Astrocytomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ASTROCYTOMAS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES ...

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ASTROCYTOMAS 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., 1960Astrocytomas: 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: 0-497-00107-1 1. Astrocytomas-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 astrocytomas. 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 ASTROCYTOMAS ....................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Astrocytomas ................................................................................ 3 E-Journals: PubMed Central ....................................................................................................... 29 The National Library of Medicine: PubMed ................................................................................ 32 CHAPTER 2. NUTRITION AND ASTROCYTOMAS ............................................................................. 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Astrocytomas ............................................................................... 79 Federal Resources on Nutrition ................................................................................................... 82 Additional Web Resources ........................................................................................................... 82 CHAPTER 3. ALTERNATIVE MEDICINE AND ASTROCYTOMAS ....................................................... 83 Overview...................................................................................................................................... 83 National Center for Complementary and Alternative Medicine.................................................. 83 Additional Web Resources ........................................................................................................... 91 General References ....................................................................................................................... 92 CHAPTER 4. PATENTS ON ASTROCYTOMAS .................................................................................... 93 Overview...................................................................................................................................... 93 Patents on Astrocytomas ............................................................................................................. 93 Patent Applications on Astrocytomas.......................................................................................... 96 Keeping Current .......................................................................................................................... 98 CHAPTER 5. BOOKS ON ASTROCYTOMAS ....................................................................................... 99 Overview...................................................................................................................................... 99 Book Summaries: Online Booksellers........................................................................................... 99 Chapters on Astrocytomas ........................................................................................................... 99 CHAPTER 6. PERIODICALS AND NEWS ON ASTROCYTOMAS ........................................................ 101 Overview.................................................................................................................................... 101 News Services and Press Releases.............................................................................................. 101 Academic Periodicals covering Astrocytomas............................................................................ 102 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 105 Overview.................................................................................................................................... 105 U.S. Pharmacopeia..................................................................................................................... 105 Commercial Databases ............................................................................................................... 106 Researching Orphan Drugs ....................................................................................................... 106 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 111 Overview.................................................................................................................................... 111 NIH Guidelines.......................................................................................................................... 111 NIH Databases........................................................................................................................... 113 Other Commercial Databases..................................................................................................... 115 APPENDIX B. PATIENT RESOURCES ............................................................................................... 117 Overview.................................................................................................................................... 117 Patient Guideline Sources.......................................................................................................... 117 Finding Associations.................................................................................................................. 120 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 123 Overview.................................................................................................................................... 123 Preparation................................................................................................................................. 123 Finding a Local Medical Library................................................................................................ 123 Medical Libraries in the U.S. and Canada ................................................................................. 123 ONLINE GLOSSARIES................................................................................................................ 129 Online Dictionary Directories ................................................................................................... 129

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ASTROCYTOMAS DICTIONARY ............................................................................................ 131 INDEX .............................................................................................................................................. 185

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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 astrocytomas 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 astrocytomas, 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 astrocytomas, 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 astrocytomas. 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 astrocytomas, 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 astrocytomas. 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 ASTROCYTOMAS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on astrocytomas.

Federally Funded Research on Astrocytomas The U.S. Government supports a variety of research studies relating to astrocytomas. 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 astrocytomas. 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 astrocytomas. The following is typical of the type of information found when searching the CRISP database for astrocytomas: •

Project Title: BLOOD ULTRASOUND

BRAIN

BARRIER

PERMEABILIZATION

USING

Principal Investigator & Institution: Mourad, Pierre D.; Applied Physics Laboratory; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005

2

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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Summary: (Adapted from the Applicant's Abstract): The blood-brain barrier (BBB) consists of specialized endothelial cells that line the capillaries within the brain, whose overlapping regions are held firm by "tight junctions." Among other roles it plays, the BBB is the major impediment to the flux of therapeutic drugs into the central nervous system (CNS). As a result, many therapeutic compounds known to be efficacious in vitro are prevented from entering the CNS in vivo. If a means existed to allow the targeted and transient opening of the BBB without accompanying CNS damage, then one could apply those therapeutic agents systemically yet achieve targeted delivery. Among other applications this would be useful for treating malignant astrocytomas, a uniformly and rapidly fatal grade of brain tumor that is the most common primary supratentorial cerebral neoplasm in adults. Isolated tumor cells (ITC) that migrate from the bulk tumor mass are generally thought to be responsible for recurrence following resection, likely due to their re-migration to the resection margin. To improve clinical outcome after surgery one must therefore successfully attack the ITC while maintaining the integrity of the surrounding normal brain tissue. In vivo, there is minimal success with. chemotherapy at least because the ITC are protected by an intact BBB. Therefore, opening the BBB at and beyond the resection margin would allow the targeted delivery to isolated tumor cells of chemotherapeutic agents that are introduced systemically, which should improve clinical outcome. Preliminary Results relevant to this proposal indicate that high-intensity focused Ultrasound (HIFU) applied to a rat model of normal cortex can be targeted to selectively open the BBB in a reversible, controlled manner without structural injury at or near the site of permeabilization. Specifically, we have found that MFU can open the endothelial cell tight junctions and/or induce retraction of endothelial cells, thereby permitting the flux of a large molecular complex (Evans bluealbumin; 69,500 Daltons) from the blood stream into brain tissue. Additionally HIFU mediated permeability to Evans blue reverses within 96 hours, and HIFU causes no identifiable damage to CNS tissue during this time period at and near the point of BBB opening, as assessed with light and electron microscopy. The aim of this K-25 research proposal is to explore the mechanisms, efficacy and safety of HIFU-induced BBB opening in a clinically motivated context, while giving the PI a thorough education in the associated neuroscience and techniques. The research aims are predicated on the view that the ability to use ultrasound to open the blood-brain barrier requires research on how ultrasound, with and without systemically-applied chemotherapy, alters the intercellular dynamics of invading isolated tumor cells and the endothelial cells that comprise the blood-brain barrier. And, it requires research on the intracellular processes that support those dynamics. The Specific Aims are as follows. Investigate structural and intracellular effects induced by HIFU for BBB opening. Investigate electrophysiological effects induced by HIFU applied to normal cortex for BBB opening. Investigate drug flux into normal and tumor-bearing cortex induced by HIFU for BBB opening. AIM 4. Investigate effects induced by HIFU for BBB opening on invading and re-invading ITC, and on BBB and CNS. The neuroscience-directed education the PI proposes to receive during this Career Development Award will allow him to do the proposed research and to move ahead in future, R01 -funded studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Stork, Linda C.; Children's Hospital (Denver) 1056 E 19Th Ave Denver, Co 80218 Timing: Fiscal Year 2002; Project Start 05-APR-1994; Project End 30-NOV-2002

Studies

5

Summary: The objectives of this application is to demonstrate the increasing contributions of The Children's Hospital, Denver and its network to the specific goals of Children's Cancer Group (CCG): continued increase in long-term survival of children and adolescents with cancer, improving the quality of life for these survivors, further understanding of the biology of these neoplastic processes, increased correlation of objective laboratory parameters of the malignant cells with response to treatment and outcome, and improved understanding of the epidemiology of childhood cancer which will hopefully ultimately lead to preventive measures. Our staff has become increasingly qualified and committed to contributing to these objectives. Our network has excellent balance with highly qualified pediatric specialists in every important aspect of pediatric oncology: Drs. Albano, Cullen, Greffe, Odom, and Stork in oncology, Drs. Foreman and Arenson in neuro-oncology, Dr. Wilkening in neuro-psychology, Drs. Giller and Quinonas in bone marrow transplantation, Dr. Haase and his colleagues in surgery, Dr. McGavran in cancer cytogenetics, and physician scientists Drs. Hunger and Garcea whose labs are committed to scientific advancement in this field through translational research in the molecular biology of leukemia and oncogenic viruses, Dr. Strain and colleagues in radiology, Dr. Tyson and colleagues in pathology, and Patricia McGuire-Cullen and Margi Morse and their colleagues in nursing. Significant contributions by our network to CCG goals during the next grant cycle will be accomplished through the recent appointments of Dr. Stork as chair of the standard risk ALL study, Dr. McGavran as cytogeneticist for AML studies, and Dr. Steve Hunger to the Biology Research and Young Investigator committees. Additionally, Dr. Haase remains group Vice Chair for multidisciplinary and intergroup affairs, Dr. Giller remains coordinator of Intergroup Germ Cell Tumor Studies, Dr. Arenson, chair of the protocol for high grade astrocytomas, and Mrs. McGuire-Cullen and Mrs. Morse continue to have major roles in CCG nursing activities. A sophisticated and specialized group of clinical research associates, pediatric oncology nurses, pharmacists, social workers, and nutritionists also provide important support for the clinical program and investigational research projects. This institutional network is in a strong position to make important contributions to the goals of the Children's Cancer Group during the forthcoming grant cycle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Feig, Stephen A.; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-DEC-1980; Project End 30-NOV-2002 Summary: The UCLA multidisciplinary team reaffirms its commitment to participate in and lead the clinical research studies of the Children's Cancer Group (CCG). The addition of affiliates in Albany and Las Vegas will continue to strengthen patient accrual. Growth of the core program at the UCLA Medical Center will focus on clinical and basic research in the supportive academic environment of the UCLA School of Medicine, the UCLA-Jonsson Comprehensive Cancer Center, and the Molecular Biology Institute. Our clinical research program has a long history of leadership; we shall continue to lead in the areas of hematologic neoplasms and stem cell transplantation and, with the recruitment of a new clinical director, Dr. Malogolowkin, we have expanded our area of study leadership into the solid tumors and new agents. Other new UCLA recruits will open up additional areas of research with CCG, including new approaches to the diagnosis of round cell tumors, metabolic identification of high-risk low-grade astrocytomas, diagnostic application of fluorescence in-situ hybridization,

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cord blood stem cell transplants and assessment of long-term outcome after treatment of brain tumors. The melding of a mature, active and diverse clinical research program with a productive thrust in translational and outcomes research will be an asset to CCG in the coming years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONDITIONAL NEUROFIBROMATOSIS

KNOCK

OUT

MOUSE

MODEL

FOR

Principal Investigator & Institution: Bajenaru, Michaela L.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-2002 Summary: (As provided by Applicant) This NRSA application targets one of the most important clinical issues in neurofibromatosis (NFl). Astrocytomas are the second most common tumor in NF1, often leading to blindness and neurologic impairment. Our ability to design rational therapies for these tumors is heavily dependent on a more complete understanding of the role of the Nfl gene in the development of astrocytomas. In this grant, we propose to critically test the hypothesis that loss of neurofibromin expression results in astrocytoma formation. Specifically, we plan to (1) determine the effect of loss of neurofibromin expression in vivo using a conditional knockout mouse in which Nfl gene expression has been disrupted in astrocytes by using the Cre/Lox P recombination system and (2) determine the effect of loss of neurofibromin expression in vitro by inactivating the Nfl gene in primary astrocyte cultures. Astrocytes in culture will be assessed for their growth and tumorigenic properties and since neurofibromin is a negative regulator of p21-ras, downstream effectors of the p21-ras signaling pathway will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTRIBUTIONS OF AKT TO GLIOBLASTOMA FORMATION Principal Investigator & Institution: Pieper, Russ O.; Associate Professor; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term objective of this proposal is to improve the therapy of glioblastoma multiforme (GBM), the most common and fatal of human gliomas. GBM result from the step-wise accumulation of genetic alterations and often arise from low-grade gliomas and anaplastic astrocytomas (AA). We found that 4 alterations (telomerase and Ras activation and p53/pRb inactivation) in combination allowed normal human astrocytes to form AA. Additional Akt activation, however, allowed formation of 5-fold larger, necrotic GBM. These results suggest that Akt contributes to GBM formation, a finding consistent with Akt activation in greater than 80 percent of GBM. While Akt enhances growth and angiogenesis, these effects were not seen in vitro, nor were they noted in vivo until tumors reached a critical size, at which point the Akt-expressing cells rapidly expanded into modestly vascularized (yet still hypoxic) GBM while the non-Akt expressing cells slowly expanded into AA. The growth-enhancing properties of Akt therefore appear to be unmasked by an additional event which we believe to be hypoxia. We hypothesize that the stimulus for the formation of GBM is hypoxia, and that Akt activation uniquely allows cells to grow and survive under these conditions. We will test this hypothesis with the following specific Aims: 1) to determine if the point at which the growth of model AA and GBM diverge

