM/MUC18 gene rendered them metastatic in nude mice. In addition, we have recently demonstrated that the progression of melanoma is associated with loss of expression of the c-KIT proto-oncogene tyrosine kinase receptor. Furthermore, re-expression of the c-KIT receptor in highly metastatic cell lines inhibited their tumorigenicity and metastatic potential in nude mice. Indeed, exposure of c-KITpositive melanoma cells in vitro and in vivo to stem cell factor (SCF), the ligand for cKIT, triggered apoptosis of these cells but not of normal melanocytes. The mammalian transcription factor AP-2 is a sequence-specific DNA-binding protein expressed in neural crest lineages and regulated by retinoic acid. Our preliminary data indicate that both MCAM/MUC18 and c-KIT gene expression is highly regulated by AP-2. In addition, other genes that are involved in the progression of melanoma such as MMP-2, bel-2, E-cadherin, and p21/WAF-1 are also regulated by the transcription factor AP-2. Our laboratory has recently made the observation that while several nonmetastatic melanoma cell lines express AP-2, the highly metastatic cell lines do not express this transcription factor. Therefore, we hypothesize that loss of AP-2 expression may be a crucial event in the development of malignant melanoma. We are therefore proposing the three Specific Aims: 1) to provide a direct evidence for the involvement of AP-2 in the acquisition of the metastatic phenotype by transfecting metastatic cells with w.t. AP2 and primary melanoma cells with a dominant negative AP-2B genes and subsequently analyze their tumorigenicity and metastatic potential in nude mice. 2) To study the effect of AP-2 and AP-2B on the expression of the above mentioned genes. 3) To evaluate the status of AP-2 expression and function in tumor specimens from patients in well-characterized melanoma database. These experiments will generate valuable information on the progression of melanoma, and help to develop new molecular staging markers and a common target for anti-tumor/metastasis therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT AND MOLECULAR ANALYSIS OF ATYPICAL NEVI Principal Investigator & Institution: Becker, Dorothea; Professor of Pathology; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: (adapted from the investigator's abstract) The overall objective of this proposal is to determine whether systemic treatment with the biologic agent, interferon a2a, will modulate the molecular, immunologic, histopathologic, and clinical features of atypical nevi, which are the known precursors and risk markers of malignant melanoma. In the setting of familial melanoma, the presence of atypical nevi is associated with a nearly 100% risk of developing primary melanoma by age 70. Likewise, in the case of sporadic melanomas, between 40-60% of them develop from preexisting atypical nevi. Furthermore, patients with a clinical history of primary melanoma and two or more atypical nevi are at an 8-fold greater risk of developing a second primary melanoma. Thus, in light of the rising incidence and mortality rate of
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melanoma, it is not only imperative to find and implement strategies that will help cure patients with metastatic disease but also to prevent the progression of atypical nevi to malignant melanoma. We recently demonstrated that direct gene targeting of bFGF/FGFR-1 in human melanomas causes their growth arrest and regression as a result of blocked melanoma proliferation and intratumoral angiogenesis. In addition, we documented expression of these two genes in the dermal nevocytic and stromal compartments of atypical nevi. The results of recent clinical trials provided evidence that IFNa has a significant therapeutic impact on metastatic melanoma, leading in 1995 to an FDA approval of IFNa as the first agent for adjuvant therapy of high-risk melanoma. While IFNa is known to be a potent antiviral, antiproliferative and immunomodulating agent, recent studies have shown that IFNa also functions as a strong angiogenesis inhibitor by blocking bFGF mRNA and protein in human malignancies. Given these findings, we propose to determine whether the biological, histopathological and clinical features of melanoma precursor lesions can be modulated by systemic treatment with low-dose IFNa-2a in patients who have a clinical history of melanoma and multiple atypical nevi. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TUMOR NEOVASCULATURE VECTOR TARGETING Principal Investigator & Institution: Deisseroth, Albert B.; President and Ceo; Sidney Kimmel Cancer Center San Diego, Ca 92121 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: (provided by applicant): The proposed clinical trial for melanoma is based on the protocol developed and tested successfully in a mouse xenograft model of human melanoma. The trial protocol involves administering to melanoma patients an immunoconjugate composed of a human factor VII (fVII) molecule conjugated to the Fc region of a human IgG1 immunoglobulin. The immunoconjugate binds with high affinity and specificity to its natural receptor tissue factor (TF) expressed by tumor blood vessels and tumor cells. The fVII molecule is mutated to prevent initiation of blood coagulation after it binds to TF. The gene encoding the immunoconjugate is carried by a non-replicating adenoviral vector, which is injected directly into skin tumors of a melanoma patient. The adenovirus infects mainly the cells of the injected tumor, which synthesize the immunoconjugate for secretion into the blood, establishing a steady high blood titer of the immunoconjugate for several weeks. The blood-borne immunoconjugate binds to tumor blood vessels and tumor cells throughout a patient?s body, resulting in induction of a powerful cytolytic immune attack against primary and disseminated tumors. The mouse model experiments demonstrated that the immunoconjugate causes regression of human melanoma tumors, associated with extensive destruction of the tumor vasculature. No clinically significant adverse effects on normal tissues were detected in the treated mice. The safety and efficacy of the protocol in the mouse model suggest a similar outcome for the proposed clinical trial. Designed primarily as a dose escalation study of the safety of administering intratumoral injections of an adenoviral vector encoding the fVII immunoconjugate, the trial is also designed to generate efficacy data. Each melanoma patient enrolled in the trial will receive a selected dose of the vector administered at 3-day intervals for a total of 6 doses. Toxicity will be monitored by a panel of tests during and after treatment, including several types of blood and liver function tests. Efficacy will be monitored by measurements of injected skin tumors, and also of skin tumors and internal tumors that were not injected. Because the protocol should be applicable to a broad range of human
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solid tumors, a favorable outcome for the melanoma trial could lead to a new treatment not only for melanoma but also for other types of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “melanoma” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for melanoma in the PubMed Central database: •
12(S)-Hydroxyeicosatetraenoic Acid and 13(S)-Hydroxyoctadecadienoic Acid Regulation of Protein Kinase C-[alpha] in Melanoma Cells: Role of ReceptorMediated Hydrolysis of Inositol Phospholipids. by Liu B, Khan WA, Hannun YA, Timar J, Taylor JD, Lundy S, Butovich I, Honn KV.; 1995 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40977
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A 170-kDa Membrane-Bound Protease is Associated with the Expression of Invasiveness by Human Malignant Melanoma Cells. by Aoyama A, Chen W.; 1990 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54942
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A CDKN2-like polymorphism in Xiphophorus LG V is associated with UV-B-induced melanoma formation in platyfish --swordtail hybrids. by Nairn RS, Kazianis S, McEntire BB, Della Coletta L, Walter RB, Morizot DC.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24043
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A Melanoma-Specific VH Antibody Cloned from a Fusion Phage Library of a Vaccinated Melanoma Patient. by Cai X, Garen A.; 1996 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39013
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A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. by Coulie PG, Karanikas V, Colau D, Lurquin C, Landry C, Marchand M, Dorval T, Brichard V, Boon T.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56954
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A Mouse B16 Melanoma Mutant Deficient in Glycolipids. by Ichikawa S, Nakajo N, Sakiyama H, Hirabayashi Y.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43438
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A Mutated Intron Sequence Codes for an Antigenic Peptide Recognized by Cytolytic T Lymphocytes on a Human Melanoma. by Coulie PG, Lehmann F, Lethe B, Herman J, Lurquin C, Andrawiss M, Boon T.; 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41269
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Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. by Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert DN.; 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21028
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Adoptive T cell therapy using antigen-specific CD8 + T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells. by Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD.; 2002 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138583
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AIM1, a novel non-lens member of the [beta][gamma]-crystallin superfamily, is associated with the control of tumorigenicity in human malignant melanoma. by Ray ME, Wistow G, Su YA, Meltzer PS, Trent JM.; 1997 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20351
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An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis. by Bhoumik A, Huang TG, Ivanov V, Gangi L, Qiao RF, Woo SL, Chen SH, Ronai Z.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151112
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An autologous oral DNA vaccine protects against murine melanoma. by Xiang R, Lode HN, Chao TH, Ruehlmann JM, Dolman CS, Rodriguez F, Whitton JL, Overwijk WW, Restifo NP, Reisfeld RA.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25856
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An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo. by Lahav R, Heffner G, Patterson PH.; 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18062
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Anti-Melanoma Antibodies from Melanoma Patients Immunized with Genetically Modified Autologous Tumor Cells: Selection of Specific Antibodies from SingleChain Fv Fusion Phage Libraries. by Cai X, Garen A.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41553
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Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase. by Koo HM, VanBrocklin M, McWilliams MJ, Leppla SH, Duesbery NS, Woude GF.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122471
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Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. by Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R,
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MacRae S, Willman A, Padera R, Jaklitsch MT, Shankar S, Chen TC, Korman A, Allison JP, Dranoff G.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153621 •
Biologic and Therapeutic Significance of MYB Expression in Human Melanoma. by Hijiya N, Zhang J, Ratajczak MZ, Kant JA, DeRiel K, Herlyn M, Zon G, Gewirtz AM.; 1994 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43813
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Biotransformation of the Antimelanoma Agent Betulinic Acid by Bacillus megaterium ATCC 13368. by Chatterjee P, Kouzi SA, Pezzuto JM, Hamann MT.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92230
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Changes in Expression of Putative Antigens Encoded by Pigment Genes in Mouse Melanomas at Different Stages of Malignant Progression. by Orlow SJ, Hearing VJ, Sakai C, Urabe K, Zhou B, Silvers WK, Mintz B.; 1995 Oct 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40754
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Cloning of the Gene Coding for a Shared Human Melanoma Antigen Recognized by Autologous T Cells Infiltrating into Tumor. by Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43610
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Comparison of fusion phage libraries displaying VH or single-chain Fv antibody fragments derived from the antibody repertoire of a vaccinated melanoma patient as a source of melanoma-specific targeting molecules. by Cai X, Garen A.; 1997 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23147
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Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1. by Henriet P, Zhong ZD, Brooks PC, Weinberg KI, DeClerck YA.; 2000 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27660
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Cytotoxic T-Lymphocyte Clones from Different Patients Display Limited T-CellReceptor Variable-Region Gene Usage in HLA-A2-Restricted Recognition of the Melanoma Antigen Melan-A/MART-1. by Sensi M, Traversari C, Radrizzani M, Salvi S, Maccalli C, Mortarini R, Rivoltini L, Farina C, Nicolini G, Wolfel T, Brichard V, thierry Boon, Borbignon C, Anichini A, Parmiani G.; 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41759
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Direct Gene Transfer with DNA-Liposome Complexes in Melanoma: Expression, Biologic Activity, and Lack of Toxicity in Humans. by Nabel GJ, Nabel EG, Yang Z, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE.; 1993 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47971
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Direct visualization of distinct T cell epitopes derived from a melanoma tumorassociated antigen by using human recombinant antibodies with MHC- restricted T cell receptor-like specificity. by Denkberg G, Cohen CJ, Lev A, Chames P, Hoogenboom HR, Reiter Y.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123156
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Dual Inactivation of RB and p53 Pathways in RAS-Induced Melanomas. by Bardeesy N, Bastian BC, Hezel A, Pinkel D, DePinho RA, Chin L.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86838
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Effect of public education aimed at early diagnosis of malignant melanoma: cohort comparison study. by MacKie RM, Bray CA, Leman JA.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148894
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Egress of varicella-zoster virus from the melanoma cell: a tropism for the melanocyte. by Harson R, Grose C.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189316
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Eradication of Human Hepatic and Pulmonary Melanoma Metastases in SCID Mice by Antibody--Interleukin 2 Fusion Proteins. by Becker JC, Pancook JD, Gillies SD, Mendelsohn J, Reisfeld RA.; 1996 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39694
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Exchange of Viral Promoter/Enhancer Elements with Heterologous Regulatory Sequences Generates Targeted Hybrid Long Terminal Repeat Vectors for Gene Therapy of Melanoma. by Diaz RM, Eisen T, Hart IR, Vile RG.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109437
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Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry. by Hendrix MJ, Seftor EA, Meltzer PS, Gardner LM, Hess AR, Kirschmann DA, Schatteman GC, Seftor RE.; 2001 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35460
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Expression Cloning of a CMP-NeuAc:NeuAc[alpha]2-3Gal[beta]1-4Glc[beta]1-1'Cer [alpha]2, 8-Sialyltransferase (GD3 Synthase) from Human Melanoma Cells. by Nara K, Watanabe Y, Maruyama K, Kasahara K, Nagai Y, Sanai Y.; 1994 Aug 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44522
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Expression of Tissue Factor by Melanoma Cells Promotes Efficient Hematogenous Metastasis. by Mueller BM, Reisfeld RA, Edgington TS, Ruf W.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50651
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Fc receptors are required in passive and active immunity to melanoma. by Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV.; 1998 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18475
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Fibroblast Cell Interactions with Human Melanoma Cells Affect Tumor Cell Growth as a Function of Tumor Progression. by Cornil I, Theodorescu D, Man S, Herlyn M, Jambrosic J, Kerbel RS.; 1991 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52015
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Functional Hierarchy of Simultaneously Expressed Adhesion Receptors: Integrin [alpha]2[beta]1 but Not CD44 Mediates MV3 Melanoma Cell Migration and Matrix Reorganization within Three-dimensional Hyaluronan-containing Collagen Matrices. by Maaser K, Wolf K, Klein CE, Niggemann B, Zanker KS, Brocker EB, Friedl P.; 1999 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25559
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Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration. by Panelli MC, Wang E, Phan G, Puhlmann M, Miller L, Ohnmacht GA, Klein HG, Marincola FM.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126240
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Genetic Predisposition of Transgenic Mouse Melanocytes to Melanoma Results in Malignant Melanoma After Exposure to a Low Ultraviolet B Intensity Nontumorigenic for Normal Melanocytes. by larue L, Dougherty N, Mintz B.; 1992 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50166
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Genomic Organization of the Melanoma-Associated Glycoprotein MUC18: Implications for the Evolution of the Immunoglobulin Domains. by Sers C, Kirsch K, Rothbacher U, Riethmuller G, Johnson JP.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47387
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Heparin- and Sulfatide-Binding Peptides from the Type I Repeats of Human Thrombospondin Promote Melanoma Cell Adhesion. by Guo N, Krutzsch HC, Negre E, Vogel T, Blake DA, Roberts DD.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48799
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Histopathogenesis of Malignant Skin Melanoma Induced in Genetically Susceptible Transgenic Mice. by Mintz B, Silvers WK, Klein-Szanto AJ.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47452
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HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance. by Paul P, Rouas-Freiss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal FA, Avril MF, Dausset J, Guillet JG, Carosella ED.; 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22520
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Homozygous Deletions within Human Chromosome Band 9p21 in Melanoma. by Fountain JW, Karayiorgou M, Ernstoff MS, Kirkwood JM, Vlock DR, Titus-Ernstoff L, Bouchard B, Vijayasaradhi S, Houghton AN, Lahti J, Kidd VJ, Housman DE, Dracopoli NC.; 1992 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50378
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HOXB7 constitutively activates basic fibroblast growth factor in melanomas. by Care A, Silvani A, Meccia E, Mattia G, Stoppacciaro A, Parmiani G, Peschle C, Colombo MP.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231486
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Human CD4+ T Cells Specifically Recognize a Shared Melanoma-Associated Antigen Encoded by the Tyrosinase Gene. by Topalian SL, Rivoltini L, Mancini M, Markus NR, Robbins PF, Kawakami Y, Rosenberg SA.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44832
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Human High Molecular Weight Melanoma-Associated Antigen (HMW-MAA) Mimicry by Mouse Anti-Idiotypic Monoclonal Antibody MK2-23: Induction of Humoral Anti-HMW-MAA Immunity and Prolongation of Survival in Patients with
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Stage IV Melanoma. by Mittelman A, Chen ZJ, Yang H, Wong GY, Ferrone S.; 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48259 •
Human Monoclonal Antibody with Dual GM2/GD2 Specificity Derived from an Immunized Melanoma Patient. by Yamaguchi H, Furukawa K, Fortunato SR, Livingston PO, Lloyd KO, Oettgen HF, Old LJ.; 1990 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53894
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Human single-chain Fv immunoconjugates targeted to a melanoma-associated chondroitin sulfate proteoglycan mediate specific lysis of human melanoma cells by natural killer cells and complement. by Wang B, Chen YB, Ayalon O, Bender J, Garen A.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15540
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Identification of a Human Melanoma Antigen Recognized by Tumor-Infiltrating Lymphocytes Associated with in vivo Tumor Rejection. by Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appell E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA.; 1994 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44221
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Identification of multiple cancer /testis antigens by allogeneic antibody screening of a melanoma cell line library. by Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ.; 1998 Jun 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22686
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IL-18 regulates IL-1[beta]-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. by Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martin J, Carrascal T, Walsh P, Reznikov LL, Kim SH, Novick D, Rubinstein M, Dinarello CA.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15399
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Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA --liposome complexes. by Nabel GJ, Gordon D, Bishop DK, Nickoloff BJ, Yang ZY, Aruga A, Cameron MJ, Nabel EG, Chang AE.; 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26414
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Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117) overexpression exhibits potential therapeutic implications. by Potti A, Hille RC, Koch M.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=280698
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Immunophenotyping of Melanomas for Tyrosinase: Implications for Vaccine Development. by Chen Y, Stockert E, Tsang S, Coplan KA, Old LJ.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41108
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Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with 'MCW Melanoma Cocktail' -- A mixture of monoclonal antibodies to MART-1, melan-A, and tyrosinase. by Shidham VB, Qi D, Rao RN, Acker SM, Chang CC, Kampalath B, Dawson G, Machhi JK, Komorowski RA.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161792
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In vitro loss of heterozygosity targets the PTEN /MMAC1 gene in melanoma. by Robertson GP, Furnari FB, Miele ME, Glendening MJ, Welch DR, Fountain JW, Lugo TG, Huang HJ, Cavenee WK.; 1998 Aug 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21353
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In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites. by Hishii M, Andrews D, Boyle LA, Wong JT, Pandolfi F, van den Elsen PJ, Kurnick JT.; 1997 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19799
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Inactivation of the NF1 Gene in Human Melanoma and Neuroblastoma Cell Lines Without Impaired Regulation of GTP[center dot]Ras. by Johnson MR, Look AT, DeClue JE, Valentine MB, Lowy DR.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46756
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Increased Manganese Superoxide Dismutase Expression Suppresses the Malignant Phenotype of Human Melanoma Cells. by Church SL, Grant JW, Ridnour LA, Oberley LW, Swanson PE, Meltzer PS, Trent JM.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46247
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Induction of Antigen-Specific Cytolytic T Cells in situ in Human Melanoma by Immunization with Synthetic Peptide-Pulsed Autologous Antigen Presenting Cells. by Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, Kurtzman SK, Ergin MT, Ozols J, Meehan J, Mauri F.; 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41290
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Inhibition of Carcinoma and Melanoma Cell Growth by Type 1 Transforming Growth Factor [beta] is Dependent on the Presence of Polyunsaturated Fatty Acids. by Newman MJ.; 1990 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54361
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Inhibition of melanoma tumor growth in vivo by survivin targeting. by Grossman D, Kim PJ, Schechner JS, Altieri DC.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14640
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Inhibition of Rho Is Required for cAMP-induced Melanoma Cell Differentiation. by Busca R, Bertolotto C, Abbe P, Englaro W, Ishizaki T, Narumiya S, Boquet P, Ortonne JP, Ballotti R.; 1998 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25356
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Inhibition of the Motility and Growth of B16F10 Mouse Melanoma Cells by Dominant Negative Mutants of Dok-1. by Hosooka T, Noguchi T, Nagai H, Horikawa T, Matozaki T, Ichihashi M, Kasuga M.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87266
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Integrin [alpha]v[beta]3 Rescues Melanoma Cells from Apoptosis in ThreeDimensional Dermal Collagen. by Montgomery AM, Reisfeld RA, Cheresh DA.; 1994 Sep 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44705
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Interleukin 6: A Fibroblast-Derived Growth Inhibitor of Human Melanoma Cells from Early but not Advanced Stages to Tumor Progression. by Lu C, Vickers MF, Kerbel RS.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50096
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Invasive melanoma in Cdk4-targeted mice. by Sotillo R, Garcia JF, Ortega S, Martin J, Dubus P, Barbacid M, Malumbres M.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60867
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Involvement of Integrin [alpha]v[beta]3 and Cell Adhesion Molecule L1 in Transendothelial Migration of Melanoma Cells. by Voura EB, Ramjeesingh RA, Montgomery AM, Siu CH.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59705
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Isolation of X-Ray-Inducible Transcripts from Radioresistant Human Melanoma Cells. by Boothman DA, Meyers M, Fukunaga N, Lee SW.; 1993 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47104
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Localization of a Putative Tumor Suppressor Gene by Using Homozygous Deletions in Melanomas. by Weaver-Feldhaus J, Gruis NA, Neuhausen S, Paslier DL, Stockert E, Skolnick MH, Kamb A.; 1994 Aug 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44442
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Malignancy of Eye Melanomas Originating in the Retinal Pigment Epithelium of Transgenic Mice after Genetic Ablation of Choroidal Melanocytes. by Mintz B, KleinSzanto AJ.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50562
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Malignant Melanoma in Transgenic Mice. by Bradl M, Klein-Szanto A, Porter S, Mintz B.; 1991 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50770
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Mass Spectrometric and Edman Sequencing of Lipocortin I Isolated by TwoDimensional SDS/PAGE of Human Melanoma Lysates. by Hall SC, Smith DM, Masiarz FR, Soo VW, Tran HM, Epstein LB, Burlingame AL.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45993
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mda-5: An interferon-inducible putative RNA helicase with double-stranded RNAdependent ATPase activity and melanoma growth-suppressive properties. by Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB.; 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117358
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mda-7 (IL-24) mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. by Sarkar D, Su ZZ, Lebedeva IV, Sauane M, Gopalkrishnan RV, Valerie K, Dent P, Fisher PB.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126623
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Mechanism for elimination of a tumor suppressor: Aberrant splicing of a brainspecific exon causes loss of function of Bin1 in melanoma. by Ge K, DuHadaway J, Du W, Herlyn M, Rodeck U, Prendergast GC.; 1999 Aug 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22271
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Mediation of Lung Metastasis of Murine Melanomas by a Lung-Specific Endothelial Cell Adhesion Molecule. by Zhu D, Cheng C, Pauli BU.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52759
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Melan-A /MART-1 51 --73 represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4 + T cells. by Zarour HM, Kirkwood JM, Kierstead LS, Herr W, Brusic V, Slingluff CL Jr, Sidney J, Sette A, Storkus WJ.; 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26675
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Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin. by Czubayko F, Schulte AM, Berchem GJ, Wellstein A.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26208
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Melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destruction. by Schmollinger JC, Vonderheide RH, Hoar KM, Maecker B, Schultze JL, Hodi FS, Soiffer RJ, Jung K, Kuroda MJ, Letvin NL, Greenfield EA, Mihm M, Kutok JL, Dranoff G.; 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152304
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Melanotropic peptide-conjugated beads for microscopic visualization and characterization of melanoma melanotropin receptors. by Sharma SD, Jiang J, Hadley ME, Bentley DL, Hruby VJ.; 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19401
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Modulation of tumor growth by inhibitory Fc[gamma] receptor expressed by human melanoma cells. by Cassard L, Cohen-Solal JF, Galinha A, Sastre-Garau X, Mathiot C, Galon J, Dorval T, Bernheim A, Fridman WH, Sautes-Fridman C.; 2002 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151807
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Molecular Cloning of a Human Melanoma-Associated Chondroitin Sulfate Proteoglycan. by Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA.; 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38494
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Monitoring Specific T-Cell Responses to Melanoma Vaccines: ELISPOT, Tetramers, and Beyond. by Gajewski TF.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95840
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Murine Monoclonal Anti-Idiotope Antibody Breaks Unresponsiveness and Induces a Specific Antibody Response to Human Melanoma-Associated Proteoglycan Antigen in Cynomolgus Monkeys. by Chattopadhyay P, Starkey J, Morrow WJ, Raychaudhuri S.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48726
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Mutation Hotspots Due to Sunlight in the p53 Gene of Nonmelanoma Skin Cancers. by Ziegler A, Leffell DJ, Kunala S, Sharma HW, Gailani M, Simon JA, Halperin AJ, Baden HP, Shapiro PE, Bale AE, Brash DE.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46477
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Natural killer cell lines kill autologous [beta]2-microglobulin-deficient melanoma cells: Implications for cancer immunotherapy. by Porgador A, Mandelboim O, Restifo NP, Strominger JL.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24276
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Novel Ras antagonist blocks human melanoma growth. by Jansen B, SchlagbauerWadl H, Kahr H, Heere-Ress E, Mayer BX, Eichler HG, Pehamberger H, Gana-Weisz M, Ben-David E, Kloog Y, Wolff K.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24183
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Observational study of type of surgical training and outcome of definitive surgery for primary malignant melanoma. by MacKie RM, Bray CA, Hole DJ.; 2002 Nov 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136925
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Overexpression of Plasminogen Activator Inhibitor 2 in Human Melanoma Cells Inhibits Spontaneous Metastasis in scid/scid Mice. by Mueller BM, Yu YB, Laug WE.; 1995 Jan 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42846
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Platelet-Derived Growth Factor (PDGF) in Oncogenesis: Development of a Vascular Connective Tissue Stroma in Xenotransplanted Human Melanoma Producing PDGFBB. by Forsberg K, Valyi-Nagy I, Heldin C, Herlyn M, Westermark B.; 1993 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45668
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Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect mice against lethal challenge with malignant melanoma cells expressing a model antigen. by Mandl S, Sigal LJ, Rock KL, Andino R.; 1998 Jul 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20956
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Prevalence of Germ-Line Mutations in p16, p19ARF, and CDK4 in Familial Melanoma: Analysis of a Clinic-Based Population. by FitzGerald MG, Harkin DP, Silva-Arrieta S, MacDonald DJ, Lucchina LC, Unsal H, O'Neill E, Koh J, Finkelstein DM, Isselbacher KJ, Sober AJ, Haber DA.; 1996 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38708
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Rapid Mass Spectrometric Peptide Sequencing and Mass Matching for Characterization of Human Melanoma Proteins Isolated by Two-Dimensional PAGE. by Clauser KR, Hall SC, Smith DM, Webb JW, Andrews LE, Tran HM, Epstein LB, Burlingame AL.; 1995 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41850
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Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model. by Song X, Wang B, Bromberg M, Hu Z, Konigsberg W, Garen A.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122938
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Retrovirus Targeting by Tropism Restriction to Melanoma Cells. by Martin F, Neil S, Kupsch J, Maurice M, Cosset FL, Collins M.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112777
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Ribozyme-mediated attenuation of survivin expression sensitizes human melanoma cells to cisplatin-induced apoptosis. by Pennati M, Colella G, Folini M, Citti L, Daidone MG, Zaffaroni N.; 2002 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150847
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Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line A375C6. by Muthukkumar S, Nair P, Sells SF, Maddiwar NG, Jacob RJ, Rangnekar VM.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230878
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Role of the [alpha]v[beta]3 Integrin in Human Melanoma Cell Invasion. by Seftor RE, Seftor EA, Gehlsen KR, Stetler-Stevenson WG, Brown PD, Ruoslahti E, Hendrix MJ.; 1992 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48491
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Selective increase in specific alternative splice variants of tyrosinase in murine melanomas: A projected basis for immunotherapy. by Le Fur N, Kelsall SR, Silvers WK, Mintz B.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24678
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Sequence and Insertion Sites of Murine Melanoma-Associated Retrovirus. by Li M, Huang X, Zhu Z, Gorelik E.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112951
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Serological Analysis of Melan-A(MART-1), a Melanocyte-Specific Protein Homogeneously Expressed in Human Melanomas. by Chen Y, Stockert E, Jungbluth A, Tsang S, Coplan KA, Scanlan MJ, Old LJ.; 1996 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39162
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Serological Response Patterns of Melanoma Patients Immunized with a GM2 Ganglioside Conjugate Vaccine. by Kitamura K, Livingston PO, Fortunato SR, Stockert E, Helling F, Ritter G, Oettgen HF, Old LJ.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42307
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Stimulation of cAMP and Phosphomonoester Production by Melanotropin in Melanoma Cells: 31P NMR Studies. by Degani H, DeJordy JO, Salomon Y.; 1991 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51048
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Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins. by Lougheed JC, Holton JM, Alber T, Bazan JF, Handel TM.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33244
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Subcellular Localization of Myosin-V in the B16 Melanoma Cells, a Wild-type Cell Line for the dilute Gene. by Nascimento AA, Amaral RG, Bizario JC, Larson RE, Espreafico EM.; 1997 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25653
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Subcellular trafficking of antisense oligonucleotides and down-regulation of bcl-2 gene expression in human melanoma cells using a fusogenic liposome delivery system. by Hu Q, Bally MB, Madden TD.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137064
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Suppression of Lung Metastasis of B16 Mouse Melanoma by NAcetylglucosaminyltransferase III Gene Transfection. by Yoshimura M, Nishikawa A, Ihara Y, Taniguchi S, Taniguchi N.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41045
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Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model. by Hu Z, Sun Y, Garen A.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22205
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T-Cell Receptor Usage by Melanoma-Specific Clonal and Highly Oligoclonal TumorInfiltrating Lymphocyte Lines. by Shilyansky J, Nishimura MI, Yannelli JR, Kawakami Y, Jacknin LS, Charmley P, Rosenberg SA.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43464
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Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. by Parry D, Peters G.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231381
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The extracellular human melanoma inhibitory activity (MIA) protein adopts an SH3 domain-like fold. by Stoll R, Renner C, Zweckstetter M, Bruggert M, Ambrosius D, Palme S, Engh RA, Golob M, Breibach I, Buettner R, Voelter W, Holak TA, Bosserhoff AK.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133488
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The Melanoma Differentiation Associated Gene mda-7 Suppresses Cancer Cell Growth. by Jiang H, Su Z, Lin JJ, Goldstein NI, Young CS, Fisher PB.; 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38612
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The role of MHC class I glycoproteins in the regulation of induction of cell death in immunocytes by malignant melanoma cells. by Fishman D, Irena B, Kellman-Pressman S, Karas M, Segal S.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29327
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The velocity of ultrasound in human primary melanoma tissue - implications for the clinical use of high resolution sonography. by Weichenthal M, Mohr P, Breitbart EW.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34515
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Tissue Factor Promotes Melanoma Metastasis by a Pathway Independent of Blood Coagulation. by Bromberg ME, Konigsberg WH, Madison JF, Pawashe A, Garen A.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41125
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Tissue-specific expression of an anti-ras ribozyme inhibits proliferation of human malignant melanoma cells. by Ohta Y, Kijima H, Ohkawa T, Kashani-Sabet M, Scanlon KJ.; 1996 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145712
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Transgenic Mouse Model of Malignant Skin Melanoma. by Mintz B, Silvers WK.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47451
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Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype. by Poser I, Golob M, Buettner R, Bosserhoff AK.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152547
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Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c 2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models. by Le Fur N, Silvers WK, Kelsall SR, Mintz B.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23861
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UV-induction of keratinocyte endothelin-1 downregulates E-cadherin in melanocytes and melanoma cells. by Jamal S, Schneider RJ.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150409
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Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte --macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. by Soiffer R, Lynch T, Mihm M, Jung K, Rhuda C, Schmollinger JC, Hodi FS, Liebster L, Lam P, Mentzer S, Singer S, Tanabe KK, Cosimi AB, Duda R, Sober A, Bhan A, Daley J, Neuberg D, Parry G, Rokovich J, Richards L, Drayer J, Berns A, Clift S, Cohen LK, Mulligan RC, Dranoff G.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23738
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Wavelengths Effective in Induction of Malignant Melanoma. by Setlow RB, Grist E, Thompson K, Woodhead AD.; 1993 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46993
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals.
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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To generate your own bibliography of studies dealing with melanoma, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “melanoma” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for melanoma (hyperlinks lead to article summaries): •
A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis. Author(s): Forslund O, Ly H, Reid C, Higgins G. Source: The British Journal of Dermatology. 2003 July; 149(1): 64-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890196&dopt=Abstract
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A mistake I made from which I learned much: melanoma in a preexisting congenital nevus of Unna's type. Author(s): Ackerman AB. Source: International Journal of Surgical Pathology. 2003 July; 11(3): 213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894354&dopt=Abstract
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A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Author(s): Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Fichtner I, Kratz F. Source: Cancer Research. 2003 July 15; 63(14): 4062-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874007&dopt=Abstract
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A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. Author(s): Veierod MB, Weiderpass E, Thorn M, Hansson J, Lund E, Armstrong B, Adami HO. Source: Journal of the National Cancer Institute. 2003 October 15; 95(20): 1530-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14559875&dopt=Abstract
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A randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 in the treatment of metastatic malignant melanoma. Author(s): Nicholson S, Guile K, John J, Clarke IA, Diffley J, Donnellan P, Michael A, Szlosarek P, Dalgleish AG. Source: Melanoma Research. 2003 August; 13(4): 389-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883365&dopt=Abstract
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A rare case of intracranial metastatic amelanotic melanoma with cyst. Author(s): Ogawa R, Aoki R, Hyakusoku H. Source: Journal of Clinical Pathology. 2003 July; 56(7): 548-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835304&dopt=Abstract
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About moles, melanomas, and lasers: the dermatologist's schizophrenic attitude toward pigmented lesions. Author(s): Dummer R. Source: Archives of Dermatology. 2003 November; 139(11): 1405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623699&dopt=Abstract
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Absence of BRAF and NRAS mutations in uveal melanoma. Author(s): Cruz F 3rd, Rubin BP, Wilson D, Town A, Schroeder A, Haley A, Bainbridge T, Heinrich MC, Corless CL. Source: Cancer Research. 2003 September 15; 63(18): 5761-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522897&dopt=Abstract
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Absence of HER2 overexpression in metastatic malignant melanoma. Author(s): Inman JL, Kute T, White W, Pettenati M, Levine EA. Source: Journal of Surgical Oncology. 2003 October; 84(2): 82-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502781&dopt=Abstract
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Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity. Author(s): Bosserhoff AK, Stoll R, Sleeman JP, Bataille F, Buettner R, Holak TA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 November; 83(11): 1583-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615412&dopt=Abstract
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Advances in molecular staging of melanoma patients: multimarker analysis of archival lymph node tissue. Author(s): Busam KJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 1; 21(19): 3550-1. Epub 2003 August 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913105&dopt=Abstract
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Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases. Author(s): Levanat S, Situm M, Crnic I, Marasovic D, Puizina-Ivic N, Pokupcic N, Musani V, Komar A, Kubat M, Furac I, Karija-Vlahovic M, Krizanac S. Source: Croatian Medical Journal. 2003 August; 44(4): 418-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950144&dopt=Abstract
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Analysis of a murine anti-ganglioside GD2 monoclonal antibody expressing both IgG2a and IgG3 isotypes: monoclonality, apoptosis triggering, and activation of cellular cytotoxicity on human melanoma cells. Author(s): Lin CC, Shen YC, Chuang CK, Liao SK. Source: Advances in Experimental Medicine and Biology. 2001; 491: 419-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14533812&dopt=Abstract
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Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues. Author(s): Gorden A, Osman I, Gai W, He D, Huang W, Davidson A, Houghton AN, Busam K, Polsky D. Source: Cancer Research. 2003 July 15; 63(14): 3955-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873990&dopt=Abstract
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Angiogenesis, lymphangiogenesis, and melanoma metastasis. Author(s): Streit M, Detmar M. Source: Oncogene. 2003 May 19; 22(20): 3172-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789293&dopt=Abstract
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Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both. Author(s): Moozar KL, Wong CS, Couture J. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2003 October; 46(5): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14577706&dopt=Abstract
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Antimelanoma immunity in vitiligo and melanoma patients. Author(s): Juranic ZD, Stanojevic-Bakic N, Zizak Z, Babovic N, Radovic-Kovacevic V, Stanojkovic T, Dzodic R. Source: Neoplasma. 2003; 50(4): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937846&dopt=Abstract
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Apparent primary pleural melanoma: case report and literature review. Author(s): Um SW, Yoo CG, Lee CT, Han SK, Shim YS, Kim YW. Source: Respiratory Medicine. 2003 May; 97(5): 586-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735679&dopt=Abstract
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ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma. Author(s): Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T, Taniguchi S. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 1; 107(2): 202-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949795&dopt=Abstract
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Atrioventricular nodal blocking secondary to melanoma infiltration. Author(s): Belda-Iniesta C, Sanchez-Aquino Gonzalez RM, Cuesta E, Gonzalez-Baron M. Source: Melanoma Research. 2003 August; 13(4): 433-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883373&dopt=Abstract
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Bartholin's gland carcinoma, malignant melanoma and other rare tumours of the vulva. Author(s): Finan MA, Barre G. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2003 August; 17(4): 609-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965135&dopt=Abstract
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Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968-97. Author(s): Koh D, Wang H, Lee J, Chia KS, Lee HP, Goh CL. Source: The British Journal of Dermatology. 2003 June; 148(6): 1161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828744&dopt=Abstract
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Bcl-2 expression in metastatic malignant melanoma. Importance for the therapeutic efficacy of biochemotherapy. Author(s): Hakansson A, Gustafsson B, Abdiu A, Krysander L, Hakansson L. Source: Cancer Immunology, Immunotherapy : Cii. 2003 April; 52(4): 249-54. Epub 2003 March 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669250&dopt=Abstract
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BDS Melanoma Guidelines. Author(s): Middleton M, Harris AL, Kurwa H, Millard P, Hollowood K, Cassell O. Source: The British Journal of Dermatology. 2003 May; 148(5): 1081-2; Author Reply 1082. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786860&dopt=Abstract
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Beta1,6-branched oligosaccharides and coarse vesicles: a common, pervasive phenotype in melanoma and other human cancers. Author(s): Handerson T, Pawelek JM. Source: Cancer Research. 2003 September 1; 63(17): 5363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500369&dopt=Abstract
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Betulinic acid-induced Mcl-1 expression in human melanoma--mode of action and functional significance. Author(s): Selzer E, Thallinger C, Hoeller C, Oberkleiner P, Wacheck V, Pehamberger H, Jansen B. Source: Molecular Medicine (Cambridge, Mass.). 2002 December; 8(12): 877-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606824&dopt=Abstract
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Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma. Author(s): Castiglia D, Pagani E, Alvino E, Vernole P, Marra G, Cannavo E, Jiricny J, Zambruno G, D'Atri S. Source: Genes, Chromosomes & Cancer. 2003 June; 37(2): 165-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696065&dopt=Abstract
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Bilateral uveal melanoma: a series of four cases. Author(s): Hadden PW, Damato BE, McKay IC. Source: Eye (London, England). 2003 July; 17(5): 613-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855969&dopt=Abstract
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Biochemotherapy for metastatic melanoma with limited central nervous system involvement. Author(s): Boasberg PD, O'Day SJ, Kristedja TS, Martin M, Wang H, Deck R, Shinn K, Ames P, Tamar B, Petrovich Z. Source: Oncology. 2003; 64(4): 328-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759528&dopt=Abstract
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Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Author(s): Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R, MacRae S, Willman A, Padera R, Jaklitsch MT, Shankar S, Chen TC, Korman A, Allison JP, Dranoff G. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4712-7. Epub 2003 Apr 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682289&dopt=Abstract
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Biological evaluation of an antibiotic DC-81-indole conjugate agent in human melanoma cell lines. Author(s): Ann Intern Med. 2003 Apr 15;138(8):I1 Source: Kaohsiung J Med Sci. 2003 January; 19(1): 6-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693915
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Biomarkers in melanoma: predisposition, screening and diagnosis. Author(s): Carlson JA, Slominski A, Linette GP, Mihm MC Jr, Ross JS. Source: Expert Rev Mol Diagn. 2003 March; 3(2): 163-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647994&dopt=Abstract
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Biomarkers in melanoma: staging, prognosis and detection of early metastases. Author(s): Carlson JA, Slominski A, Linette GP, Mihm MC Jr, Ross JS. Source: Expert Rev Mol Diagn. 2003 May; 3(3): 303-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779006&dopt=Abstract
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Biomolecular markers of malignancy in human uveal melanoma: the role of the cadherin-catenin complex and gene expression profiling. Author(s): Conway RM, Cursiefen C, Behrens J, Naumann GO, Holbach LM. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 January-February; 217(1): 6875. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566877&dopt=Abstract
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Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Author(s): Kivela T, Suciu S, Hansson J, Kruit WH, Vuoristo MS, Kloke O, Gore M, Hahka-Kemppinen M, Parvinen LM, Kumpulainen E, Humblet Y, Pyrhonen S. Source: European Journal of Cancer (Oxford, England : 1990). 2003 May; 39(8): 1115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736111&dopt=Abstract
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Bone marrow contains melanoma-reactive CD8+ effector T cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells. Author(s): Letsch A, Keilholz U, Assfalg G, Mailander V, Thiel E, Scheibenbogen C. Source: Cancer Research. 2003 September 1; 63(17): 5582-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500398&dopt=Abstract
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Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Author(s): Zhao W, Entschladen F, Liu H, Niggemann B, Fang Q, Zaenker KS, Han R. Source: Cancer Detection and Prevention. 2003; 27(1): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600419&dopt=Abstract
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BRAF as a melanoma susceptibility candidate gene? Author(s): Laud K, Kannengiesser C, Avril MF, Chompret A, Stoppa-Lyonnet D, Desjardins L, Eychene A, Demenais F, Lenoir GM, Bressac-de Paillerets B; French Herediatary Melanoma Study Group. Source: Cancer Research. 2003 June 15; 63(12): 3061-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810628&dopt=Abstract
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BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Author(s): Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, Aaronson SA. Source: Cancer Research. 2003 July 15; 63(14): 3883-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873977&dopt=Abstract
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Brain metastases following interleukin-2 plus interferon-alpha-2a therapy: a followup study in 94 stage IV melanoma patients. Author(s): Schmittel A, Proebstle T, Engenhart-Cabillic R, Scheibenbogen C, Geueke AM, Thiel E, Keilholz U. Source: European Journal of Cancer (Oxford, England : 1990). 2003 March; 39(4): 476-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751378&dopt=Abstract
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Can different genetic changes characterize histogenetic subtypes and biologic behavior in sporadic malignant melanoma of the skin? Author(s): Poetsch M, Dittberner T, Woenckhaus C. Source: Cellular and Molecular Life Sciences : Cmls. 2003 September; 60(9): 1923-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523552&dopt=Abstract
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Case report: magnetic resonance imaging of vaginal malignant melanoma. Author(s): Kim H, Jung SE, Lee EH, Kang SW. Source: Journal of Computer Assisted Tomography. 2003 May-June; 27(3): 357-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794599&dopt=Abstract
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Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma. Author(s): Nachmias B, Ashhab Y, Bucholtz V, Drize O, Kadouri L, Lotem M, Peretz T, Mandelboim O, Ben-Yehuda D. Source: Cancer Research. 2003 October 1; 63(19): 6340-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14559822&dopt=Abstract
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CDKN2A as a uveal and cutaneous melanoma susceptibility gene. Author(s): Kannengiesser C, Avril MF, Spatz A, Laud K, Lenoir GM, Bressac-dePaillerets B. Source: Genes, Chromosomes & Cancer. 2003 November; 38(3): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506702&dopt=Abstract
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cDNA array technology in melanoma: an overview. Author(s): Baldi A, Santini D, De Luca A, Paggi MG. Source: Journal of Cellular Physiology. 2003 August; 196(2): 219-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811814&dopt=Abstract
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Changing epidemiology of malignant cutaneous melanoma in Europe 1953-1997: rising trends in incidence and mortality but recent stabilizations in western Europe and decreases in Scandinavia. Author(s): de Vries E, Bray FI, Coebergh JW, Parkin DM. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925966&dopt=Abstract
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Changing surgical therapy for melanoma of the external ear. Author(s): Pockaj BA, Jaroszewski DE, DiCaudo DJ, Hentz JG, Buchel EW, Gray RJ, Markovic SN, Bite U. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 July; 10(6): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839855&dopt=Abstract
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Characterization of the neoplastic phenotype in the familial atypical multiple-mole melanoma-pancreatic carcinoma syndrome. Author(s): Rulyak SJ, Brentnall TA, Lynch HT, Austin MA. Source: Cancer. 2003 August 15; 98(4): 798-804. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910525&dopt=Abstract
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Chemotherapy and bio-chemotherapy in patients with advanced melanoma: combination therapy with a nitrosourea. Author(s): Ridolfi R, Tanganelli L, Scelzi E, Manente P, Palmeri S, Ravaioli A, Fiammenghi L, Romanini A; Italian Melaoma Intergroup. Source: Journal of Chemotherapy (Florence, Italy). 2003 April; 15(2): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797399&dopt=Abstract
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Choroidal vascular changes after transpupillary thermotherapy for choroidal melanoma. Author(s): Midena E, Pilotto E, de Belvis V, Zaltron S, Doro D, Segato T, Piermarocchi S. Source: Ophthalmology. 2003 November; 110(11): 2216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597533&dopt=Abstract
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Chromosomal gains and losses in ocular melanoma detected by comparative genomic hybridization in an Australian population-based study. Author(s): Vajdic CM, Hutchins AM, Kricker A, Aitken JF, Armstrong BK, Hayward NK, Armes JE. Source: Cancer Genetics and Cytogenetics. 2003 July 1; 144(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810250&dopt=Abstract
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Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colonystimulating factor in adjuvant or pulsed on dendritic cells. Author(s): Slingluff CL Jr, Petroni GR, Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, Patterson JW, Deacon DH, Hibbitts S, Teates D, Neese PY, Grosh WW, Chianese-Bullock KA, Woodson EM, Wiernasz CJ, Merrill P, Gibson J, Ross M, Engelhard VH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 November 1; 21(21): 4016-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581425&dopt=Abstract
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Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life. Author(s): Trask PC, Paterson AG, Griffith KA, Riba MB, Schwartz JL. Source: Cancer. 2003 August 15; 98(4): 854-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910531&dopt=Abstract
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Combination chemotherapy with docetaxel and irinotecan in metastatic malignant melanoma. Author(s): Tas F, Camlica H, Kurul S, Aydiner A, Topuz E. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801051&dopt=Abstract
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Comparison of clinical, echographic, and histopathological measurements from eyes with medium-sized choroidal melanoma in the collaborative ocular melanoma study: COMS report no. 21. Author(s): Collaborative Ocular Melanoma Study Group. Source: Archives of Ophthalmology. 2003 August; 121(8): 1163-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912695&dopt=Abstract
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Comparison of phaeomelanin and its precursor 5-S-cysteinyldopa in the serum of melanoma patients. Author(s): Wakamatsu K, Yokochi M, Naito A, Kageshita T, Ito S. Source: Melanoma Research. 2003 August; 13(4): 357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883361&dopt=Abstract
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Controversy regarding pre-enucleation radiation for uveal melanoma. Author(s): Char DH, Phillips TL. Source: Archives of Ophthalmology. 2003 September; 121(9): 1346. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963633&dopt=Abstract
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Cooking and uveal melanoma risk: results from two German case-control studies. Author(s): Stang A, Ahrens W, Baumgardt-Elms C, Stegmaier C, Bornfeld N, SchmidtPokrzywniak A, Jockel KH. Source: Cancer Causes & Control : Ccc. 2003 May; 14(4): 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846370&dopt=Abstract
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Cost-effectiveness of sentinel lymph node biopsy in thin melanomas. Author(s): Agnese DM, Abdessalam SF, Burak WE Jr, Magro CM, Pozderac RV, Walker MJ. Source: Surgery. 2003 October; 134(4): 542-7; Discussion 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14605613&dopt=Abstract
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Cyclooxygenase-2 expression in uveal melanoma: novel classification of mixed-celltype tumours. Author(s): Figueiredo A, Caissie AL, Callejo SA, McLean IW, Gold P, Burnier MN Jr. Source: Can J Ophthalmol. 2003 August; 38(5): 352-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956275&dopt=Abstract
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Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice. Author(s): Okada N, Masunaga Y, Okada Y, Mizuguchi H, Iiyama S, Mori N, Sasaki A, Nakagawa S, Mayumi T, Hayakawa T, Fujita T, Yamamoto A. Source: Gene Therapy. 2003 October; 10(22): 1891-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502218&dopt=Abstract
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Dermoscopic features of naevus-associated melanoma. Author(s): Stante M, Carli P, Massi D, de Giorgi V. Source: Clinical and Experimental Dermatology. 2003 September; 28(5): 476-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950330&dopt=Abstract
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Dermoscopy of melanocytic neoplasms: subpatterns of melanoma. Author(s): Grichnik JM. Source: Archives of Dermatology. 2003 August; 139(8): 1104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925405&dopt=Abstract
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Design, expression, purification, and characterization, in vitro and in vivo, of an antimelanoma single-chain Fv antibody fused to the toxin gelonin. Author(s): Rosenblum MG, Cheung LH, Liu Y, Marks JW 3rd. Source: Cancer Research. 2003 July 15; 63(14): 3995-4002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873997&dopt=Abstract
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Detection of micrometastasis in the sentinel lymph node via lymphoscintigraphy for a patient with in-transit metastatic melanoma. Author(s): Yang CH, Yeh JT, Lo YF, Kuo TT, Tasi CC, Kao PF, Chang JW. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 September; 29(9): 990-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930350&dopt=Abstract
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Development and validation of disease-specific measures for choroidal melanoma: COMS-QOLS report No. 2. Author(s): Melia M, Moy CS, Reynolds SM, Cella D, Murray TG, Hovland KR, Hayman JA, Mangione CM; The Collaborative Ocular Melanoma Study-Quality Of Life Study Group. Source: Archives of Ophthalmology. 2003 July; 121(7): 1010-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860806&dopt=Abstract
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Difference between real and perceived power of dermoscopical methods for detection of malignant melanoma. Author(s): Schiffner R, Wilde O, Schiffner-Rohe J, Stolz W. Source: Eur J Dermatol. 2003 May-June; 13(3): 288-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804992&dopt=Abstract
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Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma. Author(s): Kusters B, de Waal RM, Wesseling P, Verrijp K, Maass C, Heerschap A, Barentsz JO, Sweep F, Ruiter DJ, Leenders WP. Source: Cancer Research. 2003 September 1; 63(17): 5408-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500375&dopt=Abstract
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Differential expression of vascular endothelial growth factor-A isoforms at different stages of melanoma progression. Author(s): Gorski DH, Leal AD, Goydos JS. Source: Journal of the American College of Surgeons. 2003 September; 197(3): 408-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946796&dopt=Abstract
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Differential expression of versican isoforms is a component of the human melanoma cell differentiation process. Author(s): Domenzain C, Docampo MJ, Serra M, Miquel L, Bassols A. Source: Biochimica Et Biophysica Acta. 2003 September 23; 1642(1-2): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972299&dopt=Abstract
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Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Author(s): Ruf W, Seftor EA, Petrovan RJ, Weiss RM, Gruman LM, Margaryan NV, Seftor RE, Miyagi Y, Hendrix MJ. Source: Cancer Research. 2003 September 1; 63(17): 5381-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500372&dopt=Abstract
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Differentiation of CD8+ T cells from tumor-invaded and tumor-free lymph nodes of melanoma patients: role of common gamma-chain cytokines. Author(s): Anichini A, Scarito A, Molla A, Parmiani G, Mortarini R. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 August 15; 171(4): 2134-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902520&dopt=Abstract
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Disappearance of retinal myelinated nerve fibers after plaque radiotherapy for choroidal melanoma. Author(s): Mashayekhi A, Shields CL, Shields JA. Source: Retina (Philadelphia, Pa.). 2003 August; 23(4): 572-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972781&dopt=Abstract
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Disease-driven T cell activation predicts immune responses to vaccination against melanoma. Author(s): Speiser DE, Rimoldi D, Batard P, Lienard D, Lejeune F, Cerottini JC, Romero P. Source: Cancer Immunity [electronic Resource] : a Journal of the Academy of Cancer Immunology. 2003 September 9; 3: 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962476&dopt=Abstract
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Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Author(s): Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Source: Cancer Treatment Reviews. 2003 August; 29(4): 241-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927565&dopt=Abstract
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Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival? Author(s): Eggermont AM, Punt CJ. Source: American Journal of Clinical Dermatology. 2003; 4(8): 531-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862495&dopt=Abstract
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Does having basal cell carcinoma increase a person's risk of melanoma? Author(s): Strayer SM. Source: Health News. 2003 August; 9(8): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971322&dopt=Abstract
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Dose fractionation effects in primary and metastatic human uveal melanoma cell lines. Author(s): van den Aardweg GJ, Kilic E, de Klein A, Luyten GP. Source: Investigative Ophthalmology & Visual Science. 2003 November; 44(11): 4660-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578382&dopt=Abstract
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Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. Author(s): Takeuchi T, Heng HH, Ye CJ, Liang SB, Iwata J, Sonobe H, Ohtsuki Y. Source: American Journal of Pathology. 2003 October; 163(4): 1395-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507647&dopt=Abstract
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Duodenal metastatic amelanotic melanoma. Author(s): Chung JP, Lee SJ, Lee JI, Lee KS, Lee SI. Source: Gastrointestinal Endoscopy. 2003 July; 58(1): 101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838234&dopt=Abstract
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Early melanoma detection: nonuniform dermoscopic features and growth. Author(s): Lucas CR, Sanders LL, Murray JC, Myers SA, Hall RP, Grichnik JM. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5): 663-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734494&dopt=Abstract
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Effect of interleukin 1 receptor antagonist gene transduction on human melanoma xenografts in nude mice. Author(s): Weinreich DM, Elaraj DM, Puhlmann M, Hewitt SM, Carroll NM, Feldman ED, Turner EM, Spiess PJ, Alexander HR. Source: Cancer Research. 2003 September 15; 63(18): 5957-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522922&dopt=Abstract
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Effects of physician supply on melanoma incidence and mortality in Florida. Author(s): Van Durme DJ, Ullman R, Campbell RJ, Roetzheim R. Source: Southern Medical Journal. 2003 July; 96(7): 656-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940314&dopt=Abstract
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EGF +61 gene polymorphism and susceptibility to and prognostic markers in cutaneous malignant melanoma. Author(s): McCarron SL, Bateman AC, Theaker JM, Howell WM. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 20; 107(4): 673-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520709&dopt=Abstract
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Enhanced survival in patients with multiple primary melanoma. Author(s): Doubrovsky A, Menzies SW. Source: Archives of Dermatology. 2003 August; 139(8): 1013-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925389&dopt=Abstract
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Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Author(s): Garland CF, Garland FC, Gorham ED. Source: Annals of Epidemiology. 2003 July; 13(6): 395-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875796&dopt=Abstract
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Epidermal hyperplasia overlying human melanoma correlates with tumour depth and angiogenesis. Author(s): McCarty MF, Bielenberg DR, Nilsson MB, Gershenwald JE, Barnhill RL, Ahearne P, Bucana CD, Fidler IJ. Source: Melanoma Research. 2003 August; 13(4): 379-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883364&dopt=Abstract
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ERK and PI3K negatively regulate STAT-transcriptional activities in human melanoma cells: implications towards sensitization to apoptosis. Author(s): Krasilnikov M, Ivanov VN, Dong J, Ronai Z. Source: Oncogene. 2003 June 26; 22(26): 4092-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821943&dopt=Abstract
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ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cutaneous malignant melanoma. Author(s): Jost LM; ESMO Guidelines Task Force. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 July; 14(7): 1012-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853340&dopt=Abstract
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Evaluating health utility in patients with melanoma, breast cancer, colon cancer, and lung cancer: a nationwide, population-based assessment. Author(s): Ko CY, Maggard M, Livingston EH. Source: The Journal of Surgical Research. 2003 September; 114(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678691&dopt=Abstract
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Evaluation of melanocytic neoplasms: application of a pan-melanoma antibody cocktail. Author(s): Orchard G. Source: British Journal of Biomedical Science. 2002; 59(4): 196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572952&dopt=Abstract
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Evaluation of nodal patterns for melanoma of the ear. Author(s): Cole MD, Jakowatz J, Evans GR. Source: Plastic and Reconstructive Surgery. 2003 July; 112(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832876&dopt=Abstract
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Evaluation of sampling strategies for modeling survival of uveal malignant melanoma. Author(s): Kivela T, Grambsch PM. Source: Investigative Ophthalmology & Visual Science. 2003 August; 44(8): 3288-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882772&dopt=Abstract
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Exclusion of BRAFV599E as a melanoma susceptibility mutation. Author(s): Meyer P, Klaes R, Schmitt C, Boettger MB, Garbe C. Source: International Journal of Cancer. Journal International Du Cancer. 2003 August 10; 106(1): 78-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794760&dopt=Abstract
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Expression of AP-2alpha, c-kit, and cleaved caspase-6 and -3 in naevi and malignant melanomas of the skin. A possible role for caspases in melanoma progression? Author(s): Woenckhaus C, Giebel J, Failing K, Fenic I, Dittberner T, Poetsch M. Source: The Journal of Pathology. 2003 October; 201(2): 278-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517845&dopt=Abstract
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Expression of c-met tyrosine kinase receptor is biologically and prognostically relevant for primary cutaneous malignant melanomas. Author(s): Cruz J, Reis-Filho JS, Silva P, Lopes JM. Source: Oncology. 2003; 65(1): 72-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837985&dopt=Abstract
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Expression of cyclin-D1 in uveal malignant melanoma. Author(s): Errico ME, Staibano S, Tranfa F, Bonavolonta G, Lo Muzio L, Somma P, Lucariello A, Mansueto G, D'Aponte A, Ferrara G, De Rosa G. Source: Anticancer Res. 2003 May-June; 23(3B): 2701-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894561&dopt=Abstract
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Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells. Author(s): Greig AV, Linge C, Healy V, Lim P, Clayton E, Rustin MH, McGrouther DA, Burnstock G. Source: The Journal of Investigative Dermatology. 2003 August; 121(2): 315-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880424&dopt=Abstract
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Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development. Author(s): van der Velden PA, Zuidervaart W, Hurks MH, Pavey S, Ksander BR, Krijgsman E, Frants RR, Tensen CP, Willemze R, Jager MJ, Gruis NA. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 10; 106(4): 472-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845640&dopt=Abstract
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Extensive metastatic leptomeningeal melanomatosis as the first clinical sign of a cutaneous melanoma: morphological correlations between magnetic resonance imaging and autopsy findings. A case report. Author(s): Bussani R, Cova M, Pozzi-Mucelli R, Camilot D, Silvestri F. Source: Human Pathology. 2003 June; 34(6): 625-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827619&dopt=Abstract
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Factors of delay in the diagnosis of melanoma. Author(s): Betti R, Vergani R, Tolomio E, Santambrogio R, Crosti C. Source: Eur J Dermatol. 2003 March-April; 13(2): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695136&dopt=Abstract
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Familial and attributable risks in cutaneous melanoma: effects of proband and age. Author(s): Hemminki K, Zhang H, Czene K. Source: The Journal of Investigative Dermatology. 2003 February; 120(2): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542525&dopt=Abstract
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Familial uveal melanoma: a report on two families and a review of the literature. Author(s): Kodjikian L, Nguyen K, Lumbroso L, Gauthier-Villars M, Chauvel P, Plauchu H, Sterkers M, Devouassoux M, Grange JD. Source: Acta Ophthalmologica Scandinavica. 2003 August; 81(4): 389-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859267&dopt=Abstract
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Farnesyl thiosalicylic acid chemosensitizes human melanoma in vivo. Author(s): Halaschek-Wiener J, Kloog Y, Wacheck V, Jansen B. Source: The Journal of Investigative Dermatology. 2003 January; 120(1): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535206&dopt=Abstract
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Farnesyl transferase inhibitor SCH66336 is cytostatic, pro-apoptotic and enhances chemosensitivity to cisplatin in melanoma cells. Author(s): Smalley KS, Eisen TG. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 10; 105(2): 165-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673674&dopt=Abstract
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Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. Author(s): MacKie RM, Reid R, Junor B. Source: The New England Journal of Medicine. 2003 February 6; 348(6): 567-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571271&dopt=Abstract
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Fatty acid synthase expression in melanoma. Author(s): Innocenzi D, Alo PL, Balzani A, Sebastiani V, Silipo V, La Torre G, Ricciardi G, Bosman C, Calvieri S. Source: Journal of Cutaneous Pathology. 2003 January; 30(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534800&dopt=Abstract
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Favourable outcome of giant malignant melanoma of the conjunctiva despite poor prognostic features. Author(s): Malik KP, Dadeya S, Gulliani BP, Gupta VS. Source: Can J Ophthalmol. 2003 August; 38(5): 397-400. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956282&dopt=Abstract
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Feasibility to generate monocyte-derived dendritic cell from coculture with melanoma tumor cells in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Author(s): Kim YT, Hersh EM, Trevor KT. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2003 April; 49(4): 230-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852497&dopt=Abstract
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Five-year results of curettage-cryosurgery for 100 consecutive auricular nonmelanoma skin cancers. Author(s): Nordin P, Stenquist B. Source: The Journal of Laryngology and Otology. 2002 November; 116(11): 893-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487665&dopt=Abstract
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Fluorescence imaging analysis of upstream regulators and downstream targets of STAT3 in melanoma precursor lesions obtained from patients before and after systemic low-dose interferon-alpha treatment. Author(s): Smith AP, Kirkwood JM, Edington HD, Jukic DM, Farkas DL, Becker D. Source: Molecular Imaging : Official Journal of the Society for Molecular Imaging. 2003 January; 2(1): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926238&dopt=Abstract
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Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma. Author(s): Havenga K, Cobben DC, Oyen WJ, Nienhuijs S, Hoekstra HJ, Ruers TJ, Wobbes T. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511614&dopt=Abstract
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Fluorodeoxyglucose-positron emission tomography imaging versus sentinel node biopsy in the primary staging of melanoma patients. Author(s): Longo MI, Lazaro P, Bueno C, Carreras JL, Montz R. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 March; 29(3): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614417&dopt=Abstract
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Foramen magnum metastatic malignant melanoma. Author(s): Pai SB, Krishna KN. Source: Neurology India. 2003 March; 51(1): 79-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865527&dopt=Abstract
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Frequency of UV-inducible NRAS mutations in melanomas of patients with germline CDKN2A mutations. Author(s): Eskandarpour M, Hashemi J, Kanter L, Ringborg U, Platz A, Hansson J. Source: Journal of the National Cancer Institute. 2003 June 4; 95(11): 790-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783933&dopt=Abstract
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Function and regulation of melanoma-stromal fibroblast interactions: when seeds meet soil. Author(s): Li G, Satyamoorthy K, Meier F, Berking C, Bogenrieder T, Herlyn M. Source: Oncogene. 2003 May 19; 22(20): 3162-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789292&dopt=Abstract
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Fungal granuloma following ruthenium plaque radiotherapy of a choroidal melanoma. Author(s): Okera S, Dodd T, Selva D, Muecke J. Source: Clinical & Experimental Ophthalmology. 2003 April; 31(2): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648052&dopt=Abstract
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Future perspectives on malignant melanoma. Author(s): Leong SP. Source: The Surgical Clinics of North America. 2003 April; 83(2): 453-6, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744619&dopt=Abstract
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Gamma knife radiosurgery for intracranial metastatic melanoma: a 6-year experience. Author(s): Gonzalez-Martinez J, Hernandez L, Zamorano L, Sloan A, Levin K, Lo S, Li Q, Diaz F. Source: Journal of Neurosurgery. 2002 December; 97(5 Suppl): 494-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507084&dopt=Abstract
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Ganglioneuroblastic differentiation in a primary cutaneous malignant melanoma. Author(s): Grayson W, Mare LR. Source: The American Journal of Dermatopathology. 2003 February; 25(1): 40-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544099&dopt=Abstract
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Gangliosides from human melanoma tumors impair dendritic cell differentiation from monocytes and induce their apoptosis. Author(s): Peguet-Navarro J, Sportouch M, Popa I, Berthier O, Schmitt D, Portoukalian J. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 April 1; 170(7): 3488-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646609&dopt=Abstract
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Gender differences in rising trends in cutaneous malignant melanoma in Spain, 197598. Author(s): Nieto A, Ruiz-Ramos M, Abdel-Kader L, Conde M, Camacho F. Source: The British Journal of Dermatology. 2003 January; 148(1): 110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534603&dopt=Abstract
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Gene-expression profiling in human cutaneous melanoma. Author(s): Carr KM, Bittner M, Trent JM. Source: Oncogene. 2003 May 19; 22(20): 3076-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789283&dopt=Abstract
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Genetic epidemiology of melanoma. Author(s): Bataille V. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(10): 1341-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826035&dopt=Abstract
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Genetics of melanoma predisposition. Author(s): Hayward NK. Source: Oncogene. 2003 May 19; 22(20): 3053-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789280&dopt=Abstract
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Genomic instability in drug-resistant human melanoma cell lines detected by Alu-Iarbitrary-primed PCR. Author(s): Brkic G, Gopas J, Tanic N, Dedovic-Tanic N, Benharroch D, FinkelsteinJaworowsky E, Kedar I, Dimitrijevic B. Source: Anticancer Res. 2003 May-June; 23(3B): 2601-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894547&dopt=Abstract
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Genotypic analysis of primary and metastatic cutaneous melanoma. Author(s): Rao UN, Jones MW, Finkelstein SD. Source: Cancer Genetics and Cytogenetics. 2003 January 1; 140(1): 37-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12550756&dopt=Abstract
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Geographic variation in posttreatment surveillance intensity for patients with cutaneous melanoma. Author(s): Margenthaler JA, Meier JD, Virgo KS, Johnson DY, Goshima K, Chan D, Handler BS, Johnson FE. Source: American Journal of Surgery. 2003 August; 186(2): 194-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885617&dopt=Abstract
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Geometric cutaneous melanoma: a helpful clinical sign of malignancy? Author(s): Morris AD, Gee BC, Millard LG. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 August; 29(8): 827-8; Discussion 829. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859382&dopt=Abstract
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Germline 657del5 mutation in the NBS1 gene in patients with malignant melanoma of the skin. Author(s): Debniak T, Gorski B, Cybulski C, Jakubowska A, Kurzawski G, Lener M, Mierzejewski M, Masojc B, Medrek K, Kladny J, Zaluga E, Maleszka R, Chosia M, Lubinski J. Source: Melanoma Research. 2003 August; 13(4): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883362&dopt=Abstract