Studies

7

corresponds with the onset of hypoxia, 2) to determine if conditional activation of Akt drives proliferation/survival of hypoxic Ras tumors, and if conditional suppression of Akt inhibits proliferation/survival of hypoxic Ras+Akt tumors, 3) to determine if hypoxia selects for cells expressing high Akt levels in vivo, 4) to determine if hypoxic conditions alone allow differential proliferation/survival of Ras+ Akt versus Ras astrocytes, and 5) to determine at the molecular level if the effects of hypoxia on cell cycle regulation and survival are modulated by Akt. Defining Akt function may help identify targets useful in GBM therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONVERGENT MECHANISMS CONTRIBUTING TO CANCER Principal Investigator & Institution: Costello, Joseph F.; Assistant Professor; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Tumorigenesis is fueled in part by an accumulation of genetic and epigenetic (e.g. aberrant methylation of CpG islands) alterations that inactivate tumor suppressor genes. However, it has not been possible to understand the interaction of these mechanisms on a genome-wide scale, since whole-genome methylation profiling has not been amenable to alignment with chromosomal deletion maps. The genesis of low-grade brain tumors (WHO grade II astrocytomas) is accompanied by widespread aberrant CpG island methylation and a relatively small number of deletions, whereas in tumors that have progressed to malignant high-grade astrocytoma (WHO Grades Ill, IV), large deletions are commonplace. We hypothesize that methylation and deletion converge on particular genes during gliomagenesis, and that this convergence in low-grade tumors negatively impacts patient survival. To determine the independent and potentially convergent effects of these mechanisms on tumorigenesis and patient survival, we will; 1) generate whole-chromosome maps of potential methylation sites (CpGs within CpG islands); 2) identify chromosomal regions that are deleted in low and high-grade tumors, and align these with the maps of potentially methylated sites; 3) identify the loci where deletion and aberrant CpG island methylation converge, particularly those present in a proportion of both low and highgrade tumors and; 4) determine if the length of survival of low-grade astrocytoma patients can be predicted from the patterns of aberrant methylation and deletion. By understanding where and when methylation and deletion interact, we will gain a more complete understanding of tumorigenesis in general, and hope to devise an objective guide for improving the therapy and therapeutic decisions for low-grade astrocytoma patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: EARLY GENETIC EVENTS IN ASTROCYTOMA FORMATION Principal Investigator & Institution: Henson, John W.; Assistant Professor of Neurology; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (adapted from applicant's abstract): Astrocytomas of the adult cerebral hemispheres are among the most deadly of all human tumors. Although much is known about the genetic alterations in malignant gliomas, there is much less information about the initial genetic events leading to the formation of low-grade astrocytomas (LGA). Many LGAs undergo anaplastic progression over months to years, evolving towards

8

Astrocytomas

GBM. This evolution results in initial phase in tumor formation that is characterized by a small burden of genetic changes on downstream events and tumor behavior has been difficult to study because of the relative rarity of LGA patients, compared to patients with malignant astrocytomas. Analysis of the genetic changes in high-grade astrocytomas have suggested the presence of distinct disease entities that are manifested in different age groups and develop through different genetic pathways. Alterations of p53 and EGFR, for instance are mutually exclusive events in secondary and de novo GBM. Some genetic changes, such as p53, occur at the same frequency across all grades of astrocytoma, suggesting that these genes have a role in initial tumor formation. The investigators hypothesize that the molecular patterns defining specific subsets of gliomas are determined at the time of LGA formation, and that the initial genotype correlates with the rate of anaplastic progression and survival, and will as with subsequent genetic changes. They propose to test this hypothesis in a cohort of LGA patients with the goals of: 1) understanding early events in glioma formation, 2) understanding the molecular basis of anaplastic progression, and 3) gaining the ability to better predict clinical tumor behavior. For this purpose, they propose to obtain a large, multi-institutional, retrospective sample of LGAs, with well-defined clinical follow up, and adequate tissue for histologic and molecular studies. They will characterize specific genetics alterations, and test for correlations between subsets of these alteration and clinical and biological behavior of the tumors. They will examine genetic changes in tumors at the time of anaplastic progression for those cases in which tumor material is available. As a way forward to new hypotheses, they will determine genome-wide changes in subsets of LGA patients with good and poor outcomes using comparative genomic hybridization (CGH). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF ASTROCYTOMAS WITH HRMAS 1HMR SPECTROSCOPY Principal Investigator & Institution: Cheng, Leo L.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Astrocytomas, the most common type of brain tumors, are primarily diagnosed by the histopathological evaluation of cellular morphological changes in biopsy samples. In addition to changes in cell morphology, tumors also display altered cellular biochemistry. Tumor metabolic alterations may provide valuable information for clinical grading, biology-based prognosis, and therapeutic monitoring of astrocytomas. Conventional ex vivo 1HMRS has been used to study tumor samples; however, it is hampered by the need for the often destructive chemical extraction of tissue. We propose to evaluate the diagnostic potential of the newly developed highresolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS) on intact specimens of human astrocytomas. We plan to quantify HRMAS metabolites and measure histopathological features on the same tumor specimens, to select tumor metabolic markers, and to establish biochemical databases for astrocytoma diagnosis and prognosis. Our specific aims are: 1) To quantify metabolic concentrations with HRMAS 1HMRS in different regions of normal human brain; 2) To quantify metabolic alterations in newly diagnosed, adult supratentorial, diffuse fibrillary astrocytomas, and to use these measures to identify and define HRMAS 1HMRS markers able to type and grade these tumors; 3) To evaluate the capability of HRMAS spectroscopic markers in predicting the histological grade of adult cerebral hemisphere astrocytomas; and 4) To evaluate the usefulness of HRMAS metabolic markers as

Studies

9

independent indicators of tumor behavior and predictors of 2 year survival for patients with glioblastoma multiforme (GBM). If successful, our study will establish astrocytoma HRMAS metabolic databases and objective parameters to serve as an adjunct modality for predicting tumor development, progression and patient outcome. We expect that current diagnostic sensitivity and specificity will be improved by utilizing HRMAS 1HMRS tumor markers. The results from this study will also further current understanding of tumor neurobiology and provide new linkages among fields such as clinical pathology, clinical radiology, tumor biology and molecular genetics. Astrocytoma metabolic markers obtained from this study will have important implications on the future development of magnetic resonance spectroscopic imaging (MRSI) and localized in vivo MR spectroscopy for non-invasive diagnosis and therapeutic monitoring of these neoplasms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION BASED CLASSIFICATION OF GLIAL TUMORS Principal Investigator & Institution: Nelson, Stanley F.; Research Scientist; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JAN-2005 Summary: (Applicant's Description) Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. The current system of diagnosis and classification of brain tumors is partially predictive of outcomes, and remains based primarily upon morphologic criteria. Although recent work has shown a number of genetic differences which are critical in the oncogenesis and progression of astrocytic tumors, there is insufficient data to develop a molecular classification system. The availability of cDNA clones, large amounts of sequence, data and the technology for cDNA arrays provides a platform for the large scale analysis of gene expression in astrocytoma. We propose to identify a set of genes that will allow the molecular characterization of brain tumors by using cDNA microarray technology. Using a flexible microarray format will enable us to easily alter the arrayed genes whose expression patterns are most informative allowing us to create cost-effective glial tumorrelated reagents. It is our central hypothesis that a much more detailed analysis of the genes that are expressed in astrocytomas will provide a more precise prognostic ability, subgroup patients for optimal treatment, and help identify appropriate therapeutic targets, subgroups patients for optimal treatment 1)To determine the optimal means of sampling low grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiformes, to determine the degree of molecular heterogeneity within astrocytic tumors, to determine whether the heterogeneity is greater between tumors than within an individual tumor at each gene, and to determine the level of variance of each gene on the microarray. 2)To determine the gene expression profiles of 120 excisional glioma and meningioma brain tumor biopsies to develop a reclassification of the tumors based on gene expression profiles. 3)To develop a set of genes with prognostic importance in low grade astrocytomas. 4)To validate the importance of the genes from specific aims 2 and 3 in the prognosis of low grade astrocytomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENE THERAPY FOR HEREDITARY TUMORS IN MODELS OF NF2 % TSC Principal Investigator & Institution: Breakefield, Xandra O.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

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Astrocytomas

Timing: Fiscal Year 2002 Summary: (provided by applicant): Studies will be undertaken to develop modes of gene delivery to experimental neural tumors for therapeutic intervention. Neoplastic lesions associated with tuberous sclerosis (TSC) including subependymal glial nodules, giant cell astrocytomas and cortical hamartomas, are believed to represent the consequences of loss of tumor suppressor genes on growth of astrocytes, neuroprogenitor cells and mesenchymal elements. Tumor models in the TSC2 heterozygous and conditional knock-out mice have been chosen as they are genotypically similar to mutations seen in patient cells and derive spontaneously from endogenous cells. They include liver hemangiomas, renal cell carcinomas, cortical hamartomas, and potentially subependymal glial nodules. Gene delivery to these tumor cells will be explored using three types of hybrid amplicon vectors derived from herpes simplex virus type 1 (HSV): one bearing a tetracycline (tet)-regulatable transgene cassette; one bearing elements of adeno-associated virus (AAV) to promote chromosomal integration; and one with both Epstein Barr virus (EBV), elements to promote episomal retention, and retrovirus vector elements (RV), to convert ampliconinfected cells into retrovirus producer cells. Vectors will be delivered through the intravascular route, either directly or via endothelial carrier cells to vascularized tumor foci; by intrathecal injection for brain lesions; and by direct intratumoral injection to large tumor masses. The efficiency and longevity of gene delivery to tumors in vivo will be established using reporter genes. Effective delivery modalities will incorporate therapeutic transgenes for anti-angiogenic and apoptosis factors, and consequences to tumor growth and pathology will be evaluated. In parallel, we will incorporate additional elements into these vector systems to increase the fidelity of regulatable transgene expression and to facilitate gene delivery to slowly growing tumors, typically seen in patients. This will include, in the first case, use of a tetracycline-silencer element and elimination of the VP16 transactivating protein from virions to achieve a "full off? state in the absence of drug, and, in the second case, replacement of RV elements in the HSV/EBV vector with components of lentivirus (LV) vectors, which are able to integrate transgenes into both dividing and non-dividing cells. TSC2 +/-transgenic and TSC1 conditional knock-out animals will be provided by Dr. Kwiatkowski (Project 12); pathologic expertise by Dr. Louis (Core C); assistance with vector engineering by Dr. Sena-Esteves; and MRI analysis by Dr. Weissleder. This project is designed to develop a strategy for reducing bulk in slow growing, benign tumors using vectors safe enough for eventual human use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC PATHWAYS TOWARD GLIOMAGENESIS Principal Investigator & Institution: Maher, Elizabeth A.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 06-JUL-1999; Project End 30-JUN-2004 Summary: (Applicant's Description): Patients with de novo glioblastoma multiforme have a median survival of nine months when treated with currently available therapy. Although the prognosis for low-grade astrocytomas is significantly better, in at least 50 percent of cases, these tumors will progress to intermediate-grade (anaplastic) astrocytomas and finally to glioblastoma multiforme. Progress in the understanding of the pathogenesis of these deadly brain tumors has been hampered by the lack of a bonafide animal model that recapitulates the genetics and biology of this disease. Cytogenetic analysis of clinical glioma specimens has identified multiple genetic lesions known to be involved in oncogenic/tumor suppressor pathways. The working

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hypothesis of the applicant is that distinct genetic pathways govern the development of the two clinical subtypes of glioblastoma. Those that develop from low- or intermediategrade astrocytomas accumulate mutations over time in key pathways involved in growth, differentiation, apoptosis and angiogenesis, producing progressively more aggressive phenotypes. In contrast, de novo glioblastomas arise as a consequence of a critical combination of mutations in which the initial phenotype is the highest grade tumor. The DePinho laboratory has engineered and extensively characterized strains of mice with deletions of several of the genes which likely participate in the pathogenesis of these distinct disease entities. The availability of these mice coupled with the laboratory's expertise in transgenic and knockout technology, provides the applicant with a unique opportunity to probe the genetic mechanisms of gliomagenesis, develop a spontaneous mouse model of glioblastoma, and gain conceptual and technical experience in these areas. Aim 1: To generate a transgenic mouse that expresses fluorescently-labeled intermediate filaments, GFAP and nestin, to be used as specific markers of astrocytes and stem cells, respectively, in all experiments. Aim 2: To assess the role of overexpression of the oncogene, EGFR, in the pathogenesis of glioblastoma. Aim 3: To study the biological effects of known mutations in key tumor suppressor pathways governing growth, differentiation and survival of glial cells and how such mutations functionally interact with activated EGFR. Aim 4: To identify genes that cooperate with known oncogenes and tumor suppressors in the development and/or progression of malignant gliomas using a well-established retroviral insertional approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLIAL ASTROCYTOMAS

FILAMENT

ASSOCIATED

PROTEINS

IN

HUMAN

Principal Investigator & Institution: Skalli, Omar; Cell Biology and Anatomy; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2003; Project Start 05-APR-1996; Project End 30-APR-2007 Summary: (provided by applicant): Intermediate filaments (IF; also called glial filaments in astrocytes) are a major cytoskeletal component of astrocytoma cells. Several transfection experiments with sense and anti-sense cDNAs have shown that IF proteins influence the malignant behavior of astrocytoma cells. However, the mechanisms responsible for this effect are unknown. Our preliminary results suggest that one of these mechanisms may involve the IF protein synemin. We found that synemin is frequently expressed by astrocytoma cells in brain tumors, but not by astrocytes in normal, adult brain. Intriguingly, in astrocytoma cells, synemin, unlike other IF proteins, can be present within structures related to cell motility, such as the lamellipodium and focal contacts. Synemin is also unique among IF proteins in that it has been shown to bind to actin-associated proteins such as alpha-actinin. Interestingly, we found that the association of synemin with the lamellopodium is regulated by TGFalpha, a growth factor present in the microenvironment of astrocytic tumors. Indeed, in U373 glioblastoma cells maintained in serum-free medium, TGF-alpha induces synemin relocation from the IF network to the lamellipodium, an event which correlates with increased cell motility. Altogether these findings lead us to hypothesize that synemin, due to its unique binding properties and dynamic behavior can influence the organization and mechanical properties of cytoskeletal networks in astrocytoma cells. This would affect cellular features dependent on these properties, such as motility and cell shape. Specific aspects of this hypothesis will be examined in Aims 1 and 2. In Aim 1, we will "Investigate the Mechanisms by which TGF-alpha Regulates the Dynamic

12

Astrocytomas

Properties of Synemin in Astrocytoma cells" by examining the hypothesis that phosphorylation plays a role in directing synemin to the lamellipodium. In Aim 2, we will investigate "How Synemin/alpha-Actinin Interactions Affect the Organization and Mechanical Properties of the Cytoskeleton" by determining whether synemin crossbridges IF and/or actin filaments and how this crossbridging may affect the viscoelasticity of these biopolymers. Finally, one of the obstacles in understanding the function of IF in astrocytoma cells is our limited knowledge of the binding partners of GFAP, the astrocyte-specific IF protein. We thus propose in Aim 3 to "Identify Proteins Interacting with GFAP in Astrocytoma Cells by Using the Yeast Two-Hybrid System". Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESISTANCE

GSH

TRANSFERASE

PI

POLYMORPHISM

AND

DRUG

Principal Investigator & Institution: Ali-Osman, Francis; Professor & Head; Experimental Pediatrics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: (Applicant's Abstract) Malignant brain tumors continue to increase in incidence in the US, and currently are the most common solid tumors of childhood and adolescence. Unfortunately, however, brain tumors remain among the most therapeutically intractable of human tumors, and long term survivors are rare among patients with highly anaplastic astrocytomas or glioblastoma multiforme. A major cause of failure of brain tumor therapy, as in most other human cancers, is drug resistance, and much effort has been devoted towards understanding the cellular and molecular mechanisms that underly it. These studies have shown that drug resistance mechanisms often involve the dysregulation of genes, many of which are involved in normal cellular processes, such as metabolism, transport, DNA repair and cell cycle progression. One of the best characterized of these mechanisms is that of GST-pi over-expression. This application is founded on two significant recent findings from the applicant's laboratory related to the GST-pi gene. The first is that in gliomas, GST-pi over-expression is associated with drug resistance, malignant progression and poor patient survival. Secondly, he has made the potentially very important discovery that the human GST-pi gene locus is polymorphic and contains, at least, three allelic GST-pi gene variants. One of these variants, hGSTP1*C, is more frequently present in gliomas than in normal cells/tissues. The applicant has cloned the variant cDNAs and shown the encoded proteins to be structurally and functionally different. These findings are having a significant impact in the field of GST research. The primary goal of this application is to examine the influence of this newly discovered GST-pi genetic polymorphism on drug resistance in human gliomas and to determine whether specific GST-pi genotype/phenotypes are associated with differential therapeutic outcome and in patient survival. The Specific aims are: 1) To determine by molecular dynamic modeling, the differential binding affinities of anticancer agents to the active sites of proteins encoded by GST-pi allelic gene variants and correlate these with the differential abilities of the GST-pi proteins to inactivate anticancer agents; 2) To determine whether different GST-pi gene variants confer different levels of drug resistance to malignant glioma cells; 3) To determine whether GST-pi allelotype is related to the level of in vitro drug resistance of gliomas, and with in vivo response to therapy and survival of glioma patients following chemotherapy; and, 4) To determine whether down-regulation of GST-pi gene expression in gliomas that express different GST-pi gene variants will differentially affect drug resistance. The applicant believes that this application is well-

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focused and has a significant degree of novelty, with respect to the hypothesis, preliminary data and experimental techniques to be used. He believes the results are likely to make important and critical contributions to understanding the cellular, molecular and genetic mechanisms involved in GST-pi mediated drug resistance in human gliomas that will be applicable to many other human tumor types for which GST-pi over-expression has been shown to be an important determinant of drug resistance and failure of patients to respond to therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING

HIGH

GRADE

ASTROCYTOMA

SPECIFIC

MOLECULAR

Principal Investigator & Institution: Debinski, Waldemar; Surgery; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-MAR-2005 Summary: (provided by applicant): A restrictive receptor (R) for interleukin 13 (IL13) was found in a vast majority of human high-grade (grade Ill and IV) astrocytoma (HGA) specimens in situ, but not in low-grade (grade I and II) astrocytomas or brain tumors of non-glial origin. The HGA-associated restrictive receptor for IL 13 was identified molecularly to be IL13Ra2, a 45-kDa plasma membrane protein most of which is its extracellular domain. IL13Ra2 was also found to be a cancer/testis tumor antigen (CTA). By definition, CTAs provide extremely high specificity for molecular targeting/recognition of cancer. Moreover, IL13-based bacterial toxin-containing cytotoxins were shown to be arguably most potent anti-glioma agents in pre-clinical evaluation and they have entered or are being developed for clinical trials. Furthermore, IL13's structure-function relationship analysis revealed several macro-regions important for its interaction with respective receptors that are present in transformed cells or normal organs. It is proposed to continue the mutational analysis of ILl 3 to identify precisely the molecular requirements to bind its respective receptors, and to an HGAassociated receptor in particular. One region of IL13, a ct-helix D, appears to be pivotal for the 1113 binding to an HGA-associated receptor and will be the subject of detailed structural analysis. Guided with the results of such experiments, the minimization of the size of the ligand with an ability to bind IL13Ra2 will be attempted. Furthermore, the search will begin for small molecules that are interactive with the HGA-associated receptor. The next generation(s) of cytotoxins are expected to be developed in the course of experiments on IL13 structure-function relationship. Several members of the now third generation of IL 13 cytotoxins, based on multiply-mutated cytokine, will be. thoroughly evaluated in vivo, since they exhibit the preservation of potent cytotoxicity on HGA cells while being much less toxic than cytotoxins based on wild type or singlymutated IL13. The whole IL13 system be it ligand or receptor is of highest interest from the experimental therapeutic point of view, since the target (ILl 3Rcx2) is very specific to HGA and the ligand (IL13) is amenable to a variety of modifications for the purpose of specific molecular targeting of this incurable malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED NEUROSURGERY

TUMOR

RESECTION

IN

IMAGE-GUIDED

Principal Investigator & Institution: Zou, Kelly H.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2006

14

Astrocytomas

Summary: (provided by applicant): Image-guided neuro-surgical techniques, which utilize both pre- and intra-operative imaging data, are increasingly employed to facilitate surgical treatment of brain tumors. In the absence of a gold standard establishing the precise margin of the imaged tumor, exploiting multi-modality data is challenging. In addition, there exist high variabilities between and within segmentation performers. The goal of this proposal is to develop a computer-assisted informatics tool, namely neurosurgical decision aid (NDA), for improving tumor resection in imageguided neurosurgery. NDA a statistical algorithm-based tool designed to assist surgeons in making a pre-operative resection plan by (1) combining several human experts' decisions on target resection regions based on their independent segmentation results, and by (2) combining information derived from different imaging modalities or sequences. New expectation-maximization algorithms for estimating voxel-wise gold standards will be created. Both statistical simulations and studies using established digital phantoms with known gold standards will be conducted to test the performance of NDA. Immediately post-operatively, NDA then compares the tumor removal rate against the rate predicted in the pre-operative target resection plan. Finally, tumor recurrence rates will be compared in a two-sample clinical study of resected low-grade brain tumors including astrocytomas and oligodendrogliomas, with and without the assistance of NDA. The main goal of the proposed surgical planning and evaluation methodology is to achieve improved localization of lesions, precise definition of tumor margins, and better understanding of tumor relationship with functionally essential gray and white matter structures. The methodological development may also be applicable to other surgical applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITION OF NA-H EXCHANGER SELECTIVELY KILLS GLIOMAS Principal Investigator & Institution: Gorin, Fredric A.; Neurology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 30-APR-2004 Summary: High grade astrocytomas (, malignant gliomas) are the most commonly occurring type of lethal adult brain-tumor with an individual's average life expectancy being less than 2 years from the time of diagnosis. Neither radiation therapy nor chemotherapy has significantly improved quality or length of survival. Since Warburg's initial observation, it has been recognized that most transformed tumor cells have high rates of glycolytic metabolism and consequent H+ production. Given the optimal alkaline pH dependence of key glycolytic enzymes, such as phosphofructokinase and hexokinase, it is essential that tumor cells employ an effective means of removing free cytosolic H+ to maintain metabolism. We have determined that intracellular pH in rat and human gliomas are significantly above that of normal astrocytes (0.2-0.6 pH units) despite the tumor's high rates of metabolic H+ production. This intracellular alkalosis appears to result from persistent activation of the type 1 isoform of the Na+-H+ exchanger (NHE 1). Our preliminary investigations have determined that this altered regulation of NHE 1 is most probably posttranslational and does not result from alterations of the NHE1 gene or proteins expressed in these highly malignant astrocytomas. Unexpectedly, we found that inhibition of NHE I in rat and human glioma cell lines with the diuretic drug, amiloride, or with its derivatives, HOE 694 and EIPA, cause a 70-100 percent cell death within 48-72 hours. By, contrast, primary astrocyte cultures were unaffected by NIHE 1 inhibition. Cell culture and in vivo analyses indicate that glioma death following NHE 1 inhibition appears to be