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Germline splicing mutations of CDKN2A predispose to melanoma. Author(s): Loo JC, Liu L, Hao A, Gao L, Agatep R, Shennan M, Summers A, Goldstein AM, Tucker MA, Deters C, Fusaro R, Blazer K, Weitzel J, Lassam N, Lynch H, Hogg D. Source: Oncogene. 2003 September 25; 22(41): 6387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508519&dopt=Abstract
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Glycoinositol phospholipid-anchored interleukin 2 but not secreted interleukin 2 inhibits melanoma tumor growth in mice. Author(s): Ji J, Li J, Holmes LM, Burgin KE, Yu X, Wagner TE, Wei Y. Source: Molecular Cancer Therapeutics. 2002 October; 1(12): 1019-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481424&dopt=Abstract
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GM-CSF-secreting melanoma vaccines. Author(s): Dranoff G. Source: Oncogene. 2003 May 19; 22(20): 3188-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789295&dopt=Abstract
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Golden Jubilee Lecture. Randomised clinical trials of choroidal melanoma treatment. Author(s): Straatsma BR. Source: Indian J Ophthalmol. 2003 March; 51(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701858&dopt=Abstract
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Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma. Author(s): Weber J, Sondak VK, Scotland R, Phillip R, Wang F, Rubio V, Stuge TB, Groshen SG, Gee C, Jeffery GG, Sian S, Lee PP. Source: Cancer. 2003 January 1; 97(1): 186-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491520&dopt=Abstract
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Halo naevus or malignant melanoma? A case report. Author(s): Mandalia MR, Skillman JM, Cook MG, Powell BW. Source: British Journal of Plastic Surgery. 2002 September; 55(6): 512-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479428&dopt=Abstract
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Heat shock protein expression in the eye and in uveal melanoma. Author(s): Missotten GS, Journee-de Korver JG, de Wolff-Rouendaal D, Keunen JE, Schlingemann RO, Jager MJ. Source: Investigative Ophthalmology & Visual Science. 2003 July; 44(7): 3059-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824252&dopt=Abstract
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Heterogenous S-100B protein expression patterns in malignant melanoma and association with serum protein levels. Author(s): Banfalvi T, Udvarhelyi N, Orosz Z, Gergye M, Gilde K, Timar J. Source: Oncology. 2003; 64(4): 374-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759535&dopt=Abstract
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High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. Author(s): Morgan RA, Dudley ME, Yu YY, Zheng Z, Robbins PF, Theoret MR, Wunderlich JR, Hughes MS, Restifo NP, Rosenberg SA. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 September 15; 171(6): 328795. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960359&dopt=Abstract
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High isotope counts and sentinel node positivity in patients with melanoma. Author(s): Jacobs IA, Chang CK, DasGupta TK, Salti G. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 January; 138(1): 63-6; Discussion 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511153&dopt=Abstract
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High-compared with low-dose radiosurgery for uveal melanomas. Author(s): Langmann G, Pendl G, Mullner K, Feichtinger KH, Papaefthymiouaf G. Source: Journal of Neurosurgery. 2002 December; 97(5 Suppl): 640-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507112&dopt=Abstract
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Histamine inhibits the production of interferon-induced protein of 10 kDa in human squamous cell carcinoma and melanoma. Author(s): Kanda N, Watanabe S. Source: The Journal of Investigative Dermatology. 2002 December; 119(6): 1411-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485448&dopt=Abstract
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Histologic resolution of melanoma in situ (lentigo maligna) with 5% imiquimod cream. Author(s): Chapman MS, Spencer SK, Brennick JB. Source: Archives of Dermatology. 2003 July; 139(7): 943-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873902&dopt=Abstract
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HLA class II antigen expression in uveal melanoma: correlation with clinicopathological features. Author(s): Krishnakumar S, Abhyankar D, Lakshmi SA, Shanmugam MP, Pushparaj V, Biswas J. Source: Experimental Eye Research. 2003 August; 77(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873447&dopt=Abstract
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How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma. Author(s): Mijnhout GS, Hoekstra OS, van Lingen A, van Diest PJ, Ader HJ, Lammertsma AA, Pijpers R, Meijer S, Teule GJ. Source: Journal of Clinical Pathology. 2003 April; 56(4): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663640&dopt=Abstract
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Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient. Author(s): Zacharias DP, Lima MM, Souza AL Jr, de Abranches Oliveira Santos ID, Enokiara M, Michalany N, Curi R. Source: Cell Biochemistry and Function. 2003 March; 21(1): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579526&dopt=Abstract
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Human herpes viruses in non-melanoma skin cancers. Author(s): Zafiropoulos A, Tsentelierou E, Billiri K, Spandidos DA. Source: Cancer Letters. 2003 July 30; 198(1): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893433&dopt=Abstract
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Human melanocyte senescence and melanoma susceptibility genes. Author(s): Bennett DC. Source: Oncogene. 2003 May 19; 22(20): 3063-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789281&dopt=Abstract
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Human melanoma TrkC: its association with a purine-analog-sensitive kinase activity. Author(s): Marchetti D, Murry B, Galjour J, Wilke-Greiter A. Source: Journal of Cellular Biochemistry. 2003 April 1; 88(5): 865-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616526&dopt=Abstract
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Human melanoma/NG2 chondroitin sulfate proteoglycan is expressed in the sarcolemma of postnatal human skeletal myofibers. Abnormal expression in merosinnegative and Duchenne muscular dystrophies. Author(s): Petrini S, Tessa A, Carrozzo R, Verardo M, Pierini R, Rizza T, Bertini E. Source: Molecular and Cellular Neurosciences. 2003 June; 23(2): 219-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812755&dopt=Abstract
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Human melanoma: drug resistance. Author(s): Helmbach H, Sinha P, Schadendorf D. Source: Recent Results Cancer Res. 2003; 161: 93-110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528802&dopt=Abstract
100 Melanoma
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Human uveal melanoma expresses NG2 immunoreactivity. Author(s): Li Y, Madigan MC, Lai K, Conway RM, Billson FA, Crouch R, Allen BJ. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714409&dopt=Abstract
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Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy. Author(s): Chung MH, Gupta RK, Hsueh E, Essner R, Ye W, Yee R, Morton DL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 15; 21(2): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525524&dopt=Abstract
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Hypothesis: a role for telomere crisis in spontaneous regression of melanoma. Author(s): Bastian BC. Source: Archives of Dermatology. 2003 May; 139(5): 667-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756110&dopt=Abstract
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Hypoxic pelvic and limb perfusion with melphalan and mitomycin C for recurrent limb melanoma: a pilot study. Author(s): Guadagni S, Santinami M, Patuzzo R, Pilati PL, Miotto D, Deraco M, Rossi CR, Fiorentini G, Di Filippo F, Valenti M, Amicucci G. Source: Melanoma Research. 2003 February; 13(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569285&dopt=Abstract
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Identification of a mutated receptor-like protein tyrosine phosphatase kappa as a novel, class II HLA-restricted melanoma antigen. Author(s): Novellino L, Renkvist N, Rini F, Mazzocchi A, Rivoltini L, Greco A, Deho P, Squarcina P, Robbins PF, Parmiani G, Castelli C. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 June 15; 170(12): 6363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794170&dopt=Abstract
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Identification of a splice acceptor site mutation in p16INK4A/p14ARF within a breast cancer, melanoma, neurofibroma prone kindred. Author(s): Prowse AH, Schultz DC, Guo S, Vanderveer L, Dangel J, Bove B, Cairns P, Daly M, Godwin AK. Source: Journal of Medical Genetics. 2003 August; 40(8): E102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920094&dopt=Abstract
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Identification of AP-2-regulated genes by macroarray profiling of gene expression in human A375P melanoma. Author(s): Suyama E, Minoshima H, Kawasaki H, Taira K. Source: Nucleic Acids Res Suppl. 2002; (2): 247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903198&dopt=Abstract
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Identification of novel deletion Loci at 1p36 and 9p22-21 in melanocytic dysplastic nevi and cutaneous malignant melanomas. Author(s): Hussein MR, Roggero E, Tuthill RJ, Wood GS, Sudilovsky O. Source: Archives of Dermatology. 2003 June; 139(6): 816-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810525&dopt=Abstract
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Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Author(s): Ramirez-Montagut T, Turk MJ, Wolchok JD, Guevara-Patino JA, Houghton AN. Source: Oncogene. 2003 May 19; 22(20): 3180-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789294&dopt=Abstract
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Immunization with Melan-A peptide-pulsed peripheral blood mononuclear cells plus recombinant human interleukin-12 induces clinical activity and T-cell responses in advanced melanoma. Author(s): Peterson AC, Harlin H, Gajewski TF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2342-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805336&dopt=Abstract
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Immunological consequences of the sentinel lymph-node biopsy--lessons from a melanoma patient. Author(s): Schrama D, Eggert AA, Brocker EB, Pedersen LO, thor Straten P, Becker JC. Source: The Lancet Oncology. 2003 July; 4(7): 446-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850196&dopt=Abstract
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Immunoproteasome subunits LMP2 and LMP7 downregulation in primary malignant melanoma lesions: association with lack of spontaneous regression. Author(s): Dissemond J, Goette P, Moers J, Lindeke A, Goos M, Ferrone S, Wagner SN. Source: Melanoma Research. 2003 August; 13(4): 371-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883363&dopt=Abstract
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Immunotherapy for melanoma metastatic to the orbit. Author(s): Baroody M, Hartstein ME, Holds JB. Source: Ophthalmic Plastic and Reconstructive Surgery. 2003 July; 19(4): 270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878874&dopt=Abstract
102 Melanoma
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Impact of vaccinations and infectious diseases on the risk of melanoma--evaluation of an EORTC case-control study. Author(s): Krone B, Kolmel KF, Grange JM, Mastrangelo G, Henz BM, Botev IN, Niin M, Seebacher C, Lambert D, Shafir R, Kokoschka EM, Kleeberg UR, Gefeller O, Pfahlberg A. Source: European Journal of Cancer (Oxford, England : 1990). 2003 November; 39(16): 2372-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556930&dopt=Abstract
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Inhibition of c-Myc oncoprotein limits the growth of human melanoma cells by inducing cellular crisis. Author(s): Biroccio A, Amodei S, Antonelli A, Benassi B, Zupi G. Source: The Journal of Biological Chemistry. 2003 September 12; 278(37): 35693-701. Epub 2003 June 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824159&dopt=Abstract
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Interobserver reproducibility of ulceration assessment in primary cutaneous melanomas. Author(s): Spatz A, Cook MG, Elder DE, Piepkorn M, Ruiter DJ, Barnhill RL. Source: European Journal of Cancer (Oxford, England : 1990). 2003 September; 39(13): 1861-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932663&dopt=Abstract
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Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. Author(s): Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, Cohen PA, Koski G, Czerniecki BJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 15; 21(20): 3826-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551301&dopt=Abstract
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Intraoral melanoma: long-term follow-up and implication for dental clinicians. A case report and literature review. Author(s): Gu GM, Epstein JB, Morton TH Jr. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 October; 96(4): 404-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561964&dopt=Abstract
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Intumescent cataract after topical mitomycin-C for conjunctival malignant melanoma. Author(s): Sacu S, Segur-Eltz N, Horvat R, Lukas JR, Zehetmayer M. Source: American Journal of Ophthalmology. 2003 August; 136(2): 375-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888073&dopt=Abstract
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Invasion of melanoma cells into dermal connective tissue in vitro: evidence for an important role of cysteine proteases. Author(s): Dennhofer R, Kurschat P, Zigrino P, Klose A, Bosserhoff A, van Muijen G, Krieg T, Mauch C, Hunzelmann N. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 1; 106(3): 316-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845667&dopt=Abstract
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Iodine brachytherapy as an alternative to enucleation for large uveal melanomas. Author(s): Puusaari I, Heikkonen J, Summanen P, Tarkkanen A, Kivela T. Source: Ophthalmology. 2003 November; 110(11): 2223-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597534&dopt=Abstract
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Iris cyst secondary to latanoprost mimicking iris melanoma. Author(s): Sodhi PK. Source: American Journal of Ophthalmology. 2003 October; 136(4): 780; Author Reply 780-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516849&dopt=Abstract
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Is sentinel lymph node mapping indicated for isolated local and in-transit recurrent melanoma? Author(s): Yao KA, Hsueh EC, Essner R, Foshag LJ, Wanek LA, Morton DL. Source: Annals of Surgery. 2003 November; 238(5): 743-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578738&dopt=Abstract
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Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma (EJSO 2002; 28: 673--678). Author(s): Trost O, Danino AM, Dutronc Y, Dalac S, Lambert D, Malka G. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 699. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511622&dopt=Abstract
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Lack of BRAF mutation in primary uveal melanoma. Author(s): Cohen Y, Goldenberg-Cohen N, Parrella P, Chowers I, Merbs SL, Pe'er J, Sidransky D. Source: Investigative Ophthalmology & Visual Science. 2003 July; 44(7): 2876-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824225&dopt=Abstract
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Lack of BRAF mutations in uveal melanoma. Author(s): Rimoldi D, Salvi S, Lienard D, Lejeune FJ, Speiser D, Zografos L, Cerottini JC. Source: Cancer Research. 2003 September 15; 63(18): 5712-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522889&dopt=Abstract
104 Melanoma
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Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma. Author(s): Mortarini R, Piris A, Maurichi A, Molla A, Bersani I, Bono A, Bartoli C, Santinami M, Lombardo C, Ravagnani F, Cascinelli N, Parmiani G, Anichini A. Source: Cancer Research. 2003 May 15; 63(10): 2535-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750277&dopt=Abstract
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Laminin, hyaluronan, tenascin-C and type VI collagen levels in sera from patients with malignant melanoma. Author(s): Burchardt ER, Hein R, Bosserhoff AK. Source: Clinical and Experimental Dermatology. 2003 September; 28(5): 515-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950343&dopt=Abstract
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Laser and proton radiation to reduce uveal melanoma-associated exudative retinal detachments. Author(s): Char DH, Bove R, Phillips TL. Source: American Journal of Ophthalmology. 2003 July; 136(1): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834689&dopt=Abstract
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LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical experience. Author(s): Dieckmann K, Georg D, Zehetmayer M, Bogner J, Georgopoulos M, Potter R. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2003 May; 67(2): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812851&dopt=Abstract
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Linac radiosurgery for brain metastasis of melanoma. Author(s): Noel G, Simon JM, Valery CA, Cornu P, Boisserie G, Ledu D, Hasboun D, Tep B, Delattre JY, Marsault C, Baillet F, Mazeron JJ. Source: Stereotactic and Functional Neurosurgery. 2002; 79(3-4): 245-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890983&dopt=Abstract
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Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients. Author(s): Herfarth KK, Izwekowa O, Thilmann C, Pirzkall A, Delorme S, Hofmann U, Schadendorf D, Zierhut D, Wannenmacher M, Debus J. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2003 June; 179(6): 366-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789461&dopt=Abstract
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Linkage and association analysis of nevus density and the region containing the melanoma gene CDKN2A in UK twins. Author(s): Barrett JH, Gaut R, Wachsmuth R, Bishop JA, Bishop DT. Source: British Journal of Cancer. 2003 June 16; 88(12): 1920-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799637&dopt=Abstract
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Local recurrence in melanoma in situ: influence of sex, age, site of involvement and therapeutic modalities. Author(s): Zalaudek I, Horn M, Richtig E, Hodl S, Kerl H, Smolle J. Source: The British Journal of Dermatology. 2003 April; 148(4): 703-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752127&dopt=Abstract
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Localization and characterization of melanoma-associated glycosaminoglycans: differential expression of chondroitin and heparan sulfate epitopes in melanoma. Author(s): Smetsers TF, van de Westerlo EM, ten Dam GB, Clarijs R, Versteeg EM, van Geloof WL, Veerkamp JH, van Muijen GN, van Kuppevelt TH. Source: Cancer Research. 2003 June 1; 63(11): 2965-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782604&dopt=Abstract
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Localization of a novel melanoma susceptibility locus to 1p22. Author(s): Gillanders E, Hank Juo SH, Holland EA, Jones M, Nancarrow D, Freas-Lutz D, Sood R, Park N, Faruque M, Markey C, Kefford RF, Palmer J, Bergman W, Bishop DT, Tucker MA, Bressac-de Paillerets B, Hansson J, Stark M, Gruis N, Bishop JN, Goldstein AM, Bailey-Wilson JE, Mann GJ, Hayward N, Trent J; Lund Melanoma Study Group; Melanoma Genetics Consortium. Source: American Journal of Human Genetics. 2003 August; 73(2): 301-13. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844286&dopt=Abstract
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Localization of transfected B7-1 (CD80) DNA in human melanoma cells after particlemediated gene transfer. Author(s): McCarthy DO, Meisner LF, Bourdeau-Heller J, Roberts TR, Wu SQ, Warner TF, Albertini MR. Source: Cancer Genetics and Cytogenetics. 2003 July 15; 144(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850372&dopt=Abstract
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Long-term results of a double perfusion schedule using high dose hyperthermia and melphalan sequentially in extensive melanoma of the lower limb. Author(s): Noorda EM, Vrouenraets BC, Nieweg OE, Klaase JM, van der Zee J, Kroon BB. Source: Melanoma Research. 2003 August; 13(4): 395-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883366&dopt=Abstract
106 Melanoma
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Loss of inhibitor of apoptosis proteins as a determinant of polyamine analog-induced apoptosis in human melanoma cells. Author(s): Chen Y, Kramer DL, Li F, Porter CW. Source: Oncogene. 2003 August 7; 22(32): 4964-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902979&dopt=Abstract
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Loss of PTEN promotes tumor development in malignant melanoma. Author(s): Stahl JM, Cheung M, Sharma A, Trivedi NR, Shanmugam S, Robertson GP. Source: Cancer Research. 2003 June 1; 63(11): 2881-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782594&dopt=Abstract
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Low molecular weight heparin treatment for malignant melanoma: a pilot clinical trial. Author(s): Wojtukiewicz MZ, Kozlowski L, Ostrowska K, Dmitruk A, Zacharski LR. Source: Thrombosis and Haemostasis. 2003 February; 89(2): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574822&dopt=Abstract
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Lymph node status and survival in cutaneous malignant melanoma--sentinel lymph node biopsy impact. Author(s): Rutkowski P, Nowecki ZI, Nasierowska-Guttmejer A, Ruka W. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 September; 29(7): 611-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943629&dopt=Abstract
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Lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: therapeutic utility and implications of nodal microanatomy and molecular staging for improving the accuracy of detection of nodal micrometastases. Author(s): Morton DL, Hoon DS, Cochran AJ, Turner RR, Essner R, Takeuchi H, Wanek LA, Glass E, Foshag LJ, Hsueh EC, Bilchik AJ, Elashoff D, Elashoff R. Source: Annals of Surgery. 2003 October; 238(4): 538-49; Discussion 549-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530725&dopt=Abstract
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Lymphoscintigraphy and sentinel node biopsy accurately stage melanoma in patients presenting after wide local excision. Author(s): Evans HL, Krag DN, Teates CD, Patterson JW, Meijer S, Harlow SP, Tanabe KK, Loggie BW, Whitworth PW, Kusminsky RE, Carp NZ, Gadd MA, Slingluff CL Jr. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 May; 10(4): 416-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734091&dopt=Abstract
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Magnetic resonance imaging findings in malignant melanoma of the lacrimal sac. Author(s): Billing K, Malhotra R, Selva D, Saloniklis S, Taylor J, Krishnan S. Source: The British Journal of Ophthalmology. 2003 September; 87(9): 1187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928297&dopt=Abstract
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Malignant melanoma and levodopa in Parkinson's disease: causality or coincidence? Author(s): Fiala KH, Whetteckey J, Manyam BV. Source: Parkinsonism & Related Disorders. 2003 August; 9(6): 321-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853231&dopt=Abstract
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Malignant melanoma arising in a sebaceous nevus of the scalp. Author(s): Abe S, Yamamoto Y, Uno S, Andou M, Akasaka T, Mihm MC. Source: British Journal of Plastic Surgery. 2003 March; 56(2): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791367&dopt=Abstract
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Malignant melanoma in South Africans of mixed ancestry: a retrospective analysis. Author(s): Swan MC, Hudson DA. Source: Melanoma Research. 2003 August; 13(4): 415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883369&dopt=Abstract
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Malignant melanoma of soft parts (clear cell sarcoma): a case report. Author(s): Seike T, Matsumoto K, Nakanishi H, Hashimoto I, Kubo Y, Arase S. Source: The Journal of Dermatology. 2003 July; 30(7): 550-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928546&dopt=Abstract
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Management of melanoma patients: benefit of intense follow-up schedule is not demonstrated. Author(s): Autier P, Coebergh JW, Boniol M, Dore JF, de Vries E, Eggermont AM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 1; 21(19): 3707; Author Reply 3707-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512409&dopt=Abstract
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Management of metastatic malignant melanoma of the bladder. Author(s): Lee CS, Komenaka IK, Hurst-Wicker KS, Deraffele G, Mitcham J, Kaufman HL. Source: Urology. 2003 August; 62(2): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893353&dopt=Abstract
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Mapped serial excision for periocular lentigo maligna and lentigo maligna melanoma. Author(s): Malhotra R, Chen C, Huilgol SC, Hill DC, Selva D. Source: Ophthalmology. 2003 October; 110(10): 2011-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522781&dopt=Abstract
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Melacine: an allogeneic melanoma tumor cell lysate vaccine. Author(s): Sosman JA, Sondak VK. Source: Expert Rev Vaccines. 2003 June; 2(3): 353-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903801&dopt=Abstract
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Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53. Author(s): Kichina JV, Rauth S, Das Gupta TK, Gudkov AV. Source: Oncogene. 2003 July 31; 22(31): 4911-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894234&dopt=Abstract
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Melanoma Differentiation-associated Gene 7/Interleukin (IL)-24 Is a Novel Ligand That Regulates Angiogenesis via the IL-22 Receptor. Author(s): Ramesh R, Mhashilkar AM, Tanaka F, Saito Y, Branch CD, Sieger K, Mumm JB, Stewart AL, Boquio A, Dumoutier L, Grimm EA, Renauld JC, Kotenko S, Chada S. Source: Cancer Research. 2003 August 15; 63(16): 5105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941841&dopt=Abstract
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Melanoma in the elderly patient. Author(s): Chang CK, Jacobs IA, Vizgirda VM, Salti GI. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 October; 138(10): 1135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557133&dopt=Abstract
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Melanoma: is immunotherapy of benefit? Author(s): Faries MB, Morton DL. Source: Adv Surg. 2003; 37: 139-69. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953631&dopt=Abstract
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Melanoma-associated retinopathy: high frequency of subclinical findings in patients with melanoma. Author(s): Pfohler C, Haus A, Palmowski A, Ugurel S, Ruprecht KW, Thirkill CE, Tilgen W, Reinhold U. Source: The British Journal of Dermatology. 2003 July; 149(1): 74-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890197&dopt=Abstract
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Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation. Author(s): Cohen VM, Carter MJ, Kemeny A, Radatz M, Rennie IG. Source: Acta Ophthalmologica Scandinavica. 2003 August; 81(4): 383-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859266&dopt=Abstract
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Metastatic malignant melanoma presenting with a bruise. Author(s): Connolly CM, Soldin M, Dawson A, Cooper AC. Source: British Journal of Plastic Surgery. 2003 October; 56(7): 725. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969680&dopt=Abstract
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Metastatic melanoma in the eye and orbit. Author(s): Zografos L, Ducrey N, Beati D, Schalenbourg A, Spahn B, Balmer A, OtheninGirard CB, Chamot L, Egger E. Source: Ophthalmology. 2003 November; 110(11): 2245-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597536&dopt=Abstract
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Metastatic melanoma of the pituitary gland. Case report. Author(s): Leung GK, Chow WS, Tan KC, Fan YW, Lam KS. Source: Journal of Neurosurgery. 2003 November; 99(5): 913-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609173&dopt=Abstract
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Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study. Author(s): Spieth K, Kaufmann R, Gille J. Source: Cancer Chemotherapy and Pharmacology. 2003 November; 52(5): 377-82. Epub 2003 July 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879280&dopt=Abstract
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Mucosal malignant melanoma of the head and neck: the Marsden experience over half a century. Author(s): Yii NW, Eisen T, Nicolson M, A'Hern R, Rhys-Evans P, Archer D, Henk JM, Gore ME. Source: Clin Oncol (R Coll Radiol). 2003 June; 15(4): 199-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846499&dopt=Abstract
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N-Acetylcysteine enhances UV-mediated caspase-3 activation, fragmentation of E2F-4, and apoptosis in human C8161 melanoma: inhibition by ectopic Bcl-2 expression. Author(s): Rieber M, Rieber MS. Source: Biochemical Pharmacology. 2003 May 15; 65(10): 1593-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754095&dopt=Abstract
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Neurotrophin-induced melanoma cell migration is mediated through the actinbundling protein fascin. Author(s): Shonukan O, Bagayogo I, McCrea P, Chao M, Hempstead B. Source: Oncogene. 2003 June 5; 22(23): 3616-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789270&dopt=Abstract
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Neutrophils influence melanoma adhesion and migration under flow conditions. Author(s): Slattery MJ, Dong C. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 713-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866031&dopt=Abstract
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New prognostic factors and developing therapy of cutaneous melanoma. Author(s): Vihinen PP, Pyrhonen SO, Kahari VM. Source: Annals of Medicine. 2003; 35(2): 66-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795336&dopt=Abstract
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Nodal metastatic melanoma in the neck of a 4-year-old girl after diagnosis of Spitz nevus of the cheek. Author(s): Reynolds N, Ali-Khan AS, Rigby H, Orlando A. Source: Annals of Plastic Surgery. 2003 May; 50(5): 555-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792550&dopt=Abstract
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Nodal staging in localized melanoma. The experience of the Brescia Melanoma Unit. Author(s): Manca G, Facchetti F, Pizzocaro C, Biasca F, Farfaglia R, Simoncini E, Cristinelli MR, Flocchini M, Parrinello G, Manganoni A. Source: British Journal of Plastic Surgery. 2003 September; 56(6): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946370&dopt=Abstract
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Nodular melanoma. No longer as simple as ABC. Author(s): Kelly JW, Chamberlain AJ, Staples MP, McAvoy B. Source: Aust Fam Physician. 2003 September; 32(9): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14524207&dopt=Abstract
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Nodular melanoma: patients' perceptions of presenting features and implications for earlier detection. Author(s): Chamberlain AJ, Fritschi L, Kelly JW. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5): 694-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734497&dopt=Abstract
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Non-melanoma and non-renal cell carcinoma malignancies treated with interleukin-2. Author(s): Krastev Z, Koltchakov V, Tomov B, Koten JW. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1006-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845968&dopt=Abstract
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NRAS hypermutability in familial melanoma with CDKN2A mutations--cause and effect? Author(s): Kraemer KH. Source: Journal of the National Cancer Institute. 2003 June 4; 95(11): 768-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783922&dopt=Abstract
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Nucleolar diameter and microvascular factors as independent predictors of mortality from malignant melanoma of the choroid and ciliary body. Author(s): Al-Jamal RT, Makitie T, Kivela T. Source: Investigative Ophthalmology & Visual Science. 2003 June; 44(6): 2381-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766034&dopt=Abstract
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Number and size of nevi are influenced by different sun exposure components: implications for the etiology of cutaneous melanoma (Belgium, Germany, France, Italy). Author(s): Autier P, Severi G, Pedeux R, Cattaruzza MS, Boniol M, Grivegnee A, Dore JF; European Organisation for Research and Treatment of Cancer Melanoma Group. Source: Cancer Causes & Control : Ccc. 2003 June; 14(5): 453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946040&dopt=Abstract
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O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma. Author(s): Ma S, Egyhazi S, Ueno T, Lindholm C, Kreklau EL, Stierner U, Ringborg U, Hansson J. Source: British Journal of Cancer. 2003 October 20; 89(8): 1517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562026&dopt=Abstract
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Ocular melanoma and cutaneous melanoma. Author(s): Kricker A, Vajdic C, Armstrong B. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 20; 104(2): 259. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569586&dopt=Abstract
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Ocular melanoma is not associated with CDKN2A or MC1R variants--a populationbased study. Author(s): Vajdic C, Kricker A, Duffy DL, Aitken JF, Stark M, ter Huurne JA, Martin NG, Armstrong BK, Hayward NK. Source: Melanoma Research. 2003 August; 13(4): 409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883368&dopt=Abstract
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Ocular melanoma: a review and the relationship to cutaneous melanoma. Author(s): Hurst EA, Harbour JW, Cornelius LA. Source: Archives of Dermatology. 2003 August; 139(8): 1067-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925397&dopt=Abstract
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On the effect of biochemotherapy in metastatic malignant melanoma: an immunopathological evaluation. Author(s): Hakansson A, Hakansson L, Gustafsson B, Krysander L, Rettrup B, Ruiter D, Bernsen MR. Source: Melanoma Research. 2003 August; 13(4): 401-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883367&dopt=Abstract
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Oncogenes in melanoma. Author(s): Polsky D, Cordon-Cardo C. Source: Oncogene. 2003 May 19; 22(20): 3087-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789285&dopt=Abstract
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Orbital malignant melanoma: the 2002 Sean B Murphy lecture. Author(s): Shields JA, Shields CL. Source: Ophthalmic Plastic and Reconstructive Surgery. 2003 July; 19(4): 262-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878873&dopt=Abstract
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Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. Author(s): Margalit O, Eisenbach L, Amariglio N, Kaminski N, Harmelin A, Pfeffer R, Shohat M, Rechavi G, Berger R. Source: British Journal of Cancer. 2003 July 21; 89(2): 314-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865923&dopt=Abstract
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Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatin. Author(s): Liedert B, Materna V, Schadendorf D, Thomale J, Lage H. Source: The Journal of Investigative Dermatology. 2003 July; 121(1): 172-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839578&dopt=Abstract
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Oxidative stress in malignant melanoma and non-melanoma skin cancer. Author(s): Sander CS, Hamm F, Elsner P, Thiele JJ. Source: The British Journal of Dermatology. 2003 May; 148(5): 913-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786821&dopt=Abstract
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Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Author(s): Lee JR, Dalton RR, Messina JL, Sharma MD, Smith DM, Burgess RE, Mazzella F, Antonia SJ, Mellor AL, Munn DH. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 October; 83(10): 1457-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563947&dopt=Abstract
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Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: a key role of ezrin. Author(s): Lugini L, Lozupone F, Matarrese P, Funaro C, Luciani F, Malorni W, Rivoltini L, Castelli C, Tinari A, Piris A, Parmiani G, Fais S. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 November; 83(11): 1555-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615410&dopt=Abstract
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Primary malignant melanoma arising in the dorsum of the tongue. Author(s): Rowland HN, Schnetler JF. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 June; 41(3): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804549&dopt=Abstract
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Primary malignant melanoma of the bronchus intermedius. Author(s): Filosso PL, Donati G, Ruffini E, Croce S, Papotti M, Oliaro A, Mancuso M. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 October; 126(4): 12157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14566282&dopt=Abstract
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Primary malignant melanoma of the esophagus treated with heavy-ion radiotherapy. Author(s): Sudhamshu K C, Kouzu T, Matsutani S, Hishikawa E, Nikaido T, Taro A, Hiromitsu S. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 151-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869887&dopt=Abstract
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Primary malignant melanoma of the esophagus. Author(s): de Perrot M, Brundler MA, Robert J, Spiliopoulos A. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(2): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14601912&dopt=Abstract
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Primary malignant melanoma of the oral mucosa. Author(s): Rapidis AD, Apostolidis C, Vilos G, Valsamis S. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 October; 61(10): 1132-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586846&dopt=Abstract
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Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit. Author(s): McKinnon JG, Yu XQ, McCarthy WH, Thompson JF. Source: Cancer. 2003 September 15; 98(6): 1223-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973846&dopt=Abstract
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Prognostic value of the disodium phosphate 32P uptake test in uveal melanoma: a long-term study. Author(s): Overkleeft EN, Zuidervaart W, Hurks HM, Eilers PH, de Wolff-Rouendaal D, Jager MJ. Source: Archives of Ophthalmology. 2003 October; 121(10): 1398-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557175&dopt=Abstract
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Protocol for the examination of specimens from patients with melanoma of the skin. Author(s): Compton CC, Barnhill R, Wick MR, Balch C; Members of the Cancer Committee, College of American Pathologists. Source: Archives of Pathology & Laboratory Medicine. 2003 October; 127(10): 1253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521470&dopt=Abstract
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Quality of life evaluation in a randomised trial of chemotherapy versus biochemotherapy in advanced melanoma patients. Author(s): Chiarion-Sileni V, Del Bianco P, De Salvo GL, Lo Re G, Romanini A, Labianca R, Nortilli R, Corgna E, Dalla Palma M, Lo Presti G, Ridolfi R; Italian Melanoma Intergroup (IMI). Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(11): 1577-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855265&dopt=Abstract
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Quality of life in patients with malignant choroidal melanoma after radiotherapy. Author(s): Reimer J, Esser J, Fleiss A, Hessel A, Anastassiou G, Krausz M, Bornfeld N, Franke GH. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 May; 241(5): 371-7. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712357&dopt=Abstract
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Radiation dose as a risk factor for malignant melanoma following childhood cancer. Author(s): Guerin S, Dupuy A, Anderson H, Shamsaldin A, Svahn-Tapper G, Moller T, Quiniou E, Garwicz S, Hawkins M, Avril MF, Oberlin O, Chavaudra J, de Vathaire F. Source: European Journal of Cancer (Oxford, England : 1990). 2003 November; 39(16): 2379-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556931&dopt=Abstract
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Redox modulation of NF-kappaB nuclear translocation and DNA binding in metastatic melanoma. The role of endogenous and gamma-glutamyl transferasedependent oxidative stress. Author(s): Dominici S, Visvikis A, Pieri L, Paolicchi A, Valentini MA, Comporti M, Pompella A. Source: Tumori. 2003 July-August; 89(4): 426-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606649&dopt=Abstract
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Reduced joining of DNA ends correlates with chromosomal instability in three melanoma cell lines. Author(s): Runger TM, Kotas M, Poot M, Leverkus M, Epe B, Jeggo PA, Hellfritsch D. Source: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. 2003 March-April; 24(2): 100-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853705&dopt=Abstract
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Remodeling of the microenvironment by aggressive melanoma tumor cells. Author(s): Hendrix MJ, Seftor EA, Kirschmann DA, Quaranta V, Seftor RE. Source: Annals of the New York Academy of Sciences. 2003 May; 995: 151-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814947&dopt=Abstract
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Repression of TGF-beta signaling by the oncogenic protein SKI in human melanomas: consequences for proliferation, survival, and metastasis. Author(s): Medrano EE. Source: Oncogene. 2003 May 19; 22(20): 3123-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793438&dopt=Abstract
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Restricted T-cell receptor repertoire in melanoma metastases regressing after cytokine therapy. Author(s): Willhauck M, Scheibenbogen C, Pawlita M, Mohler T, Thiel E, Keilholz U. Source: Cancer Research. 2003 July 1; 63(13): 3483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839930&dopt=Abstract
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Review and evaluation of sentinel node procedures in 250 melanoma patients with a median follow-up of 6 years. Author(s): Estourgie SH, Nieweg OE, Valdes Olmos RA, Hoefnagel CA, Kroon BB. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 July; 10(6): 681-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839854&dopt=Abstract
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Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients. Author(s): Rousseau DL Jr, Ross MI, Johnson MM, Prieto VG, Lee JE, Mansfield PF, Gershenwald JE. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 June; 10(5): 569-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794025&dopt=Abstract
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Risk factors for cutaneous malignant melanoma among aircrews and a random sample of the population. Author(s): Rafnsson V, Hrafnkelsson J, Tulinius H, Sigurgeirsson B, Olafsson JH. Source: Occupational and Environmental Medicine. 2003 November; 60(11): 815-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14573711&dopt=Abstract
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Role of sentinel lymph node biopsy in patients with thin (<1 mm) primary melanoma. Author(s): Jacobs IA, Chang CK, DasGupta TK, Salti GI. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 June; 10(5): 558-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794023&dopt=Abstract
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sAPP as a regulator of dendrite motility and melanin release in epidermal melanocytes and melanoma cells. Author(s): Quast T, Wehner S, Kirfel G, Jaeger K, De Luca M, Herzog V. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 September; 17(12): 1739-41. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958194&dopt=Abstract
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Sentinel lymph node biopsy for melanoma of the head and neck. Author(s): Lentsch EJ, McMasters KM. Source: Expert Rev Anticancer Ther. 2003 October; 3(5): 673-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599090&dopt=Abstract
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Sentinel lymph node biopsy in children and adolescents with malignant melanoma. Author(s): Toro J, Ranieri JM, Havlik RJ, Coleman JJ 3rd, Wagner JD. Source: Journal of Pediatric Surgery. 2003 July; 38(7): 1063-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861540&dopt=Abstract
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Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy. Author(s): Jacobs IA, Chang CK, Salti GI. Source: Journal of the American Academy of Dermatology. 2003 October; 49(4): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512905&dopt=Abstract
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Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine. Author(s): Valmori D, Dutoit V, Ayyoub M, Rimoldi D, Guillaume P, Lienard D, Lejeune F, Cerottini JC, Romero P, Speiser DE. Source: Cancer Immunity [electronic Resource] : a Journal of the Academy of Cancer Immunology. 2003 October 28; 3: 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14580186&dopt=Abstract
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Site- and gender-specific time trend analyses of the incidence of skin melanomas in the former German Democratic Republic (GDR) including 19351 cases. Author(s): Stang A, Stabenow R, Eisinger B, Jockel KH. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(11): 1610-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855269&dopt=Abstract
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Skin cancer prevention and detection practices among siblings of patients with melanoma. Author(s): Geller AC, Emmons K, Brooks DR, Zhang Z, Powers C, Koh HK, Sober AJ, Miller DR, Li F, Haluska F, Gilchrest BA. Source: Journal of the American Academy of Dermatology. 2003 October; 49(4): 631-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512908&dopt=Abstract
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Spread of melanoma after lymphatic drainage: relaunching the debate. Author(s): Vereecken P, Mathieu A, Laporte M, Petein M, Heenen M. Source: Int J Clin Pract. 2003 June; 57(5): 444-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846356&dopt=Abstract
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Status of the NF1 tumor suppressor locus in uveal melanoma. Author(s): Foster WJ, Fuller CE, Perry A, Harbour JW. Source: Archives of Ophthalmology. 2003 September; 121(9): 1311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963615&dopt=Abstract
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Suppression of BRAF(V599E) in human melanoma abrogates transformation. Author(s): Hingorani SR, Jacobetz MA, Robertson GP, Herlyn M, Tuveson DA. Source: Cancer Research. 2003 September 1; 63(17): 5198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500344&dopt=Abstract
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The amount of metastatic melanoma in a sentinel lymph node: does it have prognostic significance? Author(s): Carlson GW, Murray DR, Lyles RH, Staley CA, Hestley A, Cohen C. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 June; 10(5): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794026&dopt=Abstract
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The correlation among different immunostaining evaluation methods for the assessment of proliferative activity in uveal melanoma. Author(s): Chowers I, Amer R, Pe'er J. Source: Current Eye Research. 2002 December; 25(6): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789544&dopt=Abstract
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The histone deacetylase inhibitor suberic bishydroxamate: a potential sensitizer of melanoma to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. Author(s): Zhang XD, Gillespie SK, Borrow JM, Hersey P. Source: Biochemical Pharmacology. 2003 October 15; 66(8): 1537-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555232&dopt=Abstract
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The impact of immunohistochemistry on sentinel node biopsy for primary cutaneous malignant melanoma. Author(s): Ross GL, Shoaib T, Scott J, Camilleri IG, Gray HW, MacKie R, Soutar DS. Source: British Journal of Plastic Surgery. 2003 March; 56(2): 153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791361&dopt=Abstract
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The role of Bcl-2 family members in the progression of cutaneous melanoma. Author(s): Bush JA, Li G. Source: Clinical & Experimental Metastasis. 2003; 20(6): 531-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598887&dopt=Abstract
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The significance of vascular invasion in primary melanomas of thin or intermediate thickness. Author(s): Lambert WC. Source: Archives of Dermatology. 2003 June; 139(6): 809; Author Reply 810. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810519&dopt=Abstract
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Transpupillary thermotherapy versus plaque radiotherapy for suspected choroidal melanomas. Author(s): Harbour JW, Meredith TA, Thompson PA, Gordon ME. Source: Ophthalmology. 2003 November; 110(11): 2207-14; Discussion 2215. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597531&dopt=Abstract
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Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: a matched case-control study. Author(s): Kivela T, Puusaari I, Damato B. Source: Ophthalmology. 2003 November; 110(11): 2235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597535&dopt=Abstract
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Trends in the incidence of ocular melanoma in the United States, 1974-1998. Author(s): Inskip PD, Devesa SS, Fraumeni JF Jr. Source: Cancer Causes & Control : Ccc. 2003 April; 14(3): 251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814204&dopt=Abstract
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Tyrosinase expression in the peripheral blood of stage III melanoma patients is associated with a poor prognosis: a clinical follow-up study of 110 patients. Author(s): Osella-Abate S, Savoia P, Quaglino P, Fierro MT, Leporati C, Ortoncelli M, Bernengo MG. Source: British Journal of Cancer. 2003 October 20; 89(8): 1457-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562017&dopt=Abstract
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Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma. Author(s): Brountzos EN, Panagiotou IE, Bafaloukos DI, Kelekis DA. Source: Oncol Rep. 2003 March-April; 10(2): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579298&dopt=Abstract
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Ultrasound biomicroscopy in management of malignant iris melanoma. Author(s): Nordlund JR, Robertson DM, Herman DC. Source: Archives of Ophthalmology. 2003 May; 121(5): 725-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742854&dopt=Abstract
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Ultraviolet radiation and cutaneous malignant melanoma. Author(s): Jhappan C, Noonan FP, Merlino G. Source: Oncogene. 2003 May 19; 22(20): 3099-112. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789287&dopt=Abstract
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Unilateral conjunctival-corneal argyrosis simulating conjunctival melanoma. Author(s): Zografos L, Uffer S, Chamot L. Source: Archives of Ophthalmology. 2003 October; 121(10): 1483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557191&dopt=Abstract
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Unusual cases involving the CNS and nasal sinuses: Case 1. Primary leptomeningeal melanoma. Author(s): Rosenthal G, Gomori JM, Tobias S, Diment J, Shoshan Y. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 15; 21(20): 3875-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551307&dopt=Abstract
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Upregulation of HMG1 leads to melanoma inhibitory activity expression in malignant melanoma cells and contributes to their malignancy phenotype. Author(s): Poser I, Golob M, Buettner R, Bosserhoff AK. Source: Molecular and Cellular Biology. 2003 April; 23(8): 2991-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665595&dopt=Abstract
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Use of tamoxifen in the treatment of malignant melanoma. Author(s): Lens MB, Reiman T, Husain AF. Source: Cancer. 2003 October 1; 98(7): 1355-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508820&dopt=Abstract
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Uveal melanoma and poor treatment compliance: an atypical outcome with literature review. Author(s): Park WL, Jenison-Williams T, Pasqua-Darnell T. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 2003 May; 80(5): 344-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771660&dopt=Abstract
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Uveal melanoma presenting as acute angle-closure glaucoma: report of two cases. Author(s): Escalona-Benz E, Benz MS, Briggs JW, Budenz DL, Parrish RK, Murray TG. Source: American Journal of Ophthalmology. 2003 October; 136(4): 756-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516828&dopt=Abstract
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Uveal melanoma survival in Sweden from 1960 to 1998. Author(s): Bergman L, Seregard S, Nilsson B, Lundell G, Ringborg U, RagnarssonOlding B. Source: Investigative Ophthalmology & Visual Science. 2003 August; 44(8): 3282-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882771&dopt=Abstract
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Vaccination strategies to reduce the risk of leukaemia and melanoma. Author(s): Grange JM, Stanford JL, Stanford CA, Kolmel KF. Source: Journal of the Royal Society of Medicine. 2003 August; 96(8): 389-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893854&dopt=Abstract
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Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. Author(s): Soiffer R, Hodi FS, Haluska F, Jung K, Gillessen S, Singer S, Tanabe K, Duda R, Mentzer S, Jaklitsch M, Bueno R, Clift S, Hardy S, Neuberg D, Mulligan R, Webb I, Mihm M, Dranoff G. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3343-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947071&dopt=Abstract
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Vaccine-induced CD8+ T-cell responses to MAGE-3 correlate with clinical outcome in patients with melanoma. Author(s): Reynolds SR, Zeleniuch-Jacquotte A, Shapiro RL, Roses DF, Harris MN, Johnston D, Bystryn JC. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 657-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576432&dopt=Abstract
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Value of tyrosinase RNA detection by an RT-PCR method in melanoma prognosis. Author(s): Konstantopoulos K. Source: British Journal of Cancer. 2003 March 24; 88(6): 981; Author Reply 982. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644840&dopt=Abstract
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Vascular endothelial growth factor-A determines detectability of experimental melanoma brain metastasis in GD-DTPA-enhanced MRI. Author(s): Leenders W, Kusters B, Pikkemaat J, Wesseling P, Ruiter D, Heerschap A, Barentsz J, de Waal RM. Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 1; 105(4): 437-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712432&dopt=Abstract
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Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases. Author(s): Schietroma C, Cianfarani F, Lacal PM, Odorisio T, Orecchia A, Kanitakis J, D'Atri S, Failla CM, Zambruno G. Source: Cancer. 2003 August 15; 98(4): 789-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910524&dopt=Abstract
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Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Author(s): Hendrix MJ, Seftor EA, Hess AR, Seftor RE. Source: Nature Reviews. Cancer. 2003 June; 3(6): 411-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778131&dopt=Abstract
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Vertical growth phase and positive sentinel node in thin melanoma. Author(s): Oliveira Filho RS, Ferreira LM, Biasi LJ, Enokihara MM, Paiva GR, Wagner J. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 March; 36(3): 347-50. Epub 2003 March 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640499&dopt=Abstract
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Very long-term prognosis of patients with malignant uveal melanoma. Author(s): Kujala E, Makitie T, Kivela T. Source: Investigative Ophthalmology & Visual Science. 2003 November; 44(11): 4651-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578381&dopt=Abstract
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Vitamin D-induced apoptosis and melanoma: does calpain represent the major execution protease rather than caspases? Author(s): Reichrath J, Rech M, Seifert M. Source: The Journal of Pathology. 2003 October; 201(2): 335-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517853&dopt=Abstract
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World Health Organization experience in the treatment of melanoma. Author(s): Cascinelli N, Santinami M, Maurichi A, Patuzzo R, Pennacchioli E. Source: The Surgical Clinics of North America. 2003 April; 83(2): 405-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744616&dopt=Abstract
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CHAPTER 2. NUTRITION AND MELANOMA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and melanoma.
Finding Nutrition Studies on Melanoma The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “melanoma” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “melanoma” (or a synonym): •
A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
[email protected] Source: Atkins, M B Gollob, J A Sosman, J A McDermott, D F Tutin, L Sorokin, P Parker, R A Mier, J W Clin-Cancer-Res. 2002 October; 8(10): 3075-81 1078-0432
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Acidosis plus melphalan induces nitric oxide-mediated tumor regression in an isolated limb perfusion human melanoma xenograft model. Author(s): Department of Surgery, University of Pennsylvania, Philadelphia 19104, USA. Source: Kelley, S T Menon, C Buerk, D G Bauer, T W Fraker, D L Surgery. 2002 August; 132(2): 252-8 0039-6060
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Activity of antioxidant enzymes and concentrations of thiobarbituric acid reactive substances (TBARS) in melanotic and amelanotic Bomirski melanoma tissues in the golden hamster (Mesocricetus auratus, Waterhouse). Author(s): Department of Biology, Ludwik Rydygier Medical University, Bydgoszcz, Poland.
[email protected] Source: Wozniak, A Drewa, T Drewa, G Wozniak, B Schachtschabel, D O Neoplasma. 2002; 49(6): 401-4 0028-2685
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Adjuvant therapy of malignant melanoma: is there a choice? Author(s): Melanoma Unit, Department of Medical Oncology, Charing Cross Hospital, Fulham Palace Road, W6 8RF, London, UK.
[email protected] Source: Retsas, S Crit-Rev-Oncol-Hematol. 2001 November; 40(2): 187-93 1040-8428
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Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma. Author(s): Department of Dermatology, Georg-August University Gottingen, Germany. Source: Mossner, R Schulz, U Kruger, U Middel, P Schinner, S Fuzesi, L Neumann, C Reich, K J-Invest-Dermatol. 2002 September; 119(3): 576-82 0022-202X
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An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells. Author(s): Institute of Pathology, Charite Hospital, Berlin, Germany. Source: Denkert, Carsten Siegert, Antje Leclere, Anja Turzynski, Andreas Hauptmann, Steffen Clin-Exp-Metastasis. 2002; 19(1): 79-85 0262-0898
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Analysis of O(6)-methylguanine-DNA methyltransferase in melanoma tumours in patients treated with dacarbazine-based chemotherapy. Author(s): Department of Oncology/Pathology, Radiumhemmet, Karolinska Hospital, S-171 76 Stockholm, Sweden. Source: Ma, S Egyhazi, S Martenhed, G Ringborg, U Hansson, J Melanoma-Res. 2002 August; 12(4): 335-42 0960-8931
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Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. Author(s): Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, 14195, Berlin, Germany.
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Source: Raisova, Monika Goltz, Gerit Bektas, Meryem Bielawska, Alicja Riebeling, Christian Hossini, Amir M Eberle, Jurgen Hannun, Yusuf A Orfanos, Constantin E Geilen, Christoph C FEBS-Lett. 2002 April 10; 516(1-3): 47-52 0014-5793 •
Changes in the motility of B16F10 melanoma cells induced by alterations in resting calcium influx. Author(s): Department of Biochemistry, Kirksville Cellege Osteopathic Medicine, Kirksville, MO 63501, USA.
[email protected] Source: Cox, J L Lancaster, T Carlson, C G Melanoma-Res. 2002 June; 12(3): 211-9 09608931
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Characterization of melanoma associated spongiform scleropathy. Author(s): Eye Pathology Institute, University of Copenhagen, Denmark. Source: Alyahya, Ghassan Ayish Heegaard, Steffen Prause, January Ulrik ActaOphthalmol-Scand. 2002 June; 80(3): 322-6 1395-3907
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Circuit and protocol for hypoxic hyperthermic isolated limb perfusion to treat malignant melanoma. Author(s): Department of Cardiothoracic Surgery-Perfusion, Waikato Hospital, Hamilton, New Zealand.
[email protected] Source: Innet, L M Haripershad, V Van Den Berg, J Cooper, L Perfusion. 2001 July; 16(4): 325-30 0267-6591
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Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen. Author(s): Department of Surgery, University of Queensland, Queensland. Australia. Source: Smithers, M O'Connell, K MacFadyen, S Chambers, M Greenwood, K Boyce, A Abdul Jabbar, I Barker, K Grimmett, K Walpole, E Thomas, R Cancer-ImmunolImmunother. 2003 January; 52(1): 41-52 0340-7004
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Clinical results using biochemotherapy as a standard of care in advanced melanoma. Author(s): Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, NY 10021, USA.
[email protected] Source: Chapman, P B Panageas, K S Williams, L Wolchok, J D Livingston, P O Quinn, C Hwu, W J Melanoma-Res. 2002 August; 12(4): 381-7 0960-8931
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Cloning and characterization of the expression pattern of a novel splice product MIA (splice) of malignant melanoma-derived growth-inhibiting activity (MIAY CD-RAP). Author(s): Department of Neurology, University of Regensburg, Regensburg, Germany.
[email protected] Source: Hau, P Wise, P Bosserhoff, A K Blesch, A Jachimczak, P Tschertner, I Bogdahn, U Apfel, R J-Invest-Dermatol. 2002 September; 119(3): 562-9 0022-202X
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Comparison of apoptotic, necrotic and clonogenic cell death and inhibition of cell growth following camptothecin and X-radiation treatment in a human melanoma and a human fibroblast cell line. Author(s): Ottawa Regional Cancer Centre, Ottawa, ON, K1H 1C4, Canada. Source: Quto b, Sami S Ng, Cheng E Cancer-Chemother-Pharmacol. 2002 February; 49(2): 167-75 0344-5704
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Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study. Author(s): Institute for Oncology and Radiology of Serbia, Department of Medical Oncology, Pasterova 14, 11000 Belgrade, Yugoslavia.
[email protected]
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Source: Jelic, S Babovic, N Kovcin, V Milicevic, N Milanovic, N Popov, I Radosavljevic, D Melanoma-Res. 2002 February; 12(1): 91-8 0960-8931 •
Complete remission of Bomirski Ab amelanotic melanoma in hamsters treated with the angiogenesis inhibitor TNP-470. Author(s): Department of Histology and Immunology; University of Gdansk, Gdansk, 80-210 Poland.
[email protected] Source: Mysliwski, A Koszalka, P Bigda, J Szmit, E Neoplasma. 2002; 49(5): 319-22 00282685
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Contact-mediated acceleration of migration of melanoma B16 cells depends on extracellular calcium ions. Author(s): Department of Cell Biology, Jan Zurzycki Institute of Molecular Biology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
[email protected] Source: Madeja, Z Master, A Michalik, M Sroka, J Folia-Biol-(Krakow). 2001; 49(3-4): 11324 0015-5497
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Different h2 receptor antihistamines dissimilarly retard the growth of xenografted human melanoma cells in immunodeficient mice. Author(s): Department of Dermatology, Debrecen University, Debrecen, Hungary. Source: Szincsak, N Hegyesi, H Hunyadi, J Falus, A Juhasz, I Cell-Biol-Int. 2002; 26(9): 833-6 1065-6995
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Differentiation of human melanoma cells through p38 MAP kinase is associated with decreased retinoblastoma protein phosphorylation and cell cycle arrest. Author(s): Section of Medicine, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
[email protected] Source: Smalley, K S Eisen, T G Melanoma-Res. 2002 June; 12(3): 187-92 0960-8931
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Disulfiram induces apoptosis in human melanoma cells: a redox-related process. Author(s): Department of Medicine, Chao Family Comprehensive Cancer Center, College of Medicine, University of California, Irvine, 101 City Drive South, Building 23, Suite 403, Orange, CA 92868, USA. Source: Cen, D Gonzalez, R I Buckmeier, J A Kahlon, R S Tohidian, N B Meyskens, F L Jr Mol-Cancer-Ther. 2002 January; 1(3): 197-204 1535-7163
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Effect of Caffeine, a xanthine derivative, in the inhibition of experimental lung metastasis induced by B16F10 melanoma cells. Author(s): Chemotherapy & Stem Cell Biology Division. Cancer Research Institute, Parel, Mumbai, India.
[email protected] Source: Gude, R P Menon, L G Rao, S G J-Exp-Clin-Cancer-Res. 2001 June; 20(2): 287-92 0392-9078
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Effective local control of malignant melanoma by intratumoural injection of a betaemitting radionuclide. Author(s): Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea. Source: Lee, J D Yang, W I Lee, M G Ryu, Y H Park, J H Shin, K H Kim, G E Suh, C O Seong, J S Han, B H Choi, C W Kim, E H Kim, K H Park, K B Eur-J-Nucl-Med-MolImaging. 2002 February; 29(2): 221-30 1619-7070
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Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: relationship between structure and activity. Author(s): Department of Pathology, Faculty of Medicine, University of Murcia, Murcia, Spain.
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Source: Rodriguez, J Yanez, J Vicente, V Alcaraz, M Benavente Garcia, O Castillo, J Lorente, J Lozano, J A Melanoma-Res. 2002 April; 12(2): 99-107 0960-8931 •
Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals. Author(s): Faculty of Medical Radiation Technology and Institute of Radiological Sciences, National Yang Ming University, Taiwan, ROC, China. Source: Chen, F D Hsieh, B T Wang, H E Ou, Y H Yang, W K Whang Peng, J Liu, R S Knapp, F F Ting, G Yen, S H Nucl-Med-Biol. 2001 October; 28(7): 835-44 0969-8051
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Enhancement of hyperglycemia-induced acidification of human melanoma xenografts with inhibitors of respiration and ion transport. Author(s): Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. Source: Zhou, R Bansal, N Leeper, D B Pickup, S Glickson, J D Acad-Radiol. 2001 July; 8(7): 571-82 1076-6332
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Expression of multidrug resistance genes MVP, MDR1, and MRP1 determined sequentially before, during, and after hyperthermic isolated limb perfusion of soft tissue sarcoma and melanoma patients. Author(s): Division of Surgery and Surgical Oncology, Charite, Humboldt University, Campus Berlin-Buch, Robert Rossle Hospital and Tumor Institute, Robert-Rossle-Strasse 10, 13092 Berlin, Germany.
[email protected] Source: Stein, Ulrike Jurchott, Karsten Schlafke, Matthias Hohenberger, Peter J-ClinOncol. 2002 August 1; 20(15): 3282-92 0732-183X
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Factors affecting survival after complete response to isolated limb perfusion in patients with in-transit melanoma. Author(s): Surgery Branch and the Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Source: Zogakis, T G Bartlett, D L Libutti, S K Liewehr, D J Steinberg, S M Fraker, D L Alexander, H R Ann-Surg-Oncol. 2001 December; 8(10): 771-8 1068-9265
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Farnesyl thiosalicylic acid chemosensitizes human melanoma in vivo. Author(s): Department of Clinical Pharmacology, Section of Experimental Oncology, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
[email protected] Source: Halaschek Wiener, J Kloog, Y Wacheck, V Jansen, B J-Invest-Dermatol. 2003 Jan; 120(1): 109-15 0022-202X
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Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Author(s): Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Source: Huang, E Y Madireddi, M T Gopalkrishnan, R V Leszczyniecka, M Su, Z Lebedeva, I V Kang, D Jiang, H Lin, J J Alexandre, D Chen, Y Vozhilla, N Mei, M X Christiansen, K A Sivo, F Goldstein, N I Mhashilkar, A B Chada, S Huberman, E Pestka, S Fisher, P B Oncogene. 2001 October 25; 20(48): 7051-63 0950-9232
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Hemoglobin binds melanoma cell tissue factor and enhances its procoagulant activity. Author(s): Center for Hemostasis and Thrombosis, Clinical and Research Laboratories, Florida Hospital Cancer Institute, Orlando, Florida 32804, USA.
[email protected]
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Source: Siddiqui, F A Francis, J L Blood-Coagul-Fibrinolysis. 2002 April; 13(3): 173-80 0957-5235 •
Immunohistological examination of the relationship between metastatic potential and expression of adhesion molecules and 'selectins' on melanoma cells. Author(s): Oncology and Immunology Unit, Royal Newcastle Hospital, New South Wales. Source: Si, Z Hersey, P Pathology. 1994 January; 26(1): 6-15 0031-3025
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In vitro activity of hederacolchisid A1 compared with other saponins from Hedera colchica against proliferation of human carcinoma and melanoma cells. Author(s): UMR INSERM U-484, Laboratory of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Clermont-Fd, France.
[email protected] Source: Barthomeuf, C Debiton, E Mshvildadze, V Kemertelidze, E Balansard, G PlantaMed. 2002 August; 68(8): 672-5 0032-0943
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In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid prodrug on melanoma cells: evaluation of antiproliferative activity and apoptosis induction. Author(s): Department of Medical and Surgical Specialties, University of Turin, Italy. Source: Salomone, B Ponti, R Gasco, M R Ugazio, E Quaglino, P Osella Abate, S Bernengo, M G Clin-Exp-Metastasis. 2000; 18(8): 663-73 0262-0898
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In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells. Author(s): Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital (CHUV), Lausanne, Switzerland.
[email protected] Source: Speiser, D E Lienard, D Pittet, M J Batard, P Rimoldi, D Guillaume, P Cerottini, J C Romero, P Eur-J-Immunol. 2002 March; 32(3): 731-41 0014-2980
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Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate. Author(s): Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
[email protected] Source: Malafa, M P Fokum, F D Smith, L Louis, A Ann-Surg-Oncol. 2002 December; 9(10): 1023-32 1068-9265
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Isolated limb perfusion in locally advanced cutaneous melanoma. Author(s): Department of Surgical and Oncological Sciences Clinica Chirurgica II, University of Padova, Padova, Italy. Source: Rossi, Carlo Riccardo Foletto, Mirto Pilati, Pierluigi Mocellin, Simone Lise, Mario Semin-Oncol. 2002 August; 29(4): 400-9 0093-7754
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Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function. Author(s): Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Spain. Source: Sanchez Mas, J Olivares Sanchez, C Ghanem, G Haycock, J Lozano Teruel, J A Garcia Borron, J C Jimenez Cervantes, C Eur-J-Biochem. 2002 December; 269(24): 6133-41 0014-2956
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Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy. Author(s): John Wayne Cancer Institute, Santa Monica, California 90404, USA.
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Source: O'Day, S J Boasberg, P D Piro, L Kristedja, T S Wang, H J Martin, M Deck, R Ames, P Shinn, K Kim, H Fournier, P Gammon, G Clin-Cancer-Res. 2002 September; 8(9): 2775-81 1078-0432 •
Melanoma risk in relation to height, weight, and exercise (United States). Author(s): University of Washington School of Public Health, Department of Epidemiology, Seattle, USA. Source: Shors, A R Solomon, C McTiernan, A White, E Cancer-Causes-Control. 2001 September; 12(7): 599-606 0957-5243
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Metastatic melanoma: chemotherapy. Author(s): Medical Oncology Unit B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. Source: Bajetta, E Del Vecchio, M Bernard Marty, C Vitali, M Buzzoni, R Rixe, O Nova, P Aglione, S Taillibert, S Khayat, D Semin-Oncol. 2002 October; 29(5): 427-45 0093-7754
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Phase II study of paclitaxel and carboplatin for malignant melanoma. Author(s): Adult Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Source: Hodi, F Stephen Soiffer, Robert J Clark, Jeffrey Finkelstein, Dianne M Haluska, Frank G Am-J-Clin-Oncol. 2002 June; 25(3): 283-6 0277-3732
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Prevention of growth and metastasis of murine melanoma through enhanced naturalkiller cytotoxicity by fatty acid-conjugate of protopanaxatriol. Author(s): Itto Institute of Life Science Research, Happy World, Inc., Fuchu, Tokyo, Japan.
[email protected] Source: Hasegawa, H Suzuki, R Nagaoka, T Tezuka, Y Kadota, S Saiki, I Biol-PharmBull. 2002 July; 25(7): 861-6 0918-6158
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Primary malignant melanoma of the esophagus treated by esophagectomy and systemic chemotherapy. Author(s): Department of Surgery I, Nippon Medical School, Tokyo, Japan.
[email protected] Source: Matsutani, T Onda, M Miyashita, M Hagiwara, N Akiya, Y Takubo, K Yamashita, K Sasajima, K Dis-Esophagus. 2001; 14(3-4): 241-4 1120-8694
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Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Author(s): Sydney Melanoma Unit, Royal Prince Alfred Hospital, USA. Source: Lindner, Per Doubrovsky, Anna Kam, Peter C A Thompson, John F Ann-SurgOncol. 2002 March; 9(2): 127-36 1068-9265
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Quantitative relationships between pigment-related mRNA and biochemical melanoma markers in melanoma cell lines. Author(s): Department of Biomedicine and Surgery, Division of Clinical Chemistry, Linkoping University, S-581 85 Linkoping, Sweden. Source: Johansson, M Takasaki, A Lenner, L Arstrand, K Kagedal, B Melanoma-Res. 2002 June; 12(3): 193-200 0960-8931
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Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial. Author(s): Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. Source: Mahabir, S Coit, D Liebes, L Brady, M S Lewis, J J Roush, G Nestle, M Fry, D Berwick, M Melanoma-Res. 2002 February; 12(1): 83-90 0960-8931
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Reducing renal accumulation of single-chain Fv against melanoma-associated proteoglycan by coadministration of L-lysine. Author(s): RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, HA6 2RN, UK. Source: Hamilton, S Odili, J Wilson, G D Kupsch, J M Melanoma-Res. 2002 August; 12(4): 373-9 0960-8931
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Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Author(s): Immunology Program, H Lee Moffitt Cancer Center and Research Institute, Department of Oncology, University of South Florida College of Medicine, Tampa, Florida, FL 33612, USA. Source: Niu, G Bowman, T Huang, M Shivers, S Reintgen, D Daud, A Chang, A Kraker, A Jove, R Yu, H Oncogene. 2002 October 10; 21(46): 7001-10 0950-9232
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Safety and efficacy of isolated limb perfusion in elderly melanoma patients. Author(s): Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
[email protected] Source: Noorda, E M Vrouenraets, B C Nieweg, O E van Geel, A N Eggermont, A M Kroon, B B Ann-Surg-Oncol. 2002 December; 9(10): 968-74 1068-9265
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Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. Author(s): Department Melanoma/Sarcoma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
[email protected] Source: Eton, OMarch Legha, Sewa S Bedikian, Agop Y Lee, J Jack Buzaid, Antonio C Hodges, Cynthia Ring, Sigrid E Papadopoulos, Nicholas E Plager, Carl East, Mary Jo Zhan, Feng Benjamin, Robert S J-Clin-Oncol. 2002 April 15; 20(8): 2045-52 0732-183X
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Suppressive effect of Shichimotsu-koka-to (Kampo medicine) on pulmonary metastasis of B16 melanoma cells. Author(s): Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. Source: Ohno, T Inoue, M Ogihara, Y Biol-Pharm-Bull. 2002 July; 25(7): 880-4 0918-6158
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Systemic chemotherapy for the treatment of metastatic melanoma. Author(s): Division of Hematology/Oncology, University of California, San Diego, CA, USA. Source: Li, Y McClay, E F Semin-Oncol. 2002 October; 29(5): 413-26 0093-7754
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T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants. Author(s): Swim Across America Laboratory of Tumor Immunology, Memorial SloanKettering Cancer Center, New York, New York 10021, USA. Source: Schaed, S G Klimek, V M Panageas, K S Musselli, C M Butterworth, L Hwu, W J Livingston, P O Williams, L Lewis, J J Houghton, A N Chapman, P B Clin-Cancer-Res. 2002 May; 8(5): 967-72 1078-0432
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Metaxa's Cancer Hospital, Piraeus, Greece.
[email protected] Source: Bafaloukos, D Gogas, H Georgoulias, V Briassoulis, E Fountzilas, G Samantas, E Kalofonos, Ch Skarlos, D Karabelis, A Kosmidis, P J-Clin-Oncol. 2002 January 15; 20(2): 420-5 0732-183X
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The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Author(s): Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstr. 60-62, 14 195-Berlin, Germany. Source: Riebeling, C Forsea, A M Raisova, M Orfanos, C E Geilen, C C Br-J-Cancer. 2002 July 29; 87(3): 366-71 0007-0920
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The tumour suppressor p33ING1 does not enhance camptothecin-induced cell death in melanoma cells. Author(s): Division of Dermatology, Department of Medicine, University of British Columbia, and Vancouver Hospital and Health Sciences Centre, V6H 3Z6, Canada. Source: Cheung, K John Jr Li, Gang Int-J-Oncol. 2002 June; 20(6): 1319-22 1019-6439
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Vitamin E inhibits melanoma growth in mice. Author(s): Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL 62794-9638, USA. Source: Malafa, Mokenge P Fokum, Frida D Mowlavi, Arian Abusief, Mary King, Michele Surgery. 2002 January; 131(1): 85-91 0039-6060
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to melanoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html
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Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com
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Food and Diet Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Tea Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND MELANOMA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to melanoma. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to melanoma and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “melanoma” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to melanoma: •
(+)-Tiliarine, a selective in vitro inhibitor of human melanoma cells. Author(s): Seal T, Mukherjee B. Source: Phytotherapy Research : Ptr. 2002 September; 16(6): 596-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237824&dopt=Abstract
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9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice. Author(s): Koshkina NV, Kleinerman ES, Waidrep C, Jia SF, Worth LL, Gilbert BE, Knight V. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 July; 6(7): 2876-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914737&dopt=Abstract
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A clinical trial of intravenous vinorelbine tartrate plus tamoxifen in the treatment of patients with advanced malignant melanoma. Author(s): Feun LG, Savaraj N, Hurley J, Marini A, Lai S. Source: Cancer. 2000 February 1; 88(3): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10649251&dopt=Abstract
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A feasibility study using polychemotherapy (cisplatin + vindesine + dacarbazine) plus interferon-alpha or monochemotherapy with dacarbazine plus interferon-alpha in metastatic melanoma. Author(s): Bajetta E, Del Vecchio M, Vitali M, Martinetti A, Ferrari L, Queirolo P, Sertoli MR, Cainelli T, Cellerino R, Cascinelli N. Source: Tumori. 2001 July-August; 87(4): 219-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693798&dopt=Abstract
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A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NFkappa B activity in melanoma cells. Author(s): Dhawan P, Richmond A. Source: The Journal of Biological Chemistry. 2002 March 8; 277(10): 7920-8. Epub 2001 December 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773061&dopt=Abstract
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A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma. Author(s): McDermott DF, Mier JW, Lawrence DP, van den Brink MR, Clancy MA, Rubin KM, Atkins MB. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 June; 6(6): 2201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873069&dopt=Abstract
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A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Atkins MB, Gollob JA, Sosman JA, McDermott DF, Tutin L, Sorokin P, Parker RA, Mier JW. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 October; 8(10): 3075-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374674&dopt=Abstract
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A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma. Author(s): Gibbs P, Iannucci A, Becker M, Allen J, O'Driscoll M, McDowell K, Williams P, Rosse P, Murphy J, Gonzalez R. Source: Melanoma Research. 2000 April; 10(2): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10803718&dopt=Abstract
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A phase II study of neoadjuvant biochemotherapy for stage III melanoma. Author(s): Gibbs P, Anderson C, Pearlman N, LaClaire S, Becker M, Gatlin K, O'Driscoll M, Stephens J, Gonzalez R. Source: Cancer. 2002 January 15; 94(2): 470-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900232&dopt=Abstract
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A review of the literature for whole-body FDG PET in the management of patients with melanoma. Author(s): Schwimmer J, Essner R, Patel A, Jahan SA, Shepherd JE, Park K, Phelps ME, Czernin J, Gambhir SS. Source: Q J Nucl Med. 2000 June; 44(2): 153-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10967625&dopt=Abstract
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A structured psychiatric intervention for patients with malignant melanoma: Fawzy et al. (1990b). Author(s): Payne D. Source: Advances in Mind-Body Medicine. 2001 Winter; 17(1): 21-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270055&dopt=Abstract
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Adenovirus-mediated E2F-1 gene transfer sensitizes melanoma cells to apoptosis induced by topoisomerase II inhibitors. Author(s): Dong YB, Yang HL, Elliott MJ, McMasters KM. Source: Cancer Research. 2002 March 15; 62(6): 1776-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912154&dopt=Abstract
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Adjuvant therapy for patients with high-risk malignant melanoma. Author(s): McClay EF. Source: Seminars in Oncology. 2002 August; 29(4): 389-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170442&dopt=Abstract
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Adjuvant therapy of malignant melanoma. Author(s): Molife R, Hancock BW. Source: Critical Reviews in Oncology/Hematology. 2002 October; 44(1): 81-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399001&dopt=Abstract
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Adjuvant therapy of malignant melanoma: is there a choice? Author(s): Retsas S. Source: Critical Reviews in Oncology/Hematology. 2001 November; 40(2): 187-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682325&dopt=Abstract
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Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes.