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predominantly non-apoptotic and independent of preceding caspase activation. Rat C6 gliomas were implanted into rat brains and allowed to establish for 4 days. Amiloride infusion into the cerebrospinal fluid for 8 days produced a 73 percent reduction in tumor volume. Amiloride is an oral diuretic that is approved for human use. Preliminarily, this novel intrathecal administration of amiloride in rats does not appear to cause behavioral or neuropathological alterations. Amiloride produced a dosedependent decrease in intracellular pH in malignant gliomas, but not astrocytes. We have pilot data indicating that this ApHi initiates the selective tumor death. We propose to (1) identify the intracellular mechanisms mediating glioma death; (2) use brain implanted tumor models to more thoroughly delineate selective glioma death by NIlE I inhibitors; and (3) study the pharmacological and H+ regulatory properties of surviving gliomas. NHE I inhibitors may represent a new class of pharmacological agents that are useful for treatment of these highly aggressive and lethal brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MDM2 AND CELL GROWTH AND TUMORIGENESIS Principal Investigator & Institution: Jones, Stephen N.; Assistant Professor; Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 31-DEC-2003 Summary: (adapted from the investigator's abstract) This proposal takes a genetic approach to characterize the role of the Mdm2 proto- oncogene in the regulation of cell growth and in tumorigenesis. The MDM2 gene is amplified to high copy numbers in approximately one-third of all human sarcomas, and is overexpressed in a wide range of human cancers, including osteosarcomas, malignant fibrous histiocytomas, rhabdomyosarcomas, liposarcomas, leiomyosarcomas. glioblastomas, astrocytomas myeloid leukemias, B-cell lymphomas, and oral squamous cell carcinomas. The Mdm2 protein forms a complex with the p53 tumor suppressor protein, and Mdm2 has been shown to regulate normal cell growth primarily by binding to p53 and inhibiting p53 activity. However, the results of several studies indicate that Mdm2 may play an additional role in promoting cell growth and tumorigenesis, especially when Mdm2 is overexpressed. The research outlined in this proposal utilizes genetically defined cells and mice to examine the role of Mdm2 overexpression in cell growth and in neoplasia. Analysis of the effects of Mdm2 overexpression on the growth of mouse embryonic fibroblasts, and on tumorigenesis in transgenic mice bearing amplified copy numbers of the Mdm2 gene and/or which overexpress specific spliced forms of Mdm2 will permit characterization of Mdm2 functions to be performed in minimally-perturbed experimental systems. In addition, this proposal explores a possible mechanism for Mdm2-mediated inactivation of other cell growth regulatory proteins. The results of the proposed study should define clearly the tumorigenic effects induced by Mdm2overexpression in cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METABOLIC GENES AND THE RISK AND OUTCOME OF PRIMARY BRAIN TUMORS Principal Investigator & Institution: Davis, Faith B.; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The purpose of this case-control study is to assess the contributions of the glutathione S-transferase (GST; genes and the cytochrome P-450

16

Astrocytomas

(CUP) genes to the genetic susceptibility of brain tumors and to study the effect of these genetic polymorphisms on the treatment outcome and toxicity of brain tumors. Studies to date suggest a moderate to large effect for GSTTl in selected tumor subtypes. We are targeting obtaining data on approximately 1000 cases and controls, with an adequate number of glioblastomas (n=430), astrocytomas (n=300), oligodendrogliomas (n=100) and meningiomas (n=l50) to evaluate this hypothesis with reasonable power for relative risks previously reported in the literature for GSTTl. All study subjects will be asked to complete a computer assisted self-administered questionnaire and to provide blood and/or buccal cell samples for DNA analysis. An estimated 770 recently diagnosed cases (within three months of initial diagnosis) will be recruited by research nurses from Duke University Cancer Center and 220 cases in Evanston Hospital in Evanston, IL over a four year period. An equal number of friend controls will be identified by asking each case for the name of five friends of approximately the same age (+1- 5 years), gender and race. These controls will be recruited by the research nurse and given the option of completing the protocol during an appointment at the respective clinic or using a distance based protocol. Medical records will be reviewed to obtain the clinical and treatment information for the survival and toxicity portions of the study. Linkage with the National Death Index in Year four will be completed to obtain vital statistics information and provide up to three years of follow-up time in which to assess outcomes. Study coordination and survey data management will be completed at the University of Illinois at Chicago; molecular analysis will be conducted in the laboratory of Dr. Ali-Osman at M.D. Anderson Cancer Center. The Duke Cancer Center will facilitate the neuropathology review, provide some local data collection and management support and store the remaining specimens in their central repository. Data analysis files will be compiled at UIC and statistical analysis will be completed using conditional logistic regression models as appropriate to each specific aim. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PROGRESSION

MARKERS

OF

GLIOMA

INITIATION

AND

Principal Investigator & Institution: Jenkins, Robert B.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 14-JUN-2001; Project End 31-MAY-2005 Summary: (provided by Applicant) Gliomas are a significant cause of morbidity and mortality, and thus have been the focus of frequent basic biologic, basic genetic, and clinical investigations. Numerous genetic and biologic alterations associated with gliomas have been described. However, many of the specific genes involved in gliomas have yet to be identified. A great deal still needs to be learned about the mechanisms by which the known genes are involved in the pathogenesis of gliomas. Furthermore, while much has been learned about the biology and genetics of gliomas, little of this information has been translated into clinical practice. There are still problems with the morphologic classification of gliomas - especially oligodendrogliomas and mixed oligoastrocytomas. It is difficult to predict which patients with anaplastic astrocytomas will suffer early recurrence. And while some gliomas with specific genetic alterations seem to respond to chemotherapy (e.g., Cairncross et al., JNCI 90:1473,1998), these observations need to be confirmed and extended and additional therapeutic genetic targets identified and/or developed. Through four projects and two cores this program, which builds on the past experience of the Glioma Marker Network (GMN) consortium, will study the basic biology of several specific biochemical and genetic alterations associated with gliomas. It will also continue to evaluate the predictive, prognostic, and

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pathologic relevance of these alterations. Project 1 will study the biologic and clinical relevance of 7q gain in gliomas, with emphasis on the mechanism by which this alteration predicts a poorer prognosis. Project 2 will evaluate the function of mutated and amplified EGFR in gliomas and will test several potential therapeutic approaches targeting these mutant receptors. Project 3 will identify and study the function of the 19q gene associated with gliomas and associated with a prolonged response of some gliomas to chemotherapy. Project 4 will study the biologic and clinical relevance of glycolipid and glycosyltransferase alterations in gliomas. Thus, through these projects, this highlyinteractive and experienced program will make significant progress toward understanding the pathogenesis of gliomas, and translating this knowledge into new diagnostic and therapeutic tools. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS OF HUMAN BRAIN TUMORS Principal Investigator & Institution: Israel, Mark A.; Director; Pediatrics; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: The overall goal of this proposal is to develop and exploit mouse models which faithfully recapitulate the biology and genetics of astrocytoma and oligodendroglioma, the most commonly occurring human primary brain tumors. These animals will be used to dissect the pathogenesis and biology of glioma and to improve efforts directed at cancer prevention, diagnosis, and therapy. A major additional emphasis is to contribute our unique resources and experience towards development of animal models for other human tumors studied by Consortium members. Gliomas are the leading cause of cancer deaths in children, and represent the fourth leading cause of cancer-related death in males aged 35-54. There is no current means to prevent gliomas, to diagnose gliomas before they become symptomatic, nor to effectively treat glioma. The incidence of gliomas is increasing in all age groups, and the highest grade tumors almost invariably causes death within a year of diagnosis. We propose to build upon current genetic insights to develop animal models which faithfully recapitulate the most common of these tumors, which are also among the most lethal. We have targeted expression of v-erbB, an oncogenic form of the epidermal growth factor receptor, to generate an infiltrating transgenic model for oligodendroglioma. We plan to characterize and validate these tumors, and to generate additional mice with tissue specific gain-of-function and loss-of-function mutations in genes comprising the main genetic pathways in human astrocytomas. We propose specific strategies for utilizing the mouse lines and tumors which arise from these experiments to improve our understanding of tumor biology, to identify additional genetic lesions, and to develop improved strategies for their diagnosis and treatment. Specifically we will: 1) Map and identify brain tumor modifier loci in the mouse, 2) Utilize state-of-the-art expression array technology to examine patterns of gene expression and develop array based comparative genomic hybridization in the mouse to identify new genes that contribute to the genetics of these tumors, and 3) Develop functional magnetic resonance imaging modalities for mouse brain tumors, and apply these technologies to both basic science and translational research questions. These experiments should improve our understanding of human glioma as well as glioma models, and assist in the development and evaluation of new therapeutic paradigms. In addition, the technologies developed through this proposal are readily applicable to animal models of other tumor types which might emerge from Consortium efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Astrocytomas

Project Title: PHASE I TRIAL OF A PEPTIDE VACCINE AGAINST EGFRVIII Principal Investigator & Institution: Montgomery, Robert B.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 13-AUG-1999; Project End 31-DEC-2005 Summary: (adapted from investigator's abstract) The epidermal growth factor receptor (EGFR) is overexpressed in a significant number of human malignancies and is thought to play a role in oncogenesis in these tumors. Overexpression of the receptor precedes deletional mutation of the gene or the production of aberrant transcripts for the receptor. One of these deletional mutants, EGFRvIII, is oncogenic and constitutes a tumor specific antigen. EGFRvIII is expressed in 15-75% of high grade astrocytomas, ovarian and gastric cancers and therefore represents a potential target for immunotherapy in patients with these malignancies. Patients with tumors which express EGFRvIII have evidence of antibody and T cell immunity specific to the deletional mutant and are therefore capable of recognizing the receptor as a foreign antigen. Preclinical data in a murine model demonstrates that a peptide vaccine incorporating the unique amino acid sequence of the EGFRvIII can augment an immune response of cytotoxic T lymphocytes and antibodies specific for the mutant receptor. In these animals, the induction of cytotoxic T lymphocytes and antibodies prevents tumor implantation and can induce regression of tumors expressing the receptor. Peptide vaccines targeted to another closely related EGFR family member, the HER2 oncoprotein, effectively induce T cell and humoral immunity against HER2, demonstrating feasibility of this approach. No adjuvant therapy has been found to significantly prolong the survival of patients who present with the tumor histologies which express EGFRvIII, and as a group they are at a very high risk of relapse after initial therapy. Innovative approaches to prevention and treatment of these malignancies is warranted. The objective of this proposal is to synthesize and. test peptide vaccine, followed by use of this vaccine in a phase I study in patients with EGTFRvII1 expressing malignancies. The study of this peptide vaccine will examine both the ability to induce T cell and humoral immunity to this peptide and the effect of humoral immunity on expression and signaling by EGFRvIII. The specific aims of this proposal are; 1. To evaluate the safety and define the potential toxicity of immunizing patients with an EGFRvIII based peptide vaccine. 2. To determine the level of EGFR specific antibody response after immunization with EGFRvIII peptide 3. To characterize effects of human anti-EGFRvIII antibodies on EGFRvIII signaling. 4. To determine the level of EGFR specific T cell response after immunization with EGFRvIII peptide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRECLINICAL MODELS FOR HUMAN ASTROCYTOMAS Principal Investigator & Institution: Gutmann, David H.; Associate Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-JUN-2005 Summary: The prognosis for malignant brain tumors (astrocytomas) remains essentially unchanged despite significant advancements in neuro-oncology and radiation therapy. Our ability to design targeted therapies for astrocytomas (gliomas) is heavily dependent upon a more complete understanding of the molecular pathogenesis of these tumors and the availability of appropriate preclinical models to test potential biological therapies. Genetic alterations in human astrocytomas differ between astrocytoma grades and involve gene products important for regulating (1) growth factor signaling pathways and (2) cell cycle progression. Studies from our laboratory have demonstrated

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19

that activation of p21-ras is a common feature of low and high- grade astrocytomas and that approximately 60 percent of GBMs harbor alterations in the rap1 signaling pathway. In addition, high-grade gliomas exhibit loss of PTEN/MMAC1 expression or epidermal growth factor receptor (EGF-R) amplification/activation, suggesting a role for these proteins in astrocytoma progression. Over the past year, we have developed transgenic mice with astrocyte-specific expression of EGF-R, EGF- RvIII and p21-ras (G12V). The B8 p2l-ras (G12V) transgenic mouse strain develops astrocytomas with a latency of 3-4 months that are histologically and biologically similar to human astrocytomas. In this proposal, we propose to employ transgenic mouse models to critically evaluate the hypothesis that abnormalities in growth factor signaling and cell cycle control genetically cooperate in the molecular pathogenesis of astrocytomas. Specifically, we wish to determine whether (1) abnormal ras and rap1 signaling in astrocytes is necessary or sufficient for astrocytoma development, (2) loss of PTEN/MMAC1 signaling or EGF-R alterations are associated with astrocytoma progression, and (3) abnormal rap1 and ras signaling in astrocytes combined with defective cell cycle control is associated with astrocytoma progression. The development and characterization of mouse models mimicking the histology and molecular pathogenesis of human astrocytomas would greatly advance our ability to treat human astrocytomas by serving as informative preclinical models to test novel therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRECLINICAL STUDIES OF RAPAMYCIN FOR TSC BRAIN DISEASE Principal Investigator & Institution: Kwiatkowski, David J.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-DEC-2006 Summary: (provided by applicant): Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome due to mutations in either TSC1 or TSC2. During childhood the predominant morbidity in TSC is neurologic, due to involvement of the brain by the cortical tubers and subependymal giant cell astrocytomas. Seizures are seen in 90% of patients, and mental retardation and a variety of development disorders including autism are common. Hamartomas in TSC are thought to arise through a two hit mechanism that results in complete loss of either TSC1 or TSC2. Molecular studies in cultured cells and on tumors arising in TSC patients and mouse models indicate that loss of either tuberin or hamartin leads to a molecular signature of activation of mTOR. mTOR is specifically inhibited by rapamycin and related compounds, and in vitro rapamycin completely reverts the biochemical abnormalities present in Tsc1 null or Tsc2 null cells. We have created conditional alleles of Tscl and Tsc2, and used brain-specific recombinase expressing alleles to generate mice with Tsc1 or Tsc2 null cells in the brain. These mice have multiple features matching those of TSC patients: developmental abnormalities, seizures, and premature mortality. Brain pathology shows enlarged cells similar to those seen in TSC cortical tubers and subependymal giant cell astrocytomas. We propose to systematically explore the potential benefit of rapamcyin therapy, in two different mouse models of TSC brain disease, using survival, development, seizure frequency, and biochemical studies and pathology on brain samples as therapeutic endpoints. We will then test two newer analogues of rapamycin, CCI-779 and everolimus, in these models. These studies will provide critical preclinical data that will support the use of rapamycin or analogues in the treatment of TSC patients with cortical tubers and subependymal giant cell astrocytomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Astrocytomas

Project Title: ROLE OF ATM IN RADIOSENSITIVITY OF GLIOMAS Principal Investigator & Institution: Guha, Chandan; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Glioblastoma multiforme (GBM) is one of the most lethal cancers. Radiotherapy prolongs survival only modestly, because the dose is limited by the tolerance of the normal brain tissues. In order to improve the results of radiotherapy we propose to increase the intrinsic radiosensitivity of GBM by selectively targeting ATM (Ataxia-Telangiectasia mutated), which is a key mediator of the DNA damage surveillance pathway in an irradiated cell. As proof of principle, we downregulated ATM expression in GBM cells and enhanced their radiosensitivity. Invitro, the surviving fraction after 2 Gy (SF2) decreased, from >0.5 without antisense to 0.28-0.35 with antisense. It is notable that the average SF2 of cells isolated from GBMs, which are incurable by radiotherapy, is 0.5 whereas the average SF2 of cells isolated from anaplastic astrocytomas, which are curable by radiotherapy, is 0.34. In-vivo about half the tumors were cured, with a dose of irradiation that, without the antisense, cured a few. In order to increase the transduction efficiency of our genetic antisense vectors in GBM cells, we constructed an E1B-deleted replicating adenoviral vector (Adeno-E1BE alphaATM) and successfully attenuated ATM protein expression in U-87 (p53 w.t.) and U-138 (p53 mut) GBM cells resulting in enhanced radiosensitivity in vitro. Interestingly, BIBA-Adeno-aATM enhanced the tumoricidal effects of the parent Adeno-E1B virus, even without irradiation. We further demonstrated the safety of Adeno-E1B -alphaATM in human umbilical vein endothelial cells and mouse astrocytes in vitro, and the mouse brain in vivo. Finally, we demonstrated that the human hexokinase II (hHKII) promoter is induced 15-fold in GBM cells when compared to expression in cultured normal neurons and astrocytes. Hypoxia and irradiation further induced the hHKII promoter. We now propose: (I) To investigate the role of ATM and its downstream targets in determining the radiosensitivity of GBM cells. The adenoviral vectors will be used as tools to down regulate ATM in molecularly well-chracterized GBM cells. (II) To further enhance the therapeutic benefit of Adeno-E1B cLATM virus by regulating the expression of the antisense ATM RNA under the control of a tumor-specific, hypoxiasensitive, radio-inducible hHKII promoter. The infectivity/tropism of Adeno-EIBAaATM virus to GBM cells will be increased by constructing vectors with adenoviral fiber mutation, F/K20. (III) To construct conditionally replicating antisense-ATM herpes simplex virus (HSV) vectors, expressing antisense-ATM under the control of the HKII promoter. We will also examine whether neural progenitor cells can be used to deliver the HSV antisense-ATM vector to tumor cells in the brain. (IV) To investigate the combined toxicity of the virus vectors, ATM attenuation and radiation therapy in cultured endothelial cells, astrocytes, oligodendrocytes, neurons and brain tissues in mice models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF LRP IN ASTROCYTOMA MIGRATION Principal Investigator & Institution: Hussaini, Isa M.; Associate Professor; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 31-MAR-2008 Summary: (provided by applicant): The majority of the intracranial tumors are diffusetype astrocytomas. These gliomas generally have the common biologic features of 1) micro-infiltrative growth into surrounding brain, and 2) a significant potential for

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malignant progression to occur over time (i.e. in the residual, infiltrating tumor). The first accounts for the failure of surgery alone and inevitable tumor recurrence, even with gross total resection of the tumor mass. The second accounts for the high rate of increased biologic malignancy in the recurrent tumor. These collectively account for the lack of progress in accurate diagnostic grading and therapy for this class of tumors. The paucity of therapeutic innovations in neuro-oncology reflects the limited understanding of how the migration and invasion of these tumors are controlled, so that the invading tumor cells can be more specifically targeted. Low density lipoprotein receptor-related protein (LRP) is an endocytic receptor involved in the trafficking of a variety of protein/protein complexes that have pathophysiologic relevance in the central nervous system, including urokinase (uPA) and its receptor (uPAR), lipoprotein metabolites, and activated alpha2-macroglobulin. Although the function of LRP in the CNS is not clear, there are abundant data in the literature to indicate that some of its ligands may be involved in key pathophysiologic processes. A variety of cytokines and growth factors, including epidermal growth factor receptor (EGFR) ligands, colony stimulating factor-1 and interferon-gamma, regulate the expression of LRP in both peripheral and central nervous systems. Therefore, changes in LRP expression can alter the levels of its ligands and exert significant biologic effects during cellular responses in the nervous system. Astroglial cells in the human brain express LRP and the level of the receptor is altered in certain reactive states and following neoplastic transformation. Based on our preliminary results in this grant and published data, LRP serves a role as an important endocytic receptor that regulates the level of uPA and its receptor (uPAR), known modulators of migration and invasion, around the microenvironment of astrocytic tumors. We hypothesize that LRP expression regulates the migration and invasion of astrocytic tumor cells. The first goal (Aims 1&2) of this grant is to determine whether the regulation of LRP expression differ between neoplastic (primary astrocytomas; glioblastoma cell lines) and non-neoplastic astrocytes and assess how EGFR or PKC-eta activation alters the expression and endocytic function of LRP. The second goal (Aim 3) is to determine whether overexpression or deficiency of LRP or its ligands (uPA/uPAR) affects astrocytic tumor migration and invasion in vitro and in vivo. Understanding the role of LRP in the migration and invasion astrocytic tumors will provide information on possible specific targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TFPI-2 IN HUMAN GLIOMAS INVASIVENESS Principal Investigator & Institution: Rao, Jasti S.; Professor and Head; Biomedical & Therapeutic Sci; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The long-term objective of our laboratory is to understand the regulatory roles of TFPI-2 in the invasive and malignant behavior of glioblastomas. TFPI-2 inhibits six different serine proteases, including plasmin, an enzyme that appears to be directly involved in the invasive behavior of primary tumors, particularly glioblastomas. In preliminary studies, TFPI-2 was undetectable in both glioblastomas and an established glioblastoma cell line that is highly invasive in vitro and in vivo. In contrast, the TFPI-2 protein was detected in normal human brain and, to a lesser extent, in low-grade gliomas and anaplastic astrocytomas as well as in cell lines derived from these tumors. These findings show an inverse correlation between the TFPI-2 levels and the progression of gliomas. We postulate that modulation of TFPI-2 expression will alter the invasive behavior of gliomas in vitro and in vivo. The central hypothesis is that TFPI-2 is a key negative regulator of proteases that promote glioma