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Author(s): Greenberg DB, Jonasch E, Gadd MA, Ryan BF, Everett JR, Sober AJ, Mihm MA, Tanabe KK, Ott M, Haluska FG. Source: Cancer. 2000 July 15; 89(2): 356-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918166&dopt=Abstract •
Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Author(s): Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 December 10; 99(25): 16168-73. Epub 2002 November 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427970&dopt=Abstract
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Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma. Author(s): O'Day SJ, Gammon G, Boasberg PD, Martin MA, Kristedja TS, Guo M, Stern S, Edwards S, Fournier P, Weisberg M, Cannon M, Fawzy NW, Johnson TD, Essner R, Foshag LJ, Morton DL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 September; 17(9): 2752-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561350&dopt=Abstract
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Alterations of DNA repair in melanoma cell lines resistant to cisplatin, fotemustine, or etoposide. Author(s): Runger TM, Emmert S, Schadendorf D, Diem C, Epe B, Hellfritsch D. Source: The Journal of Investigative Dermatology. 2000 January; 114(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10620112&dopt=Abstract
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An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells. Author(s): Denkert C, Siegert A, Leclere A, Turzynski A, Hauptmann S. Source: Clinical & Experimental Metastasis. 2002; 19(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918086&dopt=Abstract
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Analysis of G(1)/S checkpoint regulators in metastatic melanoma. Author(s): Sauroja I, Smeds J, Vlaykova T, Kumar R, Talve L, Hahka-Kemppinen M, Punnonen K, Jansen CT, Hemminki K, Pyrhonen S. Source: Genes, Chromosomes & Cancer. 2000 August; 28(4): 404-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862049&dopt=Abstract
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Analysis of O(6)-methylguanine-DNA methyltransferase in melanoma tumours in patients treated with dacarbazine-based chemotherapy. Author(s): Ma S, Egyhazi S, Martenhed G, Ringborg U, Hansson J.
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Source: Melanoma Research. 2002 August; 12(4): 335-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170182&dopt=Abstract •
Anti-invasion and anti-angiogenesis effect of taxol and camptothecin on melanoma cells. Author(s): Wang F, Cao Y, Liu HY, Xu SF, Han R. Source: Journal of Asian Natural Products Research. 2003 June; 5(2): 121-9. Erratum In: J Asian Nat Prod Res. 2003 September; 5(3): 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765196&dopt=Abstract
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Antitumor activity of Virulizin, a novel biological response modifier (BRM) in a panel of human pancreatic cancer and melanoma xenografts. Author(s): Feng N, Jin H, Wang M, Du C, Wright JA, Young AH. Source: Cancer Chemotherapy and Pharmacology. 2003 March; 51(3): 247-55. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655444&dopt=Abstract
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Antitumoral action of 2-deoxy-D-glucose tetraacetate in human melanoma cells. Author(s): Reinhold U, Ugurel S, Tilgen W, Kadiata MM, Olivares E, Nadi AB, Malaisse WJ. Source: Oncol Rep. 2000 September-October; 7(5): 1093-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10948345&dopt=Abstract
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Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase. Author(s): Koo HM, VanBrocklin M, McWilliams MJ, Leppla SH, Duesbery NS, Woude GF. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 March 5; 99(5): 3052-7. Epub 2002 February 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867750&dopt=Abstract
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Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells. Author(s): Fei XF, Wang BX, Tashiro S, Li TJ, Ma JS, Ikejima T. Source: Acta Pharmacologica Sinica. 2002 April; 23(4): 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931705&dopt=Abstract
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Association of genomic imbalances with resistance to therapeutic drugs in human melanoma cell lines. Author(s): Nessling M, Kern MA, Schadendorf D, Lichter P. Source: Cytogenetics and Cell Genetics. 1999; 87(3-4): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10702697&dopt=Abstract
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Augmented growth inhibition of B16-BL6 melanoma by combined treatment with a selective matrix metalloproteinase inhibitor, MMI-166, and cytotoxic agents. Author(s): Hojo K, Maki H, Sawada TY, Maekawa R, Yoshioka T. Source: Anticancer Res. 2002 November-December; 22(6A): 3253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530072&dopt=Abstract
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Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia. Author(s): Wachsberger PR, Burd R, Wahl ML, Leeper DB. Source: International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2002 March-April; 18(2): 153-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911485&dopt=Abstract
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Betulinic acid-induced Mcl-1 expression in human melanoma--mode of action and functional significance. Author(s): Selzer E, Thallinger C, Hoeller C, Oberkleiner P, Wacheck V, Pehamberger H, Jansen B. Source: Molecular Medicine (Cambridge, Mass.). 2002 December; 8(12): 877-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606824&dopt=Abstract
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Binding of mistletoe lectins to cutaneous malignant melanoma: implications for prognosis and therapy. Author(s): Thies A, Pfuller U, Schachner M, Horny HP, Molls I, Schumacher U. Source: Anticancer Res. 2001 July-August; 21(4B): 2883-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712781&dopt=Abstract
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Biochemotherapy for advanced melanoma: maybe it is real. Author(s): Khayat D, Bernard-Marty C, Meric JB, Rixe O. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 May 15; 20(10): 2411-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011117&dopt=Abstract
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Biochemotherapy for metastatic melanoma with limited central nervous system involvement. Author(s): Boasberg PD, O'Day SJ, Kristedja TS, Martin M, Wang H, Deck R, Shinn K, Ames P, Tamar B, Petrovich Z. Source: Oncology. 2003; 64(4): 328-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759528&dopt=Abstract
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Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium ATCC 13368. Author(s): Chatterjee P, Kouzi SA, Pezzuto JM, Hamann MT.
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Source: Applied and Environmental Microbiology. 2000 September; 66(9): 3850-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10966400&dopt=Abstract •
Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Author(s): Kivela T, Suciu S, Hansson J, Kruit WH, Vuoristo MS, Kloke O, Gore M, Hahka-Kemppinen M, Parvinen LM, Kumpulainen E, Humblet Y, Pyrhonen S. Source: European Journal of Cancer (Oxford, England : 1990). 2003 May; 39(8): 1115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736111&dopt=Abstract
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Bolus high dose interleukin-2 for the treatment of malignant melanoma. Author(s): Pappo I, Lotem M, Klein M, Orda R. Source: Isr Med Assoc J. 2001 March; 3(3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303372&dopt=Abstract
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Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Author(s): Zhao W, Entschladen F, Liu H, Niggemann B, Fang Q, Zaenker KS, Han R. Source: Cancer Detection and Prevention. 2003; 27(1): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600419&dopt=Abstract
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Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: association with decreased pRb phosphorylation. Author(s): Albino AP, Juan G, Traganos F, Reinhart L, Connolly J, Rose DP, Darzynkiewicz Z. Source: Cancer Research. 2000 August 1; 60(15): 4139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945621&dopt=Abstract
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Challenging cases and diagnostic dilemmas: case 3. Positron emission tomography scan mimicking lymph node metastases in a high-risk melanoma patient. Author(s): Spieth K, Risse J, Kaufmann R, Gille J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 August 1; 20(15): 3349-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149310&dopt=Abstract
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Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma. Author(s): Pyrhonen S, Hahka-Kemppinen M, Muhonen T, Nikkanen V, Eskelin S, Summanen P, Tarkkanen A, Kivela T. Source: Cancer. 2002 December 1; 95(11): 2366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436444&dopt=Abstract
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Cisplatin and UV radiation induce activation of the stress-activated protein kinase p38gamma in human melanoma cells. Author(s): Pillaire MJ, Nebreda AR, Darbon JM. Source: Biochemical and Biophysical Research Communications. 2000 November 30; 278(3): 724-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095975&dopt=Abstract
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Clinical results using biochemotherapy as a standard of care in advanced melanoma. Author(s): Chapman PB, Panageas KS, Williams L, Wolchok JD, Livingston PO, Quinn C, Hwu WJ. Source: Melanoma Research. 2002 August; 12(4): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170188&dopt=Abstract
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Cloning and characterization of anti-cathepsin L single chain variable fragment whose expression inhibits procathepsin L secretion in human melanoma cells. Author(s): Guillaume-Rousselet N, Jean D, Frade R. Source: The Biochemical Journal. 2002 October 1; 367(Pt 1): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241546&dopt=Abstract
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Cloning and characterization of human ubiquitin-processing protease-43 from terminally differentiated human melanoma cells using a rapid subtraction hybridization protocol RaSH. Author(s): Kang D, Jiang H, Wu Q, Pestka S, Fisher PB. Source: Gene. 2001 April 18; 267(2): 233-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313150&dopt=Abstract
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c-Myc down-regulation increases susceptibility to cisplatin through reactive oxygen species-mediated apoptosis in M14 human melanoma cells. Author(s): Biroccio A, Benassi B, Amodei S, Gabellini C, Del Bufalo D, Zupi G. Source: Molecular Pharmacology. 2001 July; 60(1): 174-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408612&dopt=Abstract
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Combination chemotherapy with docetaxel and irinotecan in metastatic malignant melanoma. Author(s): Tas F, Camlica H, Kurul S, Aydiner A, Topuz E. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801051&dopt=Abstract
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Comparative cytotoxicity and pharmacokinetics of antimelanoma immunotoxins containing either natural or recombinant gelonin. Author(s): Rosenblum MG, Marks JW, Cheung LH.
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Source: Cancer Chemotherapy and Pharmacology. 1999; 44(4): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447583&dopt=Abstract •
Comparison of apoptotic, necrotic and clonogenic cell death and inhibition of cell growth following camptothecin and X-radiation treatment in a human melanoma and a human fibroblast cell line. Author(s): Quto b SS, Ng CE. Source: Cancer Chemotherapy and Pharmacology. 2002 February; 49(2): 167-75. Epub 2001 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862432&dopt=Abstract
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Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10. Author(s): Zarkovic N, Kalisnik T, Loncaric I, Borovic S, Mang S, Kissel D, Konitzer M, Jurin M, Grainza S. Source: Cancer Biotherapy & Radiopharmaceuticals. 1998 April; 13(2): 121-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850348&dopt=Abstract
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Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study. Author(s): Jelic S, Babovic N, Kovcin V, Milicevic N, Milanovic N, Popov I, Radosavljevic D. Source: Melanoma Research. 2002 February; 12(1): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828263&dopt=Abstract
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Consistent antibody response against ganglioside GD2 induced in patients with melanoma by a GD2 lactone-keyhole limpet hemocyanin conjugate vaccine plus immunological adjuvant QS-21. Author(s): Ragupathi G, Livingston PO, Hood C, Gathuru J, Krown SE, Chapman PB, Wolchok JD, Williams LJ, Oldfield RC, Hwu WJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 November 1; 9(14): 5214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614001&dopt=Abstract
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Coping with melanoma--ten strategies that promote psychological adjustment. Author(s): Kneier AW. Source: The Surgical Clinics of North America. 2003 April; 83(2): 417-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744617&dopt=Abstract
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Cucurbitacins from Trichosanthes kirilowii as the inhibitory components on tyrosinase activity and melanin synthesis of B16/F10 melanoma cells. Author(s): Oh H, Mun YJ, Im SJ, Lee SY, Song HJ, Lee HS, Woo WH.
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Source: Planta Medica. 2002 September; 68(9): 832-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357397&dopt=Abstract •
Cutaneous malignant melanoma in children. Author(s): Vandeweyer E, Sales F, Deraemaecker R. Source: European Journal of Pediatrics. 2000 August; 159(8): 582-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968235&dopt=Abstract
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Deregulated E2F transcriptional activity in autonomously growing melanoma cells. Author(s): Halaban R, Cheng E, Smicun Y, Germino J. Source: The Journal of Experimental Medicine. 2000 March 20; 191(6): 1005-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727462&dopt=Abstract
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Design, expression, purification, and characterization, in vitro and in vivo, of an antimelanoma single-chain Fv antibody fused to the toxin gelonin. Author(s): Rosenblum MG, Cheung LH, Liu Y, Marks JW 3rd. Source: Cancer Research. 2003 July 15; 63(14): 3995-4002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873997&dopt=Abstract
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DFNA5 (ICERE-1) contributes to acquired etoposide resistance in melanoma cells. Author(s): Lage H, Helmbach H, Grottke C, Dietel M, Schadendorf D. Source: Febs Letters. 2001 April 6; 494(1-2): 54-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297734&dopt=Abstract
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Diagnostic accuracy and predictive value of the tumor-associated antigen S100 in malignant melanomas: validation by whole body FDG-PET and conventional diagnostics. Author(s): Mruck S, Baum RP, Rinne D, Hor G. Source: Anticancer Res. 1999 July-August; 19(4A): 2685-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470220&dopt=Abstract
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Dietary factors in the prevention and treatment of nonmelanoma skin cancer and melanoma. Author(s): Bialy TL, Rothe MJ, Grant-Kels JM. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 December; 28(12): 1143-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472495&dopt=Abstract
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Differentiation- and apoptosis-inducing activities by pentacyclic triterpenes on a mouse melanoma cell line. Author(s): Hata K, Hori K, Takahashi S.
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Source: Journal of Natural Products. 2002 May; 65(5): 645-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027734&dopt=Abstract •
Differentiation of human malignant melanoma cells that escape apoptosis after treatment with 9-nitrocamptothecin in vitro. Author(s): Pantazis P, Chatterjee D, Han Z, Wyche J. Source: Neoplasia (New York, N.Y.). 1999 August; 1(3): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935478&dopt=Abstract
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Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells. Author(s): Darbon JM, Penary M, Escalas N, Casagrande F, Goubin-Gramatica F, Baudouin C, Ducommun B. Source: The Journal of Biological Chemistry. 2000 May 19; 275(20): 15363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10809772&dopt=Abstract
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Docetaxel in combination with dacarbazine in patients with advanced melanoma. Author(s): Bafaloukos D, Aravantinos G, Fountzilas G, Stathopoulos G, Gogas H, Samonis G, Briasoulis E, Mylonakis N, Skarlos DV, Kosmidis P. Source: Oncology. 2002; 63(4): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417787&dopt=Abstract
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Drug resistance towards etoposide and cisplatin in human melanoma cells is associated with drug-dependent apoptosis deficiency. Author(s): Helmbach H, Kern MA, Rossmann E, Renz K, Kissel C, Gschwendt B, Schadendorf D. Source: The Journal of Investigative Dermatology. 2002 June; 118(6): 923-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060385&dopt=Abstract
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Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma. Author(s): Szende B, Horvath A, Bokonyi G, Keri G. Source: British Journal of Cancer. 2003 January 13; 88(1): 132-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556972&dopt=Abstract
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Effect of naturally occurring allyl and phenyl isothiocyanates in the inhibition of experimental pulmonary metastasis induced by B16F-10 melanoma cells. Author(s): Manesh C, Kuttan G. Source: Fitoterapia. 2003 June; 74(4): 355-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781806&dopt=Abstract
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Effect of Wf-536, a novel ROCK inhibitor, against metastasis of B16 melanoma. Author(s): Nakajima M, Hayashi K, Egi Y, Katayama K, Amano Y, Uehata M, Ohtsuki M, Fujii A, Oshita K, Kataoka H, Chiba K, Goto N, Kondo T. Source: Cancer Chemotherapy and Pharmacology. 2003 October; 52(4): 319-24. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783205&dopt=Abstract
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Effects of betulinic acid alone and in combination with irradiation in human melanoma cells. Author(s): Selzer E, Pimentel E, Wacheck V, Schlegel W, Pehamberger H, Jansen B, Kodym R. Source: The Journal of Investigative Dermatology. 2000 May; 114(5): 935-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10771474&dopt=Abstract
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Effects of genistein and daidzein on the cell growth, cell cycle, and differentiation of human and murine melanoma cells(1). Author(s): Wang HZ, Zhang Y, Xie LP, Yu XY, Zhang RQ. Source: The Journal of Nutritional Biochemistry. 2002 July; 13(7): 421-426. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121829&dopt=Abstract
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Effects of genistein, a soybean-derived isoflavone, on proliferation and differentiation of B16-BL6 mouse melanoma cells. Author(s): Yan CH, Chen XG, Li Y, Han R. Source: Journal of Asian Natural Products Research. 1999; 1(4): 285-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11523549&dopt=Abstract
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Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: relationship between structure and activity. Author(s): Rodriguez J, Yanez J, Vicente V, Alcaraz M, Benavente-Garcia O, Castillo J, Lorente J, Lozano JA. Source: Melanoma Research. 2002 April; 12(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930105&dopt=Abstract
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Effects of several polyhydroxylated flavonoids on the growth of B16F10 melanoma and Melan-a melanocyte cell lines: influence of the sequential oxidation state of the flavonoid skeleton. Author(s): Martinez C, Yanez J, Vicente V, Alcaraz M, Benavente-Garcia O, Castillo J, Lorente J, Lozano JA. Source: Melanoma Research. 2003 February; 13(1): 3-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569278&dopt=Abstract
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Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Author(s): Casagrande F, Darbon JM.
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Source: Biochemical Pharmacology. 2001 May 15; 61(10): 1205-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322924&dopt=Abstract •
Effects of wine phenolics and sorghum tannins on tyrosinase activity and growth of melanoma cells. Author(s): Gomez-Cordoves C, Bartolome B, Vieira W, Virador VM. Source: Journal of Agricultural and Food Chemistry. 2001 March; 49(3): 1620-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11312905&dopt=Abstract
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Enhancement of NK cytotoxicity, antimetastasis and elongation effect of survival time in B16-F10 melanoma cells by oregonin. Author(s): Joo SS, Kim MS, Oh WS, Lee DI. Source: Arch Pharm Res. 2002 August; 25(4): 493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214862&dopt=Abstract
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Erk 1/2 differentially regulates the expression from the 1G/2G single nucleotide polymorphism in the MMP-1 promoter in melanoma cells. Author(s): Tower GB, Coon CC, Benbow U, Vincenti MP, Brinckerhoff CE. Source: Biochimica Et Biophysica Acta. 2002 April 24; 1586(3): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997078&dopt=Abstract
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ERK and PI3K negatively regulate STAT-transcriptional activities in human melanoma cells: implications towards sensitization to apoptosis. Author(s): Krasilnikov M, Ivanov VN, Dong J, Ronai Z. Source: Oncogene. 2003 June 26; 22(26): 4092-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821943&dopt=Abstract
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Evaluation of high-risk melanoma: comparison of [18F]FDG PET and high-dose 67Ga SPET. Author(s): Kalff V, Hicks RJ, Ware RE, Greer B, Binns DS, Hogg A. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 April; 29(4): 506-15. Epub 2002 February 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914889&dopt=Abstract
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Expression of classic and nonclassic HLA class I antigens in uveal melanoma. Author(s): Anastassiou G, Rebmann V, Wagner S, Bornfeld N, Grosse-Wilde H. Source: Investigative Ophthalmology & Visual Science. 2003 May; 44(5): 2016-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714638&dopt=Abstract
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Farnesyl anthranilate suppresses the growth, in vitro and in vivo, of murine B16 melanomas. Author(s): Mo H, Tatman D, Jung M, Elson CE.
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Source: Cancer Letters. 2000 September 1; 157(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936674&dopt=Abstract •
FDG PET for mucosal malignant melanoma of the head and neck. Author(s): Goerres GW, Stoeckli SJ, von Schulthess GK, Steinert HC. Source: The Laryngoscope. 2002 February; 112(2): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889401&dopt=Abstract
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FDG positron emission tomography in isolated limb perfusion therapy in patients with locally advanced melanoma: preliminary results. Author(s): Mercier GA, Alavi A, Fraker DL. Source: Clinical Nuclear Medicine. 2001 October; 26(10): 832-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564919&dopt=Abstract
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First total synthesis of (+/-)-Linderol A, a tricyclic hexahydrodibenzofuran constituent of Lindera umbellata bark, with potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells. Author(s): Yamashita M, Ohta N, Shimizu T, Matsumoto K, Matsuura Y, Kawasaki I, Tanaka T, Maezaki N, Ohta S. Source: The Journal of Organic Chemistry. 2003 February 21; 68(4): 1216-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585858&dopt=Abstract
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Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Author(s): Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M. Source: International Journal of Cancer. Journal International Du Cancer. 2000 August 15; 87(4): 595-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918203&dopt=Abstract
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Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Author(s): Iwashita K, Kobori M, Yamaki K, Tsushida T. Source: Bioscience, Biotechnology, and Biochemistry. 2000 September; 64(9): 1813-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055382&dopt=Abstract
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Fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in malignant melanoma. Diagnostic comparison with conventional imaging methods. Author(s): Krug B, Dietlein M, Groth W, Stutzer H, Psaras T, Gossmann A, Scheidhauer K, Schicha H, Lackner K. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2000 September; 41(5): 446-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016764&dopt=Abstract
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Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma. Author(s): Havenga K, Cobben DC, Oyen WJ, Nienhuijs S, Hoekstra HJ, Ruers TJ, Wobbes T. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511614&dopt=Abstract
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Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma. A prospective study. Author(s): Nieder C. Source: Cancer. 1999 September 1; 86(5): 900-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463993&dopt=Abstract
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Further characterization of the Sho-saio-to-mediated anti-tumor effect on melanoma developed in RET-transgenic mice. Author(s): Kato M, Isobe K, Dai Y, Liu W, Takahashi M, Nakashima I. Source: The Journal of Investigative Dermatology. 2000 March; 114(3): 599-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10777360&dopt=Abstract
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Generation of melanoma-specific cytotoxic T lymphocytes for allogeneic immunotherapy. Author(s): Nolte A, Scheffold C, Slotty J, Huenefeld C, Schultze JL, Grabbe S, Berdel WE, Kienast J. Source: Journal of Immunotherapy (Hagerstown, Md. : 1997). 2003 May-June; 26(3): 25769. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806279&dopt=Abstract
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Genetic epidemiology of melanoma. Author(s): Bataille V. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(10): 1341-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826035&dopt=Abstract
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Genistein enhances the cisplatin-induced inhibition of cell growth and apoptosis in human malignant melanoma cells. Author(s): Tamura S, Bito T, Ichihashi M, Ueda M. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2003 October; 16(5): 470-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950722&dopt=Abstract
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Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Author(s): Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, Kang D, Jiang H, Lin JJ, Alexandre D, Chen Y, Vozhilla N, Mei MX, Christiansen KA, Sivo F, Goldstein NI, Mhashilkar AB, Chada S, Huberman E, Pestka S, Fisher PB. Source: Oncogene. 2001 October 25; 20(48): 7051-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704829&dopt=Abstract
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Heterogeneous susceptibility to spontaneous and induced apoptosis characterizes two related transplantable melanomas with different biological properties. Author(s): Kozlowska K, Cichorek M, Zarzeczna M, Brozek J, Witkowski JM. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2002 June; 15(3): 233-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028588&dopt=Abstract
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High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma. Author(s): Nikkola J, Vihinen P, Vlaykova T, Hahka-Kemppinen M, Kahari VM, Pyrhonen S. Source: International Journal of Cancer. Journal International Du Cancer. 2002 February 1; 97(4): 432-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802203&dopt=Abstract
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High levels of MMP-1 expression in the absence of the 2G single nucleotide polymorphism is mediated by p38 and ERK1/2 mitogen-activated protein kinases in VMM5 melanoma cells. Author(s): Benbow U, Tower GB, Wyatt CA, Buttice G, Brinckerhoff CE. Source: Journal of Cellular Biochemistry. 2002; 86(2): 307-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112000&dopt=Abstract
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Identification of differentially expressed genes in human melanoma cells with acquired resistance to various antineoplastic drugs. Author(s): Grottke C, Mantwill K, Dietel M, Schadendorf D, Lage H. Source: International Journal of Cancer. Journal International Du Cancer. 2000 November 15; 88(4): 535-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11058868&dopt=Abstract
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IL-32 Adjuvant therapy in melanoma. Author(s): Brochez L. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2003 October; 16(5): 588. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950790&dopt=Abstract
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Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells. Author(s): Prignano F, Coronnello M, Pimpinelli N, Cappugi P, Mini E, Giannotti B. Source: Cancer Letters. 2002 December 5; 186(2): 183-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213288&dopt=Abstract
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Improvement of the recurrence-free interval using biological adjuvant therapy in uveal melanoma. Author(s): Tallberg T, Uusitalo R, Sarna S, Seregard S, Werschnik C. Source: Anticancer Res. 2000 May-June; 20(3B): 1969-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928136&dopt=Abstract
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In vitro activity of hederacolchisid A1 compared with other saponins from Hedera colchica against proliferation of human carcinoma and melanoma cells. Author(s): Barthomeuf C, Debiton E, Mshvildadze V, Kemertelidze E, Balansard G. Source: Planta Medica. 2002 August; 68(8): 672-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221585&dopt=Abstract
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Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma. Author(s): Haas A, Pinter O, Papaefthymiou G, Weger M, Berghold A, Schrottner O, Mullner K, Pendl G, Langmann G. Source: Ophthalmology. 2002 May; 109(5): 909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986096&dopt=Abstract
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Increased uptake of technetium-99m-hexamethylpropyleneamine oxime related to primary leptomeningeal melanoma. Author(s): Sagiuchi T, Ishii K, Utsuki S, Asano Y, Tsukahara S, Kan S, Fujii K, Hayakawa K. Source: Ajnr. American Journal of Neuroradiology. 2002 September; 23(8): 1404-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223386&dopt=Abstract
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Induction of apoptosis in HL-60 leukemia and B16 melanoma cells by the acronycine derivative S23906-1. Author(s): Kluza J, Lansiaux A, Wattez N, Hildebrand MP, Leonce S, Pierre A, Hickman JA, Bailly C. Source: Biochemical Pharmacology. 2002 April 15; 63(8): 1443-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996885&dopt=Abstract
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Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines. Author(s): Ishii Y, Ogura T, Tatemichi M, Fujisawa H, Otsuka F, Esumi H.
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Source: International Journal of Cancer. Journal International Du Cancer. 2003 January 10; 103(2): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455029&dopt=Abstract •
Influence of quercetin on B16 melanotic melanoma growth in C57BL/6 mice and on activity of some acid hydrolases in melanoma tissue. Author(s): Drewa G, Wozqak A, Palgan K, Schachtschabel DO, Grzanka A, Sujkowska R. Source: Neoplasma. 2001; 48(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327532&dopt=Abstract
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Inhibition of lung metastasis of B16 melanoma cells exposed to blue light in mice. Author(s): Ohara M, Kawashima Y, Kitajima S, Mitsuoka C, Watanabe H. Source: International Journal of Molecular Medicine. 2002 December; 10(6): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429995&dopt=Abstract
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Inhibition of melanoma growth and metastasis by combination with (-)epigallocatechin-3-gallate and dacarbazine in mice. Author(s): Liu JD, Chen SH, Lin CL, Tsai SH, Liang YC. Source: Journal of Cellular Biochemistry. 2001; 83(4): 631-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746506&dopt=Abstract
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Inhibitory effect of epigallocatechin gallate on adhesion of murine melanoma cells to laminin. Author(s): Suzuki Y, Isemura M. Source: Cancer Letters. 2001 November 8; 173(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578804&dopt=Abstract
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Inhibitory effect of glycyrrhizin on experimental pulmonary metastasis in mice inoculated with B16 melanoma. Author(s): Kobayashi M, Fujita K, Katakura T, Utsunomiya T, Pollard RB, Suzuki F. Source: Anticancer Res. 2002 November-December; 22(6C): 4053-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553032&dopt=Abstract
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Investigation of signal transduction pathways involved in melanoma cell spreading. Author(s): Seller Z, Hart IR. Source: Indian J Exp Biol. 2000 March; 38(3): 211-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927861&dopt=Abstract
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Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A. Author(s): Weinzweig J, Tattini C, Lynch S, Zienowicz R, Weinzweig N, Spangenberger A, Edstrom L.
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Source: Plastic and Reconstructive Surgery. 2003 July; 112(1): 152-8; Discussion 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832888&dopt=Abstract •
L-methionine supplementation accelerates tumour growth and shifts the phospholipid derivative pattern in a murine model of malignant melanoma. A proton HRMAS NMR spectroscopy study. Author(s): Demidem A, Morvan D, Papon J, Madelmont JC. Source: Iarc Sci Publ. 2002; 156: 423-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484228&dopt=Abstract
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Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy. Author(s): O'Day SJ, Boasberg PD, Piro L, Kristedja TS, Wang HJ, Martin M, Deck R, Ames P, Shinn K, Kim H, Fournier P, Gammon G. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 September; 8(9): 2775-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231516&dopt=Abstract
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Malignant melanoma: effects of a brief, structured psychiatric intervention on survival and recurrence at 10-year follow-up. Author(s): Fawzy FI, Canada AL, Fawzy NW. Source: Archives of General Psychiatry. 2003 January; 60(1): 100-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511177&dopt=Abstract
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Malignant melanoma: treatments emerging, but early detection is still key. Author(s): Masci P, Borden EC. Source: Cleve Clin J Med. 2002 July; 69(7): 529, 533-4, 536-8 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109636&dopt=Abstract
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Metastatic melanoma: chemotherapy. Author(s): Bajetta E, Del Vecchio M, Bernard-Marty C, Vitali M, Buzzoni R, Rixe O, Nova P, Aglione S, Taillibert S, Khayat D. Source: Seminars in Oncology. 2002 October; 29(5): 427-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407508&dopt=Abstract
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Microbial transformations of the antimelanoma agent betulinic acid. Author(s): Kouzi SA, Chatterjee P, Pezzuto JM, Hamann MT. Source: Journal of Natural Products. 2000 December; 63(12): 1653-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11141108&dopt=Abstract
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Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells.
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Author(s): Kortylewski M, Heinrich PC, Kauffmann ME, Bohm M, MacKiewicz A, Behrmann I. Source: The Biochemical Journal. 2001 July 1; 357(Pt 1): 297-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11415463&dopt=Abstract •
Modulation of DNA topoisomerase II activity and expression in melanoma cells with acquired drug resistance. Author(s): Lage H, Helmbach H, Dietel M, Schadendorf D. Source: British Journal of Cancer. 2000 January; 82(2): 488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646909&dopt=Abstract
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Mucosal metastases in malignant melanoma. Author(s): Fink W, Zimpfer A, Ugurel S. Source: Onkologie. 2003 June; 26(3): 249-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845209&dopt=Abstract
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Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma). Author(s): Sertoli MR, Queirolo P, Bajetta E, DelVecchio M, Comella G, Barduagni L, Bernengo MG, Vecchio S, Criscuolo D, Bufalino R, Morabito A, Cascinelli N. Source: Melanoma Research. 1999 October; 9(5): 503-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10596917&dopt=Abstract
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Myelodysplastic syndrome following treatment of malignant melanoma with vincristine, ACNU, and dacarbazine. Author(s): Kageshita T, Kuribayashi N, Ono T. Source: The Journal of Dermatology. 2000 March; 27(3): 178-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774145&dopt=Abstract
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N-3 polyunsaturated fatty acids accentuate B16 melanoma growth and metastasis through suppression of tumoricidal function of T cells and macrophages. Author(s): Salem ML, Kishihara K, Abe K, Matsuzaki G, Nomoto K. Source: Anticancer Res. 2000 September-October; 20(5A): 3195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11062743&dopt=Abstract
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New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma. Author(s): Cobben DC, Koopal S, Tiebosch AT, Jager PL, Elsinga PH, Wobbes T, Hoekstra HJ.
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Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2002 November; 28(7): 692-700. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431464&dopt=Abstract •
O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma. Author(s): Ma S, Egyhazi S, Ueno T, Lindholm C, Kreklau EL, Stierner U, Ringborg U, Hansson J. Source: British Journal of Cancer. 2003 October 20; 89(8): 1517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562026&dopt=Abstract
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p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells. Author(s): Casagrande F, Darbon JM. Source: Experimental Cell Research. 2000 July 10; 258(1): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912792&dopt=Abstract
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p53-dependent apoptosis in melanoma cells after treatment with camptothecin. Author(s): Li G, Bush JA, Ho VC. Source: The Journal of Investigative Dermatology. 2000 March; 114(3): 514-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692111&dopt=Abstract
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Paclitaxel and tamoxifen: An active regimen for patients with metastatic melanoma. Author(s): Nathan FE, Berd D, Sato T, Mastrangelo MJ. Source: Cancer. 2000 January 1; 88(1): 79-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618609&dopt=Abstract
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Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a “humanized” SCID mouse model. Author(s): Kunstfeld R, Wickenhauser G, Michaelis U, Teifel M, Umek W, Naujoks K, Wolff K, Petzelbauer P. Source: The Journal of Investigative Dermatology. 2003 March; 120(3): 476-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603862&dopt=Abstract
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Phase II study of paclitaxel and carboplatin for malignant melanoma. Author(s): Hodi FS, Soiffer RJ, Clark J, Finkelstein DM, Haluska FG. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 June; 25(3): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040289&dopt=Abstract
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Phase II trial of 9-nitrocamptothecin (RFS 2000) for patients with metastatic cutaneous or uveal melanoma. Author(s): Ellerhorst JA, Bedikian AY, Smith TM, Papadopoulos NE, Plager C, Eton O. Source: Anti-Cancer Drugs. 2002 February; 13(2): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901310&dopt=Abstract
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Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma. Author(s): Feun LG, Savaraj N, Hurley J, Marini A. Source: Cancer Investigation. 2002; 20(3): 357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025231&dopt=Abstract
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Pilot study of intra-arterial cisplatin and intravenous vinblastine and dacarbazine in patients with melanoma in-transit metastases. Author(s): Eton O, East M, Legha SS, Bedikian A, Buzaid AC, Papadopoulos N, Hodges C, Gianan M, Carrasco CH, Benjamin RS. Source: Melanoma Research. 1999 October; 9(5): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10596915&dopt=Abstract
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Positron emission tomography for staging and management of malignant melanoma. Author(s): Prichard RS, Hill AD, Skehan SJ, O'Higgins NJ. Source: The British Journal of Surgery. 2002 April; 89(4): 389-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952577&dopt=Abstract
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Positron emission tomography of experimental melanoma with. Author(s): Mars U, Tolmachev V, Sundin A. Source: Nuclear Medicine and Biology. 2000 November; 27(8): 845-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150719&dopt=Abstract
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Potentiation of antitumor effects of IL-12 in combination with paclitaxel in murine melanoma model in vivo. Author(s): Zagozdzon R, Golab J, Mucha K, Foroncewicz B, Jakobisiak M. Source: International Journal of Molecular Medicine. 1999 December; 4(6): 645-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10567677&dopt=Abstract
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Prevention of growth and metastasis of murine melanoma through enhanced naturalkiller cytotoxicity by fatty acid-conjugate of protopanaxatriol. Author(s): Hasegawa H, Suzuki R, Nagaoka T, Tezuka Y, Kadota S, Saiki I. Source: Biological & Pharmaceutical Bulletin. 2002 July; 25(7): 861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132658&dopt=Abstract
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Primary malignant melanoma of the esophagus treated by esophagectomy and systemic chemotherapy.
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Author(s): Matsutani T, Onda M, Miyashita M, Hagiwara N, Akiya Y, Takubo K, Yamashita K, Sasajima K. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2001; 14(3-4): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869329&dopt=Abstract •
Primary malignant melanoma of the oral mucosa. Author(s): Rapidis AD, Apostolidis C, Vilos G, Valsamis S. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 October; 61(10): 1132-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586846&dopt=Abstract
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Psychological adjustment to the melanoma experience. Author(s): Boyle DA. Source: Semin Oncol Nurs. 2003 February; 19(1): 70-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638383&dopt=Abstract
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Pulmonary metastatic melanoma -- the survival benefit associated with positron emission tomography scanning. Author(s): Dalrymple-Hay MJ, Rome PD, Kennedy C, Fulham M, McCaughan BC. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 April; 21(4): 611-4; Discussion 614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932155&dopt=Abstract
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Pyrazolotriazolopyrimidine derivatives sensitize melanoma cells to the chemotherapic drugs: taxol and vindesine. Author(s): Merighi S, Mirandola P, Varani K, Gessi S, Capitani S, Leung E, Baraldi PG, Tabrizi MA, Borea PA. Source: Biochemical Pharmacology. 2003 September 1; 66(5): 739-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948854&dopt=Abstract
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Quantitative PET studies in pretreated melanoma patients: a comparison of 6[18F]fluoro-L-dopa with 18F-FDG and (15)O-water using compartment and noncompartment analysis. Author(s): Dimitrakopoulou-Strauss A, Strauss LG, Burger C. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 February; 42(2): 248-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216523&dopt=Abstract
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Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia. Author(s): Piantelli M, Tatone D, Castrilli G, Savini F, Maggiano N, Larocca LM, Ranelletti FO, Natali PG.
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Source: Melanoma Research. 2001 October; 11(5): 469-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595883&dopt=Abstract •
Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression. Author(s): Zhang X, Xu Q, Saiki I. Source: Clinical & Experimental Metastasis. 2000; 18(5): 415-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467774&dopt=Abstract
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Radioiodinated N-[3-(4-morpholino)propyl]-N-methyl-2-hydroxy-5-iodo-3methylbenzylamine (ERC9): a new potential melanoma imaging agent. Author(s): Salopek TG, Scott JR, Joshua AV, Smylie M, Logus JW, Morin CA, McEwan AJ. Source: European Journal of Nuclear Medicine. 2001 April; 28(4): 408-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357490&dopt=Abstract
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Radiosensitization of a mouse melanoma by withaferin A: in vivo studies. Author(s): Devi PU, Kamath R, Rao BS. Source: Indian J Exp Biol. 2000 May; 38(5): 432-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272405&dopt=Abstract
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Radiosensitizing effect of withaferin A combined with hyperthermia on mouse fibrosarcoma and melanoma. Author(s): Uma Devi P, Kamath R. Source: Journal of Radiation Research. 2003 March; 44(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841592&dopt=Abstract
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Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial. Author(s): Mahabir S, Coit D, Liebes L, Brady MS, Lewis JJ, Roush G, Nestle M, Fry D, Berwick M. Source: Melanoma Research. 2002 February; 12(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828262&dopt=Abstract
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Rationale for intergroup trial E-3695 comparing concurrent biochemotherapy with cisplatin, vinblastine, and DTIC alone in patients with metastatic melanoma. Author(s): Flaherty LE. Source: Cancer J Sci Am. 2000 February; 6 Suppl 1: S15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685653&dopt=Abstract
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Reduction of cisplatin-induced nephrotoxicity by cystone, a polyherbal ayurvedic preparation, in C57BL/6J mice bearing B16F1 melanoma without reducing its
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antitumor activity. Author(s): Rao M, Praveen Rao PN, Kamath R, Rao MN. Source: Journal of Ethnopharmacology. 1999 December 15; 68(1-3): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624865&dopt=Abstract •
Regulation of mda-7 gene expression during human melanoma differentiation. Author(s): Madireddi MT, Dent P, Fisher PB. Source: Oncogene. 2000 March 2; 19(10): 1362-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713678&dopt=Abstract
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Relationship between expression of topoisomerase II isoforms and chemosensitivity in choroidal melanoma. Author(s): Satherley K, de Souza L, Neale MH, Alexander RA, Myatt N, Foss AJ, Hungerford JL, Hickson ID, Cree IA. Source: The Journal of Pathology. 2000 October; 192(2): 174-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004693&dopt=Abstract
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Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission tomography in recurrent melanoma. Author(s): Mijnhout GS, Comans EF, Raijmakers P, Hoekstra OS, Teule GJ, Boers M, De Gast GC, Ader HJ. Source: Nuclear Medicine Communications. 2002 May; 23(5): 475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973489&dopt=Abstract
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Resveratrol is a potent inducer of apoptosis in human melanoma cells. Author(s): Niles RM, McFarland M, Weimer MB, Redkar A, Fu YM, Meadows GG. Source: Cancer Letters. 2003 February 20; 190(2): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565170&dopt=Abstract
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Risk of cutaneous malignant melanoma in relation to use of sunbeds: further evidence for UV-A carcinogenicity. Author(s): Westerdahl J, Ingvar C, Masback A, Jonsson N, Olsson H. Source: British Journal of Cancer. 2000 May; 82(9): 1593-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789730&dopt=Abstract
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Roxithromycin and clarithromycin, 14-membered ring macrolides, potentiate the antitumor activity of cytotoxic agents against mouse B16 melanoma cells. Author(s): Yatsunami J, Fukuno Y, Nagata M, Tsuruta N, Aoki S, Tominaga M, Kawashima M, Taniguchi S, Hayashi S. Source: Cancer Letters. 1999 December 1; 147(1-2): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10660084&dopt=Abstract
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Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. Author(s): Eton O, Legha SS, Bedikian AY, Lee JJ, Buzaid AC, Hodges C, Ring SE, Papadopoulos NE, Plager C, East MJ, Zhan F, Benjamin RS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 April 15; 20(8): 2045-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956264&dopt=Abstract
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Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus sentinel node detection. Author(s): Belhocine T, Pierard G, De Labrassinne M, Lahaye T, Rigo P. Source: The Oncologist. 2002; 7(4): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185291&dopt=Abstract
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Suppressing effects of dietary supplementation of the organoselenium 1,4phenylenebis(methylene)selenocyanate and the Citrus antioxidant auraptene on lung metastasis of melanoma cells in mice. Author(s): Tanaka T, Kohno H, Murakami M, Kagami S, El-Bayoumy K. Source: Cancer Research. 2000 July 15; 60(14): 3713-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10919638&dopt=Abstract
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Suppressive effect of Shichimotsu-koka-to (Kampo medicine) on pulmonary metastasis of B16 melanoma cells. Author(s): Ohno T, Inoue M, Ogihara Y. Source: Biological & Pharmaceutical Bulletin. 2002 July; 25(7): 880-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132662&dopt=Abstract
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Survival and tumor localization of adoptively transferred Melan-A-specific T cells in melanoma patients. Author(s): Meidenbauer N, Marienhagen J, Laumer M, Vogl S, Heymann J, Andreesen R, Mackensen A. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 15; 170(4): 2161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574389&dopt=Abstract
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Synergistic anti-tumoral effect of paclitaxel (Taxol)+AS101 in a murine model of B16 melanoma: association with ras-dependent signal-transduction pathways. Author(s): Kalechman Y, Longo DL, Catane R, Shani A, Albeck M, Sredni B. Source: International Journal of Cancer. Journal International Du Cancer. 2000 April 15; 86(2): 281-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738258&dopt=Abstract
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Systemic chemotherapy for the treatment of metastatic melanoma. Author(s): Li Y, McClay EF.
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Source: Seminars in Oncology. 2002 October; 29(5): 413-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407507&dopt=Abstract •
Targeting and anti-tumor efficacy of liposomal 5'-O-dipalmitoylphosphatidyl 2'-Ccyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in mice lung bearing B16BL6 melanoma. Author(s): Asai T, Shuto S, Matsuda A, Kakiuchi T, Ohba H, Tsukada H, Oku N. Source: Cancer Letters. 2001 January 10; 162(1): 49-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121862&dopt=Abstract
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, Kalofonos Ch, Skarlos D, Karabelis A, Kosmidis P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 15; 20(2): 420-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786569&dopt=Abstract
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Temperature sensitive liposomes of plumbagin: characterization and in vivo evaluation in mice bearing melanoma B16F1. Author(s): Tiwari SB, Pai RM, Udupa N. Source: Journal of Drug Targeting. 2002 December; 10(8): 585-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683662&dopt=Abstract
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Ten-year survival in advanced malignant melanoma following treatment with interferon and vindesine. Author(s): Iqbal M, Marshall E, Green JA. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 April; 11(4): 483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847471&dopt=Abstract
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tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo. Author(s): Lambert JD, Meyers RO, Timmermann BN, Dorr RT. Source: Cancer Letters. 2001 September 28; 171(1): 47-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485827&dopt=Abstract
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The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. Author(s): Raisova M, Hossini AM, Eberle J, Riebeling C, Wieder T, Sturm I, Daniel PT, Orfanos CE, Geilen CC. Source: The Journal of Investigative Dermatology. 2001 August; 117(2): 333-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511312&dopt=Abstract
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The effect of fluorine-18 fluorodeoxyglucose positron emission tomography on the management of cutaneous malignant melanoma. Author(s): Jadvar H, Johnson DL, Segall GM. Source: Clinical Nuclear Medicine. 2000 January; 25(1): 48-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634531&dopt=Abstract
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The first total synthesis of (+/-)-linderol A, a tricyclic hexahydrodibenzofuran constituent of Lindera umbellata bark, with potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells. Author(s): Yamashita M, Ohta N, Kawasaki I, Ohta S. Source: Organic Letters. 2001 May 3; 3(9): 1359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11348234&dopt=Abstract
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The impact of 2-deoxy-2[18F] fluoro-D-glucose whole body positron emission tomography for managing patients with melanoma: the referring physician's perspective. Author(s): Wong C, Silverman DH, Seltzer M, Schiepers C, Ariannejad M, Gambhir SS, Phelps ME, Rao J, Valk P, Czernin J. Source: Molecular Imaging and Biology : Mib : the Official Publication of the Academy of Molecular Imaging. 2002 March; 4(2): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14537142&dopt=Abstract
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The influence of P170-glycoprotein modulators on the efficacy and the distribution of vincristine as well as on MDR1 expression in BRO/mdr1.1 human melanoma xenografts. Author(s): Boven E, Jansen WJ, Hulscher TM, Beijnen JH, van Tellingen O. Source: European Journal of Cancer (Oxford, England : 1990). 1999 May; 35(5): 840-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10505047&dopt=Abstract
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The MEK1 inhibitor PD98059 sensitizes C8161 melanoma cells to cisplatin-induced apoptosis. Author(s): Mandic A, Viktorsson K, Heiden T, Hansson J, Shoshan MC. Source: Melanoma Research. 2001 February; 11(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254111&dopt=Abstract
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The p53-stabilizing compound, CP-31398, does not enhance chemosensitivity in human melanoma cells. Author(s): Luu Y, Li G. Source: Anticancer Res. 2003 January-February; 23(1A): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680200&dopt=Abstract
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The role of mitogen-activated protein kinase activation in determining cellular outcomes in polyamine analogue-treated human melanoma cells. Author(s): Chen Y, Alm K, Vujcic S, Kramer DL, Kee K, Diegelman P, Porter CW.
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Source: Cancer Research. 2003 July 1; 63(13): 3619-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839950&dopt=Abstract •
The tumour suppressor p33ING1 does not enhance camptothecin-induced cell death in melanoma cells. Author(s): Cheung KJ Jr, Li G. Source: International Journal of Oncology. 2002 June; 20(6): 1319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012016&dopt=Abstract
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The use of lymphoscintigraphy and PET in the management of head and neck melanoma. Author(s): Kokoska MS, Olson G, Kelemen PR, Fosko S, Dunphy F, Lowe VJ, Stack BC Jr. Source: Otolaryngology and Head and Neck Surgery. 2001 September; 125(3): 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555756&dopt=Abstract
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The use of positron emission tomography to develop boron neutron capture therapy treatment plans for metastatic malignant melanoma. Author(s): Kabalka GW, Nichols TL, Smith GT, Miller LF, Khan MK, Busse PM. Source: Journal of Neuro-Oncology. 2003 March-April; 62(1-2): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749713&dopt=Abstract
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Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen, or vindesine plus tamoxifen: a prospective randomized study. Author(s): Cocconi G, Passalacqua R, Foladore S, Carlini P, Acito L, Maiello E, Marchi M, Gebbia V, Di Sarra S, Beretta M, Bacchi M. Source: Melanoma Research. 2003 February; 13(1): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569288&dopt=Abstract
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Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cisdiamminedichloroplatinum(II): therapeutic implications. Author(s): Chu W, Pak BJ, Bani MR, Kapoor M, Lu SJ, Tamir A, Kerbel RS, Ben-David Y. Source: Oncogene. 2000 January 20; 19(3): 395-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656687&dopt=Abstract
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U0126, a mitogen-activated protein kinase kinase inhibitor, inhibits the invasion of human A375 melanoma cells. Author(s): Ge X, Fu YM, Meadows GG. Source: Cancer Letters. 2002 May 28; 179(2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888667&dopt=Abstract
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Unexpected cytokines in serum of malignant melanoma patients during sequential biochemotherapy. Author(s): Grimm EA, Smid CM, Lee JJ, Tseng CH, Eton O, Buzaid AC. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 3895-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051235&dopt=Abstract
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Use of [F]-fluorodeoxyglucose positron emission tomography in monitoring response of recurrent neurotropic desmoplastic melanoma to radiotherapy. Author(s): Hannah A, Feigen M, Quong G, Akhurst T, Berlangieri SU, Zimet A, Zalcberg J, McKay WJ, Scott AM. Source: Otolaryngology and Head and Neck Surgery. 2000 February; 122(2): 304-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652412&dopt=Abstract
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Uveal melanoma and poor treatment compliance: an atypical outcome with literature review. Author(s): Park WL, Jenison-Williams T, Pasqua-Darnell T. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 2003 May; 80(5): 344-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771660&dopt=Abstract
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Uveal melanoma. Author(s): Kincaid MC. Source: Cancer Control : Journal of the Moffitt Cancer Center. 1998 July; 5(4): 299-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761079&dopt=Abstract
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Uveal melanoma: mean of the longest nucleoli measured on silver-stained sections. Author(s): Moshari A, McLean IW. Source: Investigative Ophthalmology & Visual Science. 2001 May; 42(6): 1160-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328722&dopt=Abstract
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Vinblastin-carboplatin for metastatic cutaneous melanoma as first-line chemotherapy and in dacarbazine failures: a single-center study. Author(s): Jelic S, Babovic N, Stamatovic L, Kreacic M, Matkovic S, Popov I. Source: Medical Oncology (Northwood, London, England). 2001; 18(3): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917943&dopt=Abstract
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Volatile isoprenoid constituents of fruits, vegetables and herbs cumulatively suppress the proliferation of murine B16 melanoma and human HL-60 leukemia cells. Author(s): Tatman D, Mo H. Source: Cancer Letters. 2002 January 25; 175(2): 129-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741740&dopt=Abstract
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What can we learn from phase II adjuvant trials in melanoma? Author(s): Keilholz U, Suciu S, Eggermont AM. Source: British Journal of Cancer. 2000 July; 83(1): 6-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883660&dopt=Abstract
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Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma. Author(s): Crippa F, Leutner M, Belli F, Gallino F, Greco M, Pilotti S, Cascinelli N, Bombardieri E. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 September; 41(9): 1491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994727&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to melanoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com
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Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vitiligo Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Brahmi Alternative names: Centella asiatica, Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Centella Source: Integrative Medicine Communications; www.drkoop.com
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Centella Asiatica Alternative names: Centella asiatica, Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com GLA Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com
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Linseed Source: Integrative Medicine Communications; www.drkoop.com Linum Usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Luffa Alternative names: Luffa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tocotrienols Source: Healthnotes, Inc.; www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com Tyrosine Source: Integrative Medicine Communications; www.drkoop.com
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Yucca Alternative names: Yucca schidigera , Yucca spp. Source: Healthnotes, Inc.; www.healthnotes.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON MELANOMA Overview In this chapter, we will give you a bibliography on recent dissertations relating to melanoma. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “melanoma” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on melanoma, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Melanoma ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to melanoma. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Novel Candidate Ovarian Cancer and Melanoma Tumor Suppressor Gene on Chromosome 6q24.3 by Rice, Andrew Jason; PhD from University of Southern California, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3093811
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Analysis of DNA Sequences in a Human Melanoma by Higgins, Michael Joseph; PhD from Queen's University at Kingston (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL38467
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Antisense Rna Inhibition of Cathepsin L Expression Influences Metastatic Ability of B16f10 Melanoma Cells by Yang, Zhen; MS from Truman State University, 2002, 70 pages http://wwwlib.umi.com/dissertations/fullcit/1411755
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Arsenic Exposure, Artificial Tanning and Melanoma in Iowa by Beane Freeman, Laura Elizabeth; PhD from The University of Iowa, 2003, 214 pages http://wwwlib.umi.com/dissertations/fullcit/3087609
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Association between Dna Amplification and Enhanced Malignancy in a Human Melanoma Cell-line by Gitelman, Inna; PhD from Queen's University at Kingston (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL32189
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Cell Kinetics of B16 Melanoma and the Induction of in Vivo Cell Synchrony by Cytosine Arabinoside by Gibson, Maurice Henry Lindsay; PhD from The University of Manitoba (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK10964
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Continuity of Care As a Predictor of Melanoma Thickness: Analysis of Nove Scotia Population-based Secondary Data Resources by Di Quinzio, Melanie L.; MSC from Dalhousie University (Canada), 2002, 85 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75461
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Enhancing Drug Sensitivity in Melanoma Cells Through Pro-apoptotic Pathways That Subvert Chemoresistance Mechanisms by Bush, Jason Allan; PhD from The University of British Columbia (Canada), 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75001
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Expression of Cytosolic and Mitochondrial Superoxide Dismutases: Their Role in the Chemoresistance of Malignant Melanoma by Sulaimon, Shola Shakirat; PhD from University of Illinois at Urbana-Champaign, 2003, 269 pages http://wwwlib.umi.com/dissertations/fullcit/3086192
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Localization of a Melanoma Tumor Suppressor Gene on Chromosome 11q23 by Goldberg, Eleonora Kawka; PhD from University of Southern California, 2002, 261 pages http://wwwlib.umi.com/dissertations/fullcit/3093766
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Malignant Melanoma in Southern Sweden: Histopathology, Prognosis and Aetiology by Masback, Anna; from Lunds Universitet (Sweden), 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/f824593
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Melanoma: a Decision Analysis to Estimate the Effectiveness and Cost-effectiveness of Screening and an Analysis of the Relevant Epidemiology of the Disease by Beddingfield, Frederick Coston, III; PhD from The Rand Graduate School, 2002, 107 pages http://wwwlib.umi.com/dissertations/fullcit/3066090
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Molecular Dissection of Melanoma Tumor Cell Vasculogenic Mimicry by Hess, Angela Rose; PhD from The University of Iowa, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3050808
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Physical and Molecular Characterization of Human Malignant Melanoma Antigens Defined by a Monkey Antiserum and a Mouse Monoclonal Antibody by Khosravi, Mohammad Javad; PhD from McMaster University (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65445
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Psychological Variables and Health-risk Behaviors in the Development of Malignant Melanoma by Byers, Karen; PsyD from Hofstra University, 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/3072169
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Putting Melanoma in Context: Regulation and Function of Intercellular Communications in Melanocytic Homeostasis by Li, Gang; PhD from University of Pennsylvania, 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3054970
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Reduced Tumorigenicity of B16-f10 Mouse Melanoma Transfected with Mycobacterial Ag85a by Tarrant, Jillian Paige; MSC from Dalhousie University (Canada), 2002, 116 pages http://wwwlib.umi.com/dissertations/fullcit/MQ67574
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Regulatory Pathways in Melanoma Cell Apoptosis by McGill, Gael-Christophe Garth; PhD from Harvard University, 2002, 274 pages http://wwwlib.umi.com/dissertations/fullcit/3067419
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Signaling Pathways Involved in Polyamine Analog-induced Apoptosis in Melanoma Cell Lines by Chen, Ying; PhD from State University of New York at Buffalo, 2002, 215 pages http://wwwlib.umi.com/dissertations/fullcit/3052495
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The Genetics of Melanoma Metastasis: Characterization of a Metastasis Suppression Pathway by Goldberg, Steven Frank; PhD from The Pennsylvania State University, 2002, 381 pages http://wwwlib.umi.com/dissertations/fullcit/3051656
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The Role of Endogenous Ifn-beta in Cutaneous Melanoma: Consequences of Epidermal Hyperplasia by McCarty, Marya Faith; PhD from The Univ. of Texas H.S.C. at Houston Grad. Sch. of Biomed. Sci., 2002, 161 pages http://wwwlib.umi.com/dissertations/fullcit/3046064
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The Role of Interleukin-8 Receptors in Human Melanoma Cells with Different Metastatic Potentials by Rao, Sushma; Ms from Stephen F. Austin State University, 2003, 67 pages http://wwwlib.umi.com/dissertations/fullcit/1413233
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Transcriptional Regulation of Cathepsin B Expression in a Highly Metastatic Murine Melanoma Variant by Ahmed, Yasmin; PhD from Loyola University of Chicago, 2002, 211 pages http://wwwlib.umi.com/dissertations/fullcit/3056399
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Ultrastructural Features of the Harding-passey Melanoma Following Maximal, Minimal and Intermittent Colchicine Chemotherapy by Loader, Kenneth Robert; PhD from The University of Manitoba (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15517
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Uvb Cell Cycle Checkpoint Loss in Melanoma Progression by Petrocelli, Teresa; PhD from University of Toronto (Canada), 2002, 158 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74702
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND MELANOMA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning melanoma.
Recent Trials on Melanoma The following is a list of recent trials dedicated to melanoma.8 Further information on a trial is available at the Web site indicated. •
A Phase II Study of Isolated Hepatic Perfusion (IHP) in Patients with Ocular Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Ocular melanoma, or cancer of the eye, is a rare form of cancer that can spread to the liver. A tumor in the liver, because of its size or location, sometimes cannot be removed with surgery. The purpose of this study is to determine whether chemotherapy delivered only to the liver, called isolated hepatic perfusion (IHP), followed by systemic (to the whole body) chemotherapy improves the ability to treat cancer. Study participants must be 18 years or older and have ocular melanoma that has spread to the liver. Before enrolling in the study, they will undergo the following evaluations: a physical exam; x-rays; blood tests; electrocardiogram; computed tomography (CT) scan of the chest, abdomen and pelvis; and a magnetic resonance imaging (MRI) scan of the liver. The study includes a 15-minute quality-of-life questionnaire. Participants will complete the questionnaire 7 times over a period of 2 years to help investigators gauge their health status and progress. A laparotomy is done, which allows a surgeon to view the tumor in the liver through a small incision in the abdomen while the patient is under general anesthesia. Sometimes the tumor can spread outside the liver in a way that cannot be seen by pre-operative scans. When this happens, the participant is ineligible to continue in the study, since an important part of
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These are listed at www.ClinicalTrials.gov.