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invasion and angiogenesis. To test this hypothesis, first we examine Specific Aim 1: Construct an expression vector cassette containing a 0.7-kb fragment of human TFPI-2 in the sense orientation in an E1-deleted region driven by an independent cytomegalovirus (CMV) promoter and the polyadenylation signal bovine growth hormone (BGHpA) and study its (Ad-TFPI-2) effect on the levels of TFPI-2, other proteases in glioma cells and their invasive behavior both in vitro and in vivo models and its effect on glioma growth in vivo. 1a) Construct and determine the effect of the Ad-TFPI-2 construct on the levels of TFPI-2 and proteases, 1b) Determine the effect of the Ad-TFPI-2 construct on glioma cell growth, adhesion and migration with that of mock and Ad-CMV construct, 1c) Investigate the effect of the TFPI-2 construct on the invasive behavior of human glioma cells in vitro models, 1d) Determine the effect of Ad-TFPI-2 construct to inhibit the invasion and growth of human glioma cell lines injected subcutaneously and intracerebrally in nude mice. 1e) Evaluate the toxicity of Ad-TFPI-2 construct with that of Ad-CMV construct given as intracerebral injections. Specific Aim 2: Identify the molecular mechanisms that regulate cerebral angiogenesis in relation to the production of TFPI-2 in co-cultures of endothelial and glioma cells both in vitro and in vivo. 2a) Determine that levels of TFPI-2, VEGF, TF and other proteases and the length of capillary-like structures formed during cocultures of endothelial cells with sense/antisense TFPi-2 stable clones or glioblastoma cell lines and primary glioblastoma cells infected with Ad-CMV and Ad-TFPI-2 sense constructs or in the presence of an inhibitor and 2b) Determine the effect of sense and antisense stable transfectants or infection of Ad-TFPI-2 sense construct or in the presence of an inhibitor specified in specific aim 2a on tumor angiogenesis. We believe that by determining the role of TFPI-2 in the invasiveness of glioblastomas and its role in angiogenesis, it will be possible to design further studies that will evaluate the therapeutic role of this novel protease inhibitor in brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION AS THERAPY FOR MALIGNANT GLIOMAS Principal Investigator & Institution: Pollack, Ian F.; Walter Dandy Professor of Neurosurgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: Malignant astrocytomas are the most common primary brain tumors, and are the group most poorly controlled with current treatments. Their limited response to conventional therapies in part reflects a resistance to undergoing apoptosis in response to DNA damage or mitogen depletion, which results from a combination of tumor suppressor gene mutations and aberrant activation of growth factor-stimulated pathways. However, our recent in vitro studies indicate that, despite the limitation of apoptotic triggering in these tumors, the effector pathways of apoptotic signaling remain intact and can be activated by inhibition of growth factor signaling or stimulation of death receptor pathways. Our preliminary studies also suggest a number of intriguing interactions between these strategies and other treatment approaches. We hypothesize that agents which block aberrantly activated growth signaling pathways, or directly activate apoptotic signaling, will have efficacy for inducing glioma apoptosis in vivo and will potential the efficacy of other therapeutic modalities. To test this hypothesis, we will examine the effects of glioma growth and viability in vitro and in vivo inhibitors of protein kinase C and ras, proteins that play critical roles in prolifer4ative signaling induced by aberrantly activated upstream receptors. These

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studies will incorporate a panel of established and low-passage cell lines with defined genetic alterations to assess whether genotypic features influence the response to these agents, and to establish reliable biological surrogates of tumor response. Second, we will examine whether apoptotic signaling can be directly induced by Apo2L/TRAIL, a ligand for the DR4 and DR5 members of the TNF4 family of death receptors, and evaluate TRAIL receptor expression patterns, genotypic features, and biological surrogates that may predict efficacy in vivo. Both studies will be integrated with Project 3, which will provide viral vectors for local delivery of TRAIL and for reversing selected tumor suppressor gene deletions. Third, we will determine whether signal transduction inhibition or activation of apoptotic signaling can enhance the efficacy of radiotherapy and conventional chemotherapy for promoting cytotoxicity in all, or a genotypically defined subset of, malignant gliomas. Fourth, because our preliminary studies indicate that induction of glioma cell apoptosis by signal transduction modulation may be an effective mechanism for "priming" dendritic cells to promote an anti-tumor immune response, we will build on longstanding interactions with Project 2 to determine whether signal transduction modulation can potentiate the efficacy of DC-based immunotherapy approaches. Taken together, these studies will provide a foundation for the clinical translation of signal transduction inhibition and death receptor activation as therapeutic approaches for malignant gliomas, and indicate ways in which these strategies can be used to enhance the efficacy of other therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNIFICANCE OF CHROMOSOME 7 ALTERATIONS IN GLIAL TUMORS Principal Investigator & Institution: Feuerstein, Burt G.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: (provided by Applicant) Gliomas are an important clinical problem. Prognostic variables include histology (cell type and grade), age, and performance status. Unfortunately, the histology of gliomas is not simple, and pathologists often disagree in their diagnosis. Since diagnosis is an important parameter in patient selection for clinical trials, studies may suffer from entry criteria that are not objective, and comparisons across studies that target these tumors are therefore unreliable. Furthermore, since cases in the community are treated according to these diagnoses, optimal therapy may not ever reach a particular patient. We and others have found that chromosome aberrations occur commonly in these tumors and a pilot study has suggested that some of them are prognostic. This proposal seeks to validate this finding and to determine more particular regions on chromosomes responsible for this behavior. The aims are: 1) Define the minimum recurrent 7q amplicon in grade 3 astrocytomas. 2) Functional characterization of genomic sequence spanning critical region defined in aim 1. 3) Determine whether copy number aberrations (CNAs) and/or small genetic elements on chromosomes 7, 10, 4q, and 12q predict survival in grade 2 and 3 astrocytoma patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TGF BETA AND BRAIN TUMORS Principal Investigator & Institution: Rich, Jeremy N.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003

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Summary: (provided by applicant): Brain tumors remain one of the most challenging forms of cancer despite continuing advances in diagnosis and treatment. Improved therapies will require a greatly-improved understanding of how specific genetic alterations can lead to the development and growth of brain tumors. We are seeking to develop an improved model system in which normal human astrocytes can be transformed through the introduction of defined genetic alterations to analyze the biologic alterations caused by these changes. An analysis of the genetic alterations frequently found in human brain tumor samples allows for the development of a set of targets that are likely required for alteration in the transformation of the normal precursor cell for astrocytomas, the astrocyte. Our hypothesis is that the transformation of normal human astrocytes into gliomas can be modeled by a restricted set of minimal required genetic alterations and that targeting of these pathways will permit the development of therapies useful in a broad range of gliomas. We plan to use the previously established system of amphotropic retroviruses with SV-40 large T antigen, hTERT, and HrasV12G to transform human astrocytes. Our Specific Aims include to determine: 1) if large T antigen, hTERT, and HrasVl2G are sufficient to transform human astrocytes and measure genomic instability and gene expression changes, 2) the relative importance of different rasactivated pathways in astrocyte transformation, 3) if a constitutively active EGF receptor mutant is sufficient to replace activated ras in transforming astrocytes, 4) the effect of TGF beta expression on tumor growth and development, 5) if the loss of the tumor suppressor gene Pten is sufficient to activate ras pathways to permit transformation, and 6) if pathway-specific inhibitors can prevent astrocyte transformation and tumor growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ASTROCYTOMAS

CELL-CYCLE

CONTROL

OF

ASTROCYTES

AND

Principal Investigator & Institution: Weinstein, David E.; Chief Scientific Officer; Gliamed, Inc. Audubon Biomedical Sci/Tech Park New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 30-JUN-2005 Summary: (provided by applicant): This year, and in every year in the foreseeable future, 17,000 Americans will develop primary brain cancers. Of these, the most common tumor is astrocytoma. Of the 8,000 people to be diagnosed with astrocytoma, all will eventually die of their disease. The vulnerability of the astrocyte to transformation lies in its ability to re-enter the cell-cycle at any point in the life-time of an organism. In spite of the ability to proliferate, astrocytes are kept mostly quiescent, except in response to disease or trauma, where there is a concomitant neuronal loss. A number of years ago, we and others demonstrated that astrocyte proliferative control is effected by contact with neuronal membranes, although the precise molecular mechanism by which neurons exert this control has remained elusive. My laboratory has recently identified a receptor on the surface of the astrocyte, CD8 1, which is absolutely required for neuron-induced astrocyte cell-cycle arrest (see Preliminary Data, and appended manuscript for details). In this application, we propose a series of biochemical, molecular and cell biological experiments aimed at the identification and characterization of neuronal CD8 1 binding proteins. In addition, we will begin to query the astrocytic signaling mechanism following neuronal binding. Our findings for the requirement for astrocyte expressed CD8 1 for neuron-induced growth control takes on added significance, based on our observation that all of the astrocytoma cell lines we have examined to date have absolutely down regulated CD8 1 protein and message. To determine if CD8 1 expression can rescue the ability of these cells to respond to neuron-

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induced by cell-cycle arrest, we have expressed a CD8 1 -GFP fusion construct in the astrocytoma cell lines. The transfectants will be assayed for in vitro neuronal responsiveness, and in vivo tumor progression and metastasis in nude mice. In parallel with these experiments, we will continue a series of affinity chromatographic purification of neuronal membrane proteins that are active inhibitors of astrocyte proliferation. While we hope and anticipate that our two lines of inquiry on neuronal mediators of astrocyte growth control will converge, it is quite possible that we will identify separate, redundant mechanisms that are involved in maintaining CNS numerical homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF EPH-EPHRIN INTERACTIONS IN GLIOMA MIGRATION Principal Investigator & Institution: Canoll, Peter D.; Pathology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The objective of the following research program is to develop the candidate into an independent biomedical investigator in the area of brain tumor research. The candidate's clinical training in Anatomic Pathology and Neuropathology, and his past research experience the field of glial cell biology, provide a firm foundation on which to build a career devoted to basic research on human disease. The diverse clinical and basic science research programs at Columbia Presbyterian Medical Center, especially in the field of Neuroscience, provide an excellent environment in which the candidate can interact and establish collaborations and develop as an independent researcher and physician. Human gliomas, including glioblastomas, astrocytomas and oligodendrogliomas, have a remarkable capacity to infiltrate the brain, making complete surgical resection impossible. Glioma cell migration is not random, but rather follows preferred paths, such as along blood vessels and myelinated fiber tract. Our goal is to understand the molecular mechanisms that regulate glioma migration. Towards this end, we have developed an experimental system to monitor glioma cells migrating in living slices of rodent brain using time-lapse videomicroscopy. We are using this system, in combination with a variety of well established in vitro migration assays, to test the effects of specific guidance molecules on glioma migration. Our initial analysis is focused on a group of molecules called Eph receptors and their binding partners the ephrins. Eph-ephrin signaling mediate repulsive interactions that guide migrating cells during embryonic development. We hypothesize that these molecules play a similar role in glioma migration. To test this we will interfere with Eph-ephrin signaling using molecular and pharmacological techniques and then measure the effects on glioma migration in two different rodent glioma models. The first model uses stereotactic transplantation of genetically modified glioma cells (C6-GFP) into rodent forebrain. The second model uses avian retroviral vector(s) to deliver oncogenes selectively into glial progenitors via infection of transgenic mice that express the avian retrovirus receptor (t-va) from specific promoters. We will first characterize the expression of Ephs and ephrins in these models and then combine these animal models with in vitro and ex vivo migration assays to study how interfering with Eph-ephrin signaling effects glioma migration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF TSP-1 AND 2 IN THE BIOLOGY OF ASTROCYTOMAS Principal Investigator & Institution: Gladson, Candece L.; Associate Professor; Pathology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Malignant astrocytomas demonstrate a prominent angiogenic response that promotes the highly invasive and proliferative phenotype of these tumors. Tumors typically synthesize both anti- and pro-angiogenic molecules; however, when the balance shifts toward pro-angiogenic molecules tumors exhibit very aggressive behavior. Intact thrombospondin (TSP)-1 and 2 and peptides derived from the type 1 repeat domain of TSP-1 and 2 have been shown to act as anti-angiogenic molecules. However, the amino terminal domain of TSP-1 and 2 may have a different function than the type 1 repeat domain, as recent in vitro data from other investigators indicates that the amino-terminal domain of TSP-1 can be pro-angiogenic. In this regard, we have preliminary data indicating that an amino-terminal domain fragment of TSP-1 and 2 is proteolytically generated in vivo in malignant astrocytomas but is minimally detected in the normal brain. The mechanism by which the amino-terminal domain of TSP-1 and 2 can promote angiogenesis is unclear. TSP-1 and 2 complex with matrix metalloproteinases (MMP)-2 and 9 and the complex is internalized by the LDL receptorrelated protein (LRP), reducing the activity of MMP-2 and 9. TSP-1 and 2 bind to LRP through their amino terminal domain. We hypothesize that the in vivo amino-terminal fragments of TSP-1 and 2 compete with intact TSP-1 or 2 (complexed with MMP-2 or 9) for binding to and internalization by LRP. The latter competition should result in increased MMP-2 and 9 activity in these tumors, promoting angiogenesis and tumor invasion.The aims of this project are as follows. 1) Characterize the proteolytic fragments of TSP-1 and 2 that are found in malignant astrocytomas, and create recproteins corresponding to these in vivo fragments. 2) Test the angiogenic modulatory effect of rec-TSP- 1 and 2 fragments in capillary tube formation assays and the corneal model of angiogenesis, and determine whether the amino-terminal fragments of TSP-1 and 2 inhibit LRP internalization of intact TSP-1or 2 complexed with MMP-2 or 9. 3) Determine the biologic role of host or stromal cell-derived TSP-2 in malignant gliomas, and the effect on the angiogenic phenotype of stable tumor cell over-expression of TSP-2 fragments identified in patient biopsies in aim 1. Mouse malignant glioma cell clones will be injected intracerebrally into the TSP-2 knockout mouse and the wild-type mouse, and studies to analyze tumor angiogenesis and proliferation performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOWARD A MOLECULAR CLASSIFICATION OF HUMAN GLIOMAS Principal Investigator & Institution: Louis, David N.; Professor and Associate Chief; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 31-JAN-2004 Summary: (adapted from the investigator's abstract) Dr. Louis states that malignant gliomas are the most common primary human brain tumors, but their classification remains controversial and effective therapies remain elusive for the majority of cases. The common malignant gliomas can be divided into astrocytomas (including the highly malignant glioblastoma), oligodendrogliomas and oligoastrocytomas. He has clarified some of the genetic events that underlie the formation of these tumors, and has begun to correlate such genetic data with clinical and histopathological parameters. Recently, he has shown that certain genetic events may predict chemosensitivity and survival in