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the treatment is given only to the liver. If the laparotomy reveals that the participant is eligible for the remainder of the study, the participant will receive IHP treatment during the surgery. Plastic tubes called catheters are placed in the vein and artery that feed and drain the liver. This creates a separate blood supply for the liver alone. Heated chemotherapy is then given into the liver blood supply for one hour, while being carefully kept out of the rest of the body. After recovering from the surgery, eligible participants will receive a systemic chemotherapy called temozolomide for up to one year. This chemotherapy is taken by mouth in capsule form. Participants will be asked to return to NIH 10-11 times during the first year to evaluate their progress. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062933 •
CTLA-4 Antibody (MDX-010) Plus Interleukin-2 to Treat Advanced Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine the highest dose of MDX-010 that can safely be given in conjunction with interleukin2 (IL-2) to patients with advanced melanoma, and to examine its effectiveness against the cancer. MDX-010 is designed to increase immunity to cancer. It is a laboratory-produced antibody to the CTLA-4 protein found on certain lymphocytes (a type of white blood cell). When lymphocytes recognize a foreign substance, such as a virus or bacteria, they initiate an immune response to fight and control the infection. Once this is achieved, CTLA-4 proteins help stop the immune response, decreasing the number of immune cells against the virus or bacteria. When an immune response is mounted against tumor cells, however, it may be beneficial not to stop the immune response, but instead, to keep a large number of lymphocytes available to recognize and fight tumor cells. In this study, MDX-010 will be used to block CTLA-4 and maintain immune activity. IL-2 is a naturally occurring substance whose main function is to signal immune cells to become active. FDA has approved IL-2 for treating patients with advanced melanoma and kidney cancer. Patients 16 years of age and older with stage IV melanoma (melanoma that has spread to the lymph nodes or other sites) and whose tumor is not responding to standard treatments may be eligible for this study. Each candidate will be screened with a history, physical examination, blood test, and electrocardiogram (EKG). X-rays and scans will be done to evaluate the size and extent of their tumor, if current ones are not available. Participants will receive up to four MDX-010 treatments 21 days apart. Each treatment consists of a dose of MDX-010 given intravenously (through a vein) via a catheter (thin plastic tube) over 90 minutes. IL-2 will also be given after the second and third injection of MDX-010 through a small catheter over a 15-minute period every 8 hours for as many doses as are tolerated. In addition to treatment, patients will have the following tests and procedures: - Blood tests before and during the first injection of MDX-010 and blood tests before, during and for 6 days after the second injections of MDX-010 to measure levels of the antibody, and then blood tests every 21 days (every treatment visit) to examine the body's reaction to the treatment. -Leukapheresis to study the effects of treatment on the immune system. For this procedure, blood is drawn through a needle in an arm vein and circulated through a machine that separates the blood into its components (red cells, white cells,
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platelets, and plasma). The lymphocytes are extracted and the rest of the blood is returned to the patient through a needle in the other arm. Leukapheresis is done just before beginning treatment and may be repeated about three weeks after the fourth treatment. - Biopsy of normal skin and tumor or lymph node to examine the effects of antibody on the immune cells in the tumor. For this procedure, a needle is put into the skin or tumor and a small amount of tissue is pulled out with the needle. Biopsies are optional; they are not required for participation in the study. - Follow-up visit 3 weeks after the fourth treatment for a checkup examination, scans and X-rays, and blood tests. Patients will be watched closely for treatment side effects. Those who develop severe drug side effects, whose bodies develop an immune reaction against the MDX-010 antibody, or whose conditions worsen during treatment may be withdrawn from the study. Those whose tumors have stabilized or shrunk will continue follow-up visits. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055211 •
gp100 and MDX-CTLA4 Vaccination for Stage IV Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the safety and effectiveness of an experimental vaccine given with an immune booster to treat advanced melanoma. The vaccine contains peptides (pieces of proteins) of two gp100 proteins, which are produced by melanoma tumors. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptides. The vaccine will be given along with CTLA-4 antibody, an immune booster. Patients 16 years of age and older with melanoma that has spread from the primary site and does not respond to standard treatment may be eligible for this study. Candidates will be screened with a physical examination, eye examination, blood tests, electrocardiogram, and imaging studies (x-rays and scans) to check the size and extent of tumor, and lung function tests, if medically indicated. Because the vaccine formulation is based on tissue type, only patients with tissue type HLA-A*0201 may participate. Tissue type is determined by a blood test. Participants will receive CTLA-4 antibody, administered intravenously (IV) over 90 minutes through a catheter (plastic tube) placed in a vein. They will then be given four injections of the peptide vaccines in the thigh. The vaccination plus antibody treatments will be given four times-once every 3 weeks. Participants will have blood tests and physical examinations at each clinic visit to measure CTLA-4 antibody levels and look for changes in the blood that signal reactions to the vaccine or antibody, and to check for side effects. During the first injection of CTLA-4 antibody and for 6 hours after, six small blood samples will be taken to measure levels of the antibody. Once a day for 3 days after the first vaccine injection, and once a week for the next 3 weeks, a nurse will call the patient at home to check health status and drug side effects. Patients will also undergo plasmapheresis-a procedure to collect quantities of white blood cells-before treatment begins and possibly again 3 weeks after the second and fourth vaccinations. For this procedure, blood is drawn through a needle in the arm and circulated through a machine that spins it to separate the components. The white cells are removed and the plasma and red cells are
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returned to the patient through a needle in the other arm. Some patients may also have a biopsy of normal skin and tumor or lymph node tissue to examine the effects of the vaccine on the tumor immune cells. This involves drawing a small amount of tissue through a needle put in the skin. Patients will return to the clinic 3 weeks after the fourth vaccination for a follow-up examination and blood tests. Patients who experience severe side effects to the vaccine or develop an immune reaction against CTLA-4 antibody, or whose condition worsens with treatment, may be taken off the study. Patients whose disease has not progressed or whose tumor has shrunk may receive another course of four vaccinations, with continued follow-up if the disease improves. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029549 •
Hyperthermic Isolated Limb Perfusion and Melphalan with or without Tumor Necrosis Factor to Treat Advanced Melanoma in a Limb Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study, conducted by the American College of Surgeons Oncology Group, will examine the safety and effectiveness of adding tumor necrosis factor (TNF) to a regimen of hyperthermic isolated limb perfusion (ILP) plus chemotherapy for treating melanoma in an arm or leg. With ILP, chemotherapy is given in high concentrations directly into the main blood vessels supplying the affected limb. The drugs circulate through the blood vessels for a short time and are then flushed out of the body. Before giving the drugs, the blood in the limb is heated in a process called hyperthermia to enhance the drugs' effectiveness. The anti-cancer drug melphalan is used in standard hyperthermic ILP treatment. This study will see if adding TNF to the treatment regimen can enhance tumor shrinkage and prolong disease remission. It will also compare the side effects and long-term effects of the two treatments. Patients 18 years of age or older with advanced melanoma in an arm or leg may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, electrocardiogram, tumor biopsy, Computed Tomography (CT) imaging scans of the chest, abdomen, pelvis and brain, and a magnetic resonance imaging (MRI) scan of the brain. Whole body scans will be done, if needed. These tests will be done within 90 days of starting treatment. Participants will be randomly assigned to one of two treatment groups. Group 1 will receive ILP with hyperthermia using melphalan. Group 2 will receive ILP with hyperthermia using melphalan and TNF. All participants will receive hyperthermia under general anesthesia in the operating room. Tubes will be inserted into a vein in the neck or under the collarbone and then into blood vessels leading to the affected limb. A machine like the one used in open-heart surgery will circulate the blood and the drugs through these tubes during the procedure. A tourniquet will be placed on the limb to keep the drugs from entering the blood supply to the rest of the body. The blood from the limb will be heated to 102(Infinite) F to 105(Infinite) F (about the temperature of a hot tub) while it circulates through the machine. A radioactive chemical will be put in the blood to see how much of the drugs get into the blood supply and if any drug leaks to the rest of the body. In patients with melanoma in the leg, the lymph nodes in the groin will be removed if the cancer has spread to those nodes. In patients with melanoma in an arm, lymph nodes in
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the armpit will be removed whether or not they appear to contain cancer cells. Patients' heart and blood pressure will be monitored closely for 1 to 2 days, and total hospitalization time will be 4 to 8 days. In addition to treatment, patients will undergo the following tests before ILP and at various intervals after the procedure: Measurements, photographs and biopsies of tumor deposits in the affected limb; Ultrasound, CT scan or MRI of the affected limb for measurement of deep-lying tumors; - Referral to cardiologist for examination and tests, as needed, in patients 40 years old or older; - Pregnancy test for women of child-bearing potential. If needed, patients will have ultrasound of the limb within a few days after treatment to look for blood clots. Patients receiving TNF will have blood samples collected from the affected limb before and after TNF is given to measure TNF blood levels. Patients will be followed for the rest of their life to determine long-term effects of the study procedures. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056732 •
Immunotherapy After Surgery in Treating Patients With Breast Cancer, Colon Cancer, or Melanoma Condition(s): Breast Cancer; Colon Cancer; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Centro Oncologico de Excelencia Purpose - Excerpt: RATIONALE: Immunotherapy uses different ways to stimulate the immune system and stop cancer cells from growing. Immunotherapy biological extracts may be useful as adjuvant therapy in treating patients who have had surgery for breast cancer, colon cancer, or melanoma. PURPOSE: Phase III trial to study the effectiveness of Corynebacterium granulosum extract as maintenance immunotherapy following surgery in treating patients with breast cancer, colon cancer, or melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002455
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Isolated Limb Infusion of Chemotherapy in Treating Patients With Melanoma or Soft Tissue Sarcoma of the Arm or Leg That Cannot Be Removed By Surgery Condition(s): adult soft tissue sarcoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Infusing chemotherapy to the tumor area only may kill more tumor cells and cause less damage to healthy tissues. PURPOSE: Phase II trial to study the effectiveness of isolated limb infusion of chemotherapy in treating patients who have melanoma or soft tissue sarcoma of the arm or leg that cannot be removed by surgery. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004250 •
Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer Condition(s): acute leukemia; atypical chronic myeloid leukemia; Melanoma; myelodysplastic and myeloproliferative disease; Non-small cell lung cancer; ovarian epithelial cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian epithelial cancer, melanoma, acute myeloid leukemia, myelodysplastic syndrome, or non-small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039091
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Novel Adjuvants for Peptide-Based Melanoma Vaccines Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: This is a study to determine the efficacy of a melanoma vaccine chemotherapy cocktail composed of CTLA-4 antibody; tyrosinase, gp100, and MART-1 peptides; and incomplete Freund's adjuvant (IFA) with or without interleukin-12 in patients with resected stage III or IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028431
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Peptide Vaccination for Patients at High Risk for Recurrent Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the effectiveness and side effects of an experimental vaccine to prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes, and in patients who have had surgery for
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metastatic disease (cancer that has spread beyond the primary site). Melanoma tumors produce proteins called gp100 and MART-1. Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide. Patients 16 years of age and older whose melanoma has been surgically removed and who are currently free of disease may be eligible for this study. Candidates will be screened with a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other imaging studies will be done if recent results are not available. Some candidates may require heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In addition, all candidates will be tested for HLA tissue type; patients must be type HLA-A*0201, the type on which this vaccine is based. Participants will be randomly assigned to receive one of four different vaccines to determine which peptides offer the best immunity. Each treatment course consists of two injections of the vaccines every 3 weeks for four times. The injections are given under the skin of the thigh. After every other treatment course (every 6 months), patients will undergo a series of x-rays and scans to look for tumor. The immunizations may continue for up to 12 months as long as the melanoma does not return. The injections are given at the NIH Clinical Center. Patients are monitored for 1 hour after each injection and have blood tests and a physical examination to look for treatment side effects. Patients will be followed with blood tests every 12 weeks to monitor body functions. They will also undergo leukapheresis-a procedure to collect white blood cells-before starting treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect the action of the immune system cells. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the lymphocytes (white blood cells), and the rest of the blood is returned through a needle in the other arm. Some patients may undergo a biopsy-surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells. Patients whose disease returns during the first course of vaccine therapy will have surgery to remove the tumor and will continue to receive the vaccine treatment. Patients whose tumor returns after completing one course of therapy may receive a substance called interleukin-2 (IL-2), which can boost immune function against the tumor. IL-2 is given intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This regimen is repeated after 10 to 14 days. Those who respond to IL-2 will have a third course of treatment after 2 months. Patients whose disease recurs after treatment will be taken off the study and will be referred back to their referring physician or to another study, if an appropriate one is available. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059475 •
Phase II Trial of Allovectin-7(r) for Metastatic Melanoma Condition(s): Melanoma; Metastatic Melanoma; Malignant Melanoma; Skin Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Vical
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Purpose - Excerpt: The purpose of this clinical trial is to determine if Allovectin-7(r), an experimental gene-based immunotherapy, can shrink melanoma tumors. The trial will also examine if this treatment can improve the time to disease progression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044356 •
Study of Heat Shock Protein-Peptide Complex (HSPPC-96) versus IL-2/DTIC for Stage IV Melanoma Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Antigenics Purpose - Excerpt: The primary goal of this study is to determine if people with metastatic melanoma who receive Heat Shock Protein-Peptide Complex - 96 (HSPPC-96 or Oncophage) after surgery live longer than people who may or may not have surgery but who receive conventional chemotherapy including IL-2/DTIC. A second goal is to determine the safety and frequency of side effects in subjects who receive therapy with HSPPC-96. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039000
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Study of ILX651 in Patients with Recurrent or Metastatic Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): ILEX Products Purpose - Excerpt: This is a Phase II, non-randomized, open label study of ILX651 in patients with recurrent or metastatic melanoma after prior biological therapy. Approximately 60 patients will be enrolled in this study that is expected to last 18 months. All patients will be treated with ILX651 administered IV daily for 5 consecutive days once every 21 days. The primary objective of this study is to determine the overall response rate for recurrent or metastatic melanoma patients who are treated with ILX651. The secondary objectives are to determine the progression free survival at 18 weeks, duration of response, time to tumor progression, survival, safety/tolerability of ILX651 and to evaluate the pharmacokinetic profile. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068211
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Surgery vs. Chemotherapy in Patients with Stage IV Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will compare the effectiveness of surgery versus drug therapy in prolonging life and improving the quality of life of patients with stage IV melanoma. Currently, no treatment strategy can definitely improve the quality or length of life of patients with this advanced disease. Patients 16 years of age and older with metastatic melanoma (melanoma that has spread from the original site to other parts of the body) whose disease has worsened while receiving interleukin-2 (IL-2) therapy, or who are ineligible to receive high-dose IL-2 therapy may participate in this study. Candidates must have disease that can be treated surgically. Patients with primary ocular or mucosal melanoma are excluded from this study. Candidates will be screened with a medical history and physical examination, CT or MRI of the chest, abdomen and pelvis, MRI of the brain, PET imaging, blood and urine tests, EKG, review of pathology slides, and pregnancy testing for women capable of bearing children. Participants will be randomly assigned to one of the following treatment groups: Surgery Patients in this group will have all known tumors removed surgically. After surgery, they will have xrays every 3 to 6 months to check for new tumors. If the cancer recurs, repeat surgery will be considered, or chemotherapy with dacarbazine or cisplatin, or both, may be offered. Patients for whom these drugs are not appropriate will be advised of other research protocols that may be available. Chemotherapy Patients in this group will receive dacarbazine or cisplatin, or both, depending on their previous drug treatment. Chemotherapy will be given in 3-week cycles. Dacarbazine will be infused over 30 to 60 minutes through a catheter (plastic tube) placed in a vein. Infusions will be given on the first 3 days of each cycle. Cisplatin will also be given through a vein over 30 minutes on the first 3 days of each cycle. Patients receiving cisplatin will come to the Clinical Center the night before the infusions to receive intravenous fluids throughout the night, continuing until 3 hours after completing cisplatin in order to protect the kidneys from the effects of the chemotherapy. X-rays will be taken every 3 months to determine the response to treatment. Chemotherapy will continue until the tumors disappear or the side effects of the treatment become too severe. Patients whose tumors grow during treatment will be taken off the study and referred to another protocol if an appropriate one is available. Surgical removal of some or all of the tumors will be considered if they are causing significant problems. Patients in either group who stop treatment may be asked to return to NIH for follow-up evaluations every 3 to 4 months for 2 years and then every 6 months until the end of 5 years. Participants will also be asked to complete two quality of life questionnaires before beginning treatment and again at the 3-month, 6-month, and 12-month clinic visits. The questionnaires are designed to evaluate how people in this study feel, how well they are able to perform their usual activities, and how the treatment affects their general health and well-being. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068939
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Temozolomide, Thalidomide, and Lomustine in Treating Patients With Unresectable Stage III or Stage IV Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as temozolomide and lomustine, use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide and thalidomide with lomustine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and thalidomide with lomustine in treating patients who have unresectable stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072345
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Tyrosinase-Related Protein (TRP-2) Vaccination for Metastatic Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will test the safety and effectiveness of an experimental vaccine for fighting metastatic melanoma. The vaccine contains a peptide (piece of a protein) called tyrosinase-related protein-2 (TRP-2), which is made by some kinds of cancers. It also contains an oil-based liquid called Montanide ISA-51, another experimental substance, which is intended to boost the immune reaction to the peptide. Patients 16 years of age and older who have metastatic melanoma that does not respond to standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination, chest X-ray, electrocardiogram, blood and urine tests, and X-rays and scans to the evaluate the extent and size of the tumor. Because the vaccine formulation is based on tissue type, only patients with tissue type HLA-A*0201 may participate. Tissue type is determined by a blood test. Depending on the size and extent of tumor, participants will receive either the vaccine alone or the vaccine plus interleukin-2 (IL-2), a drug that boosts the immune reaction to the tumor. Patients who do not immediately require IL-2 will be randomly assigned to receive the vaccine either 1) once a week for 4 weeks, followed by a 3-week break, and then again once a week for 4 weeks; or 2) once every 3 weeks for four times. The vaccine is given as an injection (shot) in the thigh. A physical examination and blood tests will be done at each treatment visit to monitor side effects and any reaction to the vaccine. For patients receiving IL-2, this drug will be infused through a vein over 15 minutes every 8 hours for 4 days after each vaccine injection. They will be required to stay in the hospital for about one week during each treatment cycle. About 40 cc (8 teaspoons) of blood will be drawn every 3 weeks to monitor body functions. Patients will undergo leukapheresis to evaluate how the vaccine affects the action of lymphocytes-white blood cells of the immune system. For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed and the rest of the blood-red cells,
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platelets and plasma-is returned to the body through a second needle in the other arm. All patients will undergo leukapheresis just before beginning treatment. The procedure may be repeated after the fourth and eighth vaccines in patients receiving weekly injections, and after the second and fourth vaccine cycles in patients receiving injections every 3 weeks. Patients will return for follow-up studies after the fourth and eighth weekly injections, or after the second and fourth injections for those on the every-3weeks injection schedule. If the tumor has responded to the vaccine, the treatment may be repeated on the same schedule for up to 12 months, with continuing follow-up visits. Some patients may have a needle biopsy of normal skin and tumor or lymph node to examine the effects of the vaccine on the immune cells in the tumor. For this procedure, a needle is put into the skin or tumor and a small amount of tissue is withdrawn. Patients whose cancer progresses during treatment with the peptide vaccine alone may then receive IL-2 if their condition permits. In other studies with melanoma patients, those who received a peptide vaccine plus IL-2 had more tumor shrinkage than those receiving just vaccine alone or just IL-2 alone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017849 •
Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Southern California; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031733
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Vaccine Therapy and/or Sargramostim in Treating Patients With Locally Advanced or Metastatic Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. It is not yet
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known which treatment regimen is more effective for metastatic melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of peptide vaccine therapy and/or sargramostim in treating patients who have locally advanced or metastatic melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005034 •
Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage III or stage IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053391
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Vaccine Therapy With High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Illinois; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response that will kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with interleukin-2 in treating patients with metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003568
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Vaccine Therapy With or Without Sargramostim in Treating Patients With High-Risk or Metastatic Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI)
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Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells. PURPOSE: Randomized phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037037 •
Vaccine Treatment for Advanced Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the safety and effectiveness of treatment with an experimental vaccine for melanoma, a type of cancer that arises from pigmented areas, usually of the skin. Melanoma tumors produce a protein called gp100. Vaccination with this protein may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide. Patients 16 years of age and older with metastatic melanoma (melanoma that has spread beyond the original tumor site) that is not responding to conventional treatment may be eligible for this study. Candidates will be screened with a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other imaging studies will be done if recent results are not available. Some candidates may require heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In addition, all candidates will be tested for HLA tissue type. All patients will receive the gp100 protein vaccine. Patients who have tissue type HLA-A0201 will be randomly assigned to receive either 1) the gp100 protein alone, or 2) the gp100 protein plus gp100 peptide (a peptide is a part of the protein). Each treatment consists of four vaccine injections every 3 weeks for four times. The shots are given under the skin of the thigh. At each clinic visit, patients are monitored with blood tests and physical examinations to look for treatment side effects. Patients also undergo leukapheresis-a procedure to collect white blood cells-to evaluate how the vaccines affect the action of the immune system cells. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the lymphocytes (white blood cells), and the rest of the blood is returned through a needle in the other arm. In addition, some patients may undergo a biopsy-surgical removal of a small piece of tissue under local anestheticof normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells. Three to four weeks after completing the course of injections, patients have a physical examination and scans to evaluate the tumor's response to treatment. Patients whose tumors have stabilized or shrunk may continue immunizations for up to 12 months total (another 3 courses). Patients whose disease has not improved after the first course of therapy and who have not previously received high-dose interleukin-2 (IL-2) treatment may then be given protein plus peptide along with IL-2 if they meet the criteria for administration of IL-2. This substance may increase the immune reaction to the vaccine. IL-2 is given intravenously (through a small tube
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placed in a vein) every 8 hours for up to 4 days after each vaccine injection. It will be repeated every 3 weeks for four times (one treatment course). IL-2 therapy requires a 1week hospital admission. Patients whose tumors respond to this therapy may receive a total of four courses of vaccinations plus IL-2. Patients whose disease does not respond to therapy or recurs after treatment will be taken off the study and will be referred back to their referring physician or to another study, if an appropriate one is available. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069043 •
Chemotherapy Plus Bone Marrow Transplantation in Treating Patients With Metastatic Melanoma Condition(s): Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Louisiana State University Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Clinical trial to study the effectiveness of chemotherapy plus bone marrow transplantation in treating patients with metastatic melanoma that has not responded to previous therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003060
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Combination Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy consisting of acetaminophen plus carmustine in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003346
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Combination Chemotherapy, Interferon alfa, and Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of the cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known which treatment regimen is more effective in treating melanoma. PURPOSE: Randomized phase II trial to compare the effectiveness of two regimens of combination chemotherapy plus interferon alfa and interleukin-2 in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002669
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Flavopiridol in Treating Patients With Metastatic Malignant Melanoma Condition(s): Stage IV Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of flavopiridol in treating patients who have metastatic malignant melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005971
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Interferon alfa and Thalidomide in Treating Patients With Stage IV Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Interferon alfa may interfere with the growth of cancer cells and slow the growth of the tumor. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining interferon alfa with thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of interferon alfa and thalidomide in treating patients who have stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026520
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Melanoma Vaccine With or Without Sargramostim in Treating Patients With Stage IV Malignant Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Mayo Clinic Cancer Center Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. PURPOSE: Randomized phase I trial to compare the effectiveness of melanoma vaccine with or without sargramostim in treating patients who have stage IV malignant melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006243
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Phase I Study of gp75 Vaccine in Patients with Stage III and IV Melanoma Condition(s): Malignant Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): ImClone Systems; Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: Up to 24 patients with stage III or stage IV melanoma will be enrolled. Patients who are currently disease-free but at high risk for relapse are also eligible. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are eligible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034554
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Temozolomide and Thalidomide in Treating Patients With Stage III or Stage IV Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of melanoma by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness temozolomide plus thalidomide in treating patients who have stage III or stage IV melanoma that cannot be removed during surgery. Phase(s): Phase I; Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005815 •
Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain Condition(s): Stage IV Melanoma; Recurrent Melanoma; brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00020839
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Thalidomide and SU5416 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Texas Purpose - Excerpt: RATIONALE: Thalidomide combined with SU5416 may stop the growth of metastatic melanoma by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and SU5416 in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017316
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Vaccine Therapy Followed by Biological Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): University of Southern California; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from melanoma cells may make the body build an immune response to kill tumor cells. Biological therapies such as interferon gamma and interleukin-2 use different ways to stimulate the immune system and stop cancer cells from growing. Combining vaccine therapy with biological therapy
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may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of vaccine therapy, interferon gamma, and interleukin-2 in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006113 •
Vaccine Therapy in Treating Patients Who Have Stage II, Stage III, or Stage IV Melanoma Condition(s): Stage IV Melanoma; stage II melanoma; stage III melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Genzyme Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage II, stage III, or stage IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010309
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Vaccine Therapy in Treating Patients With Melanoma of the Eye Condition(s): ciliary body and choroid melanoma, medium/large size Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group; EORTC Ophthalmic Oncology Task Force Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells and decrease the recurrence of melanoma of the eye. PURPOSE: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who are at high risk for recurrent melanoma of the eye. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036816
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Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma Condition(s): Stage IV Melanoma; stage III melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Genzyme Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells combined with melanoma antigens may make the body build an immune response to
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tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Combining vaccine therapy with interleukin-2 may be an effective treatment for stage III or stage IV melanoma. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have stage III or stage IV melanoma that cannot be surgically removed. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004025 •
Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002786
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Comparison of Two Kinds of Dendritic Cell Immunizations in Treating Melanoma Condition(s): Melanoma; Neoplasm Metastasis Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will look at the safety and effectiveness of immunizations derived from two different substances in fighting melanoma. Both immunizations will contain dendritic cells-a type of cell that boosts immune system activity-but the cells will be produced by two different methods and their effects on the immune response compared. The body normally produces small amounts of dendritic cells, but large numbers of these cells can be made in the laboratory. In this study, one group of patients will receive dendritic cells derived from a type of white blood cell called monocytes, and a second group will receive cells derived from what are called stem cells. Small amounts of protein substances called gp100 and MART-1 that are found in most melanoma cells will be added to both types of dendritic cells. These protein substances may provoke the immune system to attack the tumor cells in much the same way a vaccine works. Patients in both groups will receive four cycles of immunizations four weeks apart. In the first two cycles, the cells will be injected into lymph vessels, and in the next two, they will be injected under the skin. Patients will also undergo apheresis-a procedure in which whole blood is drawn much like donating blood, but the lymphocytes are separated out by a machine and the rest of the blood is then returned to the body. This procedure may be repeated from two to four times during the study, depending on which immunization group the patient is in. Some patients may be asked to have a
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lymph node biopsy (removal of a few lymph nodes) to examine the effects of the dendritic cells. Some patients may also receive injections of a drug to boost white cell production. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001825 •
Comparison Study of MDX-010 (CTLA-4) Alone and Combined with DTIC in the Treatment of Metastatic Melanoma Condition(s): Melanoma Study Status: This study is completed. Sponsor(s): Medarex Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050102
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Detection of Melanoma Markers in Lymph Nodes or Peripheral Blood of Patients With Melanoma Condition(s): stage I melanoma; stage II melanoma; stage III melanoma; Stage IV Melanoma Study Status: This study is suspended. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Diagnostic procedures may improve the ability to detect the presence or recurrence of disease. PURPOSE: Diagnostic trial to detect melanoma markers in the lymph nodes or peripheral blood of patients who have melanoma. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004153
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Flt3L and CD40L to Treat Metastatic Melanoma and Kidney Cancer Condition(s): Melanoma; Renal Cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The purpose of this study is to find the largest dose of CD40 L that can be given safely with Flt3L in patients with kidney cancer or metastatic melanoma (melanoma that has spread beyond the original site). Each drug alone has been used safely, but the two have not been used in combination before this study. Flt3L increases the number of a type of immune cell called dendritic cells, which are known to enhance the immune response. CD40L works to activate the response of these cells. Patients 16
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years of age and older with metastatic melanoma or kidney cancer that cannot be cured with conventional treatments such as surgery, radiation therapy and chemotherapy may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, chest X-ray, electrocardiogram, and X-rays and scans to evaluate disease status. Participants will have an injection of Flt3L under the skin every day for 14 days. (Patients or a caregiver will be taught how to administer the injections.) On the 12th day of treatment, patients will also begin receiving CD40L under the skin, for 5 days. If the patients starting at this lowest dose of CD40L do not experience any significant side effects, the dose will be increased for the next group of patients. The dose will be increased a third time if patients in the second group do not have significant side effects. The treatment cycle may be repeated after 28 days from the start of the injections. Patients will undergo leukapheresis to collect white blood cells before beginning treatment and again around day 17. For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm. Patients will be evaluated with a physical examination, X-rays and scans after two cycles for the response to treatment. Patients whose tumors shrink and patients with a mixed response (i.e., some tumors shrink and others enlarge) may be offered up to a total of 6 treatment cycles. Patients whose disease remains stable or worsens will stop Flt3L and CD40 and may be offered treatment with interleukin-2, a substance that may boost the body's immune response to the tumor. Patients will have frequent blood tests. Some patients may have a skin biopsy to evaluate the effects of Flt3L and CD40L. For the biopsy, a small area of skin is numbed with an anesthetic and less than one-quarter inch of skin is removed for study under the microscope. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012532 •
gp100 and MART-1 Peptide Vaccine for Metastatic Ocular Melanoma Condition(s): Melanoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the effectiveness and side effects of an experimental vaccine to treat ocular metastatic melanoma. Melanoma tumors produce proteins called gp100 and MART-1. Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide. Patients 16 years of age and older with progressive metastatic ocular melanoma and for whom standard treatments no longer work may be eligible for this study. Candidates will be screened with a complete physical and examination, including an eye examination, blood and urine tests, chest X-ray, electrocardiogram, X-ray and nuclear medicine imaging scans to evaluate the size and extent of tumor, and, if needed, a cardiac stress test and lung function test. In addition, patients will be tested for their HLA tissue type; patients must be type HLA-A*0201, the type on which this vaccine is based. Participants will receive two injections of both peptide vaccines (a total of four shots) in the thigh each week for 4
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weeks. Some patients may undergo a biopsy -surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells. Patients will also undergo plasmapheresis-a procedure to collect white blood cells-before treatment begins, after the second vaccination and 3 weeks after the fourth vaccination. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the white cells (immune system cells), and the rest of the blood is returned through a needle in the other arm. Patients return for follow-up 3 to 4 weeks after the fourth injection. Patients in whom disease has not progressed or whose tumor has shrunk may receive additional 4-week treatment courses for up to 6 courses (24 immunizations). Patients whose tumor has not responded to therapy and who are physically eligible to receive a substance called interleukin-2 (IL-2) may receive a second series of vaccines together with this agent. IL-2 may boost the immune response to the peptides. It is given intravenously (through a small tube placed in a vein) every 8 hours for 5 days after each vaccination. Patients who respond to the vaccine and IL-2 may be offered additional courses of this treatment regimen. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009516 •
Pyrazoloacridine in Treating Patients With Metastatic Skin or Eye Melanoma Condition(s): ciliary body and choroid melanoma, medium/large size; Stage IV Melanoma; extraocular extension melanoma; recurrent intraocular melanoma; iris melanoma; Recurrent Melanoma; ciliary body and choroid melanoma, small size Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of pyrazoloacridine in treating patients who have metastatic skin or eye melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003802
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Stem Cell Transplant for Malignant Melanoma Condition(s): Graft vs Host Disease; Melanoma; Neoplasm Metastasis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Malignant melanoma is an uncontrolled growth of melanocytes, the cells which normally give pigment to the skin. These cancerous cells can spread (metastasize) from the original kidney tumor site to other organs such as the bones, lymph nodes, liver, lungs, and brain. Once these organs become involved, the uncontrolled growth of cells can lead to organ failure and death. There are several
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treatments available for malignant melanoma that can be successful. However, once malignant melanoma has spread to other organs, it is rarely curable. Surgery can be used to treat malignant melanoma but in many patients the disease has spread too much to be removed by surgery. Medical treatment with chemotherapy can be used to treat malignant melanoma, but it has been relatively unsuccessful for patients whose cancer has spread to other organs. Autologous bone marrow transplants (BMT) have been studied for the treatment of metastatic melanoma. This form of therapy is where marrow cells or stem cells are collected from the patient and used to rescue bone marrow function after very high doses of chemotherapy. The effects of this kind of therapy do not last long and do offer any survival advantage over treat with standard chemotherapy. Allogenic bone marrow transplants (BMT) have been used to treat cancers of the blood and bone marrow. Allogenic transplants are cells collected from relatives of the patient. However, allogenic BMTs are usually combined with powerful doses of chemotherapy and radiation therapy. These additional treatments are associated with toxic side effects, often making BMTs too dangerous to attempt in many patients. Researchers are interested in learning more about the potential benefits of modified bone marrow transplant (allogenic stem cell transplantation) for patients with advanced malignant melanoma. In this study researchers plan to treat patients with advanced malignant melanoma with transplanted stem cells from a genetically matched brother or sister. These stem cells are healthy cells collected from the bone marrow of the patient's relative. Once the stem cells are transplanted they help to make new blood cells. In addition, immune factors found in the transplant can work to destroy cancerous cells. In order to avoid the toxic side effects normally associated with BMT, the stem cell transplant will be combined with low intensity chemotherapy. The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001739 •
Vaccine Plus Interleukin-2 in Treating Patients With Advanced Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Melanoma vaccine plus interleukin-2 may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2 in treating patients who have advanced melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005949
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Vaccine Therapy in Treating Patients With Melanoma Condition(s): stage I melanoma; stage II melanoma; stage III melanoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Earle A. Chiles Research Institute Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of two different regimens of melanoma vaccine in treating patients who have melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003895
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Vaccine Therapy in Treating Patients With Stage II or Stage III Melanoma That Has Been Surgically Removed Condition(s): stage II melanoma; stage III melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Rockefeller University Purpose - Excerpt: RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage II or stage III melanoma that has been surgically removed. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045383
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Vaccine Therapy Using Melanoma Peptides for Cytotoxic T Cells and Helper T Cells in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of four different vaccines using melanoma peptides for cytotoxic T cells and helper T cells in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071981
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “melanoma” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON MELANOMA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “melanoma” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on melanoma, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Melanoma By performing a patent search focusing on melanoma, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on melanoma: •
2-phenyl-4-quinazolinone compounds, 2-phenyl-4-alkoxy-quinazoline compounds and their pharmaceutical compositions Inventor(s): Hour; Mann-Jen (Taichung, TW), Huang; Li-Jiau (Taichung, TW), Kuo; Sheng-Chu (Taichung, TW), Lee; Kuo-Hsiung (Chapel Hill, NC) Assignee(s): National Science Council (Taipei, TW) Patent Number: 6,479,499 Date filed: June 28, 2000 Abstract: Two series of 6,7,2',3',4',5'-substituted 2-phenyl-4-quinazolinones and 6,2',3',4',5'-substituted 2,3-dihydro-2-phenyl-4-quinazolinones are synthesized and evaluated for cytotoxicity against a panel of human tumor cell lines, such as epidermoid carcinoma of the nasopharynx (KB), lung carcinoma (A-549), ileocecal carcinoma (HCT8), breast cancer (MCF-7), melanoma (SKMEL-2), ovarian cancer (1A9), glioblastoma (U87-MG), bone (HOS), P-gp-expressing epidermoid carcinoma of the nasopharynx (KBVIN), and prostate cancer (PC3) cell lines, and some of the compounds are found potent. The present invention also synthesizes 2-phenyl-4-alkoxy-quinazoline compounds, wherein some of the compounds exhibit antiplatelet activity. Excerpt(s): The present invention relates to a series of substituted 2-phenyl-4quinazolinones compounds and substituted 2-phenyl4-alkoxy-quinazoline compounds; and in particular to their uses in treating human cancers and in inhibiting platelet aggregation. Microtubules provide an important framework defining cellular morphology and are essential in the division and transport of cellular chromosomes. Consequently, the microtubule has become an important target for the design of new antimitotic anticancer agents. The antimitotic agents currently in clinical use include vinca alkaloids [Rowinsky, E. K.; Donehower, R. C. The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol. Ther. 1992, 52, 3584], which inhibit microtubule polymerization, and taxoids, which promote microtubule assembly [Verweij, J.; Clavel, M.; Chevalier, B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann. Oncol. 1994, 5, 495-505]. Colchicine is another well-known antimitotic agent; however, being too toxic to be used as anticancer agent, it is used clinically only as an antigout agent [Hastie, S. B. Interactions of colchicine with tubulin. Pharmacol. Ther. 1991, 51, 377-401; Brossi,A; Yeh, H. J.; Chrzanowska, M.; Wolff, J.; Hamel, E.; Lin, C. M.; Quinn, F.; Suffness, M.; Silverton, J. Colchicine and its analogues: recent findings. Med. Res. Rev 1988, 8, 77-94]. Among these three types of heterocyclic ketones, the common structural feature is a biaryl system composed of Aand C-rings that are linked by an interposed B-ring or sometimes by a hydrocarbon bridge. However, some minor structural differences also exist. Web site: http://www.delphion.com/details?pn=US06479499__
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Acidic composition of matter for use to destroy microorganisms Inventor(s): Cummins; Barry W. (1203 Egret Ave., Fort Pierce, FL 34982) Assignee(s): none reported Patent Number: 6,242,011 Date filed: August 5, 1999 Abstract: A composition of matter and the method of making that provides a low pH acidic composition that is useful for destroying microorganisms that are undesirable and useful for destroying or reducing melanoma on human skin. The composition and method include sulfuric acid combined with distilled water and ammonium sulfate under at least 15 psi pressure in a pressurized container, all of which is heated to approximately 800.degree. F. or more for at least 3 hours. The final cooled mixture is stabilized with 10 percent of the original mixture. The resultant composition is useful for preserving food, such as fresh fish, and for skin treatment of melanoma. Excerpt(s): This invention relates to a composition of matter and the method of making improved acidic compositions that are useful for the treatment of killing bacteria or other potentially toxic cells, including disease cells, and specifically to an improved composition of matter and the method of making that can be used as a bactericide, fungicide, viricides, and for the treatment of skin diseases. The use of acids and acidic chemicals for killing deleterious organic organisms, such as bacteria, germs, and viruses is well known in the art. Chlorine or hydrochloric acid is especially useful as a bactericide and is used universally as a cleaning agent. Bacteria plays an important role in the deterioration of human foodstuffs. Foods such as fish are particularly susceptible to rapid deterioration, especially at room temperature, and compounds for the preservation of foods or the retardation of bacteria growth have been employed in the past. One of the problems with such compounds is that in certain increased levels, they can be toxic to human beings, thereby defeating the purpose of preserving the foodstuffs. Web site: http://www.delphion.com/details?pn=US06242011__
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Antagonists of alpha-melanocyte stimulating hormone and methods based thereon Inventor(s): Jayawickreme; Channa K. (2803 Bainbridge Dr., Durham, NC 27713), Lerner; Michael R. (27 Jayne La., Hamden, CT 06514), Quillan; J. Mark (1624 Yale Station, New Haven, CT 06526) Assignee(s): none reported Patent Number: 6,602,856 Date filed: January 17, 1995 Abstract: Peptide antagonists of.alpha.-melanocyte stimulating hormone are disclosed, together with methods of inhibiting the effects of.alpha.-melanocyte stimulating hormone on cells or tissues sensitive to that hormone. In particular, methods for lightening the pigmentation of skin and for treating malignant melanoma, as well as kits for practicing the invention are also disclosed. Excerpt(s): The present invention provides peptide antagonists of.alpha.-melanocyte stimulating hormone and methods of inhibiting the effects of.alpha.-melanocyte stimulating hormone on cells or tissues sensitive to that hormone, including lightening skin, modulating the immune response and treating malignant melanoma. Skin
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pigmentation and tanning are related to the amount and distribution of melanin in epidermal melanosomes. The epidermis cell population includes keratinocytes and the melanocytes that supply the keratinocytes with melanosomes, i.e., melanin containing pigment granules, via dendritic processes. Melanin is a dark pigment that is produced by the oxidation of tyrosine to dopa and dopaquinone by the enzyme tyrosinase, to produce compounds that polymerize to form melanin. There are a number of localized hyperpigmentation disorders that presently lack any safe and effective method of cosmetic treatment. These include pigmented spots such as ephelides (freckles), solar lentigines (also called liver spots), acanthosis nigricans (a hypermelanotic disorder), cafe-au-lait spots, nevi (moles), and melasma (localized post-partum darkening of the skin). There is also a continuing interest and need for a method for regulating pigmentation tone for the total skin surface, either for cosmetic purposes, e.g., to lighten the complexion, or to block the deleterious effects on the appearance caused by certain endocrine disorders. Heretofore, no safe and effective method for achieving the regulation of epidermal pigmentation tone has been available. Web site: http://www.delphion.com/details?pn=US06602856__ •
Compositions and methods of treating cancer using compositions comprising an inhibitor or endothelin receptor activity Inventor(s): Lahav; Ronit (Venice, CA), Patterson; Paul H. (Altadena, CA) Assignee(s): California Institute of Technology (Pasadena, CA) Patent Number: 6,545,048 Date filed: September 23, 1999 Abstract: Described herein are results which show that an endothelin receptor antagonist, BQ788, increases pigmentation and significantly reduces the viability of 7 human melanoma cell lines in culture. Moreover, it is described herein that administration of BQ788 significantly slows melanoma tumor growth in nude mice, including a complete growth arrest in half of the mice treated systemically. Thus, inhibitors of endothelin receptor activity are described herein as beneficial for the treatment of cancer. Excerpt(s): One-third of all individuals in the United States alone will develop cancer. Although the five year survival rate has risen dramatically nearly fifty percent as a result of progress in early diagnosis and therapy, cancer still remains second only to cardiac disease as a cause of death in the United States. Twenty percent of Americans die from cancer, half due to lung, breast, and colon-rectal cancer. Moreover, skin cancer remains a health hazard. Designing effective treatments for patients with cancer has represented a major challenge. The current regimen of surgical resection, external beam radiation therapy, and/or systemic chemotherapy has been partially successful in some kinds of malignancies, but has not produced satisfactory results in others. One approach to treating cancer has been to induce apoptosis (cell death) of targeted tumor cells; therefore, mechanisms inducing apoptosis are of interest. One such mechanism has been reported where the Fas ligand, (FasL) (also known as CD95L and APO-IL), a cell surface molecule belonging to the tumor necrosis factor family, induces apoptosis of Fas-bearing tumor cells. Seino, et al., Nature Med., 3(2):165 (1997). In another approach, cancer cell lines have been characterized. For example, it has been reported that all human melanoma lines tested in a number of studies express endothelin B-receptor (ETRB) (Yohn, et al., Biochem. Biophys. Res. Commun., 201:449-57 (1994); Kikuchi, et al., Biochem. Biophys. Res. Commun., 219:734-9 (1996); Ohtani, et al., Biochem. Biophys.
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Res. Commun., 234:526-30 (1997); Zhang, et al., Brit. J. Cancer, 78:1141-6 (1988)); moreover, expression is correlated with their differentiation state. Increased endothelin A-receptor (ETRA) expression is associated with induced differentiation of A375 melanoma cells, while they predominantly express ETRB in their malignant state (Ohtani, et al., Biochem. Biophys. Res. Commun., 234:526-30 (1997)). Unfortunately, the roles of endothelin receptors (ETRs) is not clear from previous studies. While one report indicates that endothelin-1 (ET1), acting through the ETRB, mediates mitogenic and chemokinetic effects on melanoma cells (Yohn, et al., Biochem. Biophys. Res. Commun., 201:449-57 (1994)), another report suggests other mechanisms for ET1 (Okazawa, et al., J. Biol. Chem., 273:12584-92 (1998)). Moreover, at least in one study, the focus of ETRB has been in regards to hypertension (Hashimoto, et al., Biol. Pharm. Bull., 21(8):800-804 (1998)). Additionally, endothelin-3 (ET3) has been reported on, however, many such reports are regarding developing non-malignant (normal) cells (Lahau, et al., PNAS, 93:3892-7 (1996)). Web site: http://www.delphion.com/details?pn=US06545048__ •
Compositions for preserving haptenized tumor cells for use in vaccines Inventor(s): Berd; David (Wyncote, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,248,585 Date filed: November 16, 1999 Abstract: A composition comprising an isotonic, buffered aqueous medium containing an optimized concentration of human serum albumin has been found to stabilize irradiated, haptenized tumor cells stored for some period of time after haptenization. In specific embodiments, the viability of the haptenized tumor cells stored in a composition of the invention ranged from about 60% to about 100% greater than the cell viability of cells stored in a prior art solution. In a specific embodiment, 1% human serum albumin in Hank's Buffered Salt Solution was found to stabilize haptenized melanoma cells. Methods of storing haptenized tumor cells and vaccine preparations are also provided. Excerpt(s): The invention relates to compositions comprising a haptenized tumor cell and human serum albumin (HSA) effective to stabilize the haptenized tumor cells in an aqueous buffer. In blood transfusion, bone marrow transplantation, or other cell cultures ex vivo, one of the principal problems encountered is that of the preservation of cells. It is critical to be able to preserve cells, under good conditions of viability, for time periods compatible with clinical production and storage, and to make it possible to analyze cell preparations. The most commonly used method of long-term preservation of cells is to freeze and thaw the material. However, during the freezing of cells, loss of viability may occur. This problem can be even more complex when the cells have been modified or altered prior to preservation, and when the cells are obtained by proteolytic digestion of a tissue or tumor specimen. Furthermore, preservation of cells on ice (about 0.degree. C.), refrigerated (about 4.degree. C.), or at room temperature, prior to use, is also difficult. Human serum albumin is a non-glycosylated monomeric protein consisting of 585 amino acid residues, with a molecular weight of 66 kD. Its globular structure is maintained by 17 disulfide bridges, which create a sequential series of 9 double loops (Brown, "Albumin structure, function and uses", Rosenoer, V. M. et al. (eds.), Pergamon Press, Oxford, pp. 27-51, 1977). The genes encoding for HSA are known to be highly polymorphic, and more than 30 apparently different genetic variants have been identified by electrophoretic analysis (Weitkamp, et al., Ann. Hum.
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Genet., 37:219-226, 1973). The HSA gene comprises 15 exons and 14 introns comprising 16,961 nucleotides, from the supposed "capping" site up to the first site of addition of poly(A). Web site: http://www.delphion.com/details?pn=US06248585__ •
Continuous adherent melanocyte cell line Inventor(s): Alexander; Jeannine (Clifton Park, NY), Cox; William I. (East Greenbush, NY) Assignee(s): Aventis Pasteur Limited (North York, CA) Patent Number: 6,541,250 Date filed: April 18, 2001 Abstract: The present invention comprises a novel immortal non-adherent human melanocyte cell line, designated WC-1 14.07. This cell line is stable and MHC class I negative. This continuous melanocyte cell line can be used as a source of melanin and hgp100. The Class I MHC-negative nature of this cell line allows it to be used as a target for transfection with MHC class I genes, providing a novel source of hgp100 in a predetermined MHC context. The cell line can thus be used in a variety of ways, directly or indirectly, in the development and manufacture of vaccines for melanoma. Excerpt(s): The present invention relates to the field of melanocyte cell lines. Melanocytes and melanoma cells express melanogenisis-related proteins (Orlow et al. 1995; del Marmol & Beerman, 1996). These proteins contribute to the antigenicity of melanomas, making them attractive targets for cancer vaccines. Hgp100 is a melanomaassociated glycoprotein antigen that is closely related to the melanogenesis-related protein pmel17. These proteins differ at the genetic level by an in frame deletion of a 21 base pair sequence in hgp100 (Adema et al. 1994). For purposes of this disclosure, gp100 and pmel17 are used interchangeably. Web site: http://www.delphion.com/details?pn=US06541250__
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Cribrostatins 3-5 Inventor(s): Knight; John C. (Phoenix, AZ), Pettit; George R. (Paradise Valley, AZ) Assignee(s): Arizona Board of Regents (Tempe, AZ) Patent Number: 6,437,128 Date filed: February 16, 2001 Abstract: The blue marine sponge Cribrochalina sp., collected in the Republic of Maldives was found to contain new cell growth inhibitors denominated cribrostatin 3, cribrostatin 4 and cribrostatin 5 which were found to be active against the NCI human melanoma panel and the P388 marine lymphocytic cell lines employed by the U.S. National Cancer Institute. Structural determination of all three substances were accomplished utilizing high yield NMR (400 MHz) and mass spectral studies. Cribrostatins 3-5 were also found to possess significant antibacterial and antifungal activity. Excerpt(s): The present invention relates generally to the isolation and structural elucidation of new compounds herein denominated Cribrostatin 3, Cribrostatin 4 and
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Cribrostatin 5, which are obtained from Cnbrochalina sp., (Niphatidae faily, Haplosclerida order, Demospongiae class) found off of remote islands in the Republic of Maldives. In early research devoted to the first systematic investigation of marine animals as new sources of potential anticancer drugs, the phylum Porifera rapidly became of increasing importance. Subsequent detection of antineoplastic activity in some of these sponge species led to the isolation of such cell growth inhibitory compounds, as macrocyclic lactones, pyrroles, peptides and proteins. Meanwhile the isolation of heterocyclic marine sponge constituents such as pyrroles, imidazoles, oxazoles, indoles, pyndines, quinolizidines, pteridines, acridines, other nitrogen systems and quinones has been rapidly accelerating. So far ten isoquinolinequinones have been isolated from blue species of the sponge genera Reniera and Xestospongia. In 1986, an exploratory survey of marine Porifera off remote islands in the Republic of the Maldives was conducted which located a deep blue colored specimen of Cribrochaina sp. (Haplosclerida order) that afforded an orange ethanol extract. The encrusting sponge was found in areas of strong (and dangerous) currents to -45 m in the South side of East reef passages and yielded an ethanol extract that provided 40% life extension (at mg/kg) against the U.S. National Cancer Institute's in vio murine P388 lymphocytic leukemia (PS system). Bioassay directed isolation using the in vitro PS leukemia led to the discovery of new cytostatic isoquinoline-quinones designated cribrostatin 1 and cribrostatin 2, described and claimed in U.S. Pat. No. 5,514,689. Continued investigation of cancer cell growth inhibitory constituents of the blue marine sponge Cribrochalina sp. has led to the further discovery of cribrostatins 3 (4a), 4 (5), and 5 (4b) in 10.sup.-5 to 10.sup.-7 percent yields. The structure of cribrostatin 3 (4a) was determined by results of high field (500 MH).sup.1 H- and.sup.13 C-nmr and high resolution mass spectral interpretations. The same general approach to the structures of cribrostatins 4 (5) and 5 (4b) was completed by x-ray crystal structure determinations. Cribrostatins 3,4 and 5 provided significant cancer cell line inhibitory activities. In addition, the newly isolated cribrostatins 3,4 and 5 also display antibacterial and/or antifungal activities. Web site: http://www.delphion.com/details?pn=US06437128__ •
Detection of chromosome copy number changes to distinguish melanocytic nevi from malignant melanoma Inventor(s): Bastian; Boris (San Francisco, CA), Pinkel; Daniel (Walnut Creek, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,261,775 Date filed: April 9, 1999 Abstract: The present invention provides for methods of distinguishing melanocytic nevi, such as Spitz nevi, from malignant melanoma. The methods comprise contacting a nucleic acid sample from a patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region such as 11p, which is usually amplified in Spitz nevi. The nucleic acid sample is typically from skin tumor cells located within a tumor lesion on the skin of the patient. Using another probe which binds selectively to a chromosomal region such as 1q, 6p, 7p, 9p, or 10q, which usually show altered copy number in melanoma, the method can determine that those tumor cells with no changes in copy number of 1q, 6p, 7p, 9p, or 10q, are not melanoma cells but rather Spitz nevus cells. The finding of amplifications of chromosome 11p would be an additional indication of Spitz nevus.
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Excerpt(s): The melanocyte can give rise to a plethora of morphologically different tumors. Most of them are biologically benign and are referred to as melanocytic nevi. Examples of melanocytic nevi are congenital nevi, Spitz nevi, dysplastic or Clark's nevi, blue nevi, lentigo simplex, and deep penetrating nevus. Pigmented spindle cell nevus is regarded as a subset of Spitz nevi. Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment is of great importance because advanced melanoma has a poor prognosis, but most melanomas are curable if excised in their early stages. While clinicians make the initial diagnosis of pigmented lesions of the skin, pathologists make the final diagnosis. Although, in general the histopathological diagnosis of melanoma is straightforward, there is a subset of cases in that it is difficult to differentiate melanomas from benign neoplasm of melanocytes, which have many variants that share some features of melanomas (LeBoit, P. E. STIMULANTS OF MALIGNANT MELANOMA: A ROGUE'S GALLERY OF MELANOCYTIC AND NON-MELANOCYTIC IMPOSTERS, In Malignant Melanoma and Melanocytic Neoplasms, P. E. Leboit, ed. (Philadelphia: Hanley & Belfus), pp. 195258 (1994)). Even though the diagnostic criteria for separating the many simulators of melanoma are constantly refined, a subset of cases remains, where an unambiguous diagnosis cannot be reached (Farmer et al., DISCORDANCE IN THE HISTOPATHOLOGIC DIAGNOSIS OF MELANOMA AND MELANOCYTIC NEVI BETWEEN EXPERT PATHOLOGISTS, Human Pathol. 27: 528-31 (1996)). The most frequent and important diagnostic dilemma is the differential diagnosis between Spitz nevus, a neoplasm composed of large epithelioid or spindled melanocytes, and melanoma. Misdiagnosis of Spitz nevus as melanoma and vice versa has been repeatedly reported in the literature (Goldes et al., Pediatr. Dermatol., 1: 295-8 (1984); Okun, M. R. Arch. Dermatol. 115: 1416-1420 (1979); Peters et al., Histopathology, 10, 1289-1302 (1986)). A retrospective study of 102 melanomas of childhood found that only 60 cases were classified as melanoma by a panel of experts, the majority of the remainder being classified as Spitz nevi (Spatz, S., Int. J. Cancer 68, 317-24 (1996)). The hazard of mistaking a Spitz nevus for melanoma can be severe and traumatic: The patients may be subjected to needless surgery, unable to plan for the future, and psychologically traumatized. For obvious reasons, the misdiagnosis of a melanoma as a benign nevus can have even more dramatic consequences. The presence of this diagnostic gray zone has even led the authors of a review article in the "Continuing Medical Education" section of the Journal of the American Association of Dermatology to conclude that Spitz nevus and melanoma may "actually exist on a continuum of disease" (Casso et al., J. Am. Acad. Dermatol., 27, 901-13 (1992)). The authors recommended that "treatment include complete excision of al Spitz nevi followed by reexcision of positive margins if present." The need for improved diagnostics for melanocytic neoplasms has led to numerous attempts to improve diagnostic accuracy by the use of markers that could be detected by immuno-histochemistry. While there have been prior efforts aimed at resolving this problem, none have been satisfactory. For example, even though tests employing markers such as S 100, HMB45 are useful in establishing that a poorly differentiated tumor is of melanocytic lineage, adjunctive techniques have been of little help in separating benign from malignant melanocytic lesions. Web site: http://www.delphion.com/details?pn=US06261775__
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Detection of loss of heterozygosity in tumor and serum of melanoma patients Inventor(s): Hoon; Dave S. B. (Los Angeles, CA) Assignee(s): John Wayne Cancer Institute (Santa Monica, CA) Patent Number: 6,465,177 Date filed: October 26, 1998 Abstract: A method is provided for assessing allelic losses on specific chromosomal regions in melanoma patents. The method relies on the evidence that free DNA may be released in the plasma/serum of cancer patients allowing the detection of DNA with LOH in the plasma/serum of cancer patients by analysis for microsatellite markers. The amount of and specific allelic loss allows a prognosis to be made regarding tumor diagnosis and progression, tumor metastasis, tumor recurrence, and mortality. Excerpt(s): The present invention is related to the fields of molecular biology and oncology and provides methods for diagnosis, staging and monitoring of melanoma patients. Cancer cells almost invariably undergo a loss of genetic material (DNA) when compared to normal cells. This deletion of genetic material which almost all, if not all, varieties of cancer undergo is referred to as "loss of heterozygosity" (LOH). The loss of genetic material from cancer cells can result in the selective loss of one of two or more alleles of a gene vital for cell viability or cell growth at a particular locus on the chromosome. All genes, except those of the two sex chromosomes, exist in duplicate in human cells, with one copy of each gene (allele) found at the same place (locus) on each of the paired chromosomes. Each chromosome pair thus contains two alleles for any gene, one from each parent. This redundancy of allelic gene pairs on duplicate chromosomes provides a safety system; if a single allele of any pair is defective or absent, the surviving allele will continue to produce the coded protein. Due to the genetic heterogeneity or DNA polymorphism, many of the paired alleles of genes differ from one another. When the two alleles are identical, the individual is said to be homozygous for that pair of alleles at that particular locus. Alternatively, when the two alleles are different, the individual is heterozygous at that locus. Typically both alleles are transcribed and ultimately translated into either identical proteins in the homozygous case or different proteins in the heterozygous case. If one of a pair of heterozygous alleles is lost due to a deletion of DNA from one of the paired chromosomes, only the remaining allele will be expressed and the affected cells will be functionally homozygous. This situation is termed a "loss of heterozygosity" (LOH) or reduction to homozygosity. Following this loss of an allele from a heterozygous cell, the protein or gene product thereafter expressed will be homogeneous because all of the protein will be encoded by the single remaining allele. The cell becomes effectively homozygous at the gene locus where the deletion occurred. Almost all, if not all, cancer cells undergo LOH at some chromosomal regions. Web site: http://www.delphion.com/details?pn=US06465177__
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Detection of premalignant melanocytes Inventor(s): Bastian; Boris (San Francisco, CA), Pinkel; Daniel (Walnut Creek, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,465,180 Date filed: March 17, 1999
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Abstract: The present invention provides methods of screening for the presence of premalignant melanocytes in a sample from a patient. The methods comprise contacting a nucleic acid sample from a biological sample from the patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region which is amplified in melanoma cells. Excerpt(s): Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment by complete excision is of great importance because advanced melanoma has a poor prognosis and most melanomas are curable if excised in their early stages. In most instances the transformed melanocytes produce increased amounts of pigment so that the area involved can easily be seen by the clinician. When the excision margins of a melanoma are identified based on this macroscopic appearance and no margin of seemingly uninvolved skin is excised, melanoma has the risk of local recurrence. This has led to the recommendation to remove a safety margin of normal skin that varies from 0.5 to 3 cm depending on the thickness of the primary tumor (Wingo, P. A. et al., Cancer 82:1197-207 (1998); Rigel, D. S. et al., J Am Acad Dermatol 34:839-47 (1996); McGovern, V. J. et al., Cancer 32:1446-57 (1973)). It is obvious that the resulting defect inflicted by the excision can be considerable. If a melanoma measuring 2 cm in diameter that has a thickness of >4 mm is to be excised under the current guidelines, the resulting defect would be 8 cm (2+3+3 cm) in diameter. The closure of excisions with 2-3 cm margins usually require skin grafting and have the potential of adverse consequences such as unsatisfactory cosmetic result, increased morbidity and costs, and sometimes permanent functional impairment. Even with "adequate" safety margins, the melanoma can recur locally. Obviously, it would be desirable if the margins could be tailored to the needs of the individual patient's tumor. Unfortunately, so far, no technique exists that is able to detect the extent of a tumor accurately. In some types of melanomas the horizontally expanding portion of the tumor mainly consists of single melanocytes along the basal layer of the epidermis. These melanoma types are referred to as lentiginous melanomas. In these, the amount of atypical cells often gradually diminishes towards the margins so that it can be difficult or impossible for the pathologist to determine the border of the melanoma. However, current thinking implies that in most instances, the extent of a melanoma can be assessed by pathology. The fact that the removal of a margin of "healthy" skin reduces the recurrence rate, however, suggests that this skin is actually not healthy but contains residual melanoma which is undetectable by current methods. Web site: http://www.delphion.com/details?pn=US06465180__ •
Discalamide compounds and their use as anti-proliferative agents Inventor(s): Paul; Gopal K. (Ft. Pierce, FL), Pomponi; Shirley A. (Ft. Pierce, FL), Gunasekera; Sarath P. (Vero Beach, FL), Isbrucker; Richard A. (Ontario, CA), Longley; Ross E. (Vero Beach, FL) Assignee(s): Harbor Branch Oceanographic Institution, Inc. (Fort Pierce, FL) Patent Number: 6,476,065 Date filed: April 16, 2001 Abstract: The subject invention provides novel biologically active compounds which are useful for inhibiting cellular proliferation. Because of the biological activity of these compounds, they can be used for immunomodulation and/or treating cancer. In a preferred embodiment, the novel compounds, compositions and methods of use of the subject invention can advantageously be used to inhibit the growth of tumor cells in a
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mammalian host. More particularly, the subject compounds can be used for inhibiting in a human the growth of tumor cells, including cells of breast, colon, CNS, ovarian, renal, prostate, bone, gastrointestinal, stomach, testicular, or lung tumors, as well as human leukemia or melanoma cells. Specifically exemplified are discalamides A and B. Excerpt(s): Of great importance to man is the control of pathological cellular proliferation such as that which occurs in the case of cancer. Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of, for example, tumors, new methods and antiproliferative chemical compositions are needed. In searching for new biologically active compounds, it has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity of great diversity. For example, the diterpene commonly known as Taxol, isolated from several species of yew trees, is a mitotic spindle poison that stabilizes microtubules and inhibits their depolymerization to free tubulin (Fuchs, D. A., R. K. Johnson [1978] Cancer Treat. Rep. 62:1219-1222; Schiff, P. B., J. Fant, S. B. Horwitz [1979] Nature (London) 22:665-667). Taxol is also known to have antitumor activity and has undergone a number of clinical trials which have shown it to be effective in the treatment of a wide range of cancers (Rowinski, E. K. R. C. Donehower [1995] N. Engl. J. Med 332:1004-1014). See also, e.g., U.S. Pat. Nos. 5,157,049; 4,960,790; and 4,206,221. Marine sponges have also proven to be a source of biologically active chemical molecules. A number of publications disclose organic compounds derived from marine sponges including Scheuer, P. J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978-1983, Vol. I-V; Uemura, D., K. Takahashi, T. Yamamoto, C. Katayama, J. Tanaka, Y. Okumura, Y. Hirata [1985] J. Am. Chem. Soc. 107:4796-4798; Minale, L. et al. [1976] Fortschr. Chem. Org. Naturst. 33:1-72; Faulkner, D. J. [2001] Natural Products Reports 18:1-49; Gunasekera, S. P., M. Gunasekera, R. E. Longley and G. K. Schulte [1990] "Discodermolide: A new bioactive polyhydroxy lactone from the marine sponge Discodermia dissoluta" J. Org. Chem., 55:4912-4915; [1991] J. Org. Chem. 56:1346; Hung, Deborah T., Jenne B. Nerenberg, Stuart Schreiber [1994] "Distinct binding and cellular properties of synthetic (+)- and (-) discodermolides" Chemistry and Biology 1:67-71; Hung, Deborah T., Jie Cheng, Stuart Schreiber [1996] (+)Discodermolide binds to microtubules in stoichiometric ratio to tubulin dimers, blocks Taxol binding and results in mitotic arrest" Chemistry and Biology 3:287-293. U.S. Pat. No. 4,801,606 and 4,808,590 (T. Higa, S. Sakemi and S. Cross) disclose related onnamide compounds, having antiviral, antitumor, and antifungal properties, isolated from the marine sponge Theonella sp. Web site: http://www.delphion.com/details?pn=US06476065__ •
Elucidation and synthesis of antineoplastic tetrapeptide w-aminoalkyl-amides Inventor(s): Barkoczy; Jozsef (Szirom utca 4-6/B, Budapest, HU 01016), Pettit; George R. (6232 Bret Hills Dr., Paradise Valley, AZ 85253) Assignee(s): none reported Patent Number: 6,569,834 Date filed: December 3, 1992 Abstract: Dolastatin 10, a linear pentapeptide, has shown potent antineoplastic activity profiles against various experimental cancer systems. The synthesis of structural modifications of dolastatin 10 having significant antineoplastic activity against human
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cancer cell lines has been accomplished; namely antineoplastic tetrapeptide w-amino alkyl amides related to dolastatin 10, which have been found to demonstrate effective antineoplastic activity against various human cancer cell lines. Members of this have demonstrated significant antineoplastic activity against human cancer cell lines. The human cancer cell lines against which the substances of the present invention have yielded the significant antineoplastic activity are: Ovarian OVCAR-3; Central Nervous System ("CNS") SF295; Renal A498; Lung NCI460; Colon KM20L2 and Melanoma SKMEL-3. Excerpt(s): This invention relates generally to the field of antineoplastic compounds, and more particularly to the design and synthesis of selected structural modifications of certain peptides isolated from the Indian Ocean sea hare Dolabela auriculaia, namely the tetrapeptide w-amino alkyl amides of dolastatin 10, which have been found to demonstrate effective antineoplastic activity against various human cancer cell lines. Financial assistance for this project was provided by U.S. Government Grant Number OIG-CA44344-O1A1-2: the United States Government may own certain rights to this invention. A great number of ancient marine invertebrate species in the Phyla Bryozoa, Mollusca and Porifera were well established in the earth's oceans over one billion years ago. Certainly such organisms had explored trillions of biosynthetic reactions in their evolutionary chemistry to reach present levels of cellular organization, regulation and defense. Marine sponges have changed minimally in physical appearance for nearly 500 million years, suggesting a very effective chemical evolution in response to changing environmental conditions for at least that time period. Some recognition of the potential for utilizing biologically potent marine animal constituents was recorded in Egypt about 2,700 BC, and by 200 BC sea hare extracts were being used in Greece for medicinal purposes. Such considerations, combined with the general observation that marine organisms (especially invertebrates and sharks) rarely develop cancer, led to the first systematic investigation of marine animal and plant anticancer constituents. By 1968 ample evidence had been obtained, based on the U.S. National Cancer Institute's key experimental cancer systems, that certain marine organisms would provide new and structurally novel antineoplastic and/or cytotoxic agents. Analogous considerations suggested that marine organisms could also provide effective new drugs for other severe medical challenges, such as viral diseases. Furthermore, marine organisms were expected to contain potentially useful drug candidates (and biochemical probes) of unprecedented structural types, that would have eluded discovery by contemporary techniques of medicinal chemistry. Fortunately these expectations have been realized in the intervening period. Illustrative of these successes are discoveries of the bryostatins, dolastatins, and cephalostatins where five members of these series of remarkable anticancer drug candidates are either now in human clinical trial or preclinical development. Web site: http://www.delphion.com/details?pn=US06569834__ •
Epithelial protein and DNA thereof for use in early cancer detection Inventor(s): Mulshine; James L. (Bethesda, MD), Tockman; Melvin S. (Baltimore, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD), The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,251,586 Date filed: October 2, 1996
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Abstract: The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is indicative of precancer. One epithelial protein which is an early detection marked for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C.sub.18 HPLC and analytic C.sub.4 HPLC. After an approximately 25,000 fold purification the immunostaining protein was >90% pure as judged by coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein share some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated a low level the epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals. A method of computerized diagnoses of cancer and precancer is provided which detects levels of hnRNP messenger RNA. Excerpt(s): The present invention relates to the area of cancer diagnostics and therapeutics. More specifically, the invention relates to the isolation and purification of an early cancer detection marker protein of epithelial cells and the cloning of the DNA sequence encoding the protein. The invention further relates to the protein and DNA sequence for detecting and diagnosing individuals predisposed to cancer. The present inventin relates to a computerized method for generating a discriminant function predictive of cancer. The present invention also relates to therapeutic intervention to, regulate the expression of the gene product. Lung cancer is the most frequent cause of cancer death of both males and females in the United States, accounting for one in three cancer deaths.sup.(1). In the last thirty years, cancer-related survival of this disease has improved only minimally. Successful treatment of this disease by surgical resection and drug chemotherapy is strongly dependent on identification of early-stage tumors. A conceptually attractive early detection approach is to establish the presence of a cancer by evaluation of shed bronchial epithelial cells. In the late 1960's Saccomanno et al. proposed the use of sputum cytology to evaluate cytomorphologic changes in the exfoliated bronchial epithelium as a technique to enhance the early detection of lung cancer.sup.(2). However, clinical trials using combination chest X-ray and sputum cytology have not shown any decrease in cancer-related mortality.sup.(3). In 1988, Tockman et al. reported a sensitive method for early lung cancer detection by immunostaining cells contained within sputum samples with two lung cancerassociated monoclonal antibodies.sup.(4). The basis for this approach was to identify early pre-neoplastic changes in cells shed from bronchial epithelium. The antibodies used in that study were mouse monoclonal IgG's designated 703D4, disclosed in U.S. Pat. No. 4,569,788, and 624H12. In an analysis of the contribution of the individual monoclonal antibodies to early detection of lung cancer, 703D4 alone identified 20 of the 21 detected true positive cases (4; U.S. Ser. No. 08/152,881 which issues to U.S. Pat. No. 5,455,159 on Oct. 3, 1995). 624H12 has been shown to detect an oncofetal antigen which is the Lewis.sup.x -related portion of a cell-surface glycoprotein (Mulshine/Magnani). The antigen for 703D4 was unknown. Web site: http://www.delphion.com/details?pn=US06251586__
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Gene therapy for solid tumors, papillomas and warts Inventor(s): Chen; Shu-Hsia (Houston, TX), Woo; Savio L. C. (Houston, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 6,217,860 Date filed: September 24, 1999 Abstract: The present invention provides a novel method of treating localized solid tumors (metastatic carcinomas, papilloma and warts) in an individual. The method comprises delivering a suicide gene, by way of a recombinant adenoviral vector or other DNA transport system, into the solid tumor. Subsequently, a prodrug, such as the drug ganciclovir, is administered to the individual. The methods of the present invention may used to treat several different types of solid tumors including papillomas, warts, colon carcinoma, prostate cancer, breast cancer, lung cancer, melanoma, hepatoma, brain lymphoma and head and neck cancer. Excerpt(s): The present invention relates generally to the field of gene therapy. More particularly, the present invention relates to a novel gene therapy method of treating solid tumors, papillomas and warts using an adenoviral vector, a combination of adenoviral vectors, other viral vectors, and non-viral DNA transporter systems. Direct introduction of therapeutic genes into malignant cells in vivo can provide an effective treatment of localized tumors. Several novel treatment modalities have recently been attempted. For example, one treatment involves the delivery of normal tumor suppressor genes and/or inhibitors of activated oncogenes into tumor cells. A second treatment involves the enhancement of immunogeneity of tumor cells in vivo by the introduction of cytokine genes. A third treatment involves the introduction of genes that encode enzymes capable of conferring to the tumor cells sensitivity to chemotherapeutic agents. The herpes simplex virus-thymidine kinase (HSV-TK) gene can specifically convert a nucleoside analog (ganciclovir) into a toxic intermediate and cause death in dividing cells. It has recently been reported by Culver et al. (Science 256:1550-1552, 1992) that after delivery of the HSV-TK gene by retroviral transduction, subsequent ganciclovir treatment effectively caused brain tumor regression in laboratory animals. An attractive feature of this treatment modality for localized tumors is the so called "bystander" effect. In the "by-stander" effect, the HSV-TK expressing tumor cells prevent the growth of adjacent non-transduced tumor cells in the presence of ganciclovir. Thus, not every tumor cell has to express HSV-TK for effective cancer treatment. The HSV-TK retrovirus used by Culver et al., however, was limited by low viral titer. Thus, effective treatment of brain tumors necessitated the inoculation into animals of virus-producing cells rather than the viral isolate itself. Additionally, in previous experiments with synergeneic rats treated with a retrovirus and ganciclovir, the tumors were necrotic and were invaded by macrophages and lymphocytes. In Example 1, below, athymic mice were used and the tumor cells were destroyed without apparent involvement of the cellular immune response. The prior art remains deficient in the lack of an efficient gene therapy technique for the treatment of solid tumors. Web site: http://www.delphion.com/details?pn=US06217860__
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Inhibition of abnormal cell growth with corticotropin-releasing hormone analogs Inventor(s): Slominski; Andrzej T. (Glen Ellyn, IL), Wei; Edward T. (Berkeley, CA) Assignee(s): Loyola University of Chicago (Maywood, IL), The Regents of the University of California (Oakland, CA) Patent Number: 6,319,900 Date filed: September 21, 1999 Abstract: The glutamic acid residue of corticotropin-releasing hormone analogs have had the position 20 amino acid residue replaced with a D-amino acid moiety. The resulting CRH analogs do not significantly lower blood pressure but have antiproliferative actions in cell culture and inhibit experimental cancer growth in animals (mice and rats). Novel applications of such analogs are described, such as to inhibit abnormal cell proliferation for conditions such as cancer, including melanoma, and for inflammatory dermatoses, such as psoriasis. Excerpt(s): The invention generally relates to treatments for abnormal cell proliferation, particularly for treating epidermal disorders, and more particularly relates to a method of inhibiting abnormal cell growth with the use of certain corticotropin-releasing hormone ("CRH") analogs. Inhibition of abnormal cell growth has therapeutic utility in conditions such as cancer and psoriasis. Corticotropin-releasing hormone (CRH, also called CRF or corticoliberin) was first characterized as a 41-residue peptide isolated from ovine hypothalami by Vale et al. (1981). Subsequently, the sequence of humanCRH was deduced from cDNA studies and shown to be identical to rat-CRH, and then caprine, bovine, porcine, and white sucker fish CRH were characterized. The CRH of hoofed animals show considerable differences from man, but the pig and fish sequences differ from the human/rat sequence by only 2 out of 41 residues. For some mysterious reason, peptides with homologous structures to mammalian CRH are found in cells of certain frog skins and in the urophysis of fish. In fact, the structure of sauvagine, the 40amino acid peptide isolated from the skins of Phyllomedusa frogs, was reported several years before Vale's description of ovine-CRH. The structure of sucker fish urotensin I was reported just months after the description of ovine-CRH and resulted from an independent line of inquiry by Lederis's group in Canada. Although sauvagine and urotensin I release adrenocorticotropin (ACTH) from the pituitary, the functions of these peptides in the tree-frog (Phyllomedusa species that live in arid regions of South America) and in the sucker fish remain unknown. Web site: http://www.delphion.com/details?pn=US06319900__
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Isolated nucleic acid molecules coding for tumor rejection antigen precursor MAGE-2 and uses thereof Inventor(s): Boon-Falleur; Thierry (Brussels, BE), Guagler; Beatrice (Brussels, BE), van den Bruggen; Pierre (Brussels, BE), Van den Eynde; Benoit (Brussels, BE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,552,180 Date filed: May 26, 2000 Abstract: Isolated nucleic acid molecules are described, which have complements that hybridize to a nucleic acid molecule referred to as MAGE-2. The isolated nucleic acid molecules are expressed in some melanoma cells, as well as other types of cancer cells.
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The invention also relates to nucleic acid molecules which encode fragments of the proteins encoded by these nucleic acid molecules, and nucleic acid molecules which encode the ultimate product, the so-called tumor rejection antigens. Excerpt(s): This invention relates in general to the field of immunogenetics as applied to the study of oncology. More specifically, it relates to the study and analysis of mechanisms by which tumors are recognized by the organism's immune system such as through the presentation of so-called tumor rejection antigens, and the expression of what will be referred to herein as "tumor rejection antigen precursors" or "TRAPs". Most specifically, it refers to nucleic acid molecules coding for one such TRAP, i.e., MAGE-3, which is processed to a tumor rejection antigen or "TRA" presented by HLA-A1 molecules. The study of the recognition or lack of recognition of cancer cells by a host organism has proceeded in many different directions. Understanding of the field presumes some understanding of both basic immunology and oncology. Early research on mouse tumors revealed that these displayed molecules which led to rejection of tumor cells when transplanted into syngeneic animals. These molecules are "recognized" by T-cells in the recipient animal, and provoke a cytolytic T-cell response with lysis of the transplanted cells. This evidence was first obtained with tumors induced in vitro by chemical carcinogens, such as methylcholanthrene. The antigens expressed by the tumors and which elicited the T-cell response were found to be different for each tumor. See Prehn, et al., J. Natl. Canc. Inst. 18: 769-778 (1957); Klein et al., Cancer Res. 20: 15611572 (1960); Gross, Cancer Res. 3: 326-333 (1943), Basombrio, Cancer Res. 30: 2458-2462 (1970) for general teachings on inducing tumors with chemical carcinogens and differences in cell surface antigens. This class of antigens has come to be known as "tumor specific transplantation antigens" or "TSTAs". Following the observation of the presentation of such antigens when induced by chemical carcinogens, similar results were obtained when tumors were induced in vitro via ultraviolet radiation. See Kripke, J. Natl. Canc. Inst. 53: 333-1336 (1974). Web site: http://www.delphion.com/details?pn=US06552180__ •
Melanocortin receptor antagonists and modulations of melanocortin receptor activity Inventor(s): Quillan; J. Mark (623 Deancourt Crescent, Orleans, Ontario, CA), Sadee; Wolfgang (125 Lagunitas, Ross, CA 94957), Vlasov; Guennady P. (2 Liniya, home 13/6, lodging 2 199034, Sankt Petersburg V-34, RU), Wei; Edward T. (480 Grizzly Peak Blvd., Berkeley, CA 94708) Assignee(s): none reported Patent Number: 6,228,840 Date filed: February 27, 1998 Abstract: The clinical outcome of disseminated melanoma is grim. Small molecular weight antagonists (preferably about seven amino acid residues) specific for MCR on melanoma cells are provided for the therapy of melanoma as well as in other conditions where modulation of MCR is of clinical significance. A particularly preferred antagonist is p-anisoyl-[D-Arg.sup.6,9, D-Lys.sup.11, D-Leu.sup.12 ] dynorphin A(6-12)-NH.sub.2, which is an excellent antagonist of the MCR-1 receptor. Excerpt(s): The present invention relates to pharmaceutical compositions containing melanocortin receptor antagonists, and more particularly to methods for administering melanocortin receptor antagonists so as to modulate melanocortin receptor activity. This invention was made with government support under Grant No. DA00091, awarded by
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the National Institutes of Health. The government has certain rights in this invention. Melanocytes are embryonically derived from the neural crest. These cells migrate to the skin during fetal development, sit on the basal lamina of the epidermis and interdigitate with basal cells via dendrites. Melanin is produced in the Golgi apparatus of the cell and this pigment is packaged (melanosomes) and delivered to keratinocytes and the hair follicle. In some cold-blooded vertebrates (frogs, fish, and reptiles), the cells synthesize melanosomes but do not pass it on to other cells. The melanosomes can move back and forth from the nucleus to the peripheral processes (dendrites) and this mechanism of dispersion and aggregation gives these animals the ability to change skin color from dark to light or vice versa. In cold-blooded vertebrates melanocytes are called melanophores. Web site: http://www.delphion.com/details?pn=US06228840__ •
Melanoma and prostate cancer specific antibodies for immunodetection and immunotherapy Inventor(s): Vielkind; Juergen R. (Vancouver, CA) Assignee(s): Research Corporation Technologies, Inc. (Tuscon, AZ) Patent Number: 6,291,196 Date filed: February 22, 1999 Abstract: Methods and compositions are provided for detecting antigens having a specific epitope associated with melanoma and prostatic carcinoma. The epitope is present in melanoma cells and prostatic cancer cells but is essentially absent from melanocytes and normal prostatic tissue. The antibody can be used in diagnostic methods for histochemical detection of human melanoma and prostate carcinoma, of various progression stages and in treatment of melanoma and prostate carcinoma. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer. The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It Is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is all extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface. Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate states of radial to invasive growth and
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ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal anti-nerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Web site: http://www.delphion.com/details?pn=US06291196__ •
Melanoma antigenic peptides Inventor(s): Nicolette; Charles A. (Marlborough, MA) Assignee(s): Genzyme Corporation (Framingham, MA) Patent Number: 6,306,640 Date filed: February 11, 1999 Abstract: Thus, this invention provides novel, synthetic polypeptide vaccines against human melanoma and methods for making these vaccines. Polynucleotides encoding these polypeptides are further provided herein. These compositions are useful as melanoma caccinies and in adoptive immunotherapy. Excerpt(s): This invention relates to the field of human tumor vaccines and in particular, vaccine components useful against human melanoma. Tumor specific T cells, derived from cancer patients, will bind and lyse tumor cells. This specificity is based on their ability to recognize short amino acid sequences (epitopes) presented on the surface of the tumor cells by MHC class I and class II molecules. These epitopes are derived from the proteolytic degradation of intracellular proteins called tumor antigens encoded by genes that are either uniquely or aberrantly expressed in tumor or cancer cells. The availability of specific anti-tumor T cells has enabled the identification of tumor antigens and subsequently the generation of cancer vaccines designed to provoke an anti-tumor immune response. Anti-tumor T cells are localized within cancer patients, including in the blood (where they can be found in the peripheral blood mononuclear cell fraction), in ascites fluid in ovarian cancer patients (tumor associated lymphocytes or TALs) or within the tumor itself (tumor infiltrating lymphocytes or TILs). Of these, TILs have been the most useful in the identification of tumor antigens and tumor antigen-derived peptides recognized by T cells. Web site: http://www.delphion.com/details?pn=US06306640__
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Melanotropin analogs for potential radiopharmaceuticals for diagnosis and treatment of melanoma Inventor(s): Giblin; Michael F. (Long Beach, CA), Jurisson; Silvia S. (Columbia, MO), Quinn; Thomas P. (Columbia, MO) Assignee(s): The Curators of the University of Missouri (Columbia, MO) Patent Number: 6,338,834 Date filed: April 30, 1998 Abstract: A compound for use as a diagnostic or therapeutic pharmaceutical and method of using the same where the compound consists essentially of an alphamelanotropin stimulating hormone analog which has integrally located a radionuclide. The radionuclide is administered to the body in an amount sufficient to allow uptake and retention by the tumor cells. Excerpt(s): Metal ions often play critical roles in protein structure and function. Engineered metal-binding sites in peptides and proteins have been widely used to enhance structural integrity, stabilize biologically active conformations, and confer novel enzymatic activities (Iverson, B. L., 1990; Regan, L., 1993; Kellis, J. T. Jr., 1991). Biochemical and structural analyses of transition metal coordination by proteins and peptides have traditionally focused on zinc, copper, manganese, and iron due to their roles in important biological processes (Klemba, M., 1995; Kruck, T. P. A., 1976; Lau, S., 1989; Franco, R., 1995). Other transition metals, not found in natural proteins, have coordination, isotopic, and chemical properties which make them attractive for peptide and protein engineering. Rhenium (Re) and Technetium (Tc) are group VIIB transition metals which share similar coordination geometries and form stable complexes with amine and amide nitrogens, carboxylate oxygens, and thiolate and thioether sulfurs, with a strong preference for thiolate sulfurs (Vanbilloen, H. P., 1995). Radioactive isotopes of Re and Tc have significant medical applications due to the nature of their associated radiation and physical half-life properties. The synthesis and characterization of radiolabeled antibodies, peptides, and steroid hormones as in vivo tumor imaging and therapeutic agents are active areas of cancer research today. These molecules specifically target tumor cells by virtue of their high specificities for receptors and antigens present on the surfaces of these cells. In one commonly used approach, metallic radionuclides such as.sup.186 Re,.sup.188 Re, and.sup.99m Tc are appended to the tumor targeting molecule through bifunctional chelate groups which consist of a metal chelate and an activatable crosslinker (Bakker, W. H., 1991; Fritzberg, A. R., 1988; Liu, S., 1996). The resulting radiolabeled proteins, peptides, and small molecules are decorated with one or more chelating groups. The presence of bulky metal chelating groups and their associated crosslinkers may affect receptor affinity and biodistribution in vivo (Krenning, E. P., 1992; Wraight, E. P., 1992). An alternative approach to the design of radiolabeled tumor imaging and therapeutic agents involves incorporating the metal directly into the molecule's structure (Varnum, J. M., 1994; Varnum, J. M., 1996; Chi, D. Y., 1994). Metal centers with defined coordination geometries can provide a foundation for the construction of stable molecular structures which have high affinities for specific receptors or antigenic sites. Protein, peptide, and small molecule structures can be designed to use metal coordination to reduce conformational freedom, stabilize active conformations, or mimic native conformations. Web site: http://www.delphion.com/details?pn=US06338834__
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Method for blocking endothelial cell-leukocyte attachment by inhibiting expression of adhesion molecules on the vascular endothelium for therapeutic applications Inventor(s): Dhawan; Suman (New Delhi, IN), Upadhyay; Shakti N. (New Delhi, IN) Assignee(s): National Institute of Immunology (New Delhi, IN) Patent Number: 6,395,772 Date filed: May 3, 1999 Abstract: A method for blocking the attachment of leukocytes to endothelial cells/lining of the blood vessels using a plant derived protoberberine alkaloid, berberine or its pharmaceutically acceptable salts. This prevents tissue damage to the surrounding tissue. The method also can be used to prevent and/or treat clinical manifestations that involve endothelial cell-leukocyte attachment, for example septic shock, arthritis, psoriasis, multiple sclerosis, allergic asthma, metastatic melanoma and graft rejection. Excerpt(s): It is now being recognized that the pathological consequences of many immune system mediated diseases including endotoxin induced septic shock (1), arthritis (2), psoriasis (3), multiple sclerosis (4), allergic asthma (5), metastatic melanoma (6) and as well as graft rejection (7) is the result of endothelial cell leukocyte attachment mediated by the adhesion molecules (8). Adhesion molecules expressed on the surface of endothelial lining of the blood vessels allow leukocyte attachment and trafficking to the site of inflammation. Cytokines like TNF-.alpha. produced by macrophages in response to inflammatory stimuli, induce expression of adhesion molecules (ICAM/VCAM) on the endothelial cell surface. As a result, activated lymphocytes, monocytes, or neutrophils bearing the ligand for adhesion molecules adhere to the endothelial cells and cause damage to the vascular lining and the surrounding tissue due to release of free radicals and other lytic molecules. An agent that blocks the expression of adhesion molecules at the site of inflammation in response to any inflammatory stimuli may therefore prevent endothelial--leukocyte attachment and consequently may have preventive and/or therapeutic effects in clinical situation of septic shock, arthritis, psoriasis, multiple sclerosis, allergic asthma, metastatic melanoma and graft rejection. It has been discovered that berberine or its pharmaceutically acceptable salts block adhesion of molecules to endothelial cell surface. Berberine may be isolated from Berberis airistata. Berberis aristata has been widely used in traditional Indian medicine for treatment of gastroenteritis, and skin and eye infections (Chopra et al., 1956; Nadkarni 1954). The chemistry and pharmacological effects of protoberberine alkaloids have been described in the scientific literature. Berberine has been reported to have direct anti-bacterial (Sado, 1947; Dutta and Panse, 1962), anti-amoebic (Subbaihah and Amin, 1967; Dutta and Iyer, 1968) and antileishmanial effects (Dasgupta and Dikshit, 1929; Steck, 1974; Ghosh et al., 1983, 1985) and cytotoxic effects against certain types of tumor cells (for review see Bhakuni and Jain 1986). Berberine has been shown to complex with DNA (Krey and Hahn 1969; Maitia and Chowdhuri, 1981) and is being used as a specific stain for mast cells because of its specificity of binding with herapin (Berlin and Enerback, 1983, 1984). Japanese Patent 07-316051 published Dec. 5, 1995 (Kangegafuchi Chemical Co. Ltd.) discusses the use of berberine or its pharmacologically tolerable salt as an immunosuppressant specifically for autoimmune diseases such as rheumatism and for treatment of allergies and to prevent rejection of isografts. This reference discloses that berberine inhibits antibody production by B cells, suppresses humoral immunity and has no effect on propagation of T cells. Web site: http://www.delphion.com/details?pn=US06395772__
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Methods for determining breast cancer and melanoma by assaying for a plurality of antigens associated therewith Inventor(s): Chen; Yao-Tseng (New York, NY), Old; Lloyd J. (New York, NY), Pfreundschuh; Michael (Homburg/Saar, DE), Sahin; Ugur (Homburg/Saar, DE), Tureci; Ozlem (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (NY) Patent Number: 6,338,947 Date filed: May 25, 2000 Abstract: The invention relates to assays for determining breast cancer or melanoma. It has been found that the accuracy of such assays can be improved by assaying samples for three or more known tumor rejection antigen precursors. For breast cancer, the tumor rejection antigen precursors known as SCP-1, NY-ESO-1, and SSX-2 are assayed. For melanoma, SSX-2, NY-ESO-1, and MAGE-3 are assayed. Additional known tumor rejection antigen precursors can also be determined to confirm the assays. It is preferred to carry these out via polymerase chain reactions. Excerpt(s): This invention relates to the determination of cancer, melanoma and breast cancer in particular. The methods involve assaying for members of the so-called "cancertestis" or "CT" antigen family. It is fairly well established that many pathological conditions, such as infections, cancer, autoimmune disorders, etc., are characterized by the inappropriate expression of certain molecules. These molecules thus serve as "markers" for a particular pathological or abnormal condition. Apart from their use as diagnostic "targets," i.e., materials to be identified to diagnose these abnormal conditions, the molecules serve as reagents which can be used to generate diagnostic and/or therapeutic agents. A by no means limiting example of this is the use of cancer markers to produce antibodies specific to a particular marker. Yet another non-limiting example is the use of a peptide which complexes with an MHC molecule, to generate cytolytic T cells against abnormal cells. Preparation of such materials, of course, presupposes a source of the reagents used to generate these. Purification from cells is one laborious, far from sure method of doing so. Another preferred method is the isolation of nucleic acid molecules which encode a particular marker, followed by the use of the isolated encoding molecule to express the desired molecule. Web site: http://www.delphion.com/details?pn=US06338947__
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Methods for inhibiting cell motility Inventor(s): Carlson; C. George (R.R.#1, Box 220, Kirksville, MO 63501), Cox; James L. (R.R.#3, Box 82B, Kirksville, MO 63501) Assignee(s): A.T. Still University of Health Sciences (Kirksville, MO), Carlson; C. George (Kirksville, MO), Cox; James L. (Kirksville, MO) Patent Number: 6,572,896 Date filed: May 28, 2002 Abstract: A method is provided for inhibiting and substantially decreasing the motility of cells, and especially melanoma cells. In the invention, a cell is contacted with a motility-inhibiting amount of a metal ion selected from the group consisting of cobalt ion, the lanthanide metal ions, and mixtures thereof; particularly preferred metal ions are the Co.sup.2+ and Gd.sup.3+ ions. Metal ion sources may be administered in the
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form of soluble metal halide salts to in vitro to cells dispersed in an aqueous saline medium, or by administering an aqueous dispersion thereof to an in vivo mammalian subject at or adjacent a tumor site. Excerpt(s): The present invention is concerned with methods for inhibiting and decreasing cell motility (and particularly that of melanoma cells) by contacting such cells with relatively minor amounts of metal ion(s) selected from the group consisting of cobalt ion, the lanthanide metal ions, and mixtures thereof. In practice, metal ion sources (e.g., the metal halide salts) are solubilized in an aqueous medium and are administered to melanoma cells to achieve motility inhibition. Metastasis, the spread of cancerous cells from an initial tumor to other physically separate sites in the body, is a common and life-threatening situation in many cancers. Although the precise mechanism of metastasis is not known, directional migration of melanoma cells in response to concentration gradients of soluble factors (chemotaxis) and overall motility of melanoma cells is clearly an important factor. Savarese et al., Type IV Collagen Stimulates and Increase in Intracellular Calcium; Potential Role in Tumor Cell Motility; J Biol. Chem., 267(30):21928-21935 (1992) examined the influence of two metal ions (Co.sup.2+ and La.sup.3+) on motility of A2058 human melanoma cells. The concentration of Co.sup.2+ used in this study (10.sup.-8 to 10.sup.-4 M) was completely ineffective to inhibit tumor cell motility. Indeed, only one of six agents (nifedipine) at a concentration of 100.mu.M was reported to produce inhibition of motility. Web site: http://www.delphion.com/details?pn=US06572896__ •
Monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Chatterjee; Malaya (Lexington, KY), Chatterjee; Sunil K. (Lexington, KY), Foon; Kenneth A. (Lexington, KY) Assignee(s): The Board of Trustees of the University of Kentucky (Lexington, KY) Patent Number: 6,509,016 Date filed: April 15, 1999 Abstract: The present invention relates to monoclonal antibody 1A7. This is an antiidiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered GD2 expression, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Excerpt(s): In spite of numerous advances in medical research, cancer remains the second leading cause of death in the United States. Traditional modes of clinical care, such as surgical resection, radiotherapy and chemotherapy, have a significant failure rate, especially for solid tumors. Failure occurs either because the initial tumor is unresponsive, or because of recurrence due to regrowth at the original site or metastasis.
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Cancer remains a central focus for medical research and development. Under the hypothesis that neoplastic cells are normally regulated by immune surveillance, an attractive approach is to re-focus the immune system in affected individuals back towards the tumor. Many types of cancers should be susceptible to the immune system, because they express unusual antigens that reflect the oncogenic transformation of the cell. Antibodies or T cells directed against a target antigen specifically expressed on tumor cells may be able to recruit immune effector functions, and thereby eliminate the tumor or mitigate the pathological consequences. There are several potential pitfalls in this approach. The first is that the target tumor antigen may be shed from the cell, and thereby block the approach of tumor-specific immune components. The second is that the expression of the target antigen may be heterologous. In this case, a specific immune response would be ineffective in a substantial subclass of affected individuals, or the risk of escape variants would be high. The third difficulty is that tumor-specific antigens are generally-antigenically related to autoantigens, or comprise autoantigens in an atypical mode of expression. This means that tumor-associated antigens are often poorly immunogenic; perhaps due to an active and ongoing immunosuppression against them. Furthermore, cancer patients tend to be immunosuppressed, and only respond to certain T-dependent antigens. Web site: http://www.delphion.com/details?pn=US06509016__ •
MTS2 gene Inventor(s): Kamb; Alexander (Salt Lake City, UT) Assignee(s): Myriad Genetics, Inc. (Salt Lake City, UT) Patent Number: 6,218,146 Date filed: July 22, 1998 Abstract: The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germ line mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkins lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy. Excerpt(s): The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germline mutations in the MTS gene and their use in the diagnosis of predisposition to cancer, such as melanoma, ocular melanoma, leukemia, astrocytoma, glioblastoma, lymphonia, glioma, Hodgkin's lymphoma, multiple myeloma, sarcoma, myosarcoma, cholangiocarcinoma, squamous cell carcinoma, CLL, and cancers of the pancreas, breast, brain, prostate, bladder, thyroid, ovary, uterus, testis, kidney, stomach, colon and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated herein by reference, and for convenience are referenced in the following text and
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respectively grouped in the appended List of References. The genetics of cancer is complicated, involving multiple dominant, positive regulators of the transformed state (oncogenes) as well as multiple recessive, negative regulators (tumor suppressor genes). Over one hundred oncogenes have been characterized. Fewer than a dozen tumor suppressor genes have been identified, but the number is expected to increase beyond fifty (Knudson, 1993). Web site: http://www.delphion.com/details?pn=US06218146__ •
Pox virus containing DNA encoding a cytokine and/or a tumor associated antigen Inventor(s): Cox; William I. (Troy, NY), Paoletti; Enzo (Delmar, NY), Tartaglia; James (Schenectady, NY) Assignee(s): Virogenetics Corporation (Swiftwater, PA) Patent Number: 6,265,189 Date filed: June 2, 1995 Abstract: Attenuated recombinant viruses containing DNA coding for a cytokine and/or a tumor associated antigen, as well as methods and compositions employing the viruses, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least on of: human tumor necrosis factor; nuclear phosphoprotein p53, wildtype or mutant; human melanoma-associated antigen; IL-2; IFN.gamma.; IL-4; GNCSF; IL-12; B7; erb-B-2 and carcinoembryonic antigen. The recombinant viruses and gene products therefrom are useful for cancer therapy. Excerpt(s): The present invention relates to a modified poxvirus and to methods of making and using the same. More in particular, the invention relates to improved vectors for the insertion and expression of foreign genes for use as safe immunization vehicles to protect against a variety of pathogens, as well as for use in immunotherapy. Several publications are referenced in this application. Full citation to these references is found at the end of the specification immediately preceding the claims or where the publication is mentioned; and each of these publications is hereby incorporated herein by reference. These publications relate to the art to which this invention pertains. Vaccinia virus and more recently other poxviruses have been used for the insertion and expression of foreign genes. The basic technique of inserting foreign genes into live infectious poxvirus involves recombination between pox DNA sequences flanking a foreign genetic element in a donor plasmid and homologous sequences present in the rescuing poxvirus (Piccini et al., 1987). Web site: http://www.delphion.com/details?pn=US06265189__
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Retroinverso polypeptides that mimic or inhibit thrombospondin activity Inventor(s): Actor; Paul (Phoenixville, PA), Tuszynski; George (Pittsgrove, NJ), Williams; Taffy (Lansdale, PA) Assignee(s): Inkine Pharmaceutical Company, Inc. (Blue Bell, PA) Patent Number: 6,339,062 Date filed: November 23, 1998 Abstract: The present invention relates generally to polypeptides that mimic or inhibit the biological activity of thrombospondin, and particularly to polypeptides in
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retroinverso form. These polypeptides may be used for their biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and inhibiting cellular attachment to tissue culture flacks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas. Excerpt(s): The present invention relates generally to peptide fragments and synthetic analogs of thrombospondin (also known as thrombin sensitive protein or TSP) with thrombospondin-like activity. The peptides mimic or inhibit the biological activity of TSP. These peptides may be used in biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and inhibiting cellular attachment to tissue culture flasks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas. Thrombospondin (TSP) is secreted by platelets in response to physiological activators such as thrombin and collagen (Lawler, Blood, 67:112-123 (1986)). Other cells also synthesize TSP including fibroblasts (E. A. Jaffe et al., Proc. Natl. Acad. Sci., 80:999-1002 (1983)), smooth muscle cells (Raugi, G. J. et al., J. Cell Biol. 95:351354 (1982)), and endothelial cells (J. McPhearson et al., J. Biol. Chem., 256:11330-11336). TSP has been found in certain tumor tissues, such as melanoma cells (J. Varani et al., Clin. Expl. Metastais, 7:265-76 (1989)), squamous lung carcinoma (B. L. Riser et al., Exp. Cell Res., 174:319-329 (1988)) and breast carcinoma (D. A. Pratt et al., Eur. J. Cancer Clin. Oncol. 25:343-350 (1989)). In addition, certain tumor cells in culture, such as, fibrosarcoma, rhabdomyosarcoma, glioblastoma, Wilm's tumor, neuroblastoma, teratocarcinoma, choriocarcinoma, melanoma, and lung carcinoma have been shown to synthesize TSP (D. F. Mosher, Annu. Rev. Med., 41:85-97 (1990)). The present invention provides thrombospondin fragments and analogs that mimic or inhibit the biological activity of intact thrombospondin and are, thus, useful in a variety of biological, prophylactic or therapeutic areas. These peptides are capable of modifying and inhibiting tumor cell metastasis, cell adhesion and platelet aggregation in mammals in vivo. The peptides are also useful in wound healing, for antimalarial activity, atherosclerosis, thrombotic, and thrombolytic conditions, angiogenesis, and as cell attachment promoters, complement modulators, and diagnostic reagents and in other related areas. Web site: http://www.delphion.com/details?pn=US06339062__ •
Structurally modified peptides that are resistant to peptidase degradation Inventor(s): Ayyoub; Maha (Toulouse, FR), Gairin; Jean Edouard (Toulouse, FR), Mazarguil; Honore (Toulouse, FR), Monsarrat; Bernard (Toulouse, FR), Van Den Eynde; Benoit (Brussels, BE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,623,740 Date filed: July 10, 1998 Abstract: Human melanoma cells bear antigens that are recognized by autologous CD8.sup.+ cytotoxic T-lymphocytes. The invention involves the reception of particular peptides analogues of the MZ2-E antigen by HLA molecules. Disclosed herein are peptide analogues of the tumor antigen MZ2-E that have been modified to resist peptidase degradation, and which bind HLA molecules to form a complex whose
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recognition by specific cytolytic T cells leads to lysis of the complex. The identification by cytolytic T cells of the peptide analogue/HLA complex may be used in diagnostics, or therapeutically. Excerpt(s): This invention relates to the field of immunology. In particular, it relates to peptides which form complexes with HLA molecules, and exhibit a half-life of more than 30 minutes relative to degradation by peptidase. More particularly, the present invention contemplates a class of peptides of a particular nonapeptide, MZ2-E, which have been modified to resist peptidase degradation. The contemplated peptides are useful in many ways, e.g., as immunogens and as materials which target and bind MHC/HLA molecules. The study of the recognition or lack of recognition of foreign antigen by a host organism has proceeded in many different directions. Understanding of the field presumes some understanding of both basic immunology, and protein chemistry. The immune system is constantly at war, fighting viruses, bacteria, and other pathogens that try to invade the body. In this war, it uses a diverse range of effectors in order to deal with the threat to health posed by an equally diverse range of infectious organisms that are prevalent in the environment. For example, T-lymphocytes play a central role in the induction and regulation of the immune response and in the execution of immunological functions. These cells are particularly important in tumor rejection and in fighting viral infections. Web site: http://www.delphion.com/details?pn=US06623740__ •
Treatment, diagnosis and evaluation of anti-cancer therapy resistance in melanoma Inventor(s): Ben-David; Yaacov (Toronto, CA), Kerbel; Robert S. (Toronto, CA), Pak; Brian J. (Toronto, CA) Assignee(s): Sunnybrook & Women's College Health Sciences Centre (Toronto, CA) Patent Number: 6,573,050 Date filed: October 27, 2000 Abstract: The invention relates to overcoming anti-cancer therapy resistance in melanoma by regulation of the expression of tyrosinase related protein 2 (TYRP2). Treatment of melanoma with anti-cancer therapy may be negatively impacted by anticancer resistance of melanoma cells. Altering expression of TYRP2 in melanoma cells can enhance efficacy of anti-cancer therapies, such as chemotherapy and radiotherapy. Methods for treatment of melanoma are disclosed, as well as methods for diagnosis of anti-cancer therapy resistance, and methods for evaluating candidate anti-cancer therapies for melanoma. Down-regulation of TYRP2 expression or activity can be accomplished using a genetic therapy such as antisense therapy, or by using small molecules which regulate TYRP2. Excerpt(s): The present invention relates to the treatment of melanoma, and in particular to treatment and diagnosis of anti-cancer therapy resistance in melanoma, as well as to the evaluation of resistance of a tumor or melanoma cells to anticer therapy. The tendency of tumors to express resistance to therapeutic agents remains a major obstacle in cancer treatment. Resistance mechanisms can be classified as either physiological or cellular (see Bradley et al. (1988) Biochim. Biophys. Acta 948:87-128). Physiological resistance mechanisms refer to properties of the tumor such as vascularity, that limit drug penetration into the rumor. Cellular resistance mechanisms involve the ability of individual cancer cells to undergo mutations or other types of genetic alterations which biochemically render these cells more resistant to the cytotoxic effects of anti-cancer
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therapeutic drugs. Such mechanisms include decreased drug uptake, increased drug efflux and increased drug detoxification. Resistant cancer cells may arise en masse in a de novo fashion prior to drug treatment ("intrinsic drug resistance") or they can be selected for by the drug ("acquired drug resistance"). One type of cancer which is well known for its intrinsic resistance to anti-ancer therapeutic drugs is malignant melanoma. The incidence of malignant melanoma is increasing more rapidly than any other type of human cancer in North America (Armstrong et al. (1994) Cancer Surv. 1920:219-240). Although melanoma is a curable cancer, the primary tumor must be removed at a very early stage of disease progression, i.e., before it has spread to distant sites. The presence of micrometastases can, and often do, lead to eventual symptomatic metastases. Because melanomas are intrinsically resistant to conventional methods of either chemotherapy or radiotherapy, it is virtually impossible to effectively treat such lesions in a clinically meaningful manner. Web site: http://www.delphion.com/details?pn=US06573050__ •
Use of a melanoma differentiation associated gene (mda-7) for inducing apoptosis of a tumor cell Inventor(s): Fisher; Paul B. (Scarsdale, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,355,622 Date filed: February 16, 1999 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having an amount of a nucleic acid having the melanoma differentiation associated gene (mda-7) or the gene product of a melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of each series of experiments. Cancer is a complex multifactor and multistep process involving the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13,14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with
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recombinant human interferon.beta. (IFN-.beta.) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associated (mda) genes not previously described in DNA data bases (13,14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (1316), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells. The mda-7 gene was cloned from a differentiation inducer (IFN-.beta. plus MEZ)-treated human melanoma (H0-1) subtracted library (13,14). The full-length mda-7 cDNA is 1718 nucleotides, and the major open reading frame encodes a novel protein of 206 aa with an M.sub.r of 23.8 kDa (21). Previous studies indicate that mda-7 is induced as a function of growth arrest and induction of terminal differentiation in human melanoma cells (14,21). mda-7 expression also inversely correlates with melanoma progression--i.e., actively growing normal human melanocytes express more mda-7 than metastatic human melanoma cells (21). Moreover, mda-7 is growth inhibitory toward human melanoma cells in transient transfection assays and in stable transformed cells containing a dexamethasone (DEX)inducible mda-7 gene (21). These studies indicate that mda-7 may contribute to the physiology of human melanocytes and melanomas, and this gene has growth suppressive properties when overexpressed in human melanoma cells. Web site: http://www.delphion.com/details?pn=US06355622__ •
Utilization of osteocalcin promoter to deliver therapeutic genes to tumors Inventor(s): Cheon; Jun (Anam-Dong, KR), Chung; Leland W. K. (Lovingston, VA), Kao; Chinghai (Charlottesville, VA), Ko; Song-Chu (Charlottesville, VA), Sikes; Robert A. (Charlottesville, VA) Assignee(s): The University of Virginia Patent Foundation (Charlottesville, VA) Patent Number: 6,596,534 Date filed: March 23, 2000 Abstract: A therapeutic agent based on a recombinant adenovirus which employs an osteocalcin promoter for the expression of thymidine kinase can be administered intravascularly to treat metastatic cancer, including osteosarcoma, breast cancer, prostate cancer, ocular melanoma or brain cancer. Systemic administration of this agent provides a preferred route over previous disclosure of local direct administration. The same therapeutic agent can be effectively employed in the treatment of benign conditions, including benign prostatic hypertrophy and arteriosclerosis. Excerpt(s): This invention pertains to the systemic administration of an active agent, a recombinant gene comprising an adenovirus (Ad) which contains an osteocalcin promoter (OC) which drives the expression of thymidine kinase (TK). The agent itself is fully disclosed in the parent application. This invention pertains to the discovery that Ad-OC-TK may be administered systemically, both to treat tumors, and to treat certain benign conditions such as benign prostatic hypertrophy and certain forms of arteriosclerosis. Toxic gene therapy for the treatment of cancer continues to gain prominence in basic research, but remains limited in clinical application because of an inability to deliver the toxic gene to the tumor cells with specificity. Many vectors (e.g. retroviruses, retroviral producing cells, adenoviruses, liposomes, and others) can deliver
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genes (therapeutic or toxic) to target cells. Localized delivery and restricted gene expression to the primary tumor have been accomplished via direct injection of therapeutic viruses in animal models.sup.1-4 and clinical trails.sup.5,6 This approach is not feasible for the treatment of metastatic disease because of the presence of multiple lesions that would each require separate injection and manipulation. Therefore, alternative approaches to the treatment of metastatic disease with gene therapy must be developed. Systemic delivery of therapeutic genes is attractive for targeting metastatic disease, pulmonary metastases in particular. Because the pulmonary vascular system would be the first encountered, the adenovirus would be trapped in the lung parenchyma, allowing for higher infectivity. Lesoon-Wood et al,.sup.7 reported the systemic delivery of wild type p53 complexed with liposomes, targeting the p53 mutated breast cancer cell line (MDA-MB435), inhibiting primary tumor growth by 60%, and decreasing pulmonary metastases in nude mice. Vile et al.sup.8 demonstrated inhibition of B-16 melanoma pulmonary metastases in syngeneic immunocompetent mice by a systemic delivery of retrovirus using a tyrosinase promoter to drive the expression of the toxic gene thymidine kinase (TK) gene. Web site: http://www.delphion.com/details?pn=US06596534__ •
Zinc chloride unit dose packaging, applicator, and method of use in treating cancer and other skin diseases Inventor(s): Brooks; Leslee S. (16420 Marbro Dr., Encino, CA 91436), Brooks; Norman A. (16420 Marbro Dr., Encino, CA 91436) Assignee(s): none reported Patent Number: 6,558,694 Date filed: February 16, 2000 Abstract: An improved method for the treatment of melanoma and skin diseases which utilizes a zinc chloride fixative mixture is provided. The active ingredients of the fixative mixture include zinc chloride (a deeply penetrating, tissue killing histologic preservative), and the anti-cancer plant alkaloids sanguinarine and chelerythrine. Zinc chloride allows the surgeon to perform a complete conventional surgical excision around and below a melanomatous tumor through painless, bloodless dead tissue, and because the microscopic structures are fixed in place by the zinc chloride, the excised tissue can be examined by a pathologist to confirm complete excision and clearance of the melanoma. Although zinc chloride fixative paste has been shown to be an effective treatment for human skin cancer and melanoma, this treatment has been overlooked by the medical community. The paste is difficult to maintain and complicated to apply to the affected skin. This invention allows the active ingredients of zinc chloride fixative paste to be effectively administered to the skin by providing single-use dose specific storage, application, dressing, and administration systems needed to facilitate the use of topical zinc chloride mixtures and/or zinc chloride pastes in the treatment of melanoma and other skin diseases. Enhanced zinc chloride mixture formulations are described. Excerpt(s): The present invention relates to the treatment of human melanoma, basal and squamous cell skin cancer, and a variety of other skin tumors and skin diseases. More particularly, the present invention relates to unit dose packaging of a zinc chloride mixture and used in a dosage specific applicator for the treatment of these skin diseases. Melanoma is a potentially fatal form of skin cancer, usually appearing as a black or dark brown mole. The conventional treatment of cutaneous melanoma has been excision with a deep and wide margin of normal appearing tissue surrounding the tumor depending
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on the depth and thickness of the cancerous mole. However, microscopic satellite sites potentially occurring in the otherwise normal appearing skin surrounding the melanoma may be disturbed, and host resistance may be reduced following the excision of the melanoma. A decrease in host resistance may result in the appearance of cancer in distant sites of the body (metastases). (Smolle, J. et al, Does Surgical Removal of Primary Melanoma Trigger Growth of Occult Metastases? An Analytical Epidemiological Approach. Dermatologic Surgery, November, 1997). Cancer metastases can cause death of the patient. Although it is common to excise a margin of tissue surrounding the tumor, it is well known that increasing the size of the surgical margin to greater and greater extent does not affect survival rate. Adjuvant therapy has been recommended for melanoma patients in whom clinical and histopathological parameters indicate a high risk of relapse. Interferon alpha 2B has been approved by the United States Food and Drug Administration for treatment of such high-risk melanomas. However, the survival from high-risk melanomas remains poor, and additional modalities are needed. Clinical evidence shows that the pre-surgical application of zinc chloride paste improves the prognosis of melanoma. Web site: http://www.delphion.com/details?pn=US06558694__
Patent Applications on Melanoma As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to melanoma: •
9-oxa-epothilon derivatives, method for the production and use thereof in pharmaceutical preparations Inventor(s): Buchmann, Bernd; (Hohen Neuendorf, DE), Hoffmann, Jens; (Muehlenbeck, DE), Klar, Ulrich; (Berlin, DE), Lichtner, Rosemarie; (Berlin, DE), Schwede, Wolfgang; (Berlin, DE), Skuballa, Werner; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030139460 Date filed: October 18, 2002 Abstract: The invention relates to novel epothilon derivatives which are characterized by an oxygen atom in position 9 of the epothilon skeleton. The novel compounds interact with tubulin, stabilizing formed microtubuli. They can influence cell division in a phase-specific manner and are suitable for use in the treatment of malignant tumors such as ovarian, stomach, colon, adeno, breast, lungs, head and neck carcinoma, malignant melanoma, acute lymphocytic and myelocytic leukaemia. They are also suitable for anti-angiogenesis thereapy and for use in the treatment of chronic inflamatory diseases (psoriasis, arthritis). In order to avoid uncontrolled proliferation of cells on and to improve the compatibility of medical implants, they can be placed on or in polymer materials. The inventive compounds can be used on their own or to obtain additive or synergistic effects in combination with other classes of substances and principles which can be used in tumoral therapy.
10
This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): in, e.g., Angew. Chem. [Applied Chem.] 1996, 108, 1671-1673. Because of their in-vitro selectivity for breast cell lines and intestinal cell lines and their significantly higher activity against P-glycoprotein-forming multiresistant tumor lines in comparison to taxol as well as their physical properties that are superior to those of taxol, e.g., a water solubility that is higher by a factor of 30, this novel structural class is especially advantageous for the development of a pharmaceutical agent for treating malignant tumors. The natural products are not sufficiently stable either chemically or metabolically for the development of pharmaceutical agents. To eliminate these drawbacks, modifications to the natural product are necessary. Such modifications are possible only with a total-synthesis approach and require synthesis strategies that make possible a broad modification of the natural product. The purpose of the structural changes is also to increase the therapeutic range. This can be done by improving the selectivity of the action and/or increasing the active strength and/or reducing undesirable toxic side effects, as they are described in Proc. Natl. Acad. Sci. USA 1998, 95, 9642-9647. The total synthesis of epothilone A is described by Schinzer et al. in Chem. Eur. J. 1996, 2, No. 11, 1477-1482 and in Angew. Chem. 1997, 109, No. 5, pp. 543544). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antigen binding fragments that specifically detect cancer cells, nucleotides encoding the fragments, and use thereof for the prophylaxis and detection of cancers Inventor(s): Dan, Michael D.; (Scarborough, CA), Kaplan, Howard A.; (Winnipeg, CA), Maiti, Pradip K.; (Winnipeg, CA) Correspondence: Susan K. Lehnhardt; Frommer Lawrence & Haug Llp; 745 Fifth Avenue; New York; NY; 10151; US Patent Application Number: 20030021779 Date filed: February 13, 2001 Abstract: The present invention relates to monoclonal antibody H11 and antigen binding fragments that specifically bind to the antigen recognized by H11, the C-antigen. The Cantigen is found specifically on neoplastic cells and not on normal cells. Also disclosed are polynucleotide and polypeptide derivatives based on H11, including single chain V region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the H11 antibody is effective in diagnosing, localizing, and/or treating neoplasias. The invention further provides methods for treating a neoplastic disease, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell lung carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Patients may also be treated concurrently with the antibodies and traditional anti-neoplastic agents. Excerpt(s): This invention relates to antibodies specific to an antigen detected on neoplastic cells but not on normal cells. This antigen is termed herein the "C-antigen." The C-antigen is recognized by the human monoclonal antibody (Mab) termed "H11." The invention encompasses a wide variety of antibodies, and functional derivatives thereof that retain the immunologic specificity of H11 and are termed herein ".alpha.C." The exemplary antibody, H11, compositions comprising the H11, and hybridomas producing H11 are included herein. The H11 V region polynucleotides and polypeptides encoded thereby and recombinant molecules containing these polynucleotides are also encompassed by the invention. Methods of use including
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therapeutic and diagnostic of the.alpha.C antibodies are also included in the invention. In spite of numerous advances in medical research, cancer remains the second leading cause of death in the United States. In the industrialized nations, roughly one in five persons will die of cancer. Traditional modes of clinical care, such as surgical resection, radiotherapy and chemotherapy, have a significant failure rate, especially for solid tumors. Failure occurs either because the initial tumor is unresponsive, or because of recurrence due to regrowth at the original site and/or metastases. Even in cancers such as breast cancer where the mortality rate has decreased, successful intervention relies on early detection of the cancerous cells. The etiology, diagnosis and ablation of cancer remain a central focus for medical research and development. Neoplasia resulting in benign tumors can usually be completely cured by removing the mass surgically. If a tumor becomes malignant, as manifested by invasion of surrounding tissue, it becomes much more difficult to eradicate. Once a malignant tumor metastasizes, it is much less likely to be eradicated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anti-HLA-DR antibodies and the methods of using thereof Inventor(s): Green, Jennifer McPhate; (Belmont, CA), Tso, J. Yun; (Menlo Park, CA) Correspondence: Howrey Simon Arnold & White, Llp; Box 34; 301 Ravenswood AVE.; Menlo Park; CA; 94025; US Patent Application Number: 20030138862 Date filed: October 10, 2002 Abstract: This invention provides anti-HLA-DR antibodies and the methods of use thereof for the treatment of leukemia or lymphomas, or solid tumors such as ovarian cancer or melanoma. Excerpt(s): This application claims the benefit of priority of the U.S. provisional application U.S. Ser. No. 60/329,178 filed Oct. 11, 2001 and the U.S. provisional application U.S. Ser. No. 60/331,965, filed Nov. 21, 2001, each of which is incorporated by reference in its entirety. The leukemias are a heterogeneous group of neoplasm arising from the malignant transformation of hematopoietic (blood forming) cells. Leukemic cells proliferate primarily in bone marrow and lymphoid tissues where they interfere with normal hematopoiesis and immunity. Ultimately, they emigrate into the peripheral blood and infiltrate other tissues. Leukemias are classified according to the cell types primarily involved (myloid and lymphoid) and as acute or chronic based upon the natural history of the disease. Acute leukemias, including acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), have a rapid clinical course and often result in death within a matter of months without effective treatment. In contrast, chronic leukemias have a more prolonged natural history. Chronic leukemias include chronic lymphocytic leukemia (CCL), chronic myelogenous leukemia (CML) and hairy cell leukemia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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•
Anti-idiotypic antibody which glycosphingolipid and use thereof
induces
an
immune
response
against
a
Inventor(s): Chapman, Paul B.; (New York, NY), Houghton, Alan N.; (New York, NY) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030035797 Date filed: August 13, 2002 Abstract: The present invention provides an anti-idiotypic monoclonal antibody which specifically induces an immune response against a glycosphingolipid. Additionally, this invention provides a method of producing the anti-idiotypic monoclonal antibody. Finally, this invention provides a composition of matter comprising an effective amount of a cytokine and a melanoma ganglioside-specific antibody attached to a carrier. Excerpt(s): R24, an IgG3 mouse monoclonal antibody (mAb) raised against a human melanoma, recognizes the GD.sub.3 ganglioside. The GD.sub.3 ganglioside is abundantly expressed on most melanomas, however, expression of the GD.sub.3 ganglioside on normal tissue is selective and occurs at low concentrations (1). Gangliosides are a subset of glycosphingolipids which in turn are a subset of glycolipids. Glycolipids, as their name implies, are sugar-containing lipids. In order to avoid confusion, the R24 variant from hereinafter will be referred to as "R24" and R24 comprising the three variant species will be referred to as the "R24 composition." Each variant exhibits differences which imply that the GD.sub.3-binding region (also termed "paratope") of V1-R24, V2-R24, and R24 are altered. Anti-idiotypic monoclonal antibodies which mimic and possess the internal image of a saccharidic epitope have been developed (2). The saccharidic epitope is a tumor associated globoside, i.e. a glycolipid. However, these anti-idiotypic (monoclonal antibodies do not specifically mimic a glycosphingolipid, a ganglioside, or more particularly the GD.sub.3 ganglioside. Additionally, these anti-idiotypic monoclonal antibodies are not directed against R24 or any antibodies which specifically bind a glycosphingolipid or a ganglioside, let alone the GD.sub.3 ganglioside. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antisense inhibiting melanoma invasion and functional analogs thereof Inventor(s): Brodt, Pnina; (Montreal, CA), Durko, Margaret; (Cote St-Luc, CA) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030108530 Date filed: February 11, 2003 Abstract: The present invention relates to an antisense to inhibit melanoma invasion, to an expression vector and to a method for substantially inhibiting tumor cell invasion of an extracellular matrix (ECM) and other invasive processes such as angiogenesis, and particularly plasmin-mediated proteolysis thereof in a patient, by suppression of type I collagenase (MMP-1) expression in the patient. Excerpt(s): The present invention relates to an antisense to inhibit melanoma invasion, to an expression vector comprising same and to a method for substantially inhibiting tumor cell invasion of an extracellular matrix (ECM) and particularly plasmin-mediated proteolysis thereof in a patient, by suppressing expression or function of type I
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collagenase (MMP-1) in the patient. The extracellular matrix (ECM) is a complex structure consisting mainly of basement membranes and interstitial stroma and composed of collagen, glycoproteins and proteoglycans, forming a dense meshwork normally impenetrable to migrating cells. ECM turnover is essential for normal physiological processes such as organogenesis and wound healing. In pathological processes requiring degradation of ECM such as cancer invasion and metastasis, the tight regulation of ECM turnover is disrupted, leading to increased ECM proteolysis. Several different classes of proteinases are known to participate in ECM degradation. These include matrix metalloproteinases (MMPs) such as type I (MMP-1) and type IV (MMP-2, MMP-9) collagenases and stromelysin-1 (MMP-3), and serine proteinases such as the urokinase-type plasminogen activator (uPA) and plasmin. These enzymes have all been implicated in cancer invasion and metastasis (Mignatti, P., and Rifkin, D. B. (1993) Physiol. Rev. 73, 161-195). The uPA enzyme converts the zymogen plasminogen to its enzymatically active form plasmin. Plasmin in turn can initiate the conversion of the uPA zymogen (pro-uPA) to its active form uPA, resulting in an autocatalytic loop. Activation of plasminogen to plasmin occurs at the cell surface where uPA binds through a specific cell surface receptor (urokinase-type plasminogen activator receptor, or uPAR) and plasminogen binds through as yet unidentified binding sites. Receptorbound uPA can be inactivated by the plasminogen activator inhibitors PAI-1 and PAI-2. Binding of the ECM-associated inhibitor PAI-1 to the receptor-linked uPA in turn triggers the internalization of the whole complex and the reexpression of the receptor at new sites. This provides a mechanism for coordinated regulation of uPAR turnover, cell surface plasminogen activation and cellular migration (Mignatti, P., and Rifkin, D. B. (1993) Physiol. Rev. 73, 161-195). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anti-tumor vaccine Inventor(s): Conner, John; (Sherman Oaks, CA), Minshall, Bill; (Irvine, CA), Minshall, Suzanne; (Irvine, CA), Skotzko, Michael; (Thousand Oaks, CA) Correspondence: Stetina Brunda Garred & Brucker; 75 Enterprise, Suite 250; Aliso Viejo; CA; 92656; US Patent Application Number: 20030082136 Date filed: October 30, 2001 Abstract: A therapeutic vaccine for the treatment of melanoma, mast cell tumors and sarcoma in mammals. The vaccine preferably comprises at least one allogenic cell line providing at least one, and preferably two or more gangliosides selected from the group consisting of GD-2, GD-3, GM-2, GM-3, GD-1b and GT-1b. At least one cytokine selected from the group consisting of GM-CSF, IL-2, IL-4, and IL-12 and at least one heat shock protein selected from the group consisting of HSP-60, HSP-70 and HSP-90 are added as adjuvants. A bacterial organism may further be added as an adjuvant. Excerpt(s): The present invention is directed to therapeutic vaccines and methods for treating cancerous solid tumors, namely melanoma, carcinoma and sarcoma. The present invention is believed to be particularly well suited for canines, but is further believed to be equally useful in treating such cancers found in felines, equines and possibly human beings. As is well-known, solid tumors are characterized by a localized mass of tissue comprised of cells which multiply and grow uncontrollably, and ultimately crowd out normal cells. Such tumors can develop in any tissue of any organ and at any age in virtually all species of mammals. Although all solid tumors possess
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the ability to invade local tissues and metastasize, the same can be distinguished on the basis of the type of cells the tumors are composed. In this regard, melanomas arise from the skin, mucous membranes, eyes, and central nervous system, where pigment cells occur. Sarcomas arise from connective or supporting tissues, such as bone or muscle. Carcinomas arise from glandular and epithelial cells, which line body tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Classifying cancers Inventor(s): Ben-Dor, Amir; (Bellevue, WA), Bittner, Michael; (Rockville, MD), Chen, Yidong; (Rockville, MD), Dougherty, Edward; (College Station, TX), Jiang, Yuan; (Gaithersburg, MD), Meltzer, Paul; (Rockville, MD), Sampas, Nick; (San Jose, CA), Trent, Jeff; (Rockville, MD), Weeraratna, Ashani; (Owings Mil, MD), Yakhini, Zohar; (Zikhron Yaacov, IL) Correspondence: Agilent Technologies; Legal Department, 51upd; Intellectual Property Administration; P. O. Box 58043; Santa Clara; CA; 95052-8043; US Patent Application Number: 20030152923 Date filed: August 2, 2001 Abstract: The overexpression of certain marker genes including Wnt5a has been found useful in the identification of more aggressive forms of malignant melanoma. Therefore, the overexpression of these genes in tumor samples of malignant melanoma may be useful in the diagnosis, profiling, and treatment of patients suffering from this disease. Inhibitors of Wnt5a activity may be useful in the treatment of aggressive forms of malignant melanoma. Inhibition of Wnt5a activity may be effected by any method including anti-sense therapy, gene therapy, and pharmaceutical intervention. Excerpt(s): Cancer is the second leading cause of death in the United States after cardiovascular disease (Boring et al. Cancer J. Clin. 43:7, 1993; incorporated herein by reference). One in three Americans will develop cancer in his or her lifetime, and one of every four Americans will die of cancer. In order to better combat this deadly disease, efforts have recently focused on fine tuning the categorization of tumors; by categorizing cancers, physicians hope to better treat an individual's cancer by providing more effective treatments. Researchers and physicians have categorized cancers based on invasion, metastasis, gross pathology, microscopic pathology, imunohistochemical markers, and molecular markers. With the recent advances in gene chip technology, researchers are increasingly focusing on the categorization of tumors based on the expression of marker genes. The most common human cancers are malignant neoplasms of the skin (Hall et al. J. Am. Acad. Dermatol. 40:35-42, 1999; Weyers et al. Cancer 86:288299, 1999; each of which is incorporated herein by reference). The incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease (Byers et al. Hematol. Oncol. Clin. North Am. 12:717-735, 1998; McMasters et al Ann. Surg. Oncol. 6:467-475, 1999; each of which is incorporated herein by reference). Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular, or immunohistochemical marker defines subsets of this neoplasm (Weyers et al. Cancer 86:288-299, 1999; Byers et al. Hematol. Oncol. Clin. North Am. 12:717-735, 1998; each of which is incorporated herein by reference). Accordingly, though melanoma is thought to present with different "taxonomic" forms, these are considered part of a continuous spectrum rather than discrete entities (Weyers et al Cancer 86:288-299, 1999; incorporated herein by reference). Improved characterization and understanding of this potentially deadly disease would
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be valuable. The present invention provides a system for diagnosing aggressive forms of malignant melanoma based on the expression of certain marker genes within a tumor sample. In one embodiment, expression levels are determined for one or more of the following genes: Wnt5a (Seq. ID No.: 1, 2, & 3), MART-1 (Seq. ID No.: 4 & 5), pirin (Seq. ID No.: 6 & 7), HADHB (Seq. ID No.: 8 & 9), CD63 (Seq. ID No.: 10 & 11), EDNRB (Seq. ID No.: 12 & 13), PGAM1 (Seq. ID No.: 14 & 15), HXB (Seq. ID No.: 16 & 17), RXRA (Seq. ID No.: 18 & 19), integrin 1b (Seq. ID No.: 20 & 21), syndecan 4 (Seq. ID No.: 22 & 23), tropomyosin 1 (Seq. ID No.: 24 & 25), AXL (Seq. ID No.: 26 & 27), EphA2 (Seq. ID No.: 28 & 29), GAP43 (Seq. ID. No.: 30 & 31), PFKL (Seq. ID No.: 32 & 33), synuclein a (Seq. ID No.: 34 & 35), annexin A2 (Seq. ID No.: 36 & 37), CD20 (Seq. ID No.: 38 & 39), and RAB2 (Seq. ID No.: 40 & 41). In certain preferred embodiments, expression of a plurality of these genes is detected. In particularly preferred embodiments, Wnt5a is one of the genes whose expression is detected. According to the present invention, overexpression of Wnt5a in a tumor sample indicates a more aggressive form of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
COMPOSITION, FORMULATIONS & METHOD FOR PREVENTION & TREATMENT OF DISEASES AND CONDITIONS ASSOCIATED WITH BRONCHOCONSTRICTION, ALLERGY(IES) & INFLAMMATION Inventor(s): NYCE, JONATHAN W.; (PRINCETON, NJ) Correspondence: Viviana Amzel, PH.D.; Epigenesis Pharmaceuticals, INC.; 7 Clarke Drive; Cranbury; NJ; 05812; US Patent Application Number: 20030087845 Date filed: June 9, 1998 Abstract: A pharmaceutical composition effective for preventing and alleviating bronchoconstriction, allergy(ies) and/or inflammation comprises a surfactant and a nucleic acid comprising an oligonucleotide anti-sense to an adenosine A1, A2a, A2b or A3 receptor gene, mRNA, flanking regions or regions bridging the intro/exon borders, analogues which bind thymidine but have low adenosine content or exhibit lower or no adenosine receptor agonist activity, combinations thereof, physiologically acceptable salts thereof or mixtures thereof, and optionally a carrier and other agents such as therapeutic agents and formulation products known in the art. The composition is formulated for administration by a multiplicity of routes for the prevention or alleviation of diseases and conditions associated with breathing difficulties, impeded and obstructed airways, bronchoconstriction, allergy and/or inflammation. Among the appplications of this technology are the prevention and treatment of diseases and conditions such as asthma, kidney damage or failure, ARDS, pulmonary vasoconstriction, inflammation, allergies, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic, lung, breast, and prostate metastases, etc., to counter the renal damage and failure associated with ischemic conditions and the administration of certain drugs and radio active diagnostic and therapeutic agents, as well as a joint therapy with the administration of adenosine and adenosine-like agents in the treatment of arrhythmias such as SVT and in cardiovascular function tests (stress tests). The present agent(s) is (are) also suitable for administration before, during and after other treatments, including
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radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. Alternatively, the present agent may be effectively administered preventatively, prophylactically or therapeutically, and in conjunction with other therapies, or by itself for conditions without known therapies or as a substitute for therapies that have significant negative side effects. Excerpt(s): This invention relates to compositions and formulations of oligonucleotides and surfactants, which are highly effective for the prevention and treatment of diseases and conditions associated with difficult breathing, bronchoconstriction, impeded airways, allergy(ies) and inflammation of the lungs. Adenosine A.sub.1-mediated diseases and conditions, such as asthma and Acute Respiratory Distress Syndrome (ARDS), among others, are common diseases in industrialized countries, and in the United States alone account for extremely high health care costs. These diseases or conditions have recently been increasing at an alarming rate, both in terms of prevalence and mortality. Occupational asthma is predicted to be the preeminent occupational lung disease in the next decade. In many of these, the underlying causes remain poorly understood. Adenosine, a natural nucleoside, may constitute an important natural mediator of bronchial asthma and ARDS. The potential role of adenosine in these diseases or conditions is supported by experimental findings that, for example and in contrast to normal individuals, asthmatics respond to aerosolized adenosine with marked bronchoconstriction. Similarly, asthmatic rabbits produced using the dust mite allergic rabbit model of human asthma also were shown to respond to aerosolized adenosine with marked bronchoconstriction, while non-asthmatic rabbits showed no response. Recent work using this model system has suggested that adenosine-mediated bronchoconstriction in asthma is mediated through the stimulation of the adenosine A.sub.1 receptor. Other experimental data suggest the possibility that adenosine receptors may also be involved in allergic and inflammatory responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions for treatment of melanoma and method of using same Inventor(s): Bergman, Philip J.; (Tarrytown, NY), Houghton, Alan N.; (New York, NY), Wolchok, Jedd D.; (New York, NY) Correspondence: Oppedahl And Larson Llp; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20020150589 Date filed: November 27, 2001 Abstract: Melanoma can be treated in a mammalian subject by administering to the subject an immunologically-effective amount of a xenogeneic melanoma-associated differentiation antigen. For example, genetic immunization with a plasmid containing a sequence encoding human gp75 has been shown to be effective in treatment of dogs with melanoma. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/627,694, filed Jul. 28, 2000, and of U.S. patent application Ser. No. 09/308,697 filed May 21, 1999 which is a.sctn.371 National Phase of International Application No. PCT/US97/22669. This application claims the benefit under 35 USC.sctn.119(e) of U.S. Provisional Applications Nos. 60/036,419 filed Feb. 18, 1997; 60/032,535 filed Dec. 10, 1996 and 60/180,651 filed Jan. 26, 2000. All of the above-mentioned applications are incorporated herein by reference. This application relates to compositions for treatment of melanoma and to a method of using such compositions. The invention utilizes
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compositions containing xenogeneic differentiation antigens which are associated with melanoma to provide effective therapy. Differentiation antigens are tissue-specific antigens that are shared by autologous and some allogeneic tumors of similar derivation, and on normal tissue counterparts at the same stage of differentiation. Differentiation antigens have been shown to be expressed by a variety of tumor types, including melanoma, leukemia, lymphomas, colorectal carcinoma, breast carcinoma, prostate carcinoma, ovarian carcinoma, pancreas carcinomas, and lung cancers. For example, differentiation antigens expressed by melanoma cells include MelanA/MART-1, Pmel17, tyrosinase, and gp75. Differentiation antigen expressed by lymphomas and leukemia include CD19 and CD20/CD20 B lymphocyte differentiation markers). An example of a differentiation antigen expressed by colorectal carcinoma, breast carcinoma, pancreas carcinoma, prostate carcinoma, ovarian carcinoma, and lung carcinoma is the mucin polypeptide muc-1. A differentiation antigen expressed by breast carcinoma is her2/neu. The her2/neu differentiation antigen is also expressed by ovarian carcinoma. Differentiation antigens expressed by prostate carcinoma include prostate specific antigen, prostatic acid phosphatase, and prostate specific membrane antigen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cytostatic agents Inventor(s): Ayscough, Andrew Paul; (Oxford, GB), Drummond, Alan Hastings; (Oxford, GB), Pratt, Lisa Marie; (Oxford, GB) Correspondence: Greenberg Traurig, Llp; 885 3rd Avenue; New York; NY; 10022; US Patent Application Number: 20030149084 Date filed: December 10, 2002 Abstract: This invention provides a method of inhibiting proliferation of tumor cells in a subject by administering to the subject an effective amount of ester and thioester compounds containing an N-formyl hydroxylamine group.The compounds with which this invention is concerned thus represent a selection of a subclass from the compounds known in the art as MMP inhibitors, for a specific and previously unrecognized pharmaceutical utility in the inhibition of proliferation of rapidly dividing cells, including such tumor cells as lymphoma, leukemia, myeloma, adenocarcinoma, carcinoma, mesothelioma, teratocarcinoma, choriocarcinoma, small cell carcinoma, large cell carcinoma, melanoma, retinoblastoma, fibrosarcoma, leiomyosarcoma or endothelioma cells by a mechanism other than MMP inhibition. Excerpt(s): The present invention relates to N-formyl hydroxylamine derivatives, to processes for their preparation, to pharmaceutical compositions containing them, and to the use of such compounds in medicine. In particular, the compounds are inhibitors of the proliferation of a range of rapidly dividing tumour cells, for example melanoma and/or lymphoma cells. There is a need in cancer therapy for therapeutic compounds which are inhibitors of the proliferation of tumour cells. One compound which is known to have such activity is 5-fluorouracil (5FU). Patent publication WO 98/11063 describes and claims the use of certain hydroxamic acid derivatives as inhibitors of tumour cell proliferation, and also describes and claims certain novel hydroxamic acids useful for that purpose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Detection of melanoma Inventor(s): Bastian, Boris; (San Francisco, CA), Pinkel, Daniel; (Walnut Creek, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030073119 Date filed: September 9, 2002 Abstract: The present invention provides methods of screening for the presence of premalignant melanocytes in a sample from a patient. The methods comprise contacting a nucleic acid sample from a biological sample from the patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region which is amplified in melanoma cells. Excerpt(s): Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment by complete excision is of great importance because advanced melanoma has a poor prognosis and most melanomas are curable if excised in their early stages. In most instances the transformed melanocytes produce increased amounts of pigment so that the area involved can easily be seen by the clinician. When the excision margins of a melanoma are identified based on this macroscopic appearance and no margin of seemingly uninvolved skin is excised, melanoma has the risk of local recurrence. This has led to the recommendation to remove a safety margin of normal skin that varies from 0.5 to 3 cm depending on the thickness of the primary tumor (Wingo, P. A. et al., Cancer 82:1197-207 (1998); Rigel, D. S. et al., J Am Acad Dermatol 34:839-47 (1996); McGovern, V. J. et al., Cancer 32:1446-57 (1973)). It is obvious that the resulting defect inflicted by the excision can be considerable. If a melanoma measuring 2 cm in diameter that has a thickness of >4 mm is to be excised under the current guidelines, the resulting defect would be 8 cm (2+3+3 cm) in diameter. The closure of excisions with 2-3 cm margins usually require skin grafting and have the potential of adverse consequences such as unsatisfactory cosmetic result, increased morbidity and costs, and sometimes permanent functional impairment. Even with "adequate" safety margins, the melanoma can recur locally. Obviously, it would be desirable if the margins could be tailored to the needs of the individual patient's tumor. Unfortunately, so far, no technique exists that is able to detect the extent of a tumor accurately. In some types of melanomas the horizontally expanding portion of the tumor mainly consists of single melanocytes along the basal layer of the epidermis. These melanoma types are referred to as lentiginous melanomas. In these, the amount of atypical cells often gradually diminishes towards the margins so that it can be difficult or impossible for the pathologist to determine the border of the melanoma. However, current thinking implies that in most instances, the extent of a melanoma can be assessed by pathology. The fact that the removal of a margin of "healthy" skin reduces the recurrence rate, however, suggests that this skin is actually not healthy but contains residual melanoma which is undetectable by current methods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Genetic changes in atypical nodular proliferations in congenital melanocytic nevi Inventor(s): Bastian, Boris C.; (San Francisco, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030143543 Date filed: January 4, 2002 Abstract: The invention provides methods of distinguishing benign growths arising from congenital melanocytic nevi from malignant melanoma. The methods comprise detecting a change in chromosome number that is specifically associated with benign growths. These changes include a gain of chromosome 10, a gain of chromosome 11, and a loss of chromosome 7. Excerpt(s): The melanocyte can give rise to a number of morphologically different tumors. Most of them are biologically benign and are referred to as melanocytic nevi. Examples of melanocytic nevi are congenital nevi, Spitz nevi (including pigmented spindle cell nevi, which are regarded as a subtype of Spitz nevi), dysplastic or Clark's nevi, blue nevi, lentigo simplex, and deep penetrating nevus. Patients with congenital melanocytic nevi (CMN) have an increased risk of developing melanoma. Whereas in small--(<1.5 cm) and intermediate-sized CMN (1.5-20 cm) the risk seems to be low (Rhodes, A. R., Med Clin North Am., 70:3-37 (1986); Sahin, S. et al., J Am Acad Dermatol., 39:428-33 (1998)), large CMN (>20 cm) carry a 5-15x times increased future risk to develop melanoma and rarely, other neural crest derived malignancies ((Swerdlow, A. J. et al., J Am Acad Dermatol., 32:595-9 (1995); Ruiz-Maldonado, R. et al., J Pediatr., 120:906-11 (1992); Quaba, A. A. and Wallace, A. F., Plast Reconstr Surg., 78:174-81 (1986); Gari, L. M. et al., Pediatr Dermatol., 5:151-8 (1988); Egan, C. L. et al., J Am Acad Dermatol., 39:923-32 (1998); Bittencourt, F. V. et al., Pediatrics, 106:736-41 (2000); DeDavid, M. et al., J Am Acad Dermatol., 36:409-16 (1997); Marghoob, A. A. et al., Arch Dermatol., 132:170-5 (1996)). Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment is of great importance because advanced melanoma has a poor prognosis, but most melanomas are curable if excised in their early stages. Although, in general the histopathological diagnosis of melanoma is straightforward, there is a subset of cases in that it is difficult to differentiate melanomas from benign neoplasms of melanocytes, which have many variants that share some features of melanomas (LeBoit, P. E. Stimulants of Malignant Melanoma: A Rogue's Gallery of Melanocytic and Non-Melanocytic Imposters, In Malignant Melanoma and Melanocytic Neoplasms, P. E. Leboit, ed. (Philadelphia: Hanley & Belfus), pp. 195-258 (1994)). Even though the diagnostic criteria for separating the many simulators of melanoma are constantly refined, a subset of cases remains, where an unambiguous diagnosis cannot be reached (Farmer et al., Discordance in the Histopathologic Diagnosis of Melanoma and Melanocytic Nevi Between Expert Pathologists, Human Pathol. 27: 528-31 (1996)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human-derived bradeion proteins, DNA coding for the proteins, and uses thereof Inventor(s): Tanaka, Manami; (Ibaraki, JP), Tanaka, Tomoo; (Kanagawa, JP) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030113753 Date filed: July 10, 2002 Abstract: This invention relates to a human-derived bradeion protein having the following properties:(i) it is a transmembranous protein;(ii) it has a transmembranous portion, an extracellular portion, and a cytoplasmic portion in its molecule as determined by a hydrophobicity analysis according to Kyte-Doolittle method;(iii) it is expressed in the human adult normal brain and heart, the expression level thereof in the heart being about 10% or lower of that in the brain, while it is not expressed in other adult normal organs of spleen, lung, liver, skeletal muscle, kidney and pancreas, and in fetal brain, lung, heart and kidney;(iv) it induces programmed cell death when overexpressed in a cultured human brain-derived undifferentiated nerve cell line;(v) it induces termination of cell division and aging when over-expressed in a cultured human brain-derived differentiated nerve cell;(vi) it is located in cytoplasm in the course of the induced cell death, and forms an intracellular aggregate when overexpressed; and(vii) it is expressed in a human colorectal cancer cell line or in a human malignant melanoma cell line, but not in leukemia, lymphoma and lung carcinoma,to a DNA encoding said bradeion protein, to a vector comprising said DNA, to a host cell comprising said vector, and to a method for detecting a cancer such as colorectal cancer or malignant melanoma. Excerpt(s): Japan Priority Application 325380/1998, filed Nov. 16, 1998, including the specification, drawings, claims and abstract, is incorporated herein by reference in its entirety. U.S. Priority application Ser. No. 09/440,936, filed Nov. 16, 1999, including the specification, drawings, claims and abstract, is incorporated herein by reference in its entirety. The present invention relates to a protein involved in long-term survival of cranial nerve cell, to DNA encoding the protein, and to uses thereof. More particularly, the present invention relates to human-derived bradeion protein or derivatives thereof, to DNA encoding the protein or the derivatives thereof, to a vector containing the DNA, to a host cell transformed or transfected with the vector, to an antibody immunologically reactive with the protein or the derivatives thereof, and to uses of the DNA or the antibody for detecting a cancer. Cranial nerve cells (neurons) are main elements for controlling survival of higher order animals. Once the neurons are produced, they do not divide at all and only gradually exfoliate or go through necrosis. Exfoliation of the neurons occurs in the normal state but is particularly accelerated by genetic diseases, brain ischemia, or status epilepticus, or under conditions of poor nutrition and low oxygen. Some disorders of cranial nerves associated with aging (e.g., dementia) result from deficiency of an absolute amount of functional neurons caused by accumulation of exfoliated neurons. Thus, the monitoring and control of the exfoliation, as well as regeneration of the functions of neurons, are the most demanding subject to be solved among the aging problems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Immunogenic targets for melanoma Inventor(s): Karunakaran, Liza; (Thornhill, CA), Pedyczak, Artur; (Pickering, CA), Barber, Brian; (White Plains, NY), Emtage, Peter; (Sunnyvale, CA) Correspondence: Patrick Halloran; Aventis Pasteur; One Discovery Drive; Swiftwater; PA; 18370; US Patent Application Number: 20030113919 Date filed: August 15, 2002 Abstract: The present invention relates to peptides, polypeptides, and nucleic acids and the use of the peptide, polypeptide or nucleic acid in preventing and/or treating cancer. In particular, the invention relates to peptides and nucleic acid sequences encoding such peptides for use in diagnosing, treating, or preventing melanoma. Excerpt(s): This application claims priority to U.S. Ser. No. 60/313,438 filed Aug. 17, 2003; No. 60/313,572 filed Aug. 17, 2001; No. 60/313,573 filed Aug. 17, 2001; No. 60/313,572 filed Aug. 17, 2001; and, No. 60/313,574 filed Aug. 17, 2001. There has been tremendous increase in last few years in the development of cancer vaccines with tumour-associated antigens (TAAs) due to the great advances in identification of molecules based on the expression profiling on primary tumours and normal cells with the help of several techniques such as high density microarray, SEREX, immunohistochemistry (IHC), RT-PCR, in-situ hybridization (ISH) and laser capture microscopy (Rosenberg, Immunity, 1999; Sgroi et al, 1999, Schena et al, 1995, Offringa et al, 2000). The TAAs are antigens expressed or over-expressed by tumour cells and could be specific to one or several tumours for example CEA antigen is expressed in colorectal, breast and lung cancers. Sgroi et al (1999) identified several genes differentially expressed in invasive and metastatic carcinoma cells with combined use of laser capture microdissection and cDNA microarrays. Several delivery systems like DNA or viruses could be used for therapeutic vaccination against human cancers (Bonnet et al, 2000) and can elicit immune responses and also break immune tolerance against TAAs. Tumour cells can be rendered more immunogenic by inserting transgenes encoding T cell costimulatory molecules such as B7.1 or cytokines such as IFN-.gamma., IL2, or GM-CSF, among others. Co-expression of a TAA and a cytokine or a co-stimulatory molecule can develop effective therapeutic vaccine (Hodge et al, 95, Bronte et al, 1995, Chamberlain et al, 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Intratumoral use of dinitrochorobenzene: composition and use of injections including particular applications Inventor(s): Cohen, Max Harry; (Potamac, MD) Correspondence: Max H. Cohen, M.D.; 8812 Twin Creek Court; Potomac; MD; 20854; US Patent Application Number: 20030072825 Date filed: October 17, 2001 Abstract: Dinitrohalogenated compounds may be utilized by injection in certain clinical situations to provide a possibility of long term control of human malignancy. In some of those settings no other treatment offers such potential. Preparation methods may include acetone, olive oil, microsomes, liposomes, or combinations thereof. Optimum pretreatment management, dosing and injection techniques are described.The unique
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aspects of the claims included herein include the methods of preparation of the chemical, the technique of injection, the dosage of each injection, and the range of potential tumor histologies. These techniques have resulted for example in successful treatment of locally metastatic scalp melanoma, the treatment for which had previously been uniformly unsuccessful. This example is particularly significant since this is one example of a site that is not otherwise amenable to successful treatment when affected by multiple progressive metastatic nodules. This condition was untreatable for cure by any other previous method, including surgery. Excerpt(s): Intratumoral use of dinitrochorobenzene: composition and use of injections including particular applications. This invention pertains to the treatment of benign and malignant tumors by injections. Dinitrochlorobenzene (or DNCB) and other dinitrohalogenated compounds are chemicals which, when applied to the skin, act as a haptens with associated skin proteins and elicit immunological responses in individuals with intact immune systems. DNCB has, in the past, been topically applied to the surface of the skin to areas of actinic damage, or to the surface of some human tumors, primarily superficial skin tumors such as basal cell carcinomas. The current application describes the use of the chemical as an agent for injection, and describes techniques and dosages that optimize its use as an anti-cancer agent against more aggressive malignancies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Malignancy detection apparatus Inventor(s): Rogers, Gary; (Fleggburgh, GB), Shopland, Mark Hugh; (Norwich, GB) Correspondence: Alexis Barron; Synnestvest & Lechner; 2600 Market Tower; 1101 Market Street; Philadelphia; PA; 19107-2950; US Patent Application Number: 20030167008 Date filed: May 2, 2003 Abstract: Melanoma is currently a major concern to the general public, and referrals of patients to hospitals by doctors in general practice have multiplied in number. It would be advantageous if a system were available for use by such doctors that was capable of reliably testing skin lesions to determie whether or not a particular lesion was malignant. The present invention proposes such a system using an infra-red sensor in a housing (10) that is scanned, in a measurable, position-aware manner, over the skin to sense the skin's temperature in the area of and around the suspect lesion. The sensor's output being recorded and then displayed to provide a profile of the temperature along the scanned track, from which profile can be deduced something about the likely nature of the lesion. Excerpt(s): This invention is concerned with malignancy detection apparatus, and relates in particular to a system for detecting skin and sub-skin malignancies, especially but not exclusively melanoma. The expression "sub-skin" malignancies used herein means malignancies which lie immediately beneath the skin, such as sub-skin growths of mole-like form. The invention is not intended to include the detection of deep seated malignancies, in respect of which the signal-processing techniques hereinafter described would in general be inapplicable. Melanoma is a highly malignant form of skin cancer which manifests itself as a mole-like lesion on the skin. However, at present a cancerous lesion is not readily distinguishable from a benign mole without clinical examination at a hospital, and after histological examination. Somewhat analogously, some forms of
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sub-skin breast cancer are not readily distinguishable from sub-surface cysts, and require removal and histological examination for proper identification. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mammalian alpha-kinase proteins, nucleic acids and diagnostic and therapeutic uses thereof Inventor(s): Ryazanov, Alexey; (Princeton, NJ) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20020177205 Date filed: April 10, 2001 Abstract: The present invention provides novel mammalian alpha-kinase proteins: melanoma alpha-kinase (MK), heart alpha-kinase (HK), kidney alpha-kinase (KK), skeletal muscle alpha-kinase (SK), and lymphocyte alpha-kinase (LK). In particular, a novel kinase type is herein provided, characterized by the presence of an alpha-kinase catalytic domain and an ion channel domain. Isolated nucleic acids of the alpha-kinases MK, HK, KK, SK and LK are provided. Methods for making the novel alpha-kinases, cells that express the alpha-kinases and methods for treating an animal in need of either increased or decreased activity of the alpha- kinases are provided. Excerpt(s): The present application is a continuation-in-part of copending application Ser. No. 09/632,131 filed Aug. 3, 2000, of which the instant application claims the benefit of the filing date pursuant to 35 U.S.C.sctn. 120, and which is incorporated herein by reference in its entirety. This invention relates generally to the identification of a new superfamily of eukaryotic protein alpha kinases, and particularly to members of a subfamily selected from the group of melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase. The invention further relates to the use of the alpha kinases in assays to screen for specific modulators thereof. Isolated nucleic acids encoding the alpha kinases--melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase--are provided herein. Protein phosphorylation plays a critical role in many cellular processes (Krebs (1994) Trends Biochem. Sci. 19:439; Hanks and Hunter, (1996) FASEB J 9:576-596; Hardie and Hanks, (1995) The Protein Kinase Facts Book (Academic, London)). There are two well-characterized superfamilies of protein kinases, with most of the protein kinases belonging to the serine/threonine/tyrosine kinase superfamily (Hanks and Hunter, (1996); Hardie and Hanks, (1995)). The characterization of several hundred members of this superfamily revealed that they all share a similar structural organization of their catalytic domains which consist of twelve conserved subdomains (Hanks and Hunter, (1996); Hardie and Hanks, (1995)). The other superfamily is referred to as the histidine kinase superfamily and is involved in the prokaryotic two-component signal transduction system, acting as sensor components (Stock et al., (1989) Microbiol. Rev. 53:450-490; Parkinson and Kofoid, (1992) Annu. Rev. Genet. 26:71-112; Swanson, et al., (1994) Trends Biochem. Sci. 19:485-490). Recently, eukaryotic members of this superfamily have also been described (Chang et al., (1993) Science 263:539-544; Ota and Varshavsky, (1993) Science 262:566-569; Maeda et al., (1994) Nature 369:242-245). Mitochondrial protein kinases have also recently been described that show structural homology to the histidine kinases, but phosphorylate their substrates on serine (Popov et al., (1992) J. Biol. Chem. 267:13127-13130; Popov et al., (1993) J. Biol. Chem. 268:26602-22606). Finally, several new protein kinases have been reported that show a lack of homology with either of the kinase superfamilies (Maru