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some gliomas. Despite these advances, however, he states many of the tumor suppressor genes have yet to be identified, the relationships between certain genetic events remain unclear, and the clinical significance of this genetic information has only begun to be tested. He therefore plan to test the hypotheses that: 1) Specific genetic events (loss of chromosomes 1p and 19q, deletions of the CDKN2A/p l6 gene) predict chemosensitivity and survival in human oligodendroglial tumors; 2) Genetic subsets of human glioblastomas are associated with different overall survival; and 3) Astrocytoma tumor suppressor loci reside on chromosomes 11p and 22q. To test these hypotheses, he proposes three specific aims: 1) To analyze three subtypes of oligodendroglial tumor (anaplastic oligodendrogliomas, anaplastic oligo-astrocytomas, and oligodendrogliomas) for chromosome 1p and 19q loss and CDKN2A/pl6 deletion, and correlate these genetic events with chemotherapeutic response and survival; 2) To analyze a large, homogeneous series of glioblastomas for p53 mutations and EGFR amplification, and also for alterations in the CDKN2A/p16-CDK4-RB pathway, and to correlate these genetic events with survival; and 3) To continue genetic characterization of astrocytomas, primarily through detailed analysis of tumor suppressor loci on chromosomes 11p and 22q. He believes that identification of genetic alterations that are integral to glioma tumorigenesis will contribute to a classification system for gliomas, based on their genetic and biologic characteristics, that may more accurately reflect tumor behavior and response to therapy than current histopathological schemes, and that the elucidation of these alterations will provide biological information that may eventually impact on treatments for these malignant tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSDUCTION OF TUMOR SUPPRESSOR PROTEINS INTO GLIOMAS Principal Investigator & Institution: Dowdy, Steven F.; Cellular & Molecular Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 05-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Brain tumors, gliomas and astrocytomas, are devastating malignancies that account for 2.3 percent of all US cancer deaths and represent the second most common solid tumor of children. Malignant brain tumors respond poorly to current therapies with a mean survival rate of less than one year despite treatment, Due to the invasive nature of gliomas, particularly glioblastoma multiformes (GBM), localized anti-cancer strategies, such as surgical removal, also fail to adequately halt the disease. Gliomas select for genetic inactivation of multiple tumor suppressor genes, including p53 (>60 percent), PTEN (>75 percent), p16/p I4ARF (50 percent), pRB (30 percent), and epigenetic down-regulation of the p27 Cdk inhibitor. A central hypothesis of anti-cancer therapies holds that replacement of tumor suppressor gene functions in malignant cells will result in specific death or apoptosis of the cancer cell while sparing the surrounding normal tissue. Indeed, tumor cells are undergoing continuous DNA damage and therefore, adenovirus expression of wild type p53 in gliomas by results in specific apoptosis to the glioma tumor cells. We propose to test this hypothesis by generating transducible tumor suppressor proteins. My laboratory has further developed the methodology of protein transduction. Recombinant, bacterially expressed fusion proteins containing an N' terminal protein transduction domain from HIV TAT rapidly transduce into 100 percent of cells. Using this methodology, we have generated and transduced over 60 TAT-fusion proteins from 15-120 kDa. Recently, we have demonstrated the ability of TAT-B-gal protein to transduce into most, if not all, cells and tissues of mouse models in vivo, including across the blood-brain barrier.

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Thus, in principle and practice, all mammalian cell types are susceptible to protein transduction. We propose to test the anti-cancer effectiveness and specificity of killing glioma tumors in mouse models by transducible tumor suppressor proteins, namely TAT-ARF and TAT-p53, and by a transducible pro-apoptotic viral protein, TATApoptin. TAT-fusion proteins will be analyzed and optimized in vitro and then tested against xenograft intracranial glioma tumors in nude mice and in de novo derived astrocytomas in B8 transgenic ras about2" mice. In addition, to quantify protein transduction potential in mouse models, we intend to analyze the transduction and refolding rates of TAT-reporter fusion proteins, including TAT-B-gal and TAT-TK. TATTK activity will also be monitored in vivo by microPET imaging using '8Ffluoroganciclovir as a positron emitter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TSC REGULATION OF ASTROCYTE GROWTH AND TUMOR DEVELOPMENT Principal Investigator & Institution: Uhlman, Erik J.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-DEC-2001 Summary: Individuals affected with tuberous sclerosis complex (TSC) develop subependymal giant cell astrocytomas, suggesting that the TSC gene products, hamartin and tuberin, function as a negative growth regulators for astrocytes. In this proposal, we plan to critically test the hypothesis that hamartin and tuberin regulate astrocyte growth and prevent astrocytoma formation. Previously, we have demonstrated that loss of tuberin is associated with brain tumor formation and that both reduced expression of tuberin and hamartin result in increased astrocyte growth in vivo. Specifically, we plan to determine whether (1) absent TSC expression is astrocytes results in increased astrocyte proliferation and tumor formation in vitro and in vivo and (2) tuberin and hamartin regulate astrocyte cell growth in a rap 1- and p27-Kipl-dependent fashion. These studies are aimed at understanding how tuberin and hamartin function as growth regulators for astrocytes relevant to tumor formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ZD1839 THERAPY OF GLIOBLASTOMA MULTIFORME Principal Investigator & Institution: Friedman, Henry S.; Professor; Surgery; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Provided by applicant): Despite decades of intensive nervous system (CNS) neoplasms remains very poor. Median survival for adults with the most common form of CNS tumor, the cerebral glioblastoma, is 8-12 months after diagnosis. Occasional responses to single or multiple agent chemotherapy are seen in the setting of recurrent tumor, but these responses are generally of short duration, and cures are rare. Identification of agents active against glial malignancies is challenging, with no drug tested to date reliably producing responses in a majority of treated patients. Gene amplification, related to increasing grade of glioma malignancy, has been found to occur in approximately 50 percent of all glioblastoma multiforme (GBM) cases. Although amplification of N-myc and gli (2-4 percent overall) has been reported by different groups, amplification of these genes and c-myc or K-ras are considered sporadic as compared to the amplification of c-erb 1, or the epidermal growth factor (EGFR) gene. The EGFR gene, 110 kb in size, 26 exons in organization, is localized to chromosome arm

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7pll-13. Beginning with the initial description of EGFR gene amplification by Libermann et al (1985), subsequent studies have confirmed that approximately 37-58 percent of GBMs, but only isolated anaplastic astrocytomas, amplify the EGFR gene. ZD 1839 is a potent inhibitor in vitro of EGFR tyrosine kinase, competitive with ATP, and noncompetitive with peptide substrate. ZD 1839 inhibits the proliferation of EGFstimulated KB oral squamous carcinoma cells. This effect is readily reversible on removal of the compound. Enzyme inhibition appears to be selective, with little activity against other kinases tested. Growth inhibition in vivo of a wide variety of human tumour xenograft models in nude mice was demonstrated at a range of once daily, oral doses between 12.5 and 200 mg/kg per day for up to 4 months. In some already established tumours treatment with ZD 1839 produced significant regressions. From the xenograft studies, it is not yet clear if there is a correlation between the level of EGFR expression and antitumor response. The specific aims of this proposal are: 1) To identify the activity and toxicity of ZD 1839 in the treatment of adults with glioblastoma multiforme in first relapse; 2) to determine if qualitative and quantitative levels of genotypic and phenotypic EGFR expression predict response of GBM to ZD 1839. 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 “astrocytomas” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for astrocytomas in the PubMed Central database: •

Amyloid [beta] Peptide Potentiates Cytokine Secretion by Interleukin-1 [beta]Activated Human Astrocytoma Cells. by Gitter BD, Cox LM, Rydel RE, May PC.; 1995 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40687

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An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein. by Leis JF, Kaplan NO.; 1982 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347156

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Astrocyte-Specific Inactivation of the Neurofibromatosis 1 Gene (NF1) Is Insufficient for Astrocytoma Formation. by Bajenaru ML, Zhu Y, Hedrick NM, Donahoe J, Parada LF, Gutmann DH.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139771

3 4

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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Calcium and microtubule dependence for increased ornithine decarboxylase activity stimulated by [beta]-adrenergic agonists, dibutyryl cyclic AMP, or serum in a rat astrocytoma cell line. by Gibbs JB, Hsu CY, Terasaki WL, Brooker G.; 1980 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348410

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Cell surface antigens of human astrocytoma defined by mouse monoclonal antibodies: identification of astrocytoma subsets. by Cairncross JG, Mattes MJ, Beresford HR, Albino AP, Houghton AN, Lloyd KO, Old LJ.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346960

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Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance. by Maxwell M, Naber SP, Wolfe HJ, Galanopoulos T, Hedley-Whyte ET, Black PM, Antoniades HN.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296700

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Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells. by Post GR, Collins LR, Kennedy ED, Moskowitz SA, Aragay AM, Goldstein D, Brown JH.; 1996 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276018

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Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines. by Spehar T, Strand M.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237046

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Cytomegalovirus-mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene. by Ripalti A, Boccuni MC, Campanini F, Landini MP.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188870

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Differences in the interactions of Nocardia asteroides with macrophage, endothelial, and astrocytoma cell lines. by Beaman L, Beaman BL.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186407

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Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. by Shamah SM, Stiles CD, Guha A.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=364790

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Downregulation of endothelin receptor mRNA synthesis in C6 rat astrocytoma cells by persistent measles virus and canine distemper virus infections. by Meissner NN, Koschel K.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189344

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Expression of the somatostatin gene in human astrocytoma cell lines. by Mercure L, Tannenbaum GS, Schipper HM, Phaneuf D, Wainberg MA.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170265

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Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. by Konnikova L, Kotecki M, Kruger MM, Cochran BH.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=212316

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Measles Virus-Induced Disruption of the Glial-Fibrillary-Acidic Protein Cytoskeleton in an Astrocytoma Cell Line (U-251). by Duprex WP, McQuaid S, Rima BK.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111896

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Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells. by Mallorga P, Tallman JF, Henneberry RC, Hirata F, Strittmatter WT, Axelrod J.; 1980 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348490