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and Witte, (1991) Cell 67:459-468; Beeler et al., (1994) Mol. Cell, Biol. 14:982-988; Dikstein et al., (1996) Cell 84:781-790; Futey et al., (1995) J. Biol. Chem. 270:523-529; Eichenger et al., (1996) EMBO J. 15:5547-5556). However, these protein kinases are viewed as an exception to the general rule as they have yet to be fully characterized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
MAP-2 as a determinant of metastatic potential Inventor(s): Fang, Dong; (Winston-Salem, NC), Setaluri, Vijayasaradhi; (Winston-Salem, NC), White, Wain; (Winston-Salem, NC) Correspondence: Kilpatrick Stockton Llp; 1001 West Fourth Street; Winston-salem; NC; 27101 Patent Application Number: 20020192727 Date filed: March 20, 2001 Abstract: The invention relates to detection of MAP-2 (microtubule associated protein-2) as a marker to determine the metastatic potential of a tumor, including tumors derived from the neural crest such as melanomas, gliomas, Schwanomas, chromocytomas and small cell lung cancer. In one aspect, the invention comprises a method for determining the metastatic potential of a tumor sample, wherein decreased levels of MAP-2 expression in a test sample relative to controls indicates that the sample has increased metastatic potential as compared to the control. In another aspect, the invention comprises a method to prevent tumor progression in metastatic melanoma by increasing levels of MAP-2 protein in cells. Excerpt(s): Portions of this work were funded by the National Institutes of Health (NIH) grants AR44617 and NS30985 and a Dermik Laboratory Research Fellowship grant from the Dermatology Foundation. The invention relates to methods for the detection, diagnosis, prognosis and treatment of cancer. Specifically, the invention describes the detection of microtubule associated protein-2 (MAP-2) in tumor cells, and the use of MAP-2 as an indicator of metastatic potential. The invention also describes the use of MAP-2 to prevent non-metastatic primary tumors from progressing to later stage disease. Publications referred to throughout the text of this document are incorporated by reference in their entireties in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Kawakami, Yutaka; (Rockville, MD), Rosenberg, Steven A.; (Potomac, MD) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030144482 Date filed: July 3, 2001 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this
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invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 08/231,565 filed on Apr. 22, 1994, which is herein incorporated by reference in its entirety. This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins. Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S.; W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S.; W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma associated antigenic polypeptide, epitopes thereof and vaccines against melanoma Inventor(s): Adema, Gosse Jan; (Nijmegen, NL), Figdor, Carl Gustav; (Nijmegen, NL) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030216559 Date filed: May 1, 2002 Abstract: A melanoma associated antigen known as gp100 and peptides derived from the antigen. Gp100 and its peptide derivatives can be used in vaccines for the treatment of melanoma. Another aspect of the invention is host-cells capable of expressing gp100 for the gp100-derived peptides. Furthermore, tumor-infiltrating lymphocytes (TILs) specifically recognizing gp100 are described, as are vaccines with these TILs. Also disclosed are diagnostics for the detection of melanoma and for the monitoring of vaccination. Excerpt(s): This application is a continuation of, and claims priority from, U.S. patent application Ser. No. 08/388,852, filed Feb. 19, 1995, now U.S. Pat. No. ______, which itself claims priority from EP 94200337.7, filed Feb. 16, 1994, and EP 94203709.4, filed Dec. 21, 1994. U.S. patent application Ser. No. 08/388,852, EP 94203709.4 and 94200337.7 are hereby incorporated by this reference as if set forth in their entirety herein. The present invention is concerned with cancer treatment and diagnosis, especially with a
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melanoma associated antigen, epitopes thereof, vaccines against melanoma, tumor infiltrating T lymphocytes recognizing the antigen and diagnostics for the detection of melanoma and for the monitoring of vaccination. Tumor cells may emancipate themselves from restrictive growth control by oncogene activation, and/or by the inactivation of tumor suppression genes. The course of tumor progression proceeds by a series of gradual, stepwise changes in different "unit characteristics", i.e., phenotypic traits, many of which are known to be determined or at least influenced by the altered expression of defined oncogenes and/or tumor suppressive genes. Emancipation of the cell from immunological host restriction may follow multistep pathways similar to the emancipation from growth control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma differentiation associated gene - 5 and promoter and uses thereof Inventor(s): Fisher, Paul B.; (Scarsdale, NY), Gopalkrishnan, Rahul V.; (New York, NY), Kang, Dong-Chul; (Rutherford, NJ) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20030092043 Date filed: August 26, 2002 Abstract: The invention provides for an isolated nucleic acid encoding Mda-5 (melanoma differentiation associated gene-5) and an isolated Mda-5 polypeptide. The invention further provides a vector comprising the nucleic acid encoding Mda-5, as well as a host cell comprising the vector. The invention provides an antibody which specifically binds to an Mda-5 polypeptide. The invention further provides a method for determining whether a compound is an inducer of Mda-5 gene expression and assays to determine whether a compound modifies the enzymatic activity of the Mda-5 polypeptide. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/515,363, filed Feb. 29, 2000, the contents of which are hereby incorporated by reference. Throughout this application, various publications are referenced by author and date within the text. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. All patents, patent applications and publications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Abnormalities in differentiation are common occurrences in human cancers ((1)Fisher and Grant, 1985; (2) Waxman, 1995). Moreover, as cancer cells evolve, ultimately developing new phenotypes or acquiring a further elaboration of preexisting transformation-related properties, the degree of expression of differentiation-associated traits often undergo a further decline. These observations have been exploited as a novel means of cancer therapy in which tumor cells are treated with agents that induce differentiation and a loss of cancerous properties, a strategy called `differentiation therapy` ((2-4) Waxman et al., 1988, 1991; Jiang et al., 1994; Waxman, 1995). In principle, differentiation therapy may prove less toxic than currently employed chemotherapeutic approaches, including radiation and treatment with toxic chemicals. The ability to develop rational schemes for applying differentiation therapy clinically require appropriate in vitro and in vivo model systems for identifying and characterizing the
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appropriate agent or agents that can modulate differentiation in cancer cells without causing undue toxicity to normal cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma risk detection Inventor(s): Bergman, Wilma; (Oegstgeest, NL), Box, Neil F.; (Queensland, AU), Duffy, David L.; (Stafford, AU), Frants, Rune R.; (Hoofddorp, NL), Gruis, Nelleke A.; (Leiderdorp, NL), Hayward, Nicholas K.; (Queensland, AU), Martin, Nicholas G.; (Queensland, AU), Sturm, Richard A.; (Queensland, AU), Van Der Velden, Pieter A.; (Leiden, NL) Correspondence: Akin Gump Strauss Hauer & Feld L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103-7013; US Patent Application Number: 20030175721 Date filed: March 28, 2002 Abstract: A method of determining predisposition to melanoma is provided in the form of a molecular diagnostic method that detects the presence of a cyclin dependent kinase inhibitor 2A mutant allele and/or a melanocortin-1 receptor variant allele. The presence of a cyclin dependent kinase inhibitor 2A mutant allele increases the probability that an individual carrying a melanocortin-1 receptor variant allele will develop melanoma. Similarly, the presence of a melanocortin-1 receptor variant allele increases the probability that an individual carrying a cyclin dependent kinase inhibitor 2A mutant allele will develop melanoma. Excerpt(s): This application is entitled to priority pursuant to 35 U.S.C.sctn. 119(e) to U.S. provisional patent application 60/279,515, which was filed on Mar. 28, 2001. Germline mutations in three different genes have been shown to influence risk of melanoma, specifically those encoding: cyclin dependent kinase inhibitor 2A (CDKN2A) (Hussussian et al. 1994; Kamb et al. 1994a), cyclin dependent kinase 4 (CDK4) (Zuo et al. 1996; Soufir et al. 1998) and the melanocortin-1 receptor (MC1R) (Palmer et al. 2000). The basis of melanoma risk as determined by these genes probably revolves around at least two independent pathways (Whiteman et al. 1998), one being the CDKN2A/CDK4 cell cycle and tumor suppressor gene axis, and the other a pigmentary mediated predisposition axis implicated by the recent association of MC1R variants with red hair, fair skin, freckling and melanoma (Palmer et al. 2000). Melanoma risk attributable to MC1R may arise through the action of solar UV-light on lighter skin tones with diminished tanning capacity (Bliss et al. 1995; Breitbart et al. 1997) or possibly through a more direct intrinsic effect on melanocytic cellular transformation. On the other hand, linkage of a quantitative trail locus (QTL) accounting for 33% of variance in flat mole count to the 9p21-22 region containing CDKN2A (Zhu et al. 1999) suggests that CDKN2A mutation may play a role in determination of mole density which in turn predisposes to later melanoma formation; this appears to be a risk factor quite distinct from the red hair and fair skin associated with MC1R variants (Garbe et al. 1994; Bliss et al. 1995; Grange et al. 1995; Grulich et al. 1996). The p16.sup.INK4A protein encoded by the CDKN2A locus (Kamb et al. 1994b; Nobori et al. 1994) acts as a tumor suppressor that induces G1 cell cycle arrest through binding to and inhibiting the kinase activities associated with cyclin D complexes with both cyclin-dependent kinase 4 and 6 (CDK4 and CDK6). G1-S phase transition is usually dependent upon phosphorylation of the retinoblastoma protein (pRB) by the cyclinD1/CDK4 complex (Serrano et al. 1993; Lukas et al. 1995). Inactivation of CDKN2A via one of several mechanisms (homozygous
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deletion, mutation and/or promoter methylation) is a frequent event in tumors of many types (e.g. Kamb et al. 1994b; Nobori et al. 1994; reviewed by Ruas and Peters 1998). Furthermore, presence of mutations of this locus in the germline of a small proportion of familial melanoma patients (e.g. Hussussian et al. 1994; Kamb et al. 1994a; reviewed by Hayward 1998) indicates that p16 inactivation is an early and possibly initiating step in melanoma tumorigenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and composition for selectively inhibiting melanoma Inventor(s): DasGupta, Tapas K.; (River Forest, IL), Kim, Darrick S.H.L.; (Chicago, IL), Pezzuto, John M.; (River Forest, IL) Correspondence: Marshall, Gerstein & Borun; 6300 Sears Tower; 233 South Wacker; Chicago; IL; 60606-6357; US Patent Application Number: 20030181429 Date filed: December 12, 2002 Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor. Excerpt(s): This is a continuation-in-part application of U.S. patent application Ser. No. 08/407,756, filed on Mar. 21, 1995, now U.S. Pat. No. ______. This invention relates to compositions and methods of selectively inhibiting tumors and, more particularly, to treating a malignant melanoma using plant-derived compounds and derivatives thereof. Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. It is now theorized that one in 90 American Caucasians will develop malignant melanoma in their lifetime. While an increasing proportion of melanomas are diagnosed sufficiently early to respond to surgical treatment and achieve a greater than 90% ten-year survival rate, it is estimated that nearly 7,000 individuals suffering from metastatic melanoma will die in the United States this year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for detection of melanoma Inventor(s): Vogt, Thomas; (Pentling-Grossberg, DE) Correspondence: Gary Cary Ware & Friendenrich Llp; 4365 Executive Drive; Suite 1600; San Diego; CA; 92121-2189; US Patent Application Number: 20030108896 Date filed: June 27, 2002 Abstract: The present invention provides non-invasive methods for detecting, monitoring, staging, and diagnosing malignant melanoma in a skin sample of a subject. The methods include analyzing expression in skin sample of one or more melanoma skin markers. The melanoma skin markers include IL-1 RI, endothelin-2, ephrin-A5, IGF Binding Protein 7, HLA-A0202 heavy chain, Activin A (.beta.A subunit), TNF RII, SPC4,
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and CNTF R.alpha. The skin sample can include nucleic acids, and can be a human skin sample from a lesion suspected of being melanoma. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(e) to Provisional Application Serial No. 60/302,348, filed Jun. 28, 2001, which is incorporated herein by reference in its entirety. This invention relates to methods related to melanoma patient for detecting expression of genes in a skin sample of the epidermis related to malignant melanoma. Malignant melanoma ranks second among adult cancers (behind adult leukemia) in potential years of life lost. Each year, over 47,000 new cases are diagnosed, and the incidence of cutaneous melanoma appears to be rising rapidly. Treatment of malignant melanoma involves surgical excision of the primary lesion, and vigilant monitoring to detect recurrence. Currently, there is no approved therapy for patients having intermediate risk of relapse. High-dose interferon, which can have serious side effects, is approved for treatment of patients having high-risk melanoma. There is no cure at this time for patients in whom metastasis to distant sites has occurred. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for recognizing and determining GnRH receptors and use of GnRH agonist for decreasing the replication of malignant cells bearing GnRH receptors of tumors orginating in the nervous system and/or meninges and/or of Kaposi sarcoma Inventor(s): van Groeninghen, Johannes C. J.; (Dortmund, DE) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030166503 Date filed: December 20, 2002 Abstract: A method for recognizing and determining GnRH receptors on abnormal cells of a tumor originating in the brain and/or nervous system and/or the meninges and/or on Kaposi sarcoma. Also, preparing diagnostic kits for tumors originating in the brain and/or nervous system and/or the meninges and/or for Kaposi sarcoma. Further, a method for decreasing cellular replication of GnRH-positive glioma, oat-cell carcinoma, malignant melanoma, or Kaposi sarcoma comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist. Excerpt(s): This application is a continuation in part of co-pending U.S. Ser. No. 09/446,996, filed on Dec. 30, 1999, the contents of which are incorporated by this reference. The present invention relates to tumor diagnosis and therapy. In particular, it is directed to the diagnosis and therapy of tumors carrying GnRH receptors. Postoperative treatment of prostate and mamma carcinomas with agonists of gonadotropin releasing hormone (GnRH, in the literature also referred to as luteinizing hormone releasing hormone; LH-RH) is a standard treatment; cf. Gonzalez-Barcena et al., 1994, The Prostate 24, 84-92; Emons and Schally, 1994, Human Reproduction Update 9, No. 7, 1364-1379. The GnRH receptor is a well-known target in tumor therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of isolating extract from the euphorbaciae obesa plant and methods for using the same Inventor(s): Donato, Nicholas D.; (San Marcos, CA), Donato, Nicholas J.; (Sugarland, TX), McMurray, John S.; (Houston, TX), Newman, Robert A.; (Sugarland, TX), Perez, Margot; (Houston, TX), Sample, David C.; (Porter, TX) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030118677 Date filed: December 12, 2001 Abstract: The present invention is directed to a process of isolating an extract from a Euphorbaciae obesa (EO) plant by: preparing a sample of said plant comprising removal of the latex material; dissolving said sample with first solvent to form a solution; seperating said solution into a liquid and a pulp fraction; and purifying said pulp fraction. The isolated EO extract induces apoptosis and inhibits growth of a cancerous cell. Thus, the present invention is also directed to a method for inducing apoptosis and growth inhibition of a cancerous cell by contacting the cell with an effective amount of the EO extract by the process of the invention. Preferably, the extract is administered both to the tumor directly and intravenously. The preferred lines of cancerous cells are melanoma, non-small cell lung cancer, prostate cancer, breast carcinoma, ovarian cancer, lymphoma and leukemia cells. Excerpt(s): This invention generally relates to compounds for treating cancer that are derived from plants and, in particular, the isolation and use of an extract from a Euphorbaciae obesa plant having anti-tumor effects on a variety of cancerous cells. Plants and marine organisms provide a rich source of compounds that have been investigated and exploited for a variety of medicinal and biological applications. The Euphorbiaceae family is one of the largest families of plants with about 300 genera and 7,500 species, mostly monoecious herbs, shrubs and trees, sometimes succulent and cactus-like, that are further frequently characterized by a milky sap or latex material. Members of the Euphorbiaceae family have been investigated as providing potential treatments for cancers, tumors and warts. Active components found in members of this plant family may be common to several genera or species of the family or may be limited to a particular genus or species. Certain Euphorbiaceae species have been shown to synthesize phorbol ester and diterpene diester compounds having therapeutic effects on certain cancers. For instance, the isolation and characterization of antileukemic properties from Euphorbia esula L and Croton tiglium L. have been reported. S. M. Kupchan et al., Science 191: 571-572 (1976). The fractionation of an active extract led to the characterization of the antileukemic component from Euphorbia esula L as a diterpene diester. Fractionation of croton oil led to the characterization of the active component known as a phorbol diester, phorbol 12-tiglate 13-decanoate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for inhibition of tumorigenic properties of melanoma cells Inventor(s): Herlyn, Meenhard; (Wynnewood, PA), Satyamoorthy, Kapaettu; (Swarthmore, PA) Correspondence: Licata & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20020165188 Date filed: January 30, 2002
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Abstract: The present invention provides a method for preventing proliferation of melanoma cells by contacting melanoma cells with an agent which is capable of modulating the expression of E-cadherin in the melanoma cells thereby restoring keratinocyte control over melanoma cell proliferation. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/686,257 filed Oct. 11, 2000 which claims the benefit of priority of U.S. Ser. No. 60/159,353 filed Oct. 14, 1999. Melanoma is a relatively common cancer. The incidence of cutaneous melanoma has risen rapidly in the last several decades (Parker et al., 1997, C A Cancer J. Clin 47:5-27; Ries et al., 2000, Cancer, 88:2398-424). Melanoma is notorious for its propensity to metastasize and its poor response to current therapeutic regimens. The transition from benign lesions to invasive, metastatic cancer occurs through a complex process involving changes in expression and function of oncogenes or tumor suppressor genes (Meier et al., 1998, Am. J. Pathol. 156:193-200). In the human epidermis, melanocytes residing at the basement membrane are interspersed among basal keratinocytes. E-cadherin is physiologically expressed on the cell surface of keratinocytes and melanocytes, and is the major adhesion molecule (Hsu et al., 1996, J. Investig. Dermatol. Symp. Proc. 1:188-94; Tang et al., 1994, J. Cell Sci. 107:983-92). A progressive loss of E-cadherin expression occurs during melanoma development (Danen et al., 1996, Melanoma Res., 6:127-31; Hsu et al., 1996, J. Investig. Dermatolo Symp. Proc. 1:188-94; Scott & Cassidy, J. Invest Dermatol., 1998, 111:243-50; Silye et al., 1998, J. Pathol. 186:350-55). Under natural conditions, melanocytes express E-cadherin on their surface but melanoma cells do not (Hsu et al., 1994, J. Invest. Dermatol. Symp. Proc. 1:188-194). Additionally, melanoma cells express N-cadherin, while melanocytes do not. Melanoma cells express greater amounts of Mel-CAM and.alpha.sub.v.beta.sub.3 than do melanocytes. However, both cell types express.alpha.-catenin,.beta.-catenin and plakoglobin (Ozawa et al., J. Cell Biol., 1992, 116:989-996; Knudsen et al., 1995, J. Cell Biol. 130:67-77). Growth, proliferation, dendricity and cell-surface molecule composition of melanocytes are normally under the control of basal layer-type keratinocytes (Herlyn et al., 1987, Cancer Res. 47:3057-3061; Valyi-Nagy et al., 1993, Lab. Invest 69:152-159,; Shih et al., Am. J. Of Pathol., 1994, 145:837-845). Melanoma cells are refractory to the regulatory controls normally exerted by keratinocytes and therefore proliferate in an uncontrolled manner. Isolated and cultured melanocytes lose their normal phenotype, but regain it upon co-culture with basal layer type keratinocytes. The homeostatic effects of basal layer-type keratinocytes exert these effects upon melanocytes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mixed haptenized tumor cells and extracts and methods of treating or screening for cancer Inventor(s): Berd, David; (Wyncote, PA) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030165518 Date filed: February 3, 2003 Abstract: This invention relates to compositions comprising multi-haptenized tumor cells and extracts thereof, methods for preparing the compositions, vaccines comprising such multi-haptenized tumor cells, and methods for treating cancer with such vaccines. In a specific embodiment, melanoma and ovarian adenocarcinoma cells are multihaptenized, wherein the tumor cells are differentially haptenized either with a
Patents 251
dinitrophenyl group coupled to.epsilon.-amino groups, or with a sulfanilic acid group coupled to aromatic side chains of histidine and tyrosine. A method of SA-haptenization is also provided. Excerpt(s): This application claims priority from U.S. Provisional Application Serial No. 60/353,769, filed Feb. 1, 2002, which is hereby incorporated by reference in its entirety. The invention relates to compositions comprising mixed preparations of haptenized tumor cells or cell extracts, methods for preparing the compositions, vaccines comprising such compositions, and methods for treating cancer with such vaccines. An autologous whole-cell vaccine modified with the hapten dinitrophenyl (DNP) has been shown to produce inflammatory responses in metastatic sites of melanoma patients. The survival rates of patients receiving post-surgical adjuvant therapy with DNP-modified vaccine are markedly higher than those reported for patients treated with surgery alone. Intact or viable cells are preferred for the vaccine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mole monitoring system Inventor(s): Christy, Melanie Ann; (Crown Point, IN) Correspondence: Melanie A. Christy; 5022 W. 86th Place; Crown Point; IN; 46307; US Patent Application Number: 20030098580 Date filed: November 28, 2001 Abstract: The present invention is a nontechnical, nonmechanical, easy to use, healthcare product that allows any individual to monitor changes in moles, freckles, or other skin growths in the comfort of their own home. It doubles as a record-keeping system that allows a person to compare new measures to their previously recorded measures--notice a change has occurred--and make a potentially life-saving appointment with a dermatologist. By using the flexible transparent sheets and a numeric value system, the product identifies changes in size, shape, color, "geography" of the mole and if any bleeding has occurred; all of which are important features in the development of skin cancer or melanoma. This product does not diagnose or treat a disease, but most importantly it provides people with a means of discovering a potential problem that normally would be undetected by the naked eye. This product has the potential to decrease medical care costs, reduce human suffering, and save lives. Excerpt(s): The present invention relates to methods for detecting and monitoring the growth and change in size, shape, color, "geography", and bleeding in moles, freckles and/or other pigmented skin lesions, which normally are visually unnoticed. The present invention's classification pertains to the field of healthcare. Home healthcare, dermatology, as well as all areas of the medical field would either directly or indirectly be affected by its utilization. With skin cancer and deadly melanoma on the rise and a large percentage of the population unaware of the warning signs of skin cancer, people need a product that can help educate them about the warning signs of skin cancer; and empower individuals by putting their dermatologic health literally "in their own hands". Having no way for people to compare a mole to what it looked like one of two years prior, people do not give much thought to their moles or freckles. They see no reason to make an appointment with a dermatologist--everything seems fine. People can't get treatment if they don't see a physician--they don't see a physician unless they notice they have a problem. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel nucleic acid sequences encoding melanoma associated antigen molecules, aminotransferase molecules, ATPase molecules, acyltransferase molecules, pyridoxalphosphate dependant enzyme molecules and uses therefor Inventor(s): Bandaru, Rajasekhar; (Watertown, MA), Glucksmann, Maria Alexandra; (Lexington, MA), Meyers, Rachel E.; (Newton, MA), Rudolph-Owen, Laura A.; (Jamaica Plain, MA) Correspondence: Intellectual Property Group; Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030064439 Date filed: June 7, 2002 Abstract: The invention provides isolated nucleic acids molecules that encode novel polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a sequence of the invention has been introduced or disrupted. The invention still further provides isolated proteins, fusion proteins, antigenic peptides and antibodies. Diagnostic methods utilizing compositions of the invention are also provided. Excerpt(s): This application is a continuation-in-part of Ser. No. 10/034,864, filed Dec. 27, 2001, which claims the benefit of U.S. Provisional Application No. 60/258,517, filed Dec. 28, 2000; and a continuation-in-part of Ser. No. 09/996,194, filed Nov. 28, 2001, which claims the benefit of U.S. Provisional Application No. 60/250,348, filed Nov. 30, 2000, U.S. Provisional Application No. 60/250,073, filed Nov. 30, 2000, U.S. Provisional Application No. 60/253,878, filed Nov. 29, 2000, and U.S. Provisional Application No. 60/250,338, filed Nov. 20, 2000; and a continuation-in-part of Ser. No. 09/908,928, filed Jul. 19, 2001, which claims the benefit of U.S. Provisional Application No. 60/220,465, filed Jul. 20, 2000; and a continuation-in-part of Ser. No. 09/908,180, filed Jul. 18, 2001, which claims the benefit of U.S. Provisional Application No. 60/219,740, filed Jul. 20, 2000; and a continuation-in-part of 09/887,389, filed Jun. 22, 2001, which claims the benefit of U.S. Provisional Application No. 60/214,138, filed Jun. 26, 2000; and a continuation-in-part of Ser. No. 09/789,300, filed Feb. 20, 2001, which claims the benefit of U.S. Provisional Application No. 60/183,208, filed Feb. 17, 2000; all of which are hereby incorporated herein in their entirety by reference. The invention relates to novel nucleic acid sequences and polypeptides. Also provided are vectors, host cells, and recombinant methods for making and using the novel molecules. FIGS. 1A-1B depict a cDNA sequence (SEQ ID NO:1) and predicted amino acid sequence (SEQ ID NO:2) of human 22406. The methionine-initiated open reading frame of human 22406 (without the 5' and 3' untranslated regions) extends from, nucleotide position 69 to position 1088 of SEQ ID NO:1, not including the terminal codon (coding sequence shown in SEQ ID NO:3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 253
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Novel protein related to melanoma-inhibiting protein and uses thereof Inventor(s): Barnes, Thomas M.; (Brookline, MA), Pan, Yang; (Bellevue, WA) Correspondence: Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030224451 Date filed: April 9, 2003 Abstract: Novel TANGO 130 nucleic acid molecules which encode proteins having homology to melanoma-inhibiting protein are disclosed. In addition to TANGO 130 nucleic acid molecules and proteins, the invention further provides isolated TANGO 130 fusion proteins, antigenic peptides and anti-TANGO 130 antibodies. The invention also provides vectors containing nucleic acid molecules of the invention, host cells into which the vectors have been introduced and non-human transgenic animals in which a TANGO 130 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/785,770, filed on Feb. 16, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/387,462, filed on Sep. 1, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/145,056, filed on Sep. 1, 1998. The contents of each of the applications crossreferenced in this section are incorporated into this disclosure by this reference. A variety of factors participate in the tightly controlled regulation of cell growth and differentiation. One molecule believed to be involved in such regulation is MelanomaInhibiting Protein (MIA). Human and murine MIA cDNAs were first cloned from malignant melanoma cells and shown to inhibit growth of melanoma cells in vitro (Blesch et al. (1994) Cancer Res. 54:5695). Human MIA cDNA encodes a 24 amino acid signal peptide and a mature 107 amino acid secreted protein, and shares little or no homology with other known proteins. Cancer cells and embryonic cells are growth inhibited after treatment with MIA, observed as cell cycle arrest accompanied by a rounded up cell morphology and decreased adherence to the substrate. Furthermore, MIA expression is enhanced in developing cartilage and in chondrosarcoma (Bosserhoff et al. (1997) Dev. Dyn. 208:516). Based on this data, a biological role for MIA in embryonic cell growth and morphogenesis has been suggested, and a therapeutic application of MIA in the development of an antitumor therapeutic has been proposed. Additionally, MIA expression correlates with progressive malignancy of melanocytic lesions (Bosserhoff et al. (1997) J. Biol. Chem. 271:490), and MIA protein levels are enhanced in serum of patients with malignant melanoma (Bosserhoff et al. (1997) Cancer Res. 57:3149), supporting another proposed use of MIA as a marker of cancer progression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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NSAID-containing topical formulations that demonstrate chemopreventive activity Inventor(s): Evans, Allan; (Rosslyn Park, AU), McKinnon, Ross; (Aberfoyle Park, AU) Correspondence: Hogan & Hartson Llp; IP Group, Columbia Square; 555 Thirteenth Street, N.W.; Washington; DC; 20004; US Patent Application Number: 20030143165 Date filed: December 6, 2002
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Abstract: Disclosed herein are chemopreventive methods and topical formulations for the prevention and treatment of ultraviolet light-induced skin cancers, pre-cancerous lesions, and hyperproliferative disorders in mammals, such as humans, utilizing doses of non-steroidal anti-inflammatory drugs. Low doses of non-steroidal anti-inflammatory drugs are present in the topical formulations and allow continued regular use over an extended period of time to prevent such disorders. In particular, the present invention is particularly suitable for non-melanoma skin cancers as these cancers tend to appear in areas of the skin that have had excess sun exposure (head, neck and arms) meaning that the chemopreventive agent would not need to be applied over the entire body of the typical patient. Moreover, it is possible to identify "high-risk" individuals within the populations because people who report one episode of NMSC tend to have a high incidence of a subsequent episode. Excerpt(s): This application claims benefit of priority from the filing date of U.S. provisional patent application Ser. No. 60/350,957, filed Jan. 25, 2002. The present invention relates to the prevention and treatment of skin cancer and hyperproliferative skin disorders in mammals, including humans, with the use of topical medicaments. More particularly, the present invention relates to the prevention and treatment of nonmelanoma skin cancers with topical medicaments that are safe for continued use in target populations. Skin cancer is one of the most frequently diagnosed cancers among the Western populations. Exposure to ultraviolet light (UV light) is widely acknowledged to be the major etiologic factor in the development of skin cancers such as squamous and basal cell carcinomas, and it is also a risk factor for the development of melanomas. UV light has also been found in various studies to cause inflammation of the skin, epidermal hyperplasia, and changes in the expression of numerous genes associated with cell proliferation and differentiation, eicosanoid and cytokine production, and growth factor synthesis and responsiveness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nucleic acid molecule associated immunodetection and immunotherapy
with
prostate
cancer
and
melanoma
Inventor(s): Vielkind, Juergen R.; (Vancouver, CA) Correspondence: Leopold Presser, ESQ.; Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020146702 Date filed: May 11, 2001 Abstract: The present invention relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma and compositions derived therefrom. The present invention further relates to methods for diagnosing and treating prostate cancer and melanoma and other related pathological conditions by employing such nucleic acid molecules and compositions. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/255,583 filed Feb. 22, 1999, now allowed, which is a divisional of U.S. Ser. No. 08/869,285 filed Jun. 2, 1997 which is a continuation-in-part of U.S. Ser. No. 08/654,641, filed May 28, 1996, now U.S. Pat. No. 5,719,032, which is a continuation-in-part U.S. Ser. No. 07/829,855 filed Jan. 31, 1992, now U.S. Pat. No. 5,605,831, which disclosures are herein incorporated by reference. The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase
Patents 255
for the diagnosis and therapy of melanoma and prostate cancer. This invention also relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma for diagnosing and treating pathological conditions including prostate cancer and melanoma. The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is an extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Oncolytic RNA replicons Inventor(s): Ansardi, David Calvert; (Warrior, AL), Morrow, Casey Dolan; (Birmingham, AL), Porter, Donna Coker; (Warrior, AL) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20030040498 Date filed: March 13, 2002 Abstract: The limited efficacy and/or toxicity of conventional therapies for many types of human cancers underscores the need for development of safe and effective alternative treatments. Towards this goal, the invention describes the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incapable of producing infectious virus. Replicons of the invention are cytopathic in vitro for human tumor cells originating from brain, breast, lung, ovaries and skin (melanoma). Injection of replicons into established xenograft flank tumors in scid mice resulted in oncolytic activity and extended survival. Inoculation of replicons into established intracranial xenografts tumors in scid mice resulted in tumor infection and extended survival. Histological analysis revealed that replicons infected tumor cells at the site of inoculation and, most importantly, diffused to infect tumor cells which had metastasized from the initial site of implantation. The wide spectrum of cytopathic activity for human tumors combined with effective distribution following in vivo inoculation establishes the therapeutic potential of poliovirus replicons for a variety of cancers. Excerpt(s): This application is based on U.S. Provisional Application No. 60/275,840, filed Mar. 14, 2001, which is incorporated herein in its entirety by reference. Many malignant tumors respond poorly to current methods of treatment such as surgical
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resection, radiation therapy, and chemotherapy, with such methods often producing significant side effects. Consequently, treatments with greater efficacy, but with fewer and less severe side effects, must be sought. The use of viruses for the treatment of cancer has been investigated for almost fifty years (Asano T, 1974, Cancer 34:1907-1928; Moore AE, "Viruses with oncolytic properties and their adaptation to tumors", Annals of New York Acd. of Sci, pp. 945-952; Moore J P et al., 1993, J. Virol. 67:863-875; Southam C M, 1960, "Present status of oncolytic virus studies", The New York Academy of Sciences, pp. 657-673; Taylor M W et al., 1971, Pro. Natl. Acad. Sci. USA 68:836-840). Early on, viruses were identified which could selectively kill tumor cells without killing normal non-neoplastic cells. Work with the paramyxovirus, New Castle Disease Virus, showed promise in clinical trials as an anti-neoplastic agent (Cassel W A et al., 1963, Cancer 18:863-868; Cassel W A et al., 1983, Cancer 52:856-860; Lorence R M et al., 1994, Cancer Res. 54:6017-6021; Lorence R M et al., 1994, J. Natl. Can. Inst. 86:1228-1233; Reichard K W et al., 1992, J. of Surg. Res. 52:448-453; Smith R R et al., 1956, Cancer 9:1211-1218). Even with apparent neoplastic cell specific infection though, a concern still existed with respect to reversion for growth in non-neoplastic cells. The advent of molecular biology allowed the capacity for genetic manipulation of adenovirus, herpesvirus (HSV), or proviral genomes of retroviruses, to be engineered so as to allow a single round of infection without spread to neighboring cells (Roth J A et al., 1997, J. Natl. Can. Inst. 89:21-39). Subsequently, viruses have been generated to selectively replicate in tumor, but not normal cells by virtue of a viral dependence on a tumor specific protein (Khuri F R et al., 2000, Nature Med. 6:879-885; Strong J E et al., 1998, EMBO J. 17:3351-3362). Viruses have also been engineered to encode a cytotoxic protein to express a "suicide gene" that operates in conjunction with a prodrug (Klatzmann D et al., 1996, Human Gene Therapy 7:109-126; Andreansky S S et al., 1996, Proc. Natl. Acad. Sci. USA 93:11313-11318; Andreansky S et al., 1997, Cancer Research 57:1502-1509; Hughes B W et al., 1995, Cancer Research 55:3339-3345; Mullen C A et al., 1992, Proc. Natl. Acad. Sci. USA 89:33-37; Mullen C A et al., 1994, Cancer Research 54:1503-1506). This requirement introduces more complexity into the treatment system, and the potential toxicity of the prodrug or its toxic metabolite for normal tissues also must be considered. Even with these advancements in genetic engineering of viruses, a delicate balance is maintained between the capacity to selectively kill tumor cells and potential for pathogenicity in the host that has lead to the failure of clinical trials. The potential problems associated with many of viral vectors underscores the need for additional advancements. This is particularly true of brain tumors, such as glioblastomas. Malignant gliomas have proven to be a very difficult cancer to control and have resisted the various therapeutic interventions that have been attempted to treat this devastating disease. Most patients diagnosed with glioblastoma multiforme undergo surgical intervention in conjunction with radiation therapy and/or chemotherapeutic treatments. Nevertheless, despite these aggressive approaches to therapy, most patients die within one year of diagnosis (Kim J H et al., 1994, Cancer Res. 54:6053-6055; Andreansky S et al., 1996, Proc. Natl. Acad. Sci. USA 93:11313-11318). These survival odds have changed very little during the last thirty years, despite advances in imaging and detection, surgical techniques, chemotherapy and radiation therapy (Komblith P K et al.,1993, Surg. Neurol. 39:538-543). The poor prognosis for glioma patients and the resistance of the disease to traditional therapies underscore the necessity for development of effective treatments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 257
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Oncolytic/immunogenic complementary-adenoviral vector system Inventor(s): Alemany, Ramon; (Grayslake, IL), Fang, Xiangming; (Libertyville, IL), Zhang, Wei-Wei; (Libertyville, IL) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20020142989 Date filed: May 22, 2002 Abstract: This invention encompasses a composition for killing target cells, such as tumor cells. The composition comprises a first and a second adenoviral vector that have complementary function and are mutually dependent on each other for replication in a target cell. One of said adenoviral vectors has a target cell-activated promoter or a functional deletion that controls and limits propagation of the adenoviral vectors in the target cells which directly or indirectly kills the target cells. One of the adenoviral vectors comprises a gene encoding a protein which is expressed in the target cells and can induce anticancer immune responses. The target cells may be hepatoma, breast cancer, melanoma, colon cancer, or prostate cancer cells, for example. The vectors of this invention may also be utilized to treat other diseases such as restenosis, in which case the target cell may be a vascular smooth muscle cell, for example. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 08/797,160, filed Feb. 10, 1997, now U.S. Pat. No. ______. The invention is in the field of adenoviral vectors and their use in treating disease. Adenoviruses (Ad) consist of nonenveloped icosahedral (20 facets and 12 vertices) protein capsids with a diameter of 60-90 nm and inner DNA/protein cores (Horwitz, 1990). The outer capsid is composed of 252 capsomers arranged geometrically to form 240 hexons (12 hexons per facet) and 12 penton bases; the latter are located at each vertex from which protrude the antennalike fibers. This structure is responsible for attachment of Ad to cells during infection. Wild-type Ad contain 87% protein and 13% DNA and have a density of 1.34 g/ml in CsCl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Photodynamic therapy for pre-melanomas Inventor(s): Voet, Martin A.; (San Juan Capistrano, CA) Correspondence: Stephen Donovan; Allergan, INC.; 2525 Dupont Drive, T2-7h; Irvine; CA; 92612; US Patent Application Number: 20030176411 Date filed: March 15, 2002 Abstract: Method for treating dermal pre-melanoma conditions which include administering an effective amount of a photosensitive agent to a dermal pre-melanoma cell and activating the photosensitive agent, thereby treating a dermal pre-melanoma condition. Excerpt(s): The present invention relates to methods for treating pre-melanomas. In particular the present invention relates to methods for treating a pre-melanoma cell or condition using a photosensitive agent. Photodynamic therapy (PDT) is the use of an agent, given orally, intravenously, or topically, that can be activated or energized by light to inactivate or to cause necrosis of a target tissue in which the agent has
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accumulated. Activation of the agent results in the formation of new molecules and free radicals that form other chemicals that, in turn, can destroy the target tissue to varying extents or otherwise have a deleterious effect on the target tissue. Thus, photodynamic therapy involves the application of a photosensitive (photochemotherapeutic) agent to an affected area of the body, followed by exposure of the photosensitive agent to light of a suitable wavelength to activate the photosensitive agent and convert it into a cytotoxic form, whereby the affected cells are killed or their proliferative potential is diminished. A photosensitive agent can exert its desired effects by a variety of mechanisms, directly or indirectly. Thus for example, a photosensitizer can become directly toxic when activated by light, whereas other photosensitive agents act to generate toxic species, for example, oxidizing agents such as singlet oxygen or other oxygen-derived free radicals, which are extremely destructive to cellular material and biomolecules such as lipids, proteins and nucleic acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pyridoxal analogues and methods of treatment Inventor(s): Haque, Wasimul; (Edmonton, CA) Correspondence: Attention: Anna M. Nelson; Merchant & Gould P.C.; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030195236 Date filed: June 3, 2003 Abstract: Pyridoxal analogues can be useful for treating B.sub.6 deficiency and related diseases; cardiovascular and related diseases; melanoma and related diseases; and symptoms thereof. One such analogue is a compound of the formula: 1or a pharmaceutically acceptable acid addition salt thereof, in which R.sub.1 is alkyl, alkenyl, in which alkyl or alkenyl can be interrupted by nitrogen, oxygen, or sulfur, and can be substituted at the terminal carbon by hydroxy, alkoxy, alkanoyloxy, alkanoyloxyaryl, alkoxyalkanoyl, alkoxycarbonyl, or dialkylcarbamoyloxy; alkoxy; dialkylamino; alkanoyloxy; alkanoyloxyaryl; alkoxyalkanoyl; alkoxycarbonyl; dialkylcarbamoyloxy; or aryl, aryloxy, arylthio, or aralkyl, in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nito, or alkanoyloxy. These analogues can be administered, either alone or concurrently with known medications, to treat the above-described diseases. Excerpt(s): This invention relates to 3-acylated pyridoxal analogues and pharmaceutical compositions thereof and to treatments for cardiovascular and related diseases, for example, hypertrophy, hypertension, congestive heart failure, myocardial ischemia, arrhythmia, heart failure subsequent to myocardial infarction, myocardial infarction, ischemia reperfusion injury, blood coagulation, platelet aggregation, and diseases that arise from thrombotic and prothrombotic states in which the coagulation cascade is activated; treatments for vitamin B.sub.6 deficiency and related diseases, for example, hyperhomocysteinemia; and treatments for melanoma and related diseases. PLP is the biologically active form of vitamin B6 inside cells and in blood plasma. Mammals cannot synthesize PLP de novo and must rely on dietary sources of the precursors pyridoxine, pyridoxal, and pyridoxamine, which are metabolized to PLP. For instance, mammals produce PLP by phosphorylating pyridoxine by action of pyridoxal kinase and then oxidizing the phosphorylated product. PLP can also be chemically synthesized by, for example, reacting ATP with pyridoxal, reacting phosphorus oxychloride with pyridoxal in aqueous solution, and reacting pyridoxamine with concentrated phosphoric acid and then oxidizing the phosphorylated product. PLP is a regulator of biological processes
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and a cofactor in more than 100 enzymatic reactions. It has been shown to be an antagonist of a purinergic receptor, thereby affecting ATP binding; it has been implicated in modulation of platelet aggregation; it is an inhibitor of certain phosphatase enzymes; and it has been implicated in the control of gene transcription. PLP is also a coenzyme in certain enzyme-catalyzed processes, for example, in glycogenolysis at the glycogen phosphorylase level, in the malate asparatate shuttle involving glycolysis and glycogenolysis at the transamination level, and in homocysteine metabolism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Recombinant oncolytic adenovirus for human melanoma Inventor(s): Li, Yuanhao; (Palo Alto, CA), Yu, De Chao; (Foster City, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030039633 Date filed: January 15, 2002 Abstract: The invention provides melanoma cell specific adenovirus vectors, which preferentially replicate in melanoma cells. Excerpt(s): This application in a continuation-in-part of U.S. patent application Ser. No. 09/814,357, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,015 filed Mar. 24, 2000; and a continuation-in-part of U.S. patent application Ser. No. 09/814,351, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,156 filed Mar. 24, 2000. The technical field of the invention is methods of using adenoviral vectors for the suppression of melanoma. Neoplasia, also known as cancer, is the second most common cause of death in the United States. While the survival rates for individuals with cancer have increased considerably in the last few decades, survival of the disease is far from assured. Cancer is a catch-all term for over 100 different diseases, each of which are each fundamentally characterized by the unchecked proliferation of cells. Individual cancer cells are also able to break off from the main tumor, or metastasize, creating additional tumors in other regions of the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Recombinant virus immunotherapy Inventor(s): Cox, William I.; (Troy, NY), Paoletti, Enzo; (Delmar, NY), Tartaglia, James; (Schenectady, NY) Correspondence: Patrick J. Halloran; Intellectual Property, Aventis Pasteur INC.; Discovery Drive; Swiftwater; PA; 18370; US Patent Application Number: 20030198623 Date filed: October 9, 2002 Abstract: Attenuated recombinant viruses containing DNA coding for a cytokine and/or a tumor associated antigen, as well as methods and compositions employing the viruses, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least on of: human tumor necrosis factor;
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nuclear phosphoprotein p53, wildtype or mutant; human melanoma-associated antigen; IL-2; IFNg; IL-4; GNCSF; IL-12; B7; erb-B-2 and carcinoembryonic antigen. The recombinant viruses and gene products therefrom are useful for cancer therapy. Excerpt(s): This application is a continuation-in-part of application Ser. No. 08/007,115, filed Jan. 20, 1993, incorporated herein by reference. Application Ser. No. 08/007,115 is a continuation-in-part of application Ser. No. 07/847,951, filed Mar. 6, 1992, which in turn is a continuation-in-part of application Ser. No. 07/713,967, filed Jun. 11, 1991 which in turn is a continuation-in-part of application Ser. No. 07/666,056, filed Mar. 7, 1991; and, application Ser. No. 08/007,115 is also a continuation-in-part of application Ser. No. 07/805,567, filed Dec. 16, 1991, which in turn is a continuation-in-part of application Ser. No. 07/638,080, filed Jan. 7, 1991; and, application Ser. No. 08/007,115 is also a continuation-in-part of application Ser. No. 07/847,977 filed Mar. 3, 1992 as a division of application Ser. No. 07/478,179, filed Feb. 14, 1990 as a continuation-in-part of application Ser. No. 07/320,471, filed Mar. 8, 1989; all of which are hereby incorporated herein by reference. Reference is also made to copending U.S. applications Ser. Nos. 715,921, filed Jun. 14, 1991, 736,254, filed Jul. 26, 1991, 776,867, filed Oct. 22, 1991, and 820,077, filed Jan. 13, 1992, all of which are hereby incorporated herein by reference. The present invention relates to a modified poxvirus and to methods of making and using the same. More in particular, the invention relates to improved vectors for the insertion and expression of foreign genes for use as safe immunization vehicles to protect against a variety of pathogens, as well as for use in immunotherapy. Several publications are referenced in this application. Full citation to these references is found at the end of the specification immediately preceding the claims or where the publication is mentioned; and each of these publications is hereby incorporated herein by reference. These publications relate to the art to which this invention pertains. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Retroinverso polypeptides that mimic or inhibit thrombospondin Inventor(s): Actor, Paul; (Phoenixville, PA), Tuszynski, George; (Pittsgrove, NJ), Williams, Taffy; (Lansdale, PA) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030171298 Date filed: October 3, 2001 Abstract: The present invention relates generally to polypeptides that mimic or inhibit the biological activity of thrombospondin, and particularly to polypeptides in retroinverso form. The peptides. These polypeptides may be used biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and inhibiting cellular attachment to tissue culture flasks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas. Excerpt(s): The present invention relates generally to peptide fragments and synthetic analogs of thrombospondin (also known as thrombin sensitive protein or TSP) with thrombospondin-like activity. The peptides mimic or inhibit the biological activity of TSP. These peptides may be used in biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and
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inhibiting cellular attachment to tissue culture flasks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas. Thrombospondin (TSP) is secreted by platelets in response to physiological activators such as thrombin and collagen (Lawler, Blood, 67:112-123 (1986)). Other cells also synthesize TSP including fibroblasts (E. A. Jaffe et al., Proc. Natl. Acad. Sci., 80:999-1002 (1983)), smooth muscle cells (Raugi, G. J. et al., J. Cell Biol. 95:351354 (1982)), and endothelial cells (J. McPhearson et al., J. Biol. Chem., 256:11330-11336). TSP has been found in certain tumor tissues, such as melanoma cells (J. Varani et al., Clin. Expl. Metastais, 7:319-329 (1989)), squamous lung carcinoma (B. L. Riser et al., Exp. Cell Res., 174:319-329 (1988)) and breast carcinoma (D. A. Pratt et al., Eur. J. Cancer Clin. Oncol. 25:343-350 (1989)). In addition, certain tumor cells in culture, such as, fibrosarcoma, rhabdomyosarcoma, glioblastoma, Wilm's tumor, neuroblastoma, teratocarcinoma, choriocarcinoma, melanoma, and lung carcinoma have been shown to synthesize TSP (D. F. Mosher, Annu. Rev. Med., 41:85-97 (1990)). TSP has been shown to play a role in many diverse and clinically important processes, such as: cell migration, wound healing, nerve regeneration, and tumor cell metastasis. TSP has been purified by a number or procedures including exclusion chromatography (Lawler et al., J. Cell Biol., 101:1059-71 (1986)). The complete amino acid sequence of TSP has been deduced from DNA clones prepared by various groups including Lawler et al., J. Cell Biol., 103:1635-48 (1986); Kobayashi et al., Biochemistry, 25:8418-25 (1986); Dixit et al., Proc. Ntl. Acad. Sci., 83:5449-53 (1986); and Hennessy et al., J. Cell Biol., 108:729-36 (1989). The structure of TSP is conserved among various animal species as indicated by the fact that the antiobody against the human protein cross-reacts with TSP from mouse, rat, pig, cow, sheep, dog, and turkey (H. I. Switalska et al., J. Lab Clin. Med., 106:690-700). It is now known that TSP, originally characterized from platelet released proteins, is only one member of a family of structurally related proteins encoded by different genes which include at least four new members designated TSP-2, TSP-3, TSP-4, and TSP-5/COMP (cartilage oligomeric matrix protein). Adams and Lawler, Current Biology, 3: 188-190 (1993). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic anti-melanoma compounds Inventor(s): Nicolette, Charles A.; (Framingham, MA) Correspondence: Antoinette F. Konski; Baker & Mckenzie; 660 Hansen Way; Palo Alto; CA; 94304; US Patent Application Number: 20020169132 Date filed: March 19, 2001 Abstract: The present invention provides synthetic compounds, antibodies that recognize and bind to these compounds, polynucleotides that encode these compounds, and immune effector cells raised in response to presentation of these epitopes. The invention further provides methods for inducing and immune response and administering immunotherapy to a subject by delivering the compositions of the invention. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to 35 U.S.C.sctn.119(e) to U.S. Provisional Application Serial Nos. 60/190,750 and 60/255,019, filed Mar. 20, 2000 and Dec. 12, 2000, respectively. The contents of these applications are hereby incorporated by reference into the present disclosure. The invention relates to the
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field of therapeutic compounds useful against human melanoma. The recognition of antigenic epitopes presented by molecules of the Major Histocompatibility Complex (MHC) plays a central role in the establishment, maintenance and execution of mammalian immune responses. T cell surveillance and recognition of peptide antigens presented by cell surface MHC molecules expressed by somatic cells and antigen presenting leukocytes functions to control invasion by infectious organisms such as viruses, bacteria, and parasites. In addition it has now been demonstrated that antigenspecific cytotoxic T lymphocytes (CTLs) can recognize certain cancer cell antigens and attack cells expressing these antigens. This T cell activity provides a basis for developing novel strategies for anti-cancer vaccines. Furthermore, inappropriate T cell activation plays a central role in certain debilitating autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and asthma. Thus presentation and recognition of antigenic epitopes presented by MHC molecules play a central role in mediating immune responses in multiple pathological conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic compositions and methods useful in modulating protein tyrosine phosphatases Inventor(s): Yi, Taolin; (Solon, OH) Correspondence: Benesch, Friedlander, Coplan & Aronoff Llp; Attn: IP Department Docket Clerk; 2300 BP Tower; 200 Public Square; Cleveland; OH; 44114; US Patent Application Number: 20030072738 Date filed: September 9, 2002 Abstract: In one embodiment, a therapeutic composition containing a pentavalent antimonial is provided. The pentavalent antimonial can be sodium stibogluconate, levamisole, ketoconazole, and pentamidine and biological equivalents of said compounds. Additionally, pentavalent antimonials that can be used in accordance with the present invention may be any such compounds which are anti-leishmaniasis agents. The therapeutic composition of this embodiment contains an effective amount of pentavalent antimonial that can be used in treating infectious diseases. The types of diseases that can be treated with the present invention include, but are not limited to, the following: diseases associated with PTPase activity, immune deficiency, cancer, infections (such as viral infections), hepatitis B, and hepatitis C. The types of cancers that the present embodiment can be used to treat include those such as lymphoma, multiple myeloma, leukemia, melanoma, prostate cancer, breast cancer, renal cancer, bladder cancer. The therapeutic composition enhances cytokine activity. The therapeutic composition may include a cytokine, such as interferon.alpha., interferon.beta., interferon.gamma., or granulocyte/macrophage colony stimulating factor. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/317,993 filed Sep. 7, 2001. Intercellular protein tyrosine phosphorylation is regulated by extracellular stimuli, such as cytokines, to control cell growth, differentiation and functional activities. This signaling mechanism depends on the interplay of protein tyrosine kinases, which initiate signaling cascades through phosphorylating tyrosine residues in protein substrates, and by protein tyrosine phosphatases that terminate signaling via substrate dephosphorylation. Chemical compounds that modulate the activity of protein tyrosine kinases or phosphatases can induce cellular changes through affecting the balance of intracellular protein tyrosine phosphorylation and redirecting signaling. Such compounds can be of value as experimental tools and, importantly, as
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potent therapeutic reagents. So far, few specific inhibitors of protein tyrosine phosphatases have been reported despite extensive efforts in the last decade to identify them. Although a number of chemicals that broadly inhibit protein tyrosine phosphatases are known, including sodium orthovanadate and iodoacetic acid, their usefulness as therapeutic agents is severely limited due to their general toxicity in vivo. Recently, it has been reported that Suramin, a polysulfonated naphthylurea compound, can act in vitro as a competitive and reversible inhibitor of several protein tyrosine phosphatases. Such an inhibitory activity of Suramin against protein tyrosine phosphatases is consistent with its activity in augmenting tyrosine phosphorylation of cellular proteins and may explain its antitumor activity and its therapeutic effect in treating trypanosomiasis and onchocerciasis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Zinc chloride composition, unit dose packaging, applicator, and method of use in treating cancer and other skin diseases Inventor(s): Brooks, Leslee S.; (Encino, CA), Brooks, Norman A.; (Encino, CA) Correspondence: Kelly Bauersfeld Lowry & Kelley, Llp; 6320 Canoga Avenue; Suite 1650; Woodland Hills; CA; 91367; US Patent Application Number: 20020150630 Date filed: June 12, 2002 Abstract: An improved method for the treatment of melanoma and skin tumors which utilizes a zinc chloride composition is provided. The zinc chloride composition allows the surgeon to obtain hemostasis after a biopsy, and to incise or excise a melanomatous or other skin tumor through painless, bloodless, dead tissue. Because the microscopic structures are fixed in place by the zinc chloride, excised tissue can be examined microscopically by a pathologist. This invention allows the active ingredients of zinc chloride compositions to be effectively administered to the skin by providing single-use dose specific storage, application, dressing, and administration systems needed to facilitate the use of the topical zinc chloride mixtures. Enhanced zinc chloride mixture formulations including herbal taxoids are described. Excerpt(s): This application is a continuation-in-part of non-provisional U.S. application Ser. No. 09/505,618, filed Feb. 16, 2000, which claims priority from provisional application Serial No. 60/120,656, filed Feb. 19, 1999. The present invention relates too the treatment of human melanoma, basal and squamous cell skin cancer, and a variety of other skin tumors and skin diseases. More particularly, the present invention relates to unit dose packaging of a zinc chloride mixture and used in a dosage specific applicator for the treatment of these skin diseases. Melanoma is a potentially fatal form of skin cancer, usually appearing as a black or dark brown mole. The conventional treatment of cutaneous melanoma has been excision with a deep and wide margin of normal appearing tissue surrounding the tumor depending on the depth and thickness of the cancerous mole. However, microscopic satellite sites potentially occurring in the otherwise normal appearing skin surrounding the melanoma may be disturbed, and host resistance may be reduced following the excision of the melanoma. A decrease in host resistance may result in the appearance of cancer in distant sites of the body (metastases). (Smolle, J. et al, Does Surgical Removal of Primary Melanoma Trigger Growth of Occult Metastases? An Analytical Epidemiological Approach. Dermatologic Surgery, November, 1997). Cancer metastases can cause death of the patient. Although it is common to excise a margin of tissue surrounding the tumor, it is well known that
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increasing the size of the surgical margin to greater and greater extent does not affect survival rate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with melanoma, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “melanoma” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on melanoma. You can also use this procedure to view pending patent applications concerning melanoma. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON MELANOMA Overview This chapter provides bibliographic book references relating to melanoma. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on melanoma include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “melanoma” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on melanoma: •
What You Really Need To Know About Moles and Melanoma Source: Baltimore, MD: The Johns Hopkins University Press. 2000. 232 p. Contact: Available from Johns Hopkins University Press. Hopkins Fulfillment Service, P.O. Box 50370, Baltimore, MD 21211-4370. (410) 516-6956. Fax (410) 516-6998. E-mail:
[email protected]. Website: www.jhupbooks.com. PRICE: $14.95 plus shipping and handling. ISBN 0801863945. Summary: This book provides people who have melanoma with the most up to date information on the prevention, diagnosis, and treatment of this form of skin cancer. Part one focuses on the recognition and prevention of melanoma. Topics include the structure of the skin; the features of nonmelanoma skin cancers; the characteristics of pigmented lesions such as freckles, seborrheic keratoses, lentigos, and nevi; and the causes and warning signs of melanoma. One chapter focuses on the risk factors for melanoma, including number of moles; changing, atypical, and congenital moles;
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intense, intermittent sun exposure; prior severe sunburns; melanoma in a close relative; personal history of melanoma; skin type; hair color; age; gender; immune system suppression; prior psoralen and ultraviolet A treatments to the skin; xeroderma pigmentosa; and atypical mole syndrome. Other topics include prevention and early detection of melanoma and education about skin cancer and melanoma. Part two deals with the diagnosis and treatment of melanoma. Chapters discuss removing and treating the primary lesion; determining the stage of the cancer; evaluating and treating regional lymph nodes at the time of diagnosis; and using adjuvant therapy such as immunotherapy, radiation therapy, chemotherapy, vitamins and diet therapy, and lifestyle changes. Other topics include treating melanoma that has metastasized with drugs, surgery, and experimental therapies and managing pain and the end of life. Answers to frequently asked questions about diagnosing and treating melanoma are listed. Part three focuses on unusual noncutaneous and less common forms of cutaneous melanoma and reviews melanoma research. The book contains color photographs and line drawings, a glossary, and a guide to resources such as support and advocacy organizations and websites for people who have melanoma. 11 figures, 2 tables, and 13 color plates.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “melanoma” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “melanoma” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “melanoma” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
100 Questions and Answers about Melanoma & Other Skin Cancers by Edward F. McClay, et al (2003); ISBN: 0763720364; http://www.amazon.com/exec/obidos/ASIN/0763720364/icongroupinterna
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21st Century Complete Medical Guide to Melanoma - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 159248008X; http://www.amazon.com/exec/obidos/ASIN/159248008X/icongroupinterna
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Atlas of Selective Sentinel Lymphadenectomy for Melanoma, Breast Cancer Andcolon Cancer (Cancer Treatment and Research, 111) by Stanley P. L. Leong (Editor) (2002); ISBN: 1402070136; http://www.amazon.com/exec/obidos/ASIN/1402070136/icongroupinterna
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Atlas of Surgical Treatment of Melanoma: A Case History Approach Based on Tumor Biology by Keith A. Denkler MD, Richard Sagebiel MD; ISBN: 0683181017; http://www.amazon.com/exec/obidos/ASIN/0683181017/icongroupinterna
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Basic and Clinical Aspects of Malignant Melanoma (Cancer Treatment and Research) by Larry Nathanson (1987); ISBN: 0898388562; http://www.amazon.com/exec/obidos/ASIN/0898388562/icongroupinterna
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Biology of skin cancer (excluding melanomas) : a series of workshops on the biology of human cancer, report no. 15; ISBN: 9290180633; http://www.amazon.com/exec/obidos/ASIN/9290180633/icongroupinterna
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Choroidal & Ciliary Body Malignant Melanoma: Diagnosis & Management by Robert N. Johnson (1993); ISBN: 0960810277; http://www.amazon.com/exec/obidos/ASIN/0960810277/icongroupinterna
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Clinical Management of Malignant Melanoma (1985); ISBN: 9024725844; http://www.amazon.com/exec/obidos/ASIN/9024725844/icongroupinterna
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Clinical Management of Malignant Melanoma (Cancer Treatment and Research, 21) by J.J. Costanzi (Editor) (1985); ISBN: 089838656X; http://www.amazon.com/exec/obidos/ASIN/089838656X/icongroupinterna
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Coping With Melanoma and Other Skin Cancers by Wendy Long (1999); ISBN: 0823928527; http://www.amazon.com/exec/obidos/ASIN/0823928527/icongroupinterna
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Current Research and Clinical Management of Melanoma (Cancer Treatment and Research, Vol 65) by Larry Nathanson (Editor) (1993); ISBN: 0792321529; http://www.amazon.com/exec/obidos/ASIN/0792321529/icongroupinterna
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Cutaneous Head and Neck Melanoma: Diagnosis and Treatment (Diagnostic Oncology) by Alfonsus Balm (Editor), B.B.R. Kroon (Editor); ISBN: 3805560001; http://www.amazon.com/exec/obidos/ASIN/3805560001/icongroupinterna
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Cutaneous Melanoma by Charles M. Balch (Editor), et al (2003); ISBN: 157626159X; http://www.amazon.com/exec/obidos/ASIN/157626159X/icongroupinterna
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Cutaneous Melanoma and Precursor Lesions (Developments in Oncology, Vol 25) by Kees Welvaart, et al (2002); ISBN: 0898386896; http://www.amazon.com/exec/obidos/ASIN/0898386896/icongroupinterna
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Cutaneous Melanoma: Clinical Management and Treatment Results Worldwide by Charles M. Balch, Gerald W. Milton (Editor); ISBN: 0397505876; http://www.amazon.com/exec/obidos/ASIN/0397505876/icongroupinterna
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Cutaneous Melanoma: Status of Knowledge by Umberto Veronesi (Editor), et al; ISBN: 012718855X; http://www.amazon.com/exec/obidos/ASIN/012718855X/icongroupinterna
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Diagnosis and Management of Cutaneous Malignant Melanoma by Daniel F. Roses, et al; ISBN: 0721677061; http://www.amazon.com/exec/obidos/ASIN/0721677061/icongroupinterna
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Diagnosis and Management of Melanoma in Clinical Practice by N. Kirkham (Editor), et al; ISBN: 3540197176; http://www.amazon.com/exec/obidos/ASIN/3540197176/icongroupinterna
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Epidemiological Aspects of Cutaneous Malignant Melanoma (Developments in Oncology, Vol 73) by Richard P. Gallagher (Editor), J. Mark Elwood (Editor) (1994); ISBN: 0792327403; http://www.amazon.com/exec/obidos/ASIN/0792327403/icongroupinterna
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Epidemiology of Malignant Melanoma (Recent Result in Cancer Research, Vol 102) by R.P. Gallagher (Editor) (1986); ISBN: 0387160205; http://www.amazon.com/exec/obidos/ASIN/0387160205/icongroupinterna
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Hereditary Malignant Melanoma by Henry T Lynch, Ramon m Fusaro (Editor); ISBN: 084936051X; http://www.amazon.com/exec/obidos/ASIN/084936051X/icongroupinterna
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Human Malignant Melanoma (Yarbro, Bornstein & Mastrangelo Clinical Oncology Monographs) by Clark Jr, et al; ISBN: 0808911104; http://www.amazon.com/exec/obidos/ASIN/0808911104/icongroupinterna
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Human Melanoma (1990); ISBN: 3540508147; http://www.amazon.com/exec/obidos/ASIN/3540508147/icongroupinterna
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Human Melanoma: From Basic Research to Clinical Application by Soldano Ferrone (Editor) (1990); ISBN: 0387508147; http://www.amazon.com/exec/obidos/ASIN/0387508147/icongroupinterna
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Hydroxyanisole: Recent Advances in Anti-Melanoma Therapy by P.A. Riley (Editor) (1984); ISBN: 0904147649; http://www.amazon.com/exec/obidos/ASIN/0904147649/icongroupinterna
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Immunology of Human Melanoma: Tumor-Host Interaction and Immunotherapy (Biomedical and Health Research , Vol 12) by Michele Maio (Editor); ISBN: 905199253X; http://www.amazon.com/exec/obidos/ASIN/905199253X/icongroupinterna
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Immunotherapy of Malignant Melanoma (Medical Intelligence Unit) by Stanley P. L. Leong (Editor); ISBN: 0412104911; http://www.amazon.com/exec/obidos/ASIN/0412104911/icongroupinterna
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Malignant Melanoma by Kirkman (1997); ISBN: 0443050635; http://www.amazon.com/exec/obidos/ASIN/0443050635/icongroupinterna
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Malignant Melanoma (1993); ISBN: 3794514815; http://www.amazon.com/exec/obidos/ASIN/3794514815/icongroupinterna
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Malignant Melanoma and Melanocytic by Leboit (1994); ISBN: 1560531762; http://www.amazon.com/exec/obidos/ASIN/1560531762/icongroupinterna
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MALIGNANT MELANOMA CLINICAL: Clinical and Histological Diagnosis by MCGOVERN; ISBN: 0471584177; http://www.amazon.com/exec/obidos/ASIN/0471584177/icongroupinterna
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Malignant melanoma of the skin and mucous membrane by Gerald W. Milton; ISBN: 0443014221; http://www.amazon.com/exec/obidos/ASIN/0443014221/icongroupinterna
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Malignant Melanoma: Advances of a Decade by Rona M. MacKie (Editor) (1983); ISBN: 3805536909; http://www.amazon.com/exec/obidos/ASIN/3805536909/icongroupinterna
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Malignant Melanoma: Biology, Diagnosis, and Therapy (Cancer Treatment and Research) by Larry Nathanson (Editor) (1988); ISBN: 0898383846; http://www.amazon.com/exec/obidos/ASIN/0898383846/icongroupinterna
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Malignant Melanoma: Medical and Surgical Management by Ferdy J. Lejeune, et al; ISBN: 0071054219; http://www.amazon.com/exec/obidos/ASIN/0071054219/icongroupinterna
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Management of Advanced Melanoma (Contemporary Issues in Clinical Oncology, Vol. 6) by Larry, MD Nathanson (Editor) (1986); ISBN: 0443084637; http://www.amazon.com/exec/obidos/ASIN/0443084637/icongroupinterna
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Melanogenesis and Malignant Melanoma: Biochemistry, Cell Biology, Molecular Biology, Pathophysiology, Diagnosis and Treatment by Y. Hori (Editor), et al; ISBN: 0444822097; http://www.amazon.com/exec/obidos/ASIN/0444822097/icongroupinterna
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Melanoma by MacKie (1995); ISBN: 0443053359; http://www.amazon.com/exec/obidos/ASIN/0443053359/icongroupinterna
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Melanoma Antigens and Antibodies by Ralph A. Reisfeld (Editor); ISBN: 030640852X; http://www.amazon.com/exec/obidos/ASIN/030640852X/icongroupinterna
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Melanoma of the Head and Neck (1990); ISBN: 313735501X; http://www.amazon.com/exec/obidos/ASIN/313735501X/icongroupinterna
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Melanoma Research: Genetics, Growth Factors, Metastases, and Antigens (Cancer Treatment and Research; Ctar 54) by Larry Nathanson (Editor) (1991); ISBN: 0792308956; http://www.amazon.com/exec/obidos/ASIN/0792308956/icongroupinterna
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Melanoma Techniques & Protocols: Molecular Diagnosis, Treatment, and Monitoring by Brian J., Md., Ph.D. Nickoloff (Editor), LeRoy Hood; ISBN: 0896036847; http://www.amazon.com/exec/obidos/ASIN/0896036847/icongroupinterna
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Melanoma: Critical Debates by J. A. Newton Bishop (Editor), et al (2002); ISBN: 0632057726; http://www.amazon.com/exec/obidos/ASIN/0632057726/icongroupinterna
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Melanoma: Histological Diagnosis and Prognosis (Biopsy Interpretation Series) by Vincent J. McGovern; ISBN: 0890047111; http://www.amazon.com/exec/obidos/ASIN/0890047111/icongroupinterna
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Melanoma: Prevention, Detection, and Treatment by Catherine M. Poole, DuPont, IV Guerry (Contributor) (1998); ISBN: 0300073623; http://www.amazon.com/exec/obidos/ASIN/0300073623/icongroupinterna
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Melanoma: The New Biotherapeutics for Solid Tumors by Ernest Borden (Editor) (2002); ISBN: 0896038769; http://www.amazon.com/exec/obidos/ASIN/0896038769/icongroupinterna
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Melanomas: Basic Properties and Clinical Behavior: Proceedings of the International Pigment Cell Conference, 9th, Houston, Texas, by International Pigment Cell Conference St, V. Riley (Editor) (1977); ISBN: 3805523696; http://www.amazon.com/exec/obidos/ASIN/3805523696/icongroupinterna
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Minimal Residual Disease in Melanoma: Biology, Detection and Clinical Relevance (Recent Results in Cancer Research, 158) by Uwe Reinhold (Editor), et al (2000); ISBN: 3540673490; http://www.amazon.com/exec/obidos/ASIN/3540673490/icongroupinterna
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Molecular Diagnosis and Treatment of Melanoma by John M. Kirkwood (Editor); ISBN: 082470102X; http://www.amazon.com/exec/obidos/ASIN/082470102X/icongroupinterna
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Neoplasms of the skin and malignant melanoma : a collection of papers presented at the Twentieth Annual Clinical Conference on Cancer, 1975, at the University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas; ISBN: 0815102135; http://www.amazon.com/exec/obidos/ASIN/0815102135/icongroupinterna
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New Medical Therapies: Melanoma by CenterWatch; ISBN: 1930624352; http://www.amazon.com/exec/obidos/ASIN/1930624352/icongroupinterna
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Pathobiology and Recognition of Malignant Melanoma (Monographs in Pathology, No 30) by Martin C., Jr. Mihm, et al; ISBN: 0683060163; http://www.amazon.com/exec/obidos/ASIN/0683060163/icongroupinterna
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Pathobiology of Malignant Melanoma (Pigment Cell, Vol 8) by D.E. Elder (Editor) (1987); ISBN: 3805543484; http://www.amazon.com/exec/obidos/ASIN/3805543484/icongroupinterna
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Pathology of malignant melanoma; ISBN: 0893521329; http://www.amazon.com/exec/obidos/ASIN/0893521329/icongroupinterna
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Pathology of Melanocytic Nevi and Malignant Melanoma by Raymond L., M.D. Barnhill, Klaus J., M.D. Busam; ISBN: 0750695048; http://www.amazon.com/exec/obidos/ASIN/0750695048/icongroupinterna
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Pitfalls in Histopathologic Diagnosis of Malignant Melanoma by A. Bernard Ackerman, et al; ISBN: 0812113527; http://www.amazon.com/exec/obidos/ASIN/0812113527/icongroupinterna
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Pocket Guide to Malignant Melanoma by John Buchan, Dafydd Lloyd Roberts; ISBN: 0632054212; http://www.amazon.com/exec/obidos/ASIN/0632054212/icongroupinterna
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Saving Your Skin: Prevention, Early Detection, and Treatment of Melanoma and Other Skin Cancers by Barney J. Kenet, et al (1998); ISBN: 1568581246; http://www.amazon.com/exec/obidos/ASIN/1568581246/icongroupinterna
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Surgical Approaches to Cutaneous Melanoma by C. M. Balch (Editor) (1985); ISBN: 3805540558; http://www.amazon.com/exec/obidos/ASIN/3805540558/icongroupinterna
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Symposium on Uveal Melanomas: On the Occasion of the Snellen Medal Presentation to Dr. W. A. Manschot, Utrecht by W. A. Manschot (1980); ISBN: 9061937221; http://www.amazon.com/exec/obidos/ASIN/9061937221/icongroupinterna
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Textbook of Melanoma by John F. Thompson, et al; ISBN: 1901865657; http://www.amazon.com/exec/obidos/ASIN/1901865657/icongroupinterna
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The Official Patient's Sourcebook on Melanoma: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834776; http://www.amazon.com/exec/obidos/ASIN/0597834776/icongroupinterna
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Therapy of Advanced Melanoma (Pigment Cell, Vol 10) by Rona M. MacKie (Editor) (1990); ISBN: 3805550324; http://www.amazon.com/exec/obidos/ASIN/3805550324/icongroupinterna
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Understanding Malignant Melanoma (2001); ISBN: 1901276732; http://www.amazon.com/exec/obidos/ASIN/1901276732/icongroupinterna
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Understanding Melanoma What You Need To by Perry Robins (Author); ISBN: 0096276886; http://www.amazon.com/exec/obidos/ASIN/0096276886/icongroupinterna
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Understanding Melanoma: What You Need to Know by Perry Robins, Maritza Perez; ISBN: 0962768820; http://www.amazon.com/exec/obidos/ASIN/0962768820/icongroupinterna
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What you need to know about melanoma (SuDoc HE 20.3152:M 48/998) by U.S. Dept of Health and Human Services; ISBN: B00010XDN0; http://www.amazon.com/exec/obidos/ASIN/B00010XDN0/icongroupinterna
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What You Really Need to Know About Moles and Melanoma (Johns Hopkins Press Health Book) by Jill R., Md. Schofield, William Robinson (2000); ISBN: 0801863945; http://www.amazon.com/exec/obidos/ASIN/0801863945/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “melanoma” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Current cancer research on preclinical and clinical studies on diagnosis, prognosis, therapy, and immunology of melanomas and other skin cancers Author: Current Cancer Research Project Analysis Center (U.S.); Year: 1959; [Bethesda, Md.]: U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute; Springfield, Va.: [available from] National Technical Information Service, 1979
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Enhancement of natural resistance to malignant melanoma with special reference to the beneficial effects of concurrent infections and bacterial toxin therapy. Author: Fowler, George A.,; Year: 1969; New York, 1969
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Melanoma [by] C. O. Knutson, J. M. Hori [and] J. S. Spratt, Jr. Author: Knutson, Carl O.,; Year: 1954; Chicago, Year Book Medical Publishers, 1971; ISBN: 0815199031 http://www.amazon.com/exec/obidos/ASIN/0815199031/icongroupinterna
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Melanoma and skin cancer; proceedings. [Editor: W. H. McCarthy]. Author: McCarthy, W. H.; Year: 1972; Sydney, Blight [1972]
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Melanoma of the skin, with special reference to histological differential diagnosis, clinical picture, and end results of treatment. [Tr. by Eva Palmgren]. Author: Brandt, Gunnar.; Year: 1968; Helsingfors, 1956
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Melanoma. Author: Tygart, Robert Lewis,; Year: 1956; Des Moines, 1955
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Pigmented nevi, juvenile melanomas and malignant melanomas in children. Author: McWhorter, Henry Etten,; Year: 1948; [Minneapolis] 1954
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Primary malignant melanoma of the upper respiratory tract and oral cavity. Author: Brown, Warren Franklin,; Year: 1962; [Minneapolis] 1962
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The biology of melanomas, by Myron Gordon [et al. Author: Gordon, Myron,; Year: 1966; New York] 1948
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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The nature of melanoma, by Vincent K. McGovern and Malcolm M. Lane Brown. Author: McGovern, Vincent J.; Year: 1970; Springfield, Ill., Thomas [c1969]
Chapters on Melanoma In order to find chapters that specifically relate to melanoma, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and melanoma using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “melanoma” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on melanoma: •
Chapter 92: Neoplasms: Cutaneous Melanoma Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 1080-1116. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail:
[email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on cutaneous melanoma. The incidence of potentially lethal melanocyte malignancy has been increasing steadily in the past several decades. Risk factors for cutaneous melanoma include exposure to solar radiation; phenotypic features such as light skin pigmentation, ease of sunburning, blond or red hair, pale or light skin, prominent tendency toward freckling, and blue or green eyes; reaction of the skin to sunlight; occupation and social status; family history of melanoma; presence of clinically atypical nevi; history of prior melanoma; and gender and hormonal factors. Stages of tumor progression in the melanocytic system that have been suggested include benign melanocytic nevi, melanocytic nevi with architectural and cytologic atypia, primary malignant melanoma in radial and vertical growth phases, and metastatic malignant melanoma. Tumorigenesis of melanoma must take into account various clinical observations, including the association between nevi and melanoma in at least 30 percent of cases, the role of sunlight in the pathogenesis of melanoma, pigmentary phenotype of patients in whom melanoma develops, and family history of melanoma and other genetic factors. The major growth patterns of melanoma are lentigo maligna, superficial spreading, nodular, and acral lentiginous. Other melanoma variants are melanoma of the mucosa and desmoplastic neurotropic melanoma. The article presents the clinical characteristics and histopathology of these types of melanoma, discusses clinical detection and histologic diagnosis, presents a staging system, and describes clinical and histopathologic parameters of possible prognostic significance. In addition, the article provides guidelines on evaluating suspected or newly diagnosed melanoma, reviews advances in the management of primary melanoma and regional and distant metastases, and presents suggestions on prevention and early detection. Other topics include melanoma arising in congenital nevi, melanoma and pregnancy, melanoma in childhood and adolescence, metastatic and recurrent melanoma, and metastatic melanoma with no known primary site. 22 figures, 11 tables, and 261 references.
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CHAPTER 8. MULTIMEDIA ON MELANOMA Overview In this chapter, we show you how to keep current on multimedia sources of information on melanoma. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on melanoma is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “melanoma” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “melanoma” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on melanoma: •
Sun safety: A growing health concern Source: Itasca, NY: National Safety Council. 1999. 1 videotape (11:46 minutes, VHS 1/2 inch). Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 22182-2536. Telephone: (703) 356-1964 or (888) 4344MCH / fax: (703) 821-2098 / e-mail:
[email protected] / Web site: http://www.nmchc.org. Summary: This videotape discusses safe exposure to the sun. Topics include sunburn, melanoma, and other risks.
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Bibliography: Multimedia on Melanoma The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in melanoma (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on melanoma: •
A New approach to malignant melanoma [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976
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Breakthroughs in malignant melanoma [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic and St. Joseph's Hospital; Year: 1982; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1982
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Contemporary aspects of malignant melanoma [slide] Source: Blake Cady, Samuel L. Moschella, Merle A. Legg; Year: 1974; Format: Slide; New York: Medcom, c1974
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Control and prevention of malignant melanoma [videorecording]: a program for melanoma-prone families Source: the Pigmented Lesion Study Group, the University of Pennsylvania [and] the Environmental Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, DC: National Audiovisual Center, [1981]
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Cutaneous melanoma [slide] Source: Dutch National Cancer Education Project; Year: 1985; Format: Slide; [Amsterdam]: Netherlands Cancer Foundation, c1985
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Dysplastic nevi and hereditary melanoma [videorecording]: a program for clinicians Source: Pigmented Lesion Clinical Group, University of Pennsylvania and the Environmental Epidemiology Branch, Family Studies Unit, National Cancer Institute; Year: 1981; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1981]
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Dysplastic nevi and melanoma [videorecording]: a program for pathologists Source: Pigmented Lesion Study Group, the University of Pennsylvania, the Environmental Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1981]
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Early diagnosis of malignant melanoma [motion picture] Source: U. S. Public Health Service; produced by National Medical Audiovisual Center, in cooperation with the Institute for Dermatologic Communication and Education; Year: 1968; Format: Motion picture; [Washington]: Public Health Service; [Atlanta: for loan by National Medical Audiovisual Center], 1968
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Extended surgery for cancer of the colon, cancer of the head and neck, and melanoma [sound recording]: indications and techniques Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]
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Malignant melanoma: biology, diagnosis, therapy [slide] Source: Larry Nathanson; Year: 1974; Format: Slide; New York: Medcom, c1974
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Malignant melanoma: histologic interpretation and prognostication [videorecording] Source: American Society of Clinical Pathologists; Year: 1975; Format: Videorecording; [Chicago]: The Society, c1975
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Malignant melanoma [slide] Source: Department of Orthopedic Surgery, the Mt. Sinai Medical Center, Cleveland, Ohio; Year: 1987; Format: Slide; [Park Ridge, Ill.]: American Academy of Orthopedic Surgeons, [1987]
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Malignant melanoma [slide]: diagnosis and staging Source: Everett V. Sugarbaker; Year: 1979; Format: Slide; Westport, Conn.: MEDED, c1979
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Malignant melanoma and its clinical simulators [videorecording] Source: Darrell S. Rigel; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986
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Malignant melanoma of the choroid [videorecording] Source: Ohio State University; [produced by] its Media Audio-Visual and Television Center; Year: 1975; Format: Videorecording; Columbus: The University; [San Francisco, Calif.: for sale by American Academy of Ophthalmology], c1975
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Management of melanoma [sound recording] Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]
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Melanoma prevention and screening [videorecording]: the Australian approach Source: Robin Marks, John Kelly; Year: 1991; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1991
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Melanoma research. Year: 9999; Oxford, UK: Rapid Communications of Oxford, 1991-
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Melanomas: diagnosis and treatment [motion picture] Source: American Cancer Society; [made by] Wexler Films; Year: 1973; Format: Motion picture; New York: The Society, [1973]
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Melanomas of the eye [slide] Source: [Daniel M. Albert, Carmen A. Puliafito]; Year: 1981; Format: Slide; Philadelphia, PA.: F.A. Davis, c1981
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Moles and melanoma [motion picture] Source: Bureau of Aeronautics, Navy Department, United States of America; Year: 1945; Format: Motion picture; United States: The Bureau, 1945
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Nursing management of the patient with melanoma [slide] Source: Roswell Park Memorial Institute, in cooperation with the Lakes Area Regional Medical Program; Year: 1974; Format: Slide; [Buffalo]: Communications in Learning, 1974
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Primary cutaneous malignant melanomas [slide]: recognition and management Source: Thomas B. Fitzpatrick. [et al.]; Year: 1976; Format: Slide; Evanston, Ill.: American Academy of Dermatology, c1976
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Regional perfusion for malignant melanoma [motion picture] Source: Committee on Medical Motion Pictures, American College of Surgeons; produced by Davis & Geck; Year: 1970; Format: Motion picture; Danbury, Conn.: Davis & Geck; [Atlanta: for loan by National Medical Audiovisual Center], 1970
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Skin diseases: scabies, malignant melanoma [videorecording]: a report Source: Donald P. Lookingbill; [made by] Penn State Television; Year: 1977; Format: Videorecording; University Park, Pa.: Pennsylvania State University: [for loan or sale by its Audio-Visual Services], c1977
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Temporal melanoma with left parotidectomy and left radical neck dissection [motion picture] Source: Mayo Clinic; Year: 1964; Format: Motion picture; Rochester, Minn.: The Clinic, 1964
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Treatment of melanoma [slide] Source: Roswell Park Memorial Institute, in cooperation with Lakes Area Regional Medical Program; Year: 1974; Format: Slide; [Buffalo]: Communications in Learning, 1974
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CHAPTER 9. PERIODICALS AND NEWS ON MELANOMA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover melanoma.
News Services and Press Releases One of the simplest ways of tracking press releases on melanoma is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “melanoma” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to melanoma. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “melanoma” (or synonyms). The following was recently listed in this archive for melanoma: •
Melanoma rare in children treated with radiation Source: Reuters Health eLine Date: November 28, 2003
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Childhood radiotherapy rarely tied to subsequent melanoma Source: Reuters Medical News Date: November 28, 2003
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Vaccinations, infections may lower melanoma risk Source: Reuters Health eLine Date: November 25, 2003
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Immune system challenge reduces risk of melanoma Source: Reuters Medical News Date: November 25, 2003
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Melanoma vaccine with GM-CSF elicits strong response in phase II trial Source: Reuters Industry Breifing Date: November 05, 2003
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Melanoma incidence and mortality trends declining in northern Europe Source: Reuters Medical News Date: November 04, 2003
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Melanoma deaths declining in northern Europe Source: Reuters Health eLine Date: November 04, 2003
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Molecular analysis of archived lymph nodes predicts melanoma outcomes Source: Reuters Industry Breifing Date: October 03, 2003
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New melanoma vaccine increases antitumor immunity Source: Reuters Industry Breifing Date: September 10, 2003
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When melanoma involves foot, survival drops Source: Reuters Health eLine Date: August 26, 2003
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Melanoma survival may be worse when foot or ankle is involved Source: Reuters Medical News Date: August 26, 2003
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S-100-beta levels not prognostic in uveal melanoma Source: Reuters Medical News Date: August 22, 2003
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Signs and symptoms of primary melanoma predict depth of the lesion Source: Reuters Medical News Date: July 04, 2003
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Maxim looks to sell melanoma treatment in Europe Source: Reuters Industry Breifing Date: June 23, 2003
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Eye melanoma cases in white men rise sharply: study Source: Reuters Health eLine Date: June 11, 2003
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Dramatic rise in conjunctival melanoma noted among men over last 30 years Source: Reuters Medical News Date: June 09, 2003
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Ultraviolet light-inducible mutations very common with hereditary melanomas Source: Reuters Medical News Date: June 06, 2003
Periodicals and News
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Sentinel node biopsy indicated for thin melanomas of Clark level III or greater Source: Reuters Medical News Date: May 30, 2003
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Melanoma incidence has doubled in Germany over past decade Source: Reuters Medical News Date: May 09, 2003
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Glutamate protein implicated in melanoma Source: Reuters Industry Breifing Date: April 21, 2003
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Melanoma prognosis unaffected by pregnancy Source: Reuters Medical News Date: April 17, 2003
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CancerVax resumes enrollment in phase III melanoma vaccine trials Source: Reuters Industry Breifing Date: April 15, 2003
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Detection of circulating melanoma cells does not improve prognostic assessment Source: Reuters Medical News Date: March 31, 2003
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Melanoma mortality greater in UK than in Australia Source: Reuters Industry Breifing Date: March 27, 2003
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Moles unlikely to transform into melanomas Source: Reuters Medical News Date: March 24, 2003
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Adequate follow-up contributes substantially to survival of melanoma patients Source: Reuters Medical News Date: March 13, 2003
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Some radiologic technologists at increased risk for melanoma Source: Reuters Medical News Date: March 03, 2003
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Survivin gene expression in lymph nodes prognostic in melanoma patients Source: Reuters Medical News Date: February 13, 2003
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Melanoma survivors shouldn't be organ donors: study Source: Reuters Health eLine Date: February 05, 2003
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Sentinel node with highest isotope count may not contain melanoma metastases Source: Reuters Medical News Date: January 31, 2003
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Nitric oxide may contribute to melanoma progression via MMP upregulation Source: Reuters Medical News Date: January 28, 2003
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CancerVax melanoma vaccine wins fast-track status Source: Reuters Industry Breifing Date: January 27, 2003
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Importance of post-melanoma skin surveillance reinforced by new study Source: Reuters Medical News Date: January 21, 2003
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Sentinel lymph node mapping safe and reliable for melanoma of head and neck Source: Reuters Industry Breifing Date: January 20, 2003
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Success reported in early trial of melanoma gene therapy vaccine Source: Reuters Medical News Date: January 09, 2003
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Genzyme reports success in early trial of melanoma gene-therapy vaccine Source: Reuters Industry Breifing Date: January 09, 2003
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Mitogen-activated protein kinase triggered early in melanoma progression Source: Reuters Medical News Date: January 06, 2003
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Melanoma can clinically mimic seborrheic keratosis Source: Reuters Medical News Date: December 30, 2002
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Therapeutic vaccine for disseminated melanoma prolongs survival Source: Reuters Medical News Date: December 10, 2002
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Survival after melanoma surgery unaffected by surgeon's specialty Source: Reuters Medical News Date: December 04, 2002
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Dermatoscope plus computer imaging can yield rapid melanoma diagnosis Source: Reuters Industry Breifing Date: November 21, 2002
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Computer images provide better melanoma detection Source: Reuters Health eLine Date: November 21, 2002
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Adoptive T cell therapy effective against metastatic melanoma Source: Reuters Medical News Date: November 12, 2002
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Wide excision margins yield no survival benefit for thin melanomas Source: Reuters Medical News Date: October 29, 2002
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Fotemustine has some advantages over dacarbazine in treating melanoma Source: Reuters Industry Breifing Date: October 23, 2002
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Age, gender affect melanoma chemo success Source: Reuters Health eLine Date: October 23, 2002
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Age and gender affect efficacy of chemotherapy for melanoma Source: Reuters Medical News Date: October 23, 2002
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Phase III data for Maxim's Ceplene supports sub-population treatment in melanoma Source: Reuters Industry Breifing Date: October 21, 2002
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Previous vaccinia and BCG vaccination seems to protect against melanoma Source: Reuters Industry Breifing Date: October 15, 2002
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Melanoma screening should target men over 50 years of age Source: Reuters Medical News Date: October 15, 2002 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “melanoma” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “melanoma” (or synonyms). If you know the name of a company that is relevant to melanoma, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “melanoma” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “melanoma” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on melanoma: •
Melanoma Vaccine: Breaking the Antigen Packaging Barrier Source: Dermatology Focus. 15(4):1,10-14; April 1997. Contact: Dermatology Foundation, 1560 Sherman Avenue, Evanston, IL 60201-4808. Summary: This newsletter article for health professionals discusses the development of a melanoma vaccine. The creation of a tumor rejection antigen in mice is described. Researchers transfected tumor cells from B16, a poorly immunogenic mouse-derived melanoma, with the ovalbumin (OVA) gene. This modified tumor then treated the foreign OVA deoxyribonucleic acid as its own and began producing the protein. Immunization was performed by two subcutaneous injections one week apart of the OVA protein in particulate form. Results of studies of this immunization process and studies on the loading of dendritic cells in vitro are presented. In addition, in vivo engineering of professional antigen-presenting cells is explained. The applicability of this research is considered.
Academic Periodicals covering Melanoma Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to melanoma. In addition to these sources, you can search for articles covering melanoma that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for melanoma. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with melanoma. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to melanoma: Bleomycin •
Systemic - U.S. Brands: Blenoxane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202093.html
Carboplatin •
Systemic - U.S. Brands: Paraplatin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202115.html
Carmustine •
Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202117.html
Dacarbazine •
Systemic - U.S. Brands: DTIC-Dome http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202178.html
Interferons, Alpha •
Systemic - U.S. Brands: Alferon N; Intron A; Roferon-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202299.html
Levamisole •
Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202178.html
Melphalan •
Systemic - U.S. Brands: Alkeran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202345.html
Tamoxifen •
Systemic - U.S. Brands: Nolvadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202545.html
Vinblastine •
Systemic - U.S. Brands: Velban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202593.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
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Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to melanoma by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “melanoma” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for melanoma: •
Interferon beta (recombinant) (trade name: R-IFN-beta) http://www.rarediseases.org/nord/search/nodd_full?code=101
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•
Histamine (trade name: Maxamine) http://www.rarediseases.org/nord/search/nodd_full?code=1022
•
Deoxyribose, Phosphorothioate http://www.rarediseases.org/nord/search/nodd_full?code=1055
•
Cisplatin/epinephrine (trade name: IntraDose) http://www.rarediseases.org/nord/search/nodd_full?code=1066
•
Imexon (trade name: n/a) http://www.rarediseases.org/nord/search/nodd_full?code=1172
•
Monoclonal AB(murine) Anti-Idiotype Melanoma-ASSO (trade name: Melimmune) http://www.rarediseases.org/nord/search/nodd_full?code=123
•
Recombinant Human Endostatin Protein (Trade Name: None Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1251
•
Autologous Tumor-Derived GP96 Heat Shock Protein-P (Trade Name: Oncophage) http://www.rarediseases.org/nord/search/nodd_full?code=1259
•
Recombinant Human Endostatin Protein http://www.rarediseases.org/nord/search/nodd_full?code=1284
•
Interleukin-2 (trade name: Teleleukin) http://www.rarediseases.org/nord/search/nodd_full?code=130
•
DHA-pacitaxel (trade name: Taxoprexin) http://www.rarediseases.org/nord/search/nodd_full?code=1302
•
Interleukin-2 (trade name: Teceleukin) http://www.rarediseases.org/nord/search/nodd_full?code=133
•
Technetium Tc 99m anti-melanoma murine monoclonal (trade name: Oncotrac Melanoma Imaging Kit) http://www.rarediseases.org/nord/search/nodd_full?code=307
•
Poly I: poly C12U (trade name: Ampligen) http://www.rarediseases.org/nord/search/nodd_full?code=406
•
Melanoma cell vaccine http://www.rarediseases.org/nord/search/nodd_full?code=52
•
Interferon alfa-2a (recombinant) (trade name: Roferon-A) http://www.rarediseases.org/nord/search/nodd_full?code=542
•
Amifostine (trade name: Ethyol) http://www.rarediseases.org/nord/search/nodd_full?code=533
•
Melanoma vaccine (trade name: Melacine) http://www.rarediseases.org/nord/search/nodd_full?code=67
•
Beta alethine (trade name: Betathine) http://www.rarediseases.org/nord/search/nodd_full?code=832
•
MART-1 adenoviral gene therapy for malignant melan http://www.rarediseases.org/nord/search/nodd_full?code=833
•
Temozolomide (trade name: Temodal) http://www.rarediseases.org/nord/search/nodd_full?code=948
Researching Medications
•
GP100 Adenoviral Gene Therapy http://www.rarediseases.org/nord/search/nodd_full?code=837
•
Aldesleukin (trade name: Proleukin) http://www.rarediseases.org/nord/search/nodd_full?code=873
•
Interferon alfa-2a (recombinant) (trade name: Roferon-A) http://www.rarediseases.org/nord/search/nodd_full?code=91
•
Melphalan (trade name: Alkeran for Injection) http://www.rarediseases.org/nord/search/nodd_full?code=92
•
Autologous DNP-conjugated tumor vaccine (trade name: M-Vax) http://www.rarediseases.org/nord/search/nodd_full?code=964
•
Pegylated arginine deiminase (trade name: Melanocid) http://www.rarediseases.org/nord/search/nodd_full?code=977
•
HLA-B7/Beta2M DNA Lipid (DMRIE/DOPE) Complex (trade name: Allovectin-7) http://www.rarediseases.org/nord/search/nodd_full?code=992
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If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “melanoma” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 54374 431 316 33 25 55179
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “melanoma” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Melanoma In the following section, we will discuss databases and references which relate to the Genome Project and melanoma. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “melanoma” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for melanoma: •
Absent in Melanoma 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601797
•
Absent in Melanoma 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604578
•
B Melanoma Antigen Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605167
•
Melanoma Adhesion Molecule Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155735
•
Melanoma Antigen Recognized by T Cells 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605743
•
Melanoma Antigen, Family A, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300016
•
Melanoma Antigen, Family A, 10 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300343
•
Melanoma Antigen, Family A, 11 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300344
•
Melanoma Antigen, Family A, 12 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300177
•
Melanoma Antigen, Family A, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300173
•
Melanoma Antigen, Family A, 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300174
•
Melanoma Antigen, Family A, 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300175
•
Melanoma Antigen, Family A, 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300340
•
Melanoma Antigen, Family A, 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300176
•
Melanoma Antigen, Family A, 8 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300341
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Melanoma Antigen, Family A, 9 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300342
•
Melanoma Antigen, Family B, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300097
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Melanoma Antigen, Family B, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300098
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Melanoma Antigen, Family B, 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300152
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Melanoma Antigen, Family B, 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300153
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Melanoma Antigen, Family C, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300223
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Melanoma Antigen, Family D, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300224
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Melanoma Differentiation-associated Gene 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606951
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Melanoma Inhibitory Activity Protein Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601340
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Melanoma Inhibitory Activity Protein 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608001
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Melanoma Tumor Antigen Gp90 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155770
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Melanoma, Cutaneous Malignant Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155600
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Melanoma, Cutaneous Malignant, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155601
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Melanoma, Cutaneous Malignant, 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608035
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Melanoma, Malignant Familial Intraocular Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155700
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Melanoma, Uveal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155720
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Melanoma, Uveal, Susceptibility To, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606660
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Melanoma, Uveal, Susceptibility To, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606661
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Melanoma-associated Antigen P97 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155750
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Melanoma-associated Antigen Recognized by T Lymphocytes Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604853
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Melanoma-astrocytoma Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155755
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Melanoma-pancreatic Cancer Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606719
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Preferentially Expressed Antigen in Melanoma Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606021
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Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html
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Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “melanoma” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually 24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.
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limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “melanoma” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
25
Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on melanoma can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to melanoma. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to melanoma. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “melanoma”:
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Guides on melanoma Melanoma http://www.nlm.nih.gov/medlineplus/melanoma.html Melanoma http://www.nlm.nih.gov/medlineplus/tutorials/melanomaloader.html
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Other guides Eye Cancer http://www.nlm.nih.gov/medlineplus/eyecancer.html Sun Exposure http://www.nlm.nih.gov/medlineplus/sunexposure.html Vulvar Cancer http://www.nlm.nih.gov/medlineplus/vulvarcancer.html
Within the health topic page dedicated to melanoma, the following was listed: •
General/Overviews Malignant Melanoma Source: American Academy of Dermatology http://www.aad.org/pamphlets/malmel.html Melanoma http://www.nlm.nih.gov/medlineplus/tutorials/melanomaloader.html Melanoma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00439
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Diagnosis/Symptoms How is Melanoma Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_melanoma_diag nosed_50.asp How is Melanoma Staged? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_melanoma_stage d_50.asp Melanoma: What to Look for Source: Skin Cancer Foundation http://www.skincancer.org/self_exam/look_for.html
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Treatment Biological Therapies: Using the Immune System to Treat Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_2.htm
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How Is Melanoma Skin Cancer Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_melanoma_skin_ cancer_treated_50.asp Intraocular (Eye) Melanoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/intraocularmelanoma/patient / Melanoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/melanoma/patient/ New Treatments on Horizon for Melanoma Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_New_Treatments_On _Horizon_For_Melanoma.asp What Happens After Treatment for Melanoma? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_5X_What_happens_after_t reatment_50.asp?sitearea= •
Coping Coping With Melanoma Source: Skin Cancer Foundation http://www.skincancer.org/melanoma/coping.html
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Specific Conditions/Aspects “Hidden” Melanomas Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/MelanomaRisk_november.ht m About Choroidal Melanoma Source: Johns Hopkins University http://www.jhu.edu/wctb/coms/booklet/book2.htm Atypical Nevus Source: American Academy of Dermatology http://www.aad.org/pamphlets/anevus.html What You Need to Know about Moles and Dysplastic Nevi Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/moles-and-dysplastic-nevi
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From the National Institutes of Health What You Need to Know about Melanoma Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/melanoma
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Latest News Melanoma Rare in Children Treated with Radiation Source: 11/28/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14890 .html Vaccinations, Infections May Lower Melanoma Risk Source: 11/25/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14830 .html
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Organizations American Academy of Dermatology http://www.aad.org/ American Cancer Society http://www.cancer.org/ National Cancer Institute http://www.cancer.gov/ Skin Cancer Foundation http://www.skincancer.org/
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Pictures/Diagrams ABCDs of Melanoma Detection Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/ABCDMel.html Skin Lesions Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/skin_lesions.htm
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Prevention/Screening Can Melanoma Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_can_melanoma_be_preve nted_50.asp Melanoma Cancer Questionnaire Source: Harvard Center for Cancer Prevention http://www.yourcancerrisk.harvard.edu/hccpquiz.pl?func=d_start&cancer_list=M elanoma Self-Examination for Melanoma Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/self_exam.htm What Are The Risk Factors for Melanoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_the_risk_factor s_for_melanoma_50.asp
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Research Do We Know What Causes Melanoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_do_we_know_what_caus es_melanoma_50.asp Individuals' Risk of Melanoma Increases with Time Outdoors, Especially in High-Sunlight Areas Source: National Cancer Institute http://www.cancer.gov/newscenter/individualmelanoma New Approach to Replacing Immune Cells Shrinks Tumors in Patients with Melanoma Source: National Cancer Institute http://www.nih.gov/news/pr/sep2002/nci-19.htm Researchers Shut Off Immune Cell Inhibition, Causing Tumor Shrinkage and Autoimmunity in Patients with Metastatic Melanoma Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/CTLA4 What's New in Melanoma Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_melanom a_research_and_treatment_50.asp
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Statistics SEER Cancer Statistics Review 1975-2000: Melanoma of the Skin Source: National Cancer Institute http://seer.cancer.gov/csr/1975_2000/results_merged/sect_16_melanoma.pdf What Are The Key Statistics for Melanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_melanoma_50.asp
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on melanoma. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search
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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Dysplastic Nevi and Malignant Melanoma: A Patient's Guide Source: New York, NY: Skin Cancer Foundation. 1997. 12 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. PRICE: Single copy free; bulk orders available at cost. Summary: This brochure provides people who have dysplastic nevi and malignant melanoma with information on recognizing the features of these skin disorders. Dysplastic nevi are unusual moles that are markers for an increased risk of melanoma, which is a form of skin cancer that often looks like an irregular, enlarging, or inflamed mole. The brochure compares the features of normal moles with those of dysplastic nevi and explains what happens if moles become malignant melanoma. The brochure also offers guidelines for people who have an increased risk of developing melanoma or a diagnosis of dysplastic nevus, including performing a monthly skin self-examination, having an annual medical examination, and avoiding or decreasing exposure to the sun. 13 figures.
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Melanoma Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have melanoma with information on this form of skin cancer. Melanoma, which grows from the melanocytes (the cells that color and tan the skin), often will spread to other parts of the body through the lymphatic system or the bloodstream. The disease can appear on the body as a new mole; as a mole that has changed in size, shape, feeling, or color; or as a mole that has developed oozing or bleeding. Most melanomas are dark, but they may be flesh colored or pink to red. If there is a serious question of skin cancer, the mole or pigmented area will be surgically removed. A laboratory will analyze the removed skin. If melanoma is diagnosed, a physical examination and laboratory tests will be done to look for signs that it has spread to other parts of the body. In the earliest melanoma, the abnormal cells are found only in the outer layer of skin cells. Melanomas are more advanced if they go deeper than 4 millimeters into the skin. Those that have spread are very serious. Surgery is the main treatment of all stages of melanoma. The biopsy site and a rim of seemingly normal skin are removed. Treatment of advanced melanoma may involve surgical removal of the tumor and any affected lymph nodes, followed by systemic or local mono or multiple chemotherapy. Melanoma vaccines are a promising new treatment for advanced melanoma. 3 figures.
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Many Faces of Malignant Melanoma, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website:
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www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-5. Summary: This pamphlet provides health professionals and the general public with 24 examples of malignant melanoma, which were selected to represent thin, intermediate, and thick melanomas. Tumor thickness is a key indicator in predicting which malignant melanomas are curable and which are not. Malignant melanomas that are removed when they are less than three fourths of a millimeter thick are cured in almost all cases; however, progressively thicker malignant melanomas have correspondingly poorer prognoses. The first eight photographs show examples of thin, early malignant melanomas. The second eight photographs depict examples of melanomas of intermediate thickness. The final eight photographs show examples of the thickest melanomas. The pamphlet also includes a list of the risk factors for and warning signs of malignant melanoma. 24 figures. •
ABCDs of Moles and Melanomas, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website: www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-4. Summary: This pamphlet provides the general public with information on the detection of malignant melanoma. A change in a mole or other spot on the skin may be the first sign of an early malignant melanoma or other form of skin cancer. Malignant melanoma arises in moles or in the tanning cells of the skin. People at high risk of developing malignant melanoma are those who have a family history of the disease, a previous melanoma, unusual moles on the skin, fair skin, light hair and eye color, a record of painful or blistering sunburns, and indoor occupations and outdoor recreational habits. Regular self examination is the best way to detect a malignant melanoma. Some forms of early malignant melanoma are asymmetrical, have uneven borders, are multicolored, and are larger than a pencil eraser. The pamphlet provides examples of these features. 12 figures.
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Malignant Melanoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail:
[email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have melanoma with information on its causes, symptoms, and treatment. Melanoma is a cancer of the pigment producing cells in the skin. Although it is uncertain how all cases of melanoma develop, it is clear that excessive sun exposure, especially blistering sunburns during childhood, can promote melanoma development. Ultraviolet radiation used in indoor tanning equipment may also cause melanoma. Although anyone can get melanoma, fair skinned people who tan poorly or burn easily are at greater risk. Other risk factors include a history of sunburns, many moles, atypical moles, and close relatives who had melanoma. Melanoma usually begins on the surface of the skin where it is easily treated. Left untreated, it can grow down into the skin, ultimately reaching
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the blood and lymphatic vessels and spreading around the body. Melanoma is usually brown or black in color, but may be red, skin colored, or white. Melanomas slowly get larger. Diagnosis is based on a biopsy of the lesion for examination under the microscope. Treatment begins with surgical removal of the melanoma and some normal appearing skin around the growth. The depth of invasion of the growth into the skin guides further treatment. Preventive efforts include avoiding sun exposure during times of the day when the sun is the strongest, wearing a broad spectrum sunscreen and protective clothing, and performing a monthly self examination. The pamphlet includes the asymmetry, border irregularity, color, and diameter (ABCD) rules to determine if a spot on the skin is suspicious. 5 figures. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “melanoma” (or synonyms). The following was recently posted: •
Guidelines of care for primary cutaneous melanoma Source: American Academy of Dermatology - Medical Specialty Society; 2001 March; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2741&nbr=1967&a mp;string=melanoma
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Systemic adjuvant therapy for patients at high risk for recurrent melanoma Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1998 May 27 (updated 2002 Nov); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3535&nbr=2761&a mp;string=melanoma Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
ABCD’s of Skin Cancer Summary: A general overview of three types of skin cancer-- basal cell carcinoma, squamous cell carcinoma, and melanoma are illustrated. Explains self-exam for skin cancer. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5777
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Congenital Nevi or Moles Summary: This information is intended to provide basic information only. It provides a general description for nevi and discusses the risk of skin cancer/melanoma associated with them. Source: Nevus Network http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2357
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Intraocular (Eye) Melanoma (PDQ®): Treatment Summary: Treatment information for patients based on information in the PDQ summary for health professionals on the cancer type -- intraocular melanoma. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5068
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MelanomaNet Summary: Basic facts about melanoma and its risks, prevention, and treatment. Selfexamination information is provided as well as a glossary. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6397
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What You Need To Know About™ Melanoma Summary: The National Cancer Institute (NCI) has written this booklet to help people with melanoma and their families and friends better understand this disease. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7135
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What You Need To Know About™ Moles and Dysplastic Nevi Summary: This booklet discusses common moles and unusual ones called dysplastic nevi or atypical moles. This booklet also shows what moles look like and explains how they may be related to melanoma. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7189 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to melanoma. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or
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specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to melanoma. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with melanoma. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about melanoma. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “melanoma” (or a synonym), and you will receive information on all relevant organizations listed in the database.
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Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “melanoma”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “melanoma” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “melanoma” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on melanoma: •
Basic Guidelines for Melanoma Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001442.htm Melanoma of the eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001022.htm
•
Signs & Symptoms for Melanoma Blistering Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Eyes, bulging Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003033.htm
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Hyperpigmentation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003242.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm Painful eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003032.htm Papule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003233.htm Poor vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Sunburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003227.htm •
Diagnostics and Tests for Melanoma Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Cranial CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm Lymph node biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003933.htm MRI of the head Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Punch biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Skin lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm
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•
Surgery and Procedures for Melanoma Skin graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002982.htm
•
Background Topics for Melanoma Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Cancer - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Choroid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002318.htm Conjunctiva Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002326.htm Iris Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002386.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm Melanin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002256.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Retina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002291.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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MELANOMA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow.
324 Melanoma
Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU]
Dictionary 325
Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as
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antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Sulfate: Sulfuric acid diammonium salt. It is used in fractionation of proteins. [NIH]
Amplification: The production of additional copies of a chromosomal DNA sequence,
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found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH]
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Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are
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highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the
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most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH]
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Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autocrine Motility Factor: A member of the class of cytokines secreted by tumor cells. It elicits increases in cell motility and phosphoinositide metabolism in the secreting or producing cell via a pertussis toxin-sensitive G-protein signal transduction pathway. The factor has also been used as a marker for bladder cancer. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous tumor cells: Cancer cells from an individual's own tumor. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bactericide: An agent that destroys bacteria. [EU] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical
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manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to
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fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,
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yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]
Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Self-Examination: The inspection of one's breasts, usually for signs of disease, especially neoplastic disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the
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trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Cafe-au-Lait Spots: Light brown pigmented macules associated with neurofibromatosis and Albright's syndrome (see fibrous dysplasia, polyostotic). [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions
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and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary
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when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH]
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Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Checkup: A general physical examination. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]
Chemotherapy: Treatment with anticancer drugs. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Choriocarcinoma: A malignant tumor of trophoblastic epithelium characterized by secretion of large amounts of chorionic gonadotropin. It usually originates from chorionic products of conception (i.e., hydatidiform mole, normal pregnancy, or following abortion), but can originate in a teratoma of the testis, mediastinum, or pineal gland. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye
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between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations
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which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in
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the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU]
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Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due
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to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]
Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective
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media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]
Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]
Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteinyldopa: Found in large amounts in the plasma and urine of patients with malignant melanoma. It is therefore used in the diagnosis of melanoma and for the detection of postoperative metastases. Cysteinyldopa is believed to be formed by the rapid enzymatic hydrolysis of 5-S-glutathionedopa found in melanin-producing cells. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU]
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Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH]
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Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Dendritic cell vaccine: A vaccine made of antigens and dendritic antigen-presenting cells (APCs). [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or
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concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Dolastatin 10: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several
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systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dormancy: The period when an organism (i. e., a virus or a bacterium) is in the body but not producing any ill effects. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dysplastic nevi: Atypical moles; moles whose appearance is different from that of common moles. Dysplastic nevi are generally larger than ordinary moles and have irregular and indistinct borders. Their color frequently is not uniform and ranges from pink to dark brown; they usually are flat, but parts may be raised above the skin surface. [NIH] Dysplastic nevus: An atypical mole; a mole whose appearance is different from that of a common mole. A dysplastic nevus is generally larger than an ordinary mole and has irregular and indistinct borders. Its color frequently is not uniform and ranges from pink to dark brown; it is usually flat, but parts may be raised above the skin surface. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU]
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Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emetic: An agent that causes vomiting. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat.
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Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enucleation: Removal of the nucleus from an eucaryiotic cell. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine
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based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagectomy: An operation to remove a portion of the esophagus. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by
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topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which
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occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such
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as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of microfilaments terminate and attach to the transmembrane linkers, integrins, which in turn attach through their extracellular domains to extracellular matrix proteins. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or
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asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungicide: An agent that destroys fungi. [EU] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma knife: Radiation therapy in which high-energy rays are aimed at a tumor from many angles in a single treatment session. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
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[NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids
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(steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp 100: Glycoprotein 100. A tumor-specific antigen used in the development of cancer
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vaccines. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hair Color: Color of hair or fur. [NIH] Hairy cell leukemia: A type of chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half
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of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation.
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[NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] HER2/neu: Human epidermal growth factor receptor 2. The HER2-neu protein is involved in growth of some cancer cells. Also called c-erbB-2. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU]
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Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-cell: A cell whose metabolism is used for the growth and reproduction of a virus. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydatidiform Mole: A trophoblastic disease characterized by hydrops of the mesenchymal portion of the villus. Its karyotype is paternal and usually homozygotic. The tumor is indistinguishable from chorioadenoma destruens or invasive mole ( = hydatidiform mole, invasive) except by karyotype. There is no apparent relation by karyotype to choriocarcinoma. Hydatidiform refers to the presence of the hydropic state of some or all of the villi (Greek hydatis, a drop of water). [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]
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Hydroxamic Acids: A class of weak acids with the general formula R-conhoh. [NIH] Hydroxylamine: A colorless inorganic compound (HONH2) used in organic synthesis and as a reducing agent, due to its ability to donate nitric oxide. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH]
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Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as immunoglobulins, monoclonal antibodies or antigens. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of drugs and radioisotopes in the chemotherapy and radioimmunotherapy of certain cancers. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunological adjuvant: A substance used to help boost the immune response to a vaccine so that less vaccine is needed. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]
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Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called
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intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which
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regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodoacetic Acid: Iodoacetic acid and its salts and derivatives. Iodoacetic acid reacts with cysteine (-SH) groups to form a carboxymethylated protein and is used as an enzyme inhibitor in biochemical research. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical
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or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isolated hepatic perfusion: A procedure in which a catheter is placed into the artery that provides blood to the liver; another catheter is placed into the vein that takes blood away from the liver. This temporarily separates the liver's blood supply from blood circulating throughout the rest of the body and allows high doses of anticancer drugs to be directed to the liver only. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH]
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Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Keyhole: A carrier molecule. [NIH] Keyhole limpet hemocyanin: KLH. One of a group of drugs called immune modulators, given as a vaccine to help the body respond to cancer. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH]
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Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentigo: Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the
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treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liposarcoma: A rare cancer of the fat cells. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when
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heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]
Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymph node mapping: The use of dyes and radioactive substances to identify lymph nodes that contain tumor cells. [NIH] Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic Metastasis: Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoscintigraphy: A method used to identify the sentinel node (the first draining lymph node near a tumor). A radioactive substance that can be taken up by lymph nodes is injected at the site of the tumor, and a doctor follows the movement of this substance on a computer screen. Once the lymph nodes that have taken up the substance are identified, they can be
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removed and examined to see if they contain tumor cells. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH]
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Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanoma vaccine: A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma. [NIH] Melanophores: Chromatophores (large pigment cells of fish, amphibia, reptiles and many invertebrates) which contain melanin. Short term color changes are brought about by an active redistribution of the melanophores pigment containing organelles (melanosomes). Mammals do not have melanophores; however they have retained smaller pigment cells known as melanocytes. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be
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absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylcholanthrene: A carcinogen that is often used in experimental cancer studies. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]
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Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mistletoe lectin: A substance that comes from the mistletoe plant, and that is being studied as a treatment for cancer. A lectin is a complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to
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molecules with the desired properties. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging,
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reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle
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known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naevus: A circumscribed area of pigmentation or vascularization, usually in the form of a congenital benign neoplasm occurring in the skin or in various ocular tissues. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck dissection: Surgery to remove lymph nodes and other tissues in the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]
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Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurofibroma: A fibrous tumor, usually benign, arising from the nerve sheath or the endoneurium. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevi and Melanomas: A collective term for the various types of nevi and melanomas. [NIH] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH]
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Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrocamptothecin: An alkaloid drug belonging to a class of anticancer agents called topoisomerase inhibitors. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Node-negative: Cancer that has not spread to the lymph nodes. [NIH] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoli: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH]
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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated
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by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1position and a nitrogen in the 3-position. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate
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and the posterior soft palate. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palliative therapy: Treatment given to relieve symptoms caused by advanced cancer. Palliative therapy does not alter the course of a disease but improves the quality of life. [NIH] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (=
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branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic
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nerves, sensory nerves, and motor nerves. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a
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terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a
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fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH]
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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from
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plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvalent: Having more than one valence. [EU] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Positron emission tomography scan: PET scan. A computerized image of the metabolic activity of body tissues used to determine the presence of disease. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH]
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Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatic acid phosphatase: PAP. An enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU]
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Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
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Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
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Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrazoloacridine: An anticancer drug that belongs to the family of drugs called acridines. [NIH]
Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Kinase: An enzyme that catalyzes reversibly the phosphorylation of pyridoxal in the presence of ATP with the formation of pyridoxal 5-phosphate and ADP. Pyridoxine, pyridoxamine and various derivatives can also act as acceptors. EC 2.7.1.35. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign
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conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH]
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Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration
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(= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH]
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Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for platinum and palladium. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH]
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Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]
Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self-Examination: The inspection of one's own body, usually for signs of disease (e.g., breast self-examination, testicular self-examination). [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]
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Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sentinel lymph node: The first lymph node that cancer is likely to spread to from the primary tumor. Cancer cells may appear first in the sentinel node before spreading to other lymph nodes. [NIH] Sentinel Lymph Node Biopsy: A diagnostic procedure used to determine whether lymphatic metastasis has occurred. The sentinel lymph node is the first lymph node to receive drainage from a neoplasm. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sharks: A group of elongate elasmobranchs. Sharks are mostly marine fish, with certain species large and voracious. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral
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upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation,
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maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solar radiation: Sunbathing as a therapeutic measure. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH]
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Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Standardize: To compare with or conform to a standard; to establish standards. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steady state: Dynamic equilibrium. [EU] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotactic radiosurgery: A radiation therapy technique involving a rigid head frame that is attached to the skull; high-dose radiation is administered through openings in the head frame to the tumor while decreasing the amount of radiation given to normal brain tissue. This procedure does not involve surgery. Also called stereotaxic radiosurgery and stereotactic radiation therapy. [NIH]
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Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to
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cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which
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is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thiobarbituric Acid Reactive Substances: Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU]
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Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH]
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Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH]
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Treosulfan: A substance that is being studied as a treatment for cancer. It belongs to the family of drugs called alkylating agents. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor infiltrating lymphocytes: White blood cells that have left the bloodstream and migrated into a tumor. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to
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the tumor. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosinase peptide: A tumor-specific antigen used in the development of cancer vaccines. [NIH]
Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents
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(from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Varicella: Chicken pox. [EU] Variegation: The appearance of different kinds of tissue in patterns, patches, or bands, frequently caused by the presence of special pigments or the absence of normal pigments. [NIH]
Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor
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cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] War: Hostile conflict between organized groups of people. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]
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X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX 3 3-dimensional, 43, 323, 392 A Abdominal, 323, 347, 356, 384, 386, 409 Aberrant, 42, 65, 72, 79, 323 Ablation, 71, 230, 323 Acanthosis Nigricans, 202, 323 Acceptor, 100, 323, 371, 383, 407, 408 Acetaminophen, 186, 323 Acetone, 240, 323, 369 Acetylcholine, 323, 381 Acetylgalactosamine, 323 Acetylglucosamine, 323 Acid Phosphatase, 323 Acidosis, 56, 124, 323 Actin, 89, 109, 323, 375, 379, 409 Acute leukemia, 178, 230, 323, 390, 411 Acute lymphoblastic leukemia, 323, 324 Acute lymphocytic leukemia, 230, 324 Acute myelogenous leukemia, 230, 324 Acute myeloid leukemia, 178, 324 Acute nonlymphocytic leukemia, 324 Adaptability, 324, 337 Adaptation, 256, 324, 377, 381, 388 Adduct, 324, 406 Adenine, 324, 394 Adenocarcinoma, 12, 236, 250, 324, 361, 381 Adenosine, 234, 235, 324, 330, 386 Adenovirus, 19, 63, 86, 135, 226, 256, 259, 324, 397 Adjustment, 141, 155, 324 Adjuvant Therapy, 5, 63, 149, 177, 251, 266, 308, 324 Adolescence, 272, 324 Adrenal Medulla, 324, 352 Adrenergic, 324, 349, 352, 405 Adverse Effect, 63, 325, 401 Aerosol, 133, 325, 405 Afferent, 325, 344 Affinity, 9, 22, 44, 47, 60, 63, 217, 325, 330, 373, 401 Affinity Chromatography, 44, 325 Agar, 37, 325, 341, 345, 364, 387 Agonist, 234, 248, 325, 349, 405 Airways, 234, 235, 325 Alanine, 33, 325 Albumin, 77, 203, 325, 383, 388
Algorithms, 325, 333 Alkaline, 12, 323, 325, 326, 335, 386 Alkaline Phosphatase, 12, 325 Alkaloid, 218, 325, 332, 335, 341, 381 Alkylating Agents, 325, 336, 346, 406, 409 Alleles, 8, 207, 326, 372 Allergen, 326, 400 Allogeneic, 31, 69, 108, 147, 236, 326, 359 Allylamine, 326 Alopecia, 326, 345 Alpha Particles, 326, 394 Alpha-1, 326, 387 Alternative medicine, 281, 326 Alum, 183, 326 Aluminum, 326 Amine, 217, 326, 361 Amino Acid Sequence, 216, 252, 261, 326, 328, 353, 357 Amino Acids, 326, 340, 352, 357, 380, 385, 389, 392, 400, 404 Ammonia, 326 Ammonium Sulfate, 201, 326 Amplification, 170, 326, 376 Anaesthesia, 327, 365 Anal, 211, 327, 351, 355 Analgesic, 323, 327, 370 Analog, 42, 99, 106, 171, 212, 217, 327, 355, 356 Analogous, 210, 327, 389, 408 Anaphylatoxins, 327, 342 Anatomical, 327, 330, 343, 365, 384, 399 Anemia, 298, 327, 340, 377 Anesthesia, 173, 176, 327 Anesthetics, 327, 331, 352 Anginal, 327, 381 Angiogenesis inhibitor, 63, 126, 327, 351 Animal model, 7, 10, 43, 44, 57, 227, 327, 409 Anions, 325, 327, 368, 400 Ankle, 278, 327 Annealing, 327, 389 Anomalies, 327, 406 Anorexia, 327, 356 Anterior chamber, 10, 328, 368 Anthrax, 65, 137, 328 Antibacterial, 204, 205, 328, 402 Antibiotic, 81, 328, 339, 346, 349, 352, 376, 402
416 Melanoma
Antibody, 20, 21, 25, 44, 51, 64, 65, 66, 67, 68, 69, 72, 79, 81, 86, 90, 141, 142, 170, 174, 175, 178, 215, 218, 220, 229, 231, 235, 239, 245, 325, 328, 333, 341, 352, 360, 361, 362, 364, 365, 368, 369, 374, 377, 394, 395, 400, 402, 413 Antibody therapy, 178, 235, 328 Anticoagulant, 328, 392 Antifungal, 204, 205, 209, 328, 369 Antigen-Antibody Complex, 328, 341 Antigen-presenting cell, 113, 282, 328, 347 Anti-infective, 328, 367 Anti-inflammatory, 254, 323, 328, 337, 347, 358 Anti-Inflammatory Agents, 328, 337 Antimetabolite, 328, 355 Antimitotic, 200, 328 Antineoplastic Agents, 326, 328, 411 Antioxidant, 124, 158, 328, 356, 383 Antiproliferative, 63, 128, 209, 329 Antipyretic, 323, 329 Antiseptic, 323, 329 Antiserum, 170, 329, 331 Antiviral, 63, 209, 329, 365, 366 Anus, 327, 329, 334, 395 Aphakia, 329, 397 Apheresis, 191, 329 Apolipoproteins, 329, 356 Applicability, 42, 282, 329 Aqueous, 203, 220, 258, 329, 332, 339, 345, 350, 370, 371 Arginine, 287, 327, 329, 381, 409 Aromatic, 43, 251, 329, 386 Arrhythmia, 258, 329 Arterial, 154, 326, 329, 330, 334, 343, 363, 392, 405 Arteries, 329, 330, 333, 344, 372, 375, 378, 393 Arterioles, 329, 330, 333, 375, 378 Arteriolosclerosis, 329, 330 Arteriosclerosis, 226, 329 Arteriovenous, 330, 375 Asbestos, 330, 373, 375 Ascites, 216, 330 Assay, 52, 54, 60, 330 Astrocytes, 330 Astrocytoma, 221, 297, 330, 357 Asymptomatic, 189, 330 Ataxia, 298, 330, 406 ATP, 258, 330, 348, 357, 358, 368, 386, 392, 394, 407, 408 Atrial, 330, 343, 409
Atrioventricular, 80, 330, 343 Atrium, 330, 343, 409, 411 Atrophy, 298, 330 Attenuation, 74, 330 Auricular, 93, 330 Autoantibodies, 330, 331 Autoantigens, 221, 330, 331 Autocrine Motility Factor, 44, 331 Autoimmune disease, 218, 262, 331, 377 Autoimmunity, 101, 305, 331 Autologous tumor cells, 11, 13, 15, 20, 31, 331 Autonomic, 323, 331, 344, 385 Autopsy, 5, 92, 331 Avidity, 47, 331 Axons, 331, 380, 382 B Bacillus, 66, 138, 328, 331 Bacteria, 10, 174, 201, 224, 262, 328, 331, 339, 347, 350, 351, 353, 354, 375, 388, 395, 400, 402, 408, 410 Bacterial Physiology, 324, 331 Bacterial toxin, 271, 331 Bactericidal, 331, 352 Bactericide, 201, 331 Bacteriophage, 28, 331, 387, 408 Bacterium, 331, 349 Barbiturate, 331, 406 Basal cell carcinoma, 43, 80, 88, 241, 254, 308, 331 Basal cells, 215, 331, 381 Basal Ganglia, 330, 331, 334, 356, 357 Basal Ganglia Diseases, 330, 331 Base, 13, 39, 204, 324, 331, 332, 347, 357, 369, 386, 406 Basement Membrane, 44, 232, 250, 332, 353, 369 Basophils, 332, 359, 370 Benign tumor, 230, 332 Berberine, 218, 332 Beta-Thromboglobulin, 332, 367 Bewilderment, 332, 342 Bilateral, 81, 332, 384, 397, 409 Bile, 332, 356, 362, 371, 404 Bilirubin, 325, 332 Binding Sites, 217, 232, 332 Bioassays, 243, 332 Bioavailability, 42, 332 Biogenesis, 34, 332 Biological response modifier, 137, 332, 333, 366 Biological therapy, 180, 189, 191, 332, 359
Index 417
Biomarkers, 61, 81, 333 Biosynthesis, 42, 146, 160, 333, 345, 372, 400 Biotechnology, 64, 76, 128, 146, 271, 281, 293, 295, 298, 299, 333 Biotin, 28, 333 Bladder, 107, 221, 262, 331, 333, 377, 391, 410 Bleomycin, 82, 139, 284, 333 Blood Coagulation, 63, 75, 258, 333, 335, 407 Blood Coagulation Factors, 333 Blood pressure, 177, 213, 333, 336, 363, 377, 381, 393, 401 Blood transfusion, 203, 333 Blood-Brain Barrier, 333, 370 Blot, 9, 211, 333, 364 Blotting, Western, 333, 364 Body Fluids, 333, 401, 409 Bone Marrow Cells, 334, 341, 359 Bone Marrow Transplantation, 186, 203, 334 Bone metastases, 334, 394 Bone scan, 334, 399 Boron, 161, 334 Boron Neutron Capture Therapy, 161, 334 Bowel, 327, 334, 348, 367, 370 Bowel Movement, 334, 348 Brachytherapy, 103, 119, 334, 367, 368, 394, 413 Bradykinin, 334, 381, 388 Brain Hypoxia, 334, 406 Brain Infarction, 334 Brain Ischemia, 239, 334 Brain metastases, 83, 147, 189, 334 Branch, 108, 127, 208, 274, 317, 334, 345, 364, 372, 385, 393, 402, 406 Breakdown, 334, 348, 356 Breast Self-Examination, 334, 399 Bronchi, 334, 335, 352, 374, 408 Bronchial, 211, 235, 335, 361 Bronchitis, 335, 339 Bronchoconstriction, 234, 235, 335 Bronchus, 113, 335 Butyric Acid, 128, 335 C Cafe-au-Lait Spots, 202, 335 Calcification, 330, 335 Calcium, 125, 126, 220, 330, 335, 341, 373, 378, 381, 383, 384, 392, 401, 409 Callus, 335, 350, 369 Calpain, 122, 335
Camptothecin, 125, 131, 137, 141, 153, 161, 335, 368 Cancer vaccine, 42, 51, 100, 204, 216, 240, 262, 335, 359, 374, 410 Capsid, 257, 335 Capsules, 335, 356 Carbohydrate, 42, 335, 358, 389 Carbon Dioxide, 335, 355, 396 Carboplatin, 129, 153, 162, 284, 335 Carcinoembryonic Antigen, 222, 260, 335 Carcinogen, 324, 336, 374, 375, 378 Carcinogenesis, 37, 44, 50, 211, 336, 338 Carcinogenic, 43, 326, 336, 366, 382, 391, 404, 410 Cardiac, 179, 185, 193, 202, 326, 335, 336, 343, 352, 378, 379, 398, 404 Cardiovascular, 113, 233, 234, 258, 336 Cardiovascular disease, 233, 336 Carmustine, 186, 284, 336 Carotene, 336, 397 Case report, 79, 83, 92, 97, 102, 107, 109, 336, 340 Case series, 336, 340 Case-Control Studies, 11, 86, 336, 351 Caspase, 32, 57, 79, 83, 91, 109, 336 Catabolism, 24, 336 Catalytic Domain, 242, 336 Cataract, 102, 329, 336, 397 Catheters, 174, 336, 365, 367 Cations, 336, 368 Causal, 44, 54, 336, 351 Causality, 107, 336 Cause of Death, 3, 202, 220, 230, 233, 259, 337 Celecoxib, 15, 337 Cell Adhesion, 35, 68, 69, 71, 72, 223, 337, 366 Cell Aggregation, 35, 337 Cell Cycle, 16, 23, 24, 126, 144, 171, 226, 246, 253, 337, 339, 345, 353, 393 Cell Death, 32, 49, 65, 75, 125, 131, 141, 161, 202, 239, 329, 337, 353, 379 Cell Differentiation, 70, 87, 95, 337, 401, 403 Cell Division, 12, 228, 239, 298, 331, 337, 345, 353, 359, 367, 376, 387, 399 Cell Extracts, 251, 337 Cell Fusion, 22, 337 Cell membrane, 12, 337, 347, 367, 368, 369 Cell motility, 38, 44, 219, 220, 331, 337 Cell proliferation, 23, 66, 213, 236, 250, 254, 330, 337, 397, 401
418 Melanoma
Cell Respiration, 337, 376, 396 Cell Size, 337, 355 Cell Survival, 337, 359 Cell Transplantation, 337 Cellulose, 337, 387 Central Nervous System, 35, 81, 138, 210, 233, 323, 325, 338, 356, 357, 358, 371, 377, 382, 385 Cerebellar, 330, 338, 395 Cerebral, 104, 330, 331, 333, 334, 338, 352, 353, 357, 360 Cerebral hemispheres, 331, 334, 338, 357 Cerebrovascular, 332, 336, 338, 406 Cerebrum, 338, 387, 409 Cervical, 164, 338, 360 Checkup, 175, 338 Chemokines, 54, 58, 338 Chemoprevention, 15, 31, 38, 338 Chemopreventive, 15, 253, 254, 338 Chemotactic Factors, 338, 342 Chemotaxis, 220, 338 Chemotherapeutics, 28, 200, 338 Cholesterol, 332, 338, 344, 356, 372, 404, 405 Chondroitin sulfate, 37, 69, 99, 338 Chondrosarcoma, 253, 338 Choriocarcinoma, 223, 236, 261, 338, 362 Chorioretinitis, 338, 397 Choroid, 55, 111, 190, 194, 275, 321, 338, 397 Chromatin, 329, 339, 380 Chromosomal, 8, 16, 84, 115, 127, 148, 205, 207, 208, 237, 326, 339, 388, 398, 406 Chromosome, 27, 36, 43, 68, 169, 170, 205, 207, 238, 339, 360, 371, 398, 399, 405 Chronic, 43, 55, 178, 228, 230, 234, 298, 339, 348, 351, 359, 365, 369, 370, 389, 393, 404 Chronic Disease, 339, 370 Chronic granulocytic leukemia, 339 Chronic leukemia, 230, 339, 359 Chronic lymphocytic leukemia, 230, 339 Chronic myelogenous leukemia, 230, 339 Chronic Obstructive Pulmonary Disease, 234, 339 Chronic renal, 339, 389 Ciliary, 111, 190, 194, 267, 339, 400 Ciliary Body, 111, 190, 194, 267, 339, 400 Ciliary processes, 339 CIS, 161, 302, 339, 397
Cisplatin, 14, 74, 92, 112, 124, 132, 134, 136, 140, 143, 147, 152, 154, 156, 160, 181, 286, 339 C-kit receptor, 339, 403 Clarithromycin, 157, 339 Clathrin, 339, 340, 350 Clinical Medicine, 340, 390 Clinical study, 22, 25, 163, 340, 343 Clone, 38, 54, 60, 70, 340 Cloning, 36, 44, 66, 67, 72, 125, 140, 211, 225, 333, 340, 366 Clot Retraction, 340, 388 Coagulation, 258, 333, 340, 360, 388, 407 Coated Vesicles, 339, 340, 350 Cobalt, 219, 220, 340 Coculture, 93, 340 Cod Liver Oil, 340, 350 Codon, 252, 340, 357 Coenzyme, 259, 340, 372 Cofactor, 259, 340, 392, 407 Cohort Studies, 340, 351 Colchicine, 171, 200, 341, 409 Coliphages, 331, 341 Collagen, 23, 66, 67, 70, 104, 220, 223, 232, 261, 332, 341, 353, 354, 356, 373, 388, 391 Collagenases, 232, 341 Colloidal, 325, 341, 386, 400, 405 Colony-Stimulating Factors, 341, 359 Colorectal, 236, 239, 240, 341 Colorectal Cancer, 239, 341 Combination chemotherapy, 85, 140, 186, 187, 341 Combination Therapy, 84, 341 Complement, 24, 52, 69, 215, 223, 255, 327, 341, 342, 357, 366, 373, 388, 400 Complementary and alternative medicine, 133, 167, 342 Complementary medicine, 133, 342 Complete remission, 20, 126, 342, 396 Complete response, 127, 342 Compress, 342, 407 Computational Biology, 293, 295, 342 Computed tomography, 173, 342, 399 Computerized axial tomography, 342, 399 Computerized tomography, 342 Conception, 338, 342, 354, 402, 404 Concomitant, 29, 58, 342 Cones, 342, 397 Confusion, 231, 342, 348 Congestive heart failure, 258, 342 Conjugated, 28, 63, 72, 287, 342 Conjunctiva, 93, 321, 343
Index 419
Connective Tissue, 44, 73, 103, 334, 341, 343, 354, 356, 372, 375, 392, 398 Connective Tissue Cells, 343 Consciousness, 327, 343, 346, 348, 403 Constitutional, 343, 397 Constriction, 343, 368, 398, 411 Constriction, Pathologic, 343, 411 Consultation, 59, 343 Consumption, 343, 356, 383 Continuum, 206, 343 Contraindications, ii, 343 Control group, 343, 391, 395 Controlled clinical trial, 38, 49, 61, 343 Conventional therapy, 343 Conventional treatment, 21, 185, 193, 227, 263, 343 Coordination, 61, 217, 343, 377 Cor, 213, 343, 344 Cornea, 328, 344, 358, 399, 404, 413 Corneum, 344, 352 Coronary, 336, 344, 363, 375, 378 Coronary Arteriosclerosis, 344, 378 Coronary heart disease, 336, 344 Coronary Thrombosis, 344, 375, 378 Cortex, 330, 344, 353, 391, 395 Corticotropin-Releasing Hormone, 213, 344 Cortisol, 325, 344 Cortisone, 344, 347 Cranial, 239, 320, 344, 380, 382, 385, 410 Cranial Nerves, 239, 344 Crossing-over, 344, 395 Cross-Sectional Studies, 344, 351 Croton Oil, 249, 344 Crowns, 344, 347 Cryosurgery, 5, 93, 344 Culture Media, 325, 344 Curative, 345, 406 Curettage, 93, 345 Curette, 345 Cyclic, 335, 345, 359, 381 Cyclin, 23, 27, 91, 144, 226, 246, 345 Cyclin-Dependent Kinases, 144, 226, 345 Cyclophosphamide, 49, 165, 345 Cyst, 77, 103, 345 Cystathionine beta-Synthase, 345, 363 Cysteine, 103, 335, 338, 345, 367, 404 Cysteinyldopa, 85, 345 Cystine, 345 Cytogenetics, 84, 96, 105, 137, 345, 398 Cytomegalovirus, 345, 356 Cytomegalovirus Infections, 345, 356
Cytoplasm, 239, 329, 332, 337, 345, 346, 351, 359, 379, 380 Cytoskeletal Proteins, 335, 339, 346 Cytoskeleton, 346, 366, 376 Cytostatic, 92, 205, 236, 346, 378 Cytotoxic chemotherapy, 346 Cytotoxicity, 24, 25, 79, 129, 140, 145, 154, 200, 326, 339, 346, 369 D Dacarbazine, 82, 124, 125, 134, 136, 139, 141, 143, 150, 152, 154, 161, 162, 181, 280, 284, 346 Data Collection, 49, 59, 346, 355 Databases, Bibliographic, 293, 346 Daunorubicin, 346, 349 De novo, 6, 14, 225, 258, 346 Decision Making, 37, 346 Defense Mechanisms, 346, 366 Degenerative, 346, 361, 397 Deletion, 40, 101, 204, 207, 247, 257, 329, 346, 371 Delivery of Health Care, 346, 360 Dementia, 239, 346 Denaturation, 346, 389 Dendrites, 215, 346, 347, 380 Dendritic cell vaccine, 18, 102, 347 Density, 9, 25, 105, 216, 240, 246, 257, 347, 355, 382 Dental Abutments, 347 Dental Caries, 347, 355 Dentures, 4, 347 Deoxyribonucleic, 282, 347 Deoxyribonucleic acid, 282, 347 Deoxyribonucleotides, 347 Depigmentation, 347, 412 Depolarization, 347, 401 Dermal, 63, 70, 103, 257, 347 Dermatologist, 11, 38, 78, 251, 347 Detoxification, 225, 347 Dexamethasone, 226, 347 Diabetes Mellitus, 347, 360, 385 Diagnostic procedure, 192, 199, 281, 347, 400 Diaphragm, 347, 389 Diarrhoea, 347, 356 Diastolic, 347, 363 Diffusion, 347, 364, 365, 367 Digestion, 203, 332, 334, 348, 367, 371, 404, 410 Digestive system, 197, 348, 377 Digestive tract, 348, 401, 403 Dilatation, 348, 391
420 Melanoma
Diploid, 348, 387 Disease Progression, 22, 46, 52, 180, 225, 348 Disease-Free Survival, 4, 148, 348 Disinfectant, 348, 352 Disorientation, 342, 348 Dissection, 170, 348, 372, 409 Dissociation, 325, 348, 368 DNA Topoisomerase, 348, 357 Docetaxel, 85, 130, 140, 143, 159, 165, 200, 348 Dolastatin 10, 209, 210, 348 Dopa, 155, 202, 348, 370 Dopamine, 348, 370, 386 Dormancy, 22, 128, 349 Dorsal, 12, 349, 380, 390 Dorsum, 113, 349, 356 Doxorubicin, 77, 349 Drive, ii, vi, 47, 51, 123, 126, 227, 349, 368 Drug Interactions, 285, 349 Drug Resistance, 34, 99, 152, 225, 349 Drug Tolerance, 349 Duodenum, 332, 349, 404 Dyes, 332, 349, 355, 372, 380, 404 Dysplasia, 61, 164, 298, 335, 349 Dysplastic nevi, 61, 101, 274, 306, 309, 349 Dysplastic nevus, 306, 349 Dystrophy, 298, 349 E Ectoderm, 349, 380 Ectopic, 35, 109, 349 Effector, 19, 20, 61, 82, 221, 261, 323, 341, 350, 369 Effector cell, 19, 261, 350, 369 Elasticity, 329, 344, 350 Elastin, 341, 350, 353 Elective, 74, 350 Electrocardiogram, 173, 174, 175, 176, 179, 182, 185, 193, 350 Electrocoagulation, 340, 350 Electrolyte, 350, 402 Electrons, 329, 332, 350, 368, 383, 394, 395 Electroplating, 350, 404 Embolus, 350, 365 Embryo, 337, 349, 350, 354, 365, 389 Embryogenesis, 12, 350, 403 Emetic, 344, 350 Emphysema, 234, 339, 350 Emulsion, 47, 350, 355 Encapsulated, 51, 153, 350, 371 Endemic, 350, 403 Endosomes, 10, 350
Endostatin, 10, 286, 351 Endothelial cell, 43, 75, 218, 223, 261, 333, 351, 354, 367, 407 Endothelium, 218, 351, 381, 388 Endothelium, Lymphatic, 351 Endothelium, Vascular, 351 Endothelium-derived, 351, 381 Endotoxin, 218, 351, 409 End-stage renal, 339, 351, 389 Enhancer, 54, 67, 351 Enucleation, 9, 18, 42, 49, 53, 55, 85, 103, 108, 351 Environmental Exposure, 26, 43, 351, 382 Environmental Health, 292, 294, 351 Enzymatic, 217, 245, 259, 335, 336, 341, 345, 347, 351, 361, 389, 397 Eosinophil, 351, 359 Epidemic, 37, 39, 351, 403 Epidemiologic Studies, 59, 351 Epidemiological, 26, 31, 228, 263, 267, 351 Epidermal, 7, 57, 90, 116, 171, 202, 213, 254, 351, 361, 369, 374 Epidermal Growth Factor, 351, 361 Epidermis, 57, 202, 208, 215, 237, 248, 250, 331, 344, 351, 352, 362, 363, 369, 391 Epidermoid carcinoma, 200, 352, 403 Epigastric, 352, 384 Epinephrine, 286, 324, 349, 352, 410 Epithelial, 178, 210, 211, 233, 324, 339, 352, 361, 369, 384 Epithelial Cells, 211, 233, 352, 361, 369 Epithelium, 8, 71, 211, 332, 338, 351, 352, 368, 384, 397, 413 Epitope, 22, 34, 72, 215, 231, 352 Erythema, 352, 404 Erythrocytes, 327, 334, 335, 352, 395, 400 Erythromycin, 339, 352 Escalation, 22, 63, 352 Esophagectomy, 129, 154, 352 Esophagus, 113, 129, 154, 155, 348, 352, 374, 386, 404, 411 Essential Tremor, 298, 352 Estrogen, 352, 399, 405 Ethanol, 205, 352 Etoposide, 136, 142, 143, 147, 352 Eukaryotic Cells, 346, 353, 365, 381, 382, 410 Evoke, 353, 404 Excisional, 353, 412 Excitation, 353, 355 Excitatory, 353, 358 Exfoliation, 239, 353
Index 421
Exocrine, 353, 384 Exogenous, 353, 357, 359, 392 Exon, 72, 234, 353 Expiration, 353, 396 Extensor, 353, 393, 412 External-beam radiation, 353, 368, 394, 413 Extracellular Matrix, 23, 35, 44, 231, 343, 353, 354, 355, 366, 373, 383 Extracellular Matrix Proteins, 353, 355, 373 Extracellular Space, 353 Extraction, 329, 353, 397 Extraocular, 194, 353 Extremity, 47, 353, 384 Eye Color, 307, 353 Eye Infections, 218, 324, 353 F Family Planning, 293, 354 Fat, 334, 335, 336, 343, 344, 350, 354, 369, 371, 377, 389, 398, 399, 402, 405 Fatigue, 354, 360 Fatty acids, 325, 354 Feces, 335, 354 Fertilizers, 354, 404 Fetal Development, 215, 354 Fetus, 354, 364, 410 Fibrin, 333, 340, 354, 388, 406, 407 Fibrinogen, 354, 388, 406 Fibroblast Growth Factor, 44, 68, 354 Fibroblasts, 43, 48, 223, 261, 343, 354, 367 Fibrosarcoma, 82, 139, 156, 223, 236, 261, 354 Fibrosis, 234, 298, 326, 354, 399 Filgrastim, 154, 354 Fine-needle aspiration, 354, 379 Fixation, 354, 400 Flavopiridol, 187, 355 Flow Cytometry, 9, 15, 19, 355 Fluorescence, 16, 93, 355 Fluorescent Dyes, 355 Fluorine, 160, 355 Fluorouracil, 165, 236, 355, 370 Focal Adhesions, 23, 355 Focus Groups, 59, 355 Fold, 4, 35, 39, 62, 75, 211, 355 Follow-Up Studies, 183, 355 Forearm, 333, 355 Fractionation, 10, 34, 44, 89, 249, 326, 355 Fungi, 328, 353, 355, 356, 375, 413 Fungicide, 201, 356
G Gallate, 150, 356 Gallbladder, 323, 348, 356 Gamma knife, 95, 149, 356 Gamma Rays, 356, 378, 394, 395 Ganciclovir, 212, 356 Ganglia, 323, 331, 356, 380, 385 Ganglion, 356, 380, 382, 413 Ganglioside, 10, 25, 74, 79, 141, 220, 231, 356 Gas, 326, 335, 347, 355, 356, 362, 378, 381, 405 Gastric, 352, 356, 361, 362 Gastrin, 356, 362 Gastroenteritis, 218, 356 Gastrointestinal, 89, 209, 330, 334, 335, 352, 356, 402, 404, 409 Gastrointestinal tract, 335, 352, 356, 402, 409 Gelatin, 23, 345, 356, 358, 405, 406 Gemfibrozil, 38, 356 Gene Expression, 14, 26, 43, 45, 46, 53, 62, 75, 82, 100, 157, 227, 245, 279, 299, 357 Gene Targeting, 63, 357 Gene-modified, 58, 357 Genetic Code, 357, 381 Genetic Engineering, 256, 333, 340, 357 Genetic Markers, 32, 357 Genetic testing, 357, 389 Genetics, 26, 37, 48, 84, 95, 96, 100, 105, 137, 171, 221, 222, 269, 345, 357, 364, 385 Genistein, 143, 144, 147, 153, 357 Genital, 357, 412 Genotype, 357, 386 Germ Cells, 357, 383, 402, 406 Germline mutation, 221, 246, 357, 361 Ginseng, 166, 357 Gland, 80, 324, 344, 357, 372, 384, 387, 391, 399, 404, 407 Glioblastoma, 200, 221, 223, 256, 261, 357 Glioblastoma multiforme, 256, 357 Glioma, 220, 221, 229, 248, 256, 357 Glucocorticoid, 347, 357 Glucose, 56, 137, 160, 298, 337, 347, 358, 360, 366, 387, 398 Glucuronic Acid, 358, 361 Glutamate, 34, 279, 358, 375 Glutamic Acid, 213, 358, 391 Glycerol, 335, 358 Glycine, 358, 400 Glycogen, 259, 358, 387 Glycolysis, 56, 259, 358
422 Melanoma
Glycoprotein, 68, 98, 160, 204, 211, 229, 335, 354, 358, 359, 369, 373, 407, 409 Glycosaminoglycan, 338, 358 Glycoside, 358, 362, 398 Glycosidic, 358, 380, 382, 387 Glycosylation, 17, 42, 358 Gonadal, 358, 404 Gonadotropin, 248, 338, 358 Gout, 341, 358 Governing Board, 358, 390 Gp 100, 41, 358 Grade, 45, 61, 357, 359 Graft, 194, 218, 359, 362, 365, 378, 393 Graft Rejection, 218, 359, 365 Grafting, 359, 365 Graft-versus-host disease, 359, 393 Granulocyte Colony-Stimulating Factor, 136, 341, 354, 359 Granulocyte-Macrophage ColonyStimulating Factor, 85, 121, 341, 359 Granulocytes, 341, 359, 370, 401, 412 Granuloma, 94, 359 Groin, 176, 359 Growth factors, 9, 43, 359 Growth Inhibitors, 204, 359 Guanylate Cyclase, 359, 381 H Hair Color, 57, 266, 359 Hairy cell leukemia, 230, 359 Half-Life, 217, 224, 359 Haploid, 360, 387 Haptens, 241, 325, 360 Health Care Costs, 235, 360 Health Expenditures, 360 Health Status, 173, 175, 360 Heart attack, 336, 360 Heart failure, 258, 360 Hematogenous, 35, 42, 67, 360 Hematologic malignancies, 360, 371 Hematopoiesis, 230, 360 Heme, 13, 332, 360, 383 Hemiparesis, 360 Hemiplegia, 4, 360 Hemoglobin, 127, 327, 352, 360 Hemoglobinuria, 298, 360 Hemorrhage, 350, 360, 378, 404 Hemostasis, 127, 263, 360, 366 Heparin, 68, 106, 361, 388 Hepatic, 9, 67, 69, 173, 234, 325, 361 Hepatitis, 262, 361 Hepatocellular, 234, 361 Hepatocellular carcinoma, 234, 361
Hepatocytes, 361 Hepatoma, 212, 257, 361 HER2/neu, 236, 361 Hereditary, 40, 268, 274, 278, 357, 358, 361, 397 Hereditary mutation, 357, 361 Heredity, 356, 357, 361 Herpes, 99, 212, 361 Herpes virus, 99, 361 Herpes Zoster, 361 Heterodimers, 361, 366 Heterogeneity, 39, 207, 325, 361 Histamine, 98, 286, 327, 361 Histidine, 242, 251, 361 Histone Deacetylase, 118, 361 Homeostasis, 34, 170, 361 Homogeneous, 207, 329, 343, 361 Homologous, 213, 222, 326, 344, 357, 361, 377, 399, 400, 405 Homotypic, 35, 362 Hormonal, 272, 330, 362 Hormone, 57, 201, 213, 217, 248, 324, 332, 344, 352, 356, 362, 367, 391, 398, 401, 402, 407 Hormone therapy, 324, 362 Horny layer, 352, 362 Host-cell, 244, 362 Human papillomavirus, 77, 362 Humoral, 25, 31, 68, 100, 218, 359, 362 Humour, 362 Hybrid, 36, 67, 340, 362 Hybridization, 8, 9, 16, 26, 53, 84, 140, 225, 240, 337, 362 Hybridoma, 220, 362 Hydatidiform Mole, 338, 362 Hydrochloric Acid, 201, 362 Hydrogen, 323, 326, 332, 335, 346, 353, 362, 371, 377, 380, 381, 383, 393 Hydrolases, 150, 362, 386 Hydrolysis, 64, 339, 345, 362, 368, 380, 385, 386, 389, 392, 409 Hydrophobic, 362, 368 Hydroxamic Acids, 236, 363 Hydroxylamine, 236, 363 Hydroxylysine, 341, 363 Hydroxyproline, 341, 363 Hyperglycemia, 127, 363 Hyperhomocysteinemia, 258, 345, 363 Hyperpigmentation, 202, 320, 363 Hyperplasia, 90, 171, 254, 363 Hypersensitivity, 12, 24, 326, 351, 363, 398, 400
Index 423
Hypertension, 203, 258, 329, 336, 363 Hyperthermia, 56, 105, 138, 155, 156, 176, 363 Hypertrophy, 226, 258, 344, 363, 409 Hypnotic, 331, 363, 406 Hypothalamus, 344, 363, 387, 402 Hypoxia, 43, 55, 363 I Id, 25, 132, 163, 302, 308, 310, 316, 318, 363 Idiotype, 25, 220, 286, 363 Imidazole, 333, 361, 363 Immortal, 204, 363 Immune adjuvant, 326, 363 Immune function, 179, 363 Immune Sera, 363, 364 Immune system, 9, 19, 20, 29, 30, 57, 174, 177, 179, 182, 185, 189, 191, 193, 214, 218, 221, 224, 241, 266, 278, 328, 331, 332, 350, 363, 364, 365, 372, 373, 377, 379, 386, 410, 412 Immune Tolerance, 220, 240, 364 Immunoblotting, 10, 51, 364 Immunoconjugates, 69, 364 Immunodeficiency, 298, 364 Immunodiffusion, 325, 364 Immunoelectrophoresis, 325, 364 Immunogen, 12, 244, 364 Immunogenetics, 214, 364 Immunogenic, 9, 42, 58, 72, 220, 221, 240, 244, 257, 282, 364 Immunoglobulin, 62, 63, 68, 328, 364, 377 Immunohistochemistry, 9, 17, 118, 240, 364 Immunologic, 9, 18, 22, 25, 29, 46, 58, 62, 85, 229, 338, 364, 395 Immunological adjuvant, 130, 141, 364 Immunosuppressant, 218, 326, 355, 364 Immunosuppressive, 20, 345, 358, 364, 365 Immunosuppressive therapy, 365 Immunotoxins, 140, 215, 255, 365, 394 Impairment, 208, 237, 330, 332, 354, 365, 374 Implant radiation, 365, 367, 368, 394, 413 Implantation, 255, 342, 365 In situ, 9, 16, 26, 29, 48, 70, 98, 105, 365 In Situ Hybridization, 9, 16, 26, 365 In vitro, 10, 22, 25, 29, 31, 37, 43, 44, 47, 48, 49, 56, 57, 60, 62, 65, 70, 86, 103, 128, 131, 133, 141, 142, 143, 145, 149, 205, 214, 216, 220, 245, 253, 255, 263, 282, 337, 365, 389, 407 Incision, 173, 365, 367, 369
Indicative, 211, 266, 365, 384, 411 Induction, 10, 19, 24, 32, 44, 63, 68, 70, 75, 76, 128, 149, 151, 170, 224, 226, 365 Infarction, 258, 334, 365, 396 Infiltration, 11, 80, 365, 413 Infusion, 129, 177, 365, 378, 408 Ingestion, 328, 366, 389 Inhalation, 325, 330, 366, 389 Initiation, 55, 63, 82, 366, 408 Initiator, 366 Inorganic, 339, 363, 366 Inositol, 64, 366, 375 Insertional, 22, 366 Insight, 20, 37, 366 Insulator, 366, 377 Integrins, 44, 355, 366 Interferon-alpha, 83, 88, 93, 134, 135, 366 Interleukin-1, 50, 101, 178, 183, 366 Interleukin-12, 50, 101, 178, 183, 366 Interleukin-4, 93, 367 Interleukin-8, 45, 171, 367 Intermittent, 171, 266, 367 Internal radiation, 367, 368, 394, 413 Interphase, 23, 367, 381 Interstitial, 232, 334, 353, 367, 368, 413 Intestinal, 229, 336, 367, 373 Intestine, 334, 341, 367, 370 Intracellular, 10, 14, 34, 38, 216, 220, 239, 262, 339, 365, 366, 367, 375, 381, 401 Intraocular, 30, 182, 183, 188, 194, 297, 303, 309, 367 Intravenous, 134, 154, 181, 366, 367 Intrinsic, 45, 225, 246, 325, 332, 367 Introns, 204, 367 Invasive, 40, 48, 71, 215, 223, 231, 240, 247, 250, 260, 362, 364, 367, 373 Invertebrates, 10, 210, 367, 374 Involuntary, 331, 352, 367, 378, 401 Iodine, 103, 119, 367 Iodoacetic Acid, 263, 367 Ion Transport, 127, 367 Ionization, 368 Ionizing, 43, 326, 351, 368, 394 Ions, 126, 217, 219, 220, 332, 348, 350, 362, 367, 368, 377, 392 Irinotecan, 85, 140, 368 Iris, 103, 119, 194, 321, 328, 344, 353, 368 Irradiation, 49, 55, 144, 334, 368, 413 Ischemia, 258, 330, 334, 356, 368, 378, 396 Isoelectric, 211, 368 Isoelectric Focusing, 211, 368 Isoelectric Point, 368
424 Melanoma
Isolated hepatic perfusion, 173, 368 Isolated limb perfusion, 5, 124, 125, 127, 128, 130, 146, 176, 368 Isoprenoid, 162, 368 Isothiocyanates, 143, 369 Isotonic, 203, 369, 376 J Joint, 116, 234, 369, 405 K Kb, 292, 369 Keratin, 369, 399 Keratinocytes, 30, 124, 202, 215, 250, 367, 369 Keratosis, 77, 280, 369 Ketoconazole, 262, 369 Ketone Bodies, 323, 369 Keyhole, 141, 369 Keyhole limpet hemocyanin, 141, 369 Kidney Disease, 197, 292, 298, 369 Killer Cells, 369 Kinetic, 368, 369 L Labile, 341, 369 Lacrimal, 107, 369 Laminin, 44, 104, 150, 332, 353, 369 Laparotomy, 173, 369 Large Intestine, 341, 348, 367, 370, 395, 401 Latency, 15, 370 Latent, 370, 390 Laxative, 325, 370 Lectin, 17, 141, 370, 376 Leiomyosarcoma, 236, 370 Leishmaniasis, 262, 370, 385 Lens, 5, 65, 120, 329, 336, 370, 396, 412 Lentigo, 5, 40, 98, 107, 206, 238, 272, 370 Lesion, 3, 4, 5, 6, 205, 241, 248, 266, 274, 278, 308, 320, 359, 370, 371, 400, 410 Lethal, 21, 41, 65, 73, 137, 272, 331, 370, 378 Leucocyte, 326, 351, 370, 372 Leukaemia, 121, 228, 370 Leukapheresis, 22, 174, 179, 182, 185, 193, 329, 370 Leukocytes, 218, 262, 332, 334, 338, 359, 366, 370, 380, 409 Levamisole, 262, 284, 370 Levo, 348, 370, 374 Levodopa, 107, 348, 370 Library Services, 316, 371 Ligament, 371, 391 Ligands, 47, 366, 371 Ligation, 35, 371
Limb perfusion, 56, 100, 371 Linkage, 26, 27, 105, 246, 357, 371, 385 Lipid, 38, 128, 287, 329, 330, 356, 358, 371, 377, 383, 406 Lipid Peroxidation, 371, 383, 406 Liposarcoma, 12, 371 Liposomal, 159, 371 Liposome, 66, 69, 75, 133, 371 Liver metastases, 30, 371 Liver scan, 371, 399 Localization, 10, 34, 44, 71, 74, 105, 121, 127, 148, 158, 170, 364, 371 Locomotion, 371, 387 Locoregional, 4, 371 Lomustine, 82, 139, 182, 371 Loop, 232, 371 Loss of Heterozygosity, 70, 207, 371 Lovastatin, 15, 38, 372 Low-density lipoprotein, 372 Lucida, 369, 372 Lung metastases, 11, 33, 38, 58, 133, 372 Lymph node mapping, 372 Lymphadenectomy, 11, 100, 106, 266, 372 Lymphatic, 106, 117, 306, 308, 351, 365, 372, 375, 400, 402, 403, 407 Lymphatic Metastasis, 372, 400 Lymphatic system, 306, 372, 402, 403, 407 Lymphoblasts, 323, 324, 372 Lymphocyte, 22, 29, 40, 49, 60, 64, 65, 66, 75, 81, 236, 242, 328, 369, 372, 373, 374 Lymphocytic, 12, 204, 205, 228, 372 Lymphoid, 58, 230, 328, 370, 372 Lymphoma, 19, 58, 212, 221, 236, 239, 249, 262, 298, 360, 372 Lymphoscintigraphy, 87, 106, 161, 372 Lysine, 130, 363, 373, 409 Lytic, 218, 373, 400 M Macrolides, 157, 373 Macrophage, 24, 46, 76, 93, 97, 128, 130, 151, 262, 341, 359, 366, 373 Macrophage Colony-Stimulating Factor, 76, 93, 130, 341, 373 Magnetic Resonance Imaging, 83, 92, 173, 176, 373, 399 Major Histocompatibility Complex, 9, 30, 69, 262, 367, 373 Malabsorption, 298, 373 Malignant mesothelioma, 373, 375 Malignant tumor, 7, 228, 229, 230, 241, 255, 338, 373, 377, 383, 398 Malnutrition, 325, 330, 373, 378
Index 425
Malondialdehyde, 373, 406 Mammary, 373, 405 Mania, 135, 373 Manifest, 360, 373 Matrix metalloproteinase, 23, 77, 138, 149, 232, 373 Medial, 330, 373 Mediastinum, 338, 374 Mediate, 10, 14, 29, 35, 39, 58, 69, 135, 349, 369, 374 Mediator, 37, 161, 235, 348, 366, 374, 388 Medical Records, 374, 397 MEDLINE, 293, 295, 299, 374 Melanin, 17, 37, 57, 116, 141, 146, 160, 202, 204, 215, 321, 345, 347, 368, 374, 386, 410 Melanoma vaccine, 5, 24, 37, 51, 97, 117, 178, 188, 195, 196, 278, 279, 282, 286, 306, 374 Melanophores, 215, 374 Melanosis, 323, 374 Melanosomes, 34, 202, 215, 374 Melphalan, 56, 100, 105, 124, 176, 284, 287, 374 Memory, 13, 15, 50, 58, 59, 61, 82, 327, 346, 374 Meninges, 248, 338, 374, 402 Mental Disorders, 198, 374, 391, 393 Mental Health, iv, 6, 198, 292, 294, 374, 391, 393 Mercury, 355, 374 Mesenchymal, 352, 359, 362, 373, 375 Mesothelioma, 236, 373, 375 Meta-Analysis, 88, 375 Metabolite, 256, 372, 375, 391 Metabotropic, 34, 375 Metastasize, 26, 53, 55, 194, 233, 250, 259, 375, 399 Metastatic cancer, 226, 250, 375 Methionine, 151, 252, 375, 404 Methylcholanthrene, 214, 375 Methyltransferase, 111, 124, 136, 153, 375 MI, 75, 94, 116, 322, 375 Microbe, 375, 407 Microbiology, 21, 45, 60, 139, 324, 330, 375 Microcirculation, 42, 375, 388 Microfilaments, 355, 375 Microorganism, 340, 375, 412 Micro-organism, 347, 359, 375 Microscopy, 5, 6, 34, 44, 240, 332, 376, 381 Microtubules, 200, 209, 376, 383 Migration, 35, 38, 65, 67, 71, 109, 110, 126, 136, 220, 232, 261, 376
Millimeter, 307, 376 Mistletoe lectin, 138, 376 Mitochondria, 376, 378, 382 Mitochondrial Swelling, 376, 379 Mitogen-Activated Protein Kinase Kinases, 376 Mitogen-Activated Protein Kinases, 148, 376 Mitomycin, 100, 102, 376 Mitosis, 328, 329, 376 Mitotic, 209, 348, 353, 376, 411 Mitotic inhibitors, 348, 376 Mobility, 54, 156, 376 Modeling, 31, 91, 376, 392 Modification, 12, 23, 35, 229, 357, 376, 394 Molecular Evolution, 25, 376 Molecular Structure, 217, 377, 409 Monitor, 20, 25, 36, 179, 182, 251, 336, 377, 381 Monoclonal antibodies, 42, 69, 178, 211, 216, 231, 364, 365, 377 Monocyte, 93, 373, 377 Mononuclear, 68, 101, 216, 359, 373, 377, 409 Morphogenesis, 253, 377 Morphological, 16, 92, 350, 374, 377 Morphology, 7, 27, 200, 253, 336, 377 Motility, 37, 44, 45, 70, 116, 125, 219, 220, 377 Mucocutaneous, 370, 377 Mucosa, 114, 155, 272, 377 Mucositis, 377, 407 Multidrug resistance, 127, 377 Multiple Myeloma, 221, 262, 377 Multiple sclerosis, 218, 262, 377 Multivalent, 331, 377 Muscle Fibers, 377, 409 Muscular Atrophy, 298, 377 Muscular Dystrophies, 99, 349, 378 Mustard Gas, 378 Mutagen, 129, 156, 378 Mutagenesis, 22, 33, 378, 392 Myelin, 377, 378 Myelodysplastic syndrome, 152, 178, 378, 401 Myelogenous, 378 Myeloma, 211, 236, 362, 378 Myelosuppression, 378, 411 Myocardial infarction, 258, 332, 344, 375, 378 Myocardial Ischemia, 258, 378 Myocardial Reperfusion, 378, 396
426 Melanoma
Myocardial Reperfusion Injury, 378, 396 Myocardium, 375, 378 Myofibrils, 335, 379 Myopia, 379, 396, 397 Myotonic Dystrophy, 298, 379 N Naevus, 86, 97, 379 Naive, 58, 379 Nasopharynx, 200, 379 Natural killer cells, 69, 366, 379 Natural selection, 332, 379 Nausea, 356, 379 Neck dissection, 275, 379 Necrosis, 30, 239, 257, 329, 334, 357, 365, 375, 378, 379, 396 Needle biopsy, 183, 354, 379 Neonatal, 7, 379 Neoplasia, 51, 143, 230, 259, 298, 379 Neoplasm, 57, 191, 194, 206, 230, 233, 244, 372, 379, 384, 398, 400, 410 Neoplastic, 31, 44, 84, 211, 221, 229, 256, 334, 372, 379, 382 Nephropathy, 369, 379 Nerve Fibers, 88, 380 Nerve Growth Factor, 216, 380 Nerve Regeneration, 261, 380 Nervous System, 248, 298, 325, 338, 374, 379, 380, 385, 405 Neural, 35, 62, 215, 216, 238, 243, 325, 362, 380, 397 Neural Crest, 36, 62, 215, 216, 238, 243, 380 Neuraminidase, 380, 384 Neuroblastoma, 70, 220, 223, 229, 261, 380 Neurofibroma, 100, 380 Neurologic, 357, 380 Neuronal, 34, 380 Neurons, 239, 346, 353, 356, 370, 380, 405 Neuropeptide, 344, 380 Neuroretinitis, 380, 397 Neurotoxicity, 380, 411 Neutrons, 326, 334, 368, 380, 394 Neutrophils, 110, 218, 354, 359, 362, 367, 370, 380 Nevi and Melanomas, 41, 380 Nevus, 4, 6, 40, 41, 77, 105, 107, 110, 205, 206, 238, 244, 303, 309, 349, 370, 380 Nifedipine, 220, 381 Night Blindness, 381, 397 Nitric Oxide, 55, 124, 149, 363, 381 Nitrocamptothecin, 133, 143, 154, 381 Nitrogen, 5, 205, 258, 325, 326, 345, 353, 355, 374, 381, 383, 409
Node-negative, 116, 381 Nonmelanoma skin cancer, 142, 265, 381 Nonmetastatic, 62, 381 Non-small cell lung cancer, 178, 249, 381 Nuclear Medicine, 145, 146, 154, 155, 156, 157, 160, 163, 193, 381 Nuclei, 326, 350, 357, 367, 373, 376, 380, 381, 382, 393 Nucleic Acid Hybridization, 362, 381 Nucleoli, 162, 381 Nucleolus, 56, 381 Nucleotidases, 362, 381 Nucleus, 215, 329, 331, 332, 339, 345, 351, 353, 356, 377, 380, 381, 382, 393, 404, 406 Nurse Practitioners, 5, 382 O Occult, 53, 228, 263, 382 Ocular, 9, 13, 18, 49, 53, 55, 84, 85, 87, 111, 112, 119, 173, 181, 193, 221, 226, 379, 382 Odds Ratio, 59, 382, 396 Odour, 329, 382 Oligosaccharides, 80, 380, 382 Onchocerciasis, 263, 382 Oncogenic, 42, 82, 115, 221, 366, 382, 393 Oncolysis, 382 Oncolytic, 255, 256, 257, 259, 382 Opacity, 336, 347, 382 Opsin, 382, 397 Optic Nerve, 380, 382, 397, 399 Orbit, 101, 109, 382 Organ Culture, 382, 407 Organelles, 34, 339, 345, 346, 374, 382, 388 Osmotic, 325, 376, 382, 400 Osteoblasts, 383 Osteocalcin, 226, 383 Osteogenic sarcoma, 383 Osteosarcoma, 133, 226, 383 Ovalbumin, 282, 383 Ovarian epithelial cancer, 178, 383 Ovaries, 255, 383, 400, 406 Ovary, 12, 22, 211, 221, 383, 389 Overall survival, 25, 383 Oxazoles, 205, 383 Oxidation, 144, 202, 323, 329, 345, 371, 383 Oxidative Stress, 115, 383 Oxygen Consumption, 56, 383, 396 Oxygenase, 13, 383 Oxygenation, 55, 56, 383 P P53 gene, 43, 383 Paclitaxel, 129, 153, 154, 158, 166, 200, 383 Palate, 3, 4, 379, 383
Index 427
Palladium, 384, 398 Palliative, 5, 384, 406 Palliative therapy, 5, 384 Pamidronate, 131, 384 Pancreas, 221, 236, 239, 323, 333, 348, 384, 402, 409 Pancreatic, 84, 137, 234, 297, 298, 384 Pancreatic cancer, 137, 234, 298, 384 Papilloma, 212, 384, 397 Papillomavirus, 384 Paramyxovirus, 256, 384 Parasitic, 332, 384 Parenchyma, 55, 227, 384 Paresis, 360, 384 Parietal, 384, 389 Parkinsonism, 107, 371, 384 Paroxysmal, 298, 384, 386 Partial remission, 384, 396 Particle, 28, 105, 371, 384, 408 Pathogenesis, 7, 44, 48, 272, 384 Pathologic, 9, 17, 323, 329, 333, 344, 363, 384, 385, 393, 402 Pathologic Processes, 329, 385 Patient Education, 305, 314, 316, 322, 385 PDQ, 303, 309, 385 Pedigree, 27, 385 Pelvic, 100, 385, 391 Pentamidine, 262, 385 Peptide Chain Elongation, 339, 385 Peptide Fragments, 223, 260, 385 Peptide Hydrolases, 362, 385 Perception, 50, 385 Perennial, 385, 408 Perfusion, 105, 125, 173, 176, 275, 363, 385 Periodontal disease, 4, 385 Peripheral blood, 15, 60, 68, 82, 101, 119, 183, 185, 188, 192, 216, 230, 366, 385, 390 Peripheral Nervous System, 360, 385, 402, 404 Peripheral Nervous System Diseases, 360, 385 Peritoneal, 330, 386 Peritoneal Cavity, 330, 386 Pertussis, 331, 386 Petrolatum, 350, 386 Phagocyte, 373, 386 Pharmaceutical Preparations, 228, 337, 352, 356, 386 Pharmacokinetic, 180, 386 Pharmacologic, 327, 344, 360, 386, 407 Pharynx, 379, 386, 411 Phenolphthalein, 350, 386
Phenotype, 8, 13, 18, 36, 40, 44, 45, 62, 65, 70, 76, 80, 84, 120, 225, 250, 272, 386 Phenyl, 143, 200, 386 Phenylalanine, 166, 386, 410 Phorbol, 13, 249, 386, 392 Phospholipases, 386, 401 Phosphoric Monoester Hydrolases, 362, 386 Phosphorus, 258, 335, 386, 387 Phosphorylase, 259, 335, 386 Phosphorylate, 242, 376, 387 Phosphorylated, 23, 258, 340, 376, 387 Phosphorylating, 57, 258, 262, 387 Phosphorylation, 12, 37, 44, 126, 139, 242, 246, 262, 345, 376, 387, 392, 394 Photocoagulation, 340, 387 Photodynamic therapy, 55, 257, 387 Photosensitivity, 387, 412 Photosensitizer, 258, 387 Phototherapy, 235, 387 Physical Examination, 4, 174, 175, 176, 179, 181, 182, 185, 193, 306, 338, 387 Physiologic, 52, 325, 333, 348, 354, 360, 369, 387, 395 Physiology, 55, 83, 226, 387 Pigmentation, 3, 17, 34, 77, 201, 202, 363, 374, 379, 387 Pilot study, 100, 109, 154, 387 Pineal gland, 338, 387 Pituitary Gland, 109, 344, 354, 387 Plant Growth Regulators, 359, 387 Plants, 249, 325, 332, 335, 357, 358, 370, 376, 377, 387, 389, 390, 398, 408, 409 Plaque, 22, 88, 94, 119, 387 Plasma cells, 328, 377, 378, 388 Plasma protein, 325, 351, 388, 392, 400 Plasmapheresis, 175, 194, 329, 388 Plasmid, 222, 235, 388, 411 Plasmin, 231, 388 Plasminogen, 73, 232, 388 Plasminogen Activators, 388 Plasticity, 122, 388 Plastids, 382, 388 Platelet Activation, 388, 401 Platelet Aggregation, 200, 223, 258, 260, 261, 327, 381, 388 Platelet Factor 4, 367, 388 Plateletpheresis, 329, 388 Platelets, 175, 183, 193, 223, 261, 332, 335, 378, 381, 388, 389, 398, 406, 407 Platinum, 112, 339, 371, 384, 389, 398 Pleura, 389
428 Melanoma
Pleural, 79, 389 Podophyllotoxin, 352, 389 Poisoning, 356, 375, 379, 389 Pollen, 389, 394 Polycystic, 298, 389 Polymerase, 219, 389 Polymerase Chain Reaction, 219, 389 Polymorphic, 203, 389 Polymorphism, 40, 64, 89, 145, 148, 207, 389 Polypeptide, 216, 220, 229, 236, 240, 244, 245, 326, 341, 351, 354, 362, 388, 389, 392, 402, 413 Polyposis, 341, 389 Polysaccharide, 328, 337, 358, 389, 392 Polyunsaturated fat, 152, 389 Polyvalent, 28, 46, 51, 100, 390 Population Control, 11, 59, 390 Positron emission tomography scan, 139, 155, 390 Posterior, 327, 330, 338, 349, 368, 384, 390, 399 Postnatal, 99, 390, 403 Postoperative, 345, 390 Postsynaptic, 390, 401 Potentiate, 35, 157, 390 Potentiating, 52, 390 Potentiation, 154, 390, 401 Practicability, 390, 408 Practice Guidelines, 294, 308, 390 Precancerous, 338, 390 Precipitating Factors, 337, 390 Preclinical, 46, 51, 58, 210, 271, 390 Predisposition, 8, 26, 27, 37, 41, 68, 78, 81, 95, 221, 246, 390 Preleukemia, 378, 390, 401 Premalignant, 15, 23, 207, 208, 237, 390 Prevalence, 17, 18, 54, 73, 235, 382, 391 Prickle, 369, 391 Primary endpoint, 22, 391 Primary Prevention, 32, 37, 391 Primary tumor, 5, 10, 13, 16, 17, 21, 22, 26, 43, 52, 53, 208, 225, 227, 237, 243, 391, 400 Probe, 205, 208, 237, 391 Prodrug, 77, 212, 256, 391 Progesterone, 391, 404 Prognostic factor, 27, 110, 129, 391 Progression, 8, 9, 17, 18, 23, 27, 35, 37, 40, 46, 51, 52, 53, 54, 62, 63, 66, 67, 71, 82, 87, 91, 118, 144, 171, 180, 207, 215, 226,
243, 245, 253, 272, 279, 280, 327, 345, 391, 409 Proline, 341, 363, 391 Promoter, 55, 56, 67, 145, 226, 245, 247, 257, 391 Prone, 37, 100, 274, 391 Prophylaxis, 229, 391, 410 Prospective study, 77, 147, 391 Prostatic acid phosphatase, 236, 391 Protease, 44, 64, 122, 140, 341, 391 Protective Clothing, 308, 392 Protein Binding, 35, 392 Protein C, 34, 185, 203, 224, 257, 261, 325, 326, 329, 331, 340, 369, 383, 392, 409 Protein Conformation, 326, 369, 392 Protein Engineering, 25, 217, 392 Protein Kinase C, 64, 376, 392 Protein Kinases, 151, 242, 376, 392 Protein S, 40, 45, 191, 211, 217, 232, 262, 271, 299, 331, 333, 339, 352, 357, 383, 392 Proteins, 23, 24, 33, 34, 40, 46, 47, 54, 56, 61, 67, 73, 74, 106, 174, 175, 179, 184, 193, 204, 205, 207, 214, 215, 216, 217, 220, 229, 239, 241, 242, 244, 252, 253, 255, 258, 261, 263, 326, 328, 329, 333, 335, 336, 337, 339, 340, 341, 352, 353, 358, 361, 362, 364, 366, 368, 369, 373, 377, 379, 381, 385, 388, 392, 393, 395, 400, 406, 408, 411 Protein-Serine-Threonine Kinases, 376, 392 Protein-Tyrosine Kinase, 357, 392 Proteinuria, 377, 392 Proteoglycan, 37, 69, 72, 99, 130, 388, 392 Proteolytic, 23, 203, 216, 326, 341, 354, 388, 392 Prothrombin, 392, 406 Protocol, 16, 31, 56, 63, 114, 125, 140, 181, 393 Protons, 326, 362, 368, 393, 394 Proto-Oncogene Proteins, 383, 393 Proto-Oncogene Proteins c-mos, 383, 393 Protozoa, 370, 375, 393, 409 Pruritic, 393, 399 Pruritus, 382, 393 Psoralen, 266, 393 Psoriasis, 213, 218, 228, 378, 393 Psychiatric, 135, 151, 374, 393 Psychiatry, 151, 354, 393 Public Health, 28, 32, 38, 43, 58, 129, 271, 274, 294, 393 Public Policy, 293, 393
Index 429
Publishing, 64, 393 Pulmonary, 67, 112, 130, 143, 150, 155, 158, 227, 234, 333, 343, 344, 393, 405, 411 Pulmonary Artery, 333, 393, 411 Pulmonary hypertension, 234, 344, 393 Pulse, 377, 393 Purifying, 211, 249, 394 Purines, 394, 400 Pyrazoloacridine, 194, 394 Pyridoxal, 252, 258, 345, 394 Pyridoxal Kinase, 258, 394 Q Quality of Life, 54, 85, 181, 384, 394, 405 Quercetin, 146, 150, 155, 156, 394 Quiescent, 9, 394, 412 Quinones, 205, 394 R Race, 348, 374, 376, 394 Radiation therapy, 4, 5, 24, 28, 42, 54, 55, 79, 189, 193, 195, 202, 256, 266, 321, 323, 324, 353, 355, 356, 367, 368, 394, 403, 413 Radioimmunotherapy, 364, 394, 395 Radiolabeled, 28, 217, 333, 368, 394, 413 Radiology, 102, 104, 125, 126, 127, 381, 394 Radiopharmaceuticals, 141, 217, 394 Random Allocation, 395 Randomization, 49, 61, 395 Randomized, 8, 20, 22, 25, 29, 38, 39, 49, 51, 52, 53, 77, 85, 125, 129, 130, 141, 152, 156, 158, 161, 180, 183, 184, 185, 187, 188, 189, 190, 196, 350, 395 Randomized clinical trial, 53, 395 Reactive Oxygen Species, 140, 395 Reagent, 362, 395 Recombination, 222, 357, 395 Rectal, 202, 395 Rectum, 221, 329, 334, 341, 348, 356, 370, 391, 395, 405 Recur, 208, 237, 395 Recurrence, 5, 52, 105, 149, 151, 178, 190, 192, 207, 208, 220, 229, 230, 237, 248, 338, 395 Red blood cells, 352, 378, 383, 395, 398 Red Nucleus, 330, 395 Reductase, 372, 396 Refer, 1, 224, 341, 355, 356, 361, 371, 379, 380, 394, 396 Refraction, 379, 396, 402 Refractory, 34, 250, 350, 396 Regeneration, 239, 354, 396 Regimen, 14, 46, 153, 176, 179, 184, 187, 194, 202, 350, 396
Regional lymph node, 4, 5, 119, 266, 396 Registries, 8, 396 Relapse, 10, 12, 14, 25, 188, 228, 248, 396 Relative risk, 39, 396 Reliability, 59, 396 Remission, 176, 220, 229, 395, 396 Reperfusion, 258, 378, 396 Reperfusion Injury, 258, 396 Reproductive cells, 357, 361, 396 Resected, 25, 51, 97, 178, 396 Resection, 100, 119, 202, 211, 220, 230, 256, 396 Resolving, 206, 396 Respiration, 56, 127, 234, 335, 377, 396 Respiratory distress syndrome, 234, 397 Response rate, 4, 31, 180, 397 Retina, 88, 321, 338, 339, 342, 370, 379, 380, 382, 397, 398, 400, 412 Retinal, 71, 88, 104, 382, 397, 412 Retinal Detachment, 104, 397 Retinitis, 9, 397 Retinitis Pigmentosa, 9, 397 Retinoblastoma, 41, 126, 236, 246, 298, 397 Retinoblastoma Protein, 126, 246, 397 Retinol, 397 Retinopathy, 108, 149, 387, 397 Retrospective, 52, 107, 206, 397 Retrospective study, 206, 397 Retroviral vector, 60, 397 Retrovirus, 74, 108, 212, 227, 398 Reversion, 256, 398 Rhabdomyosarcoma, 223, 261, 398 Rheumatism, 218, 398 Rheumatoid, 262, 398 Rheumatoid arthritis, 262, 398 Ribose, 324, 398 Rigidity, 47, 384, 387, 398 Risk factor, 5, 11, 31, 40, 41, 43, 50, 59, 115, 116, 246, 254, 265, 272, 307, 337, 351, 363, 391, 396, 398 Risk patient, 5, 6, 15, 25, 28, 32, 398 Rods, 382, 397, 398 Ruthenium, 94, 398 Rutin, 394, 398 S Saline, 220, 398 Salivary, 345, 348, 384, 398 Salivary glands, 345, 348, 398 Saponins, 128, 149, 398, 404 Sarcolemma, 99, 378, 398 Sarcoma, 10, 57, 107, 130, 177, 221, 232, 248, 398, 402
430 Melanoma
Sargramostim, 183, 184, 185, 188, 398 Satellite, 228, 263, 398 Scabies, 275, 399 Scans, 173, 174, 175, 176, 179, 182, 185, 193, 399 Sclera, 339, 343, 399 Sclerosis, 218, 298, 329, 330, 377, 399 Screening, 5, 32, 39, 50, 53, 69, 81, 170, 208, 220, 221, 237, 250, 253, 275, 281, 340, 385, 399 Sebaceous, 107, 399 Sebum, 399 Secondary tumor, 375, 399 Secretion, 22, 63, 78, 140, 338, 352, 361, 362, 399, 410 Secretory, 34, 399 Segregation, 395, 399 Seizures, 357, 384, 399, 403 Selective estrogen receptor modulator, 399, 405 Self-Examination, 5, 11, 39, 304, 306, 399 Sella, 349, 387, 399 Semen, 391, 399 Semisynthetic, 335, 339, 352, 365, 399 Senescence, 41, 99, 400 Senile, 370, 400 Sensitization, 56, 90, 138, 145, 400 Sensor, 241, 242, 400 Sentinel lymph node, 53, 69, 86, 87, 94, 103, 106, 116, 117, 118, 147, 280, 400 Sentinel Lymph Node Biopsy, 86, 94, 106, 116, 117, 147, 400 Septic, 218, 400 Sequence Homology, 211, 400 Sequencing, 40, 71, 73, 389, 400 Serine, 232, 242, 345, 376, 392, 393, 400, 409 Serologic, 188, 400 Serous, 351, 389, 400 Serrata, 339, 400 Serum Albumin, 203, 400 Sex Characteristics, 324, 400 Sex Determination, 298, 400 Sharks, 210, 400 Sharpness, 400, 412 Shedding, 35, 400 Shock, 56, 97, 180, 218, 232, 286, 400, 408 Signal Transduction, 35, 38, 150, 242, 366, 401 Signs and Symptoms, 396, 401 Skeletal, 99, 239, 242, 377, 378, 379, 401, 409
Skeleton, 144, 228, 323, 369, 401 Skin graft, 208, 237, 321, 401 Skin Pigmentation, 272, 401 Skull, 382, 401, 403 Small cell lung cancer, 243, 401 Small intestine, 349, 362, 367, 401, 409 Smallpox, 401, 410 Smoldering leukemia, 378, 401 Smooth muscle, 223, 257, 261, 326, 327, 335, 343, 361, 401, 404 Sneezing, 386, 400, 401 Social Environment, 394, 401 Sodium, 262, 263, 358, 401 Soft tissue, 127, 177, 220, 229, 333, 354, 401, 402 Soft tissue sarcoma, 127, 177, 220, 229, 354, 402 Solar radiation, 272, 402 Solid tumor, 17, 28, 36, 64, 212, 220, 230, 232, 327, 333, 349, 351, 371, 402 Solvent, 249, 323, 352, 358, 382, 402 Soma, 402 Somatic, 8, 40, 81, 221, 262, 324, 337, 344, 350, 362, 376, 385, 402, 410 Somatic cells, 262, 337, 376, 402 Somatic mutations, 8, 40, 221, 402 Somatostatin, 143, 402 Soybean Oil, 390, 402 Specialist, 310, 402 Specificity, 10, 28, 63, 66, 69, 216, 218, 226, 229, 325, 390, 402 Spectrum, 39, 77, 233, 255, 308, 369, 402 Sperm, 339, 357, 361, 389, 396, 402, 409 Spinal cord, 12, 330, 338, 356, 360, 374, 380, 385, 402 Spinal Cord Diseases, 360, 402 Spinous, 352, 369, 402 Spleen, 239, 345, 362, 372, 403 Sporadic, 8, 62, 83, 397, 403 Sputum, 211, 403 Squamous, 29, 43, 80, 98, 221, 223, 227, 254, 261, 263, 308, 352, 381, 403, 411 Squamous cell carcinoma, 29, 43, 80, 98, 221, 308, 352, 381, 403, 411 Squamous cells, 381, 403 Stabilization, 34, 44, 403 Staging, 4, 5, 62, 78, 81, 94, 99, 106, 110, 116, 147, 152, 154, 158, 207, 247, 272, 275, 399, 403 Standardize, 29, 61, 403 Statistically significant, 38, 403 Status Epilepticus, 239, 403
Index 431
Steady state, 34, 403 Stem Cell Factor, 62, 339, 403 Stem cell transplantation, 195, 403 Stem Cells, 191, 195, 359, 403 Stereotactic, 104, 108, 403 Stereotactic radiosurgery, 108, 403 Sterility, 345, 404 Steroid, 217, 344, 398, 404 Stimulants, 238, 357, 404 Stimulus, 38, 349, 350, 353, 367, 370, 404, 406 Stomach, 209, 221, 228, 323, 348, 352, 356, 362, 379, 386, 401, 403, 404 Strand, 40, 389, 404 Stress, 112, 124, 136, 140, 179, 185, 193, 234, 320, 344, 356, 376, 379, 383, 390, 398, 404 Stroke, 4, 198, 292, 336, 404 Stroma, 73, 232, 368, 384, 404 Stromal, 63, 94, 334, 404 Subacute, 365, 404 Subclinical, 52, 108, 365, 399, 404 Subcutaneous, 18, 58, 152, 282, 382, 404 Subspecies, 402, 404 Substance P, 352, 375, 399, 404 Substrate, 253, 262, 336, 355, 362, 380, 404 Sulfur, 258, 353, 375, 404 Sulfuric acid, 201, 326, 404 Sunburn, 164, 273, 320, 404 Supplementation, 129, 151, 156, 158, 404 Support group, 321, 404 Supportive care, 385, 405 Suppositories, 356, 405 Suppression, 36, 75, 118, 152, 171, 225, 231, 245, 259, 266, 405 Suppressive, 71, 130, 158, 226, 245, 405 Surfactant, 234, 405 Survival Rate, 4, 202, 228, 247, 251, 259, 264, 383, 405 Suspensions, 56, 405 Sympathomimetic, 349, 352, 405 Symphysis, 391, 405 Symptomatic, 225, 405 Synaptic, 401, 405 Synergistic, 158, 228, 405 Systemic therapy, 88, 405 Systolic, 363, 405 T Tamoxifen, 120, 134, 136, 152, 153, 155, 161, 284, 399, 405 Technetium, 149, 217, 286, 405 Telangiectasia, 298, 405
Telomere, 100, 405 Temozolomide, 124, 130, 134, 159, 174, 182, 188, 189, 286, 406 Teratogenic, 38, 326, 406 Teratoma, 338, 406 Terminator, 340, 406 Testicular, 209, 399, 406 Testis, 46, 69, 219, 221, 338, 406 Thalamic, 330, 406 Thalamic Diseases, 330, 406 Thalidomide, 182, 187, 188, 189, 406 Therapeutics, 7, 97, 211, 285, 406 Thermal, 330, 334, 348, 380, 389, 406 Thigh, 175, 179, 182, 185, 193, 359, 406 Thiobarbituric Acid Reactive Substances, 124, 406 Thorax, 323, 406, 411 Threonine, 242, 376, 392, 393, 400, 406 Threshold, 363, 406 Thrombin, 223, 260, 354, 388, 392, 406, 407 Thrombocytes, 389, 406 Thrombolytic, 223, 388, 406 Thrombomodulin, 392, 407 Thrombosis, 106, 127, 332, 366, 392, 404, 407 Thrombus, 344, 365, 378, 388, 406, 407 Thymidine, 212, 226, 234, 407 Thymidine Kinase, 212, 226, 407 Thymus, 364, 372, 407 Thyroid, 12, 221, 367, 407, 410 Thyroxine, 325, 386, 407 Tin, 389, 407 Tissue Culture, 27, 38, 223, 260, 261, 407 Tomography, 83, 94, 146, 147, 154, 157, 160, 161, 162, 176, 407 Tonicity, 369, 407 Tooth Preparation, 324, 407 Topical, 61, 102, 227, 253, 254, 263, 352, 386, 407 Topoisomerase inhibitors, 368, 381, 407 Torsion, 365, 407 Tourniquet, 176, 368, 371, 407 Toxicity, 16, 25, 56, 61, 63, 66, 246, 255, 256, 263, 349, 375, 407 Toxicology, 294, 407 Toxins, 328, 358, 365, 377, 394, 408 Trace element, 334, 340, 355, 407, 408 Trachea, 335, 374, 386, 407, 408 Transcriptase, 17, 398, 408 Transcription Factors, 54, 408 Transduction, 60, 89, 158, 212, 331, 401, 408
432 Melanoma
Transfection, 22, 62, 75, 204, 226, 333, 408 Transfer Factor, 364, 408 Transferases, 43, 358, 408 Transfusion, 408 Transgenes, 240, 408 Translational, 19, 58, 408 Translocation, 35, 56, 115, 339, 352, 408 Transmitter, 323, 330, 349, 374, 408 Transplantation, 186, 214, 339, 364, 373, 408 Trauma, 332, 379, 406, 408 Treatment Failure, 52, 408 Treatment Outcome, 19, 408 Trees, 209, 249, 408 Treosulfan, 109, 409 Tricuspid Atresia, 343, 409 Tricyclic, 146, 160, 409 Tropism, 67, 74, 409 Tropomyosin, 234, 409 Troponin, 409 Truncal, 117, 409 Trypanosomiasis, 263, 385, 409 Trypsin, 409 Tryptophan, 341, 409 Tuberous Sclerosis, 298, 409 Tubulin, 200, 209, 228, 376, 409 Tumor infiltrating lymphocytes, 216, 409 Tumor marker, 215, 255, 333, 409 Tumor model, 42, 409 Tumor Necrosis Factor, 24, 30, 176, 202, 222, 259, 406, 409 Tumor suppressor gene, 212, 222, 246, 250, 372, 383, 397, 409 Tumor-derived, 409 Tumor-Derived, 286 Tumorigenic, 22, 225, 249, 410 Tumour, 90, 115, 122, 131, 143, 151, 161, 236, 240, 356, 382, 410 Tyrosinase peptide, 24, 410 Tyrosine, 24, 37, 44, 62, 91, 100, 166, 202, 215, 242, 251, 254, 262, 349, 392, 410 U Ubiquitin, 23, 140, 410 Ulcer, 410 Ulceration, 26, 53, 102, 410 Unconscious, 327, 346, 363, 410 Unresectable, 182, 410 Untranslated Regions, 252, 410 Uranium, 405, 410 Urethra, 391, 410 Urinary, 410, 412
Urine, 72, 176, 179, 181, 182, 185, 193, 333, 341, 345, 351, 360, 369, 392, 410 Urokinase, 232, 410 Uterus, 221, 338, 370, 383, 391, 410 V Vaccine adjuvant, 52, 410 Vaccinia, 222, 281, 410 Vacuoles, 382, 410 Vagina, 410, 412 Vaginal, 83, 410, 412 Vagus Nerve, 409, 410 Varicella, 67, 411 Variegation, 6, 411 Variola, 410, 411 Vascular endothelial growth factor, 87, 121, 411 Vasoconstriction, 234, 352, 411 Vasodilator, 334, 349, 361, 378, 381, 411 Vector, 28, 63, 212, 231, 239, 245, 257, 366, 408, 411 Vein, 38, 174, 175, 176, 179, 181, 182, 186, 193, 194, 330, 367, 368, 381, 398, 411 Venom, 33, 411 Venous, 330, 332, 334, 392, 409, 411 Ventricle, 330, 343, 363, 393, 405, 409, 411 Ventricular, 343, 378, 409, 411 Venules, 333, 351, 375, 411 Vertebrae, 402, 411 Veterinary Medicine, 293, 411 Vinblastine, 14, 124, 134, 154, 156, 284, 409, 411 Vinca Alkaloids, 200, 411 Vincristine, 82, 139, 152, 160, 409, 411 Vindesine, 134, 152, 155, 159, 161, 411 Vinorelbine, 134, 411 Viral, 67, 210, 212, 224, 256, 262, 335, 382, 398, 408, 410, 411 Viral vector, 212, 256, 411 Virulence, 407, 412 Viscera, 402, 412 Visceral, 344, 370, 410, 412 Visual Acuity, 49, 54, 412 Visual field, 397, 412 Vitiligo, 79, 164, 393, 412 Vitreous Humor, 397, 412 Vivo, 7, 9, 10, 20, 27, 28, 29, 33, 35, 36, 44, 47, 48, 49, 54, 55, 56, 57, 62, 65, 69, 70, 86, 92, 127, 128, 136, 142, 145, 154, 156, 159, 170, 203, 212, 217, 220, 223, 245, 255, 263, 282, 337, 361, 365, 412 Vulva, 80, 412
Index 433
W War, 224, 378, 412 Wart, 369, 412 Windpipe, 335, 386, 407, 412 Womb, 410, 412 Wound Healing, 223, 232, 260, 261, 354, 366, 373, 412 X Xanthine, 126, 412 Xenograft, 63, 75, 124, 255, 327, 409, 412
Xeroderma Pigmentosum, 48, 412 X-ray, 173, 174, 175, 176, 179, 181, 182, 185, 189, 193, 205, 211, 342, 355, 356, 368, 378, 381, 394, 395, 399, 403, 412, 413 X-ray therapy, 368, 413 Y Yeasts, 355, 386, 413 Z Zoster, 67, 413 Zymogen, 232, 392, 413
434 Melanoma
Index 435
436 Melanoma