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Observation of Measles Virus Cell-to-Cell Spread in Astrocytoma Cells by Using a Green Fluorescent Protein-Expressing Recombinant Virus. by Duprex WP, McQuaid S, Hangartner L, Billeter MA, Rima BK.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112991

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Owl monkey astrocytoma cells in culture spontaneously produce infectious JC virus which demonstrates altered biological properties. by Major EO, Vacante DA, Traub RG, London WT, Sever JL.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=254120

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Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages. by Muscoli C, Salvemini D, Paolino D, Iannone M, Palma E, Cufari A, Rotiroti D, Perno CF, Aquaro S, Mollace V.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129984

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Regulation of Adenosine 3[prime prime or minute]:5[prime prime or minute]-Cyclic Monophosphate Concentration in Cultured Human Astrocytoma Cells by Catecholamines and Histamine. by Clark RB, Perkins JP.; 1971 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=389518

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Regulation of nerve growth factor biosynthesis by beta-adrenergic receptor activation in astrocytoma cells: a potential role of c-Fos protein. by Mocchetti I, De Bernardi MA, Szekely AM, Alho H, Brooker G, Costa E.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287247

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Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. by Neumann M, Felber BK, Kleinschmidt A, Froese B, Erfle V, Pavlakis GN, Brack-Werner R.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188884

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Retrieval of Human Cytomegalovirus Glycoprotein B from Cell Surface Is Not Required for Virus Envelopment in Astrocytoma Cells. by Jarvis MA, Fish KN, Soderberg-Naucler C, Streblow DN, Meyers HL, Thomas G, Nelson JA.; 2002 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136176

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The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-[kappa]B Consensus Sites. by Lim SP, Garzino-Demo A.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111637

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Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Induces CaspaseDependent Interleukin-8 Expression and Apoptosis in Human Astroglioma Cells. by Choi C, Kutsch O, Park J, Zhou T, Seol DW, Benveniste EN.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133544

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. To generate your own bibliography of studies dealing with astrocytomas, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “astrocytomas” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for astrocytomas (hyperlinks lead to article summaries): •

A comparative immunohistochemistry of O6-methylguanine-DNA methyltransferase and p53 in diffusely infiltrating astrocytomas. Author(s): Yuan Q, Matsumoto K, Nakabeppu Y, Iwaki T. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2003 September; 23(3): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570288

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A comparison of two planning techniques for radiotherapy of high grade astrocytomas. Author(s): Crosby TD, Melcher AA, Wetherall S, Brockway S, Burnet NG. Source: Clin Oncol (R Coll Radiol). 1998; 10(6): 392-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890542

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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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A review of current and future treatment strategies for malignant astrocytomas in adults. Author(s): Nieder C, Nestle U. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2000 June; 176(6): 251-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10897251

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Aberrant localization of the neuronal class III beta-tubulin in astrocytomas. Author(s): Katsetos CD, Del Valle L, Geddes JF, Assimakopoulou M, Legido A, Boyd JC, Balin B, Parikh NA, Maraziotis T, de Chadarevian JP, Varakis JN, Matsas R, Spano A, Frankfurter A, Herman MM, Khalili K. Source: Archives of Pathology & Laboratory Medicine. 2001 May; 125(5): 613-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300931

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Aberrant methylation of genes in low-grade astrocytomas. Author(s): Costello JF, Plass C, Cavenee WK. Source: Brain Tumor Pathol. 2000; 17(2): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11210171

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Accelerated fractionation for high-grade cerebral astrocytomas. Preliminary treatment results. Author(s): Shenouda G, Souhami L, Freeman CR, Hazel J, Lehnert S, Joseph L. Source: Cancer. 1991 May 1; 67(9): 2247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2013030

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Accelerated hyperfractionated radiotherapy in supratentorial malignant astrocytomas. Author(s): Genc M, Zorlu AF, Atahan IL. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2000 August; 56(2): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10927143

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Accumulation of p53 and Ki-67 expression do not predict survival in patients with fibrillary astrocytomas or the response of these tumors to radiotherapy. Author(s): Mastronardi L, Puzzilli F, Guiducci A. Source: Neurosurgery. 1998 December; 43(6): 1496. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848870

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Adult brain low-grade astrocytomas: survival after surgery and radiotherapy. Author(s): Arienti VM, Botturi A, Boiardi A, Broggi G, Collice M, Fariselli L, Zanni D, Botturi M. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2001 June; 22(3): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731876

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Adult patients with supratentorial pilocytic astrocytomas: a prospective multicenter clinical trial. Author(s): Brown PD, Buckner JC, O'Fallon JR, Iturria NL, Brown CA, O'Neill BP, Scheithauer BW, Dinapoli RP, Arusell RM, Abrams RA, Curran WJ, Shaw EG; North Central Cancer Treatment Group; Mayo Clinic. Source: International Journal of Radiation Oncology, Biology, Physics. 2004 March 15; 58(4): 1153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001258

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AgNOR staining may reflect the growth potential of pilocytic astrocytomas. Author(s): Dirven CM, Koudstaal J, Mooij JA, Molenaar WM. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 August; 15(8): 384-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10447607

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Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. Author(s): Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 February; 18(3): 636-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10653879

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Analysis of cyclin dependent kinase inhibitors in malignant astrocytomas. Author(s): Alleyne CH Jr, He J, Yang J, Hunter SB, Cotsonis G, James CD, Olson JJ. Source: International Journal of Oncology. 1999 June; 14(6): 1111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10339666

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Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. Author(s): Raffel C, Frederick L, O'Fallon JR, Atherton-Skaff P, Perry A, Jenkins RB, James CD. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 December; 5(12): 4085-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632344

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Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults. Author(s): Nakamura M, Konishi N, Tsunoda S, Nakase H, Tsuzuki T, Aoki H, Sakitani H, Inui T, Sakaki T. Source: Oncology. 2000 February; 58(2): 108-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10705237

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AP-1 and heat shock protein 27 expression in human astrocytomas. Author(s): Assimakopoulou M, Varakis J. Source: Journal of Cancer Research and Clinical Oncology. 2001 December; 127(12): 72732. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768612

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Apoptosis and survival in high-grade astrocytomas as related to tumor Fas (APO1/CD95) expression. Author(s): Frankel B, Longo SL, Leach C, Canute GW, Ryken TC. Source: Journal of Neuro-Oncology. 2002 August; 59(1): 27-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222835

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Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. Author(s): Vital A, Bringuier PP, Huang H, San Galli F, Rivel J, Ansoborlo S, Cazauran JM, Taillandier L, Kleihues P, Ohgaki H. Source: Journal of Neuropathology and Experimental Neurology. 1998 November; 57(11): 1061-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825943

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Astrocytomas of the cerebral peduncle in children: surgical experience in seven patients. Author(s): Tomita T, Cortes RF. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 May; 18(5): 225-30. Epub 2002 April 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042921

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Astrocytomas: the clinical picture. Author(s): Strickler R, Phillips ML. Source: Clinical Journal of Oncology Nursing. 2000 July-August; 4(4): 153-8. Review. Erratum In: Clin J Oncol Nurs 2001 January-February; 5(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261094

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Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. Author(s): Morrison RS, Yamaguchi F, Saya H, Bruner JM, Yahanda AM, Donehower LA, Berger M. Source: Journal of Neuro-Oncology. 1994; 18(3): 207-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7964981

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bcl-2 protein expression in astrocytomas in relation to patient survival and p53 gene status. Author(s): Newcomb EW, Bhalla SK, Parrish CL, Hayes RL, Cohen H, Miller DC. Source: Acta Neuropathologica. 1997 October; 94(4): 369-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9341939

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BCNU solubility and toxicity in the treatment of malignant astrocytomas. Author(s): Layton PB, Greenberg HS, Stetson PL, Ensminger WD, Gyves JW. Source: Journal of Neurosurgery. 1984 June; 60(6): 1134-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6726357

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BCNU treatment of astrocytomas: erratum. Author(s): Layton PB. Source: Journal of Neurosurgery. 1984 September; 61(3): 621. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6747712

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BCNU-DBD (Dibromodulcitol) chemotherapy of recurrent supratentorial anaplastic astrocytomas and glioblastomas. Author(s): Vitanovics D, Sipos L, Afra D. Source: Neoplasma. 2002; 49(5): 342-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458335

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Benign cerebellar astrocytomas in children. Author(s): Pencalet P, Maixner W, Sainte-Rose C, Lellouch-Tubiana A, Cinalli G, Zerah M, Pierre-Kahn A, Hoppe-Hirsch E, Bourgeois M, Renier D. Source: Journal of Neurosurgery. 1999 February; 90(2): 265-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9950497

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Benign cerebellar astrocytomas of childhood. Author(s): Schneider JH Jr, Raffel C, McComb JG. Source: Neurosurgery. 1992 January; 30(1): 58-62; Discussion 62-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1738456

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Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. Author(s): Kim SK, Wang KC, Cho BK, Jung HW, Lee YJ, Chung YS, Lee JY, Park SH, Kim YM, Choe G, Chi JG. Source: Journal of Neuro-Oncology. 2001 May; 52(3): 217-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519851

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Biological evaluation of biopsies from adult cerebral astrocytomas: cell-growth/cellsuicide ratios and their relationship to patient survival. Author(s): Rhodes RH. Source: Journal of Neuropathology and Experimental Neurology. 1998 August; 57(8): 746-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9720490

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Biopsy of low-grade astrocytomas. Author(s): Bernstein M, Guha A. Source: Journal of Neurosurgery. 1994 April; 80(4): 776-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8151367

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Biosynthesized products of cultured neuroglial cells: I. Selective release of proteins by cells from human astrocytomas. Author(s): McKeever PE, Quindlen E, Banks MA, Williams U, Kornblith PL, Laverson S, Greenwood MA, Smith B. Source: Neurology. 1981 November; 31(11): 1445-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7031502

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Brachytherapy and hyperthermia for malignant astrocytomas. Author(s): Sneed PK, Larson DA, Gutin PH. Source: Seminars in Oncology. 1994 April; 21(2): 186-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8153664

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Brain astrocytomas and their derivatives. Author(s): Escalona-Zapata J. Source: Pathologica. 1981 January-February; 73(1023): 134-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7312423

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Brain astrocytomas: biopsy, then irradiation. Author(s): Lunsford LD, Somaza S, Kondziolka D, Flickinger JC. Source: Clin Neurosurg. 1995; 42: 464-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846611

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Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas. Author(s): Li J, Perry A, James CD, Gutmann DH. Source: Neurology. 2001 April 10; 56(7): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294925

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Cerebellar astrocytomas: a 24-year experience. Author(s): Viano JC, Herrera EJ, Suarez JC. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2001 October; 17(10): 607-10; Discussion 611. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685523

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Cerebral granular cell astrocytomas: a Mib-1, bcl-2, and telomerase study. Author(s): Chorny JA, Evans LC, Kleinschmidt-DeMasters BK. Source: Clin Neuropathol. 2000 July-August; 19(4): 170-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919348

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Cervicomedullary astrocytomas of childhood: clinical and imaging follow-up. Author(s): Young Poussaint T, Yousuf N, Barnes PD, Anthony DC, Zurakowski D, Scott RM, Tarbell NJ. Source: Pediatric Radiology. 1999 September; 29(9): 662-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460326

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Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy. Author(s): Arnold DL, Emrich JF, Shoubridge EA, Villemure JG, Feindel W. Source: Journal of Neurosurgery. 1991 March; 74(3): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1993910

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Clinicopathological analysis of pilocytic astrocytomas and gangliogliomas in children. Author(s): Fiks T, Jesionek-Kupnicka D, Zakrzewski K, Polis L, Liberski PP. Source: Folia Neuropathol. 1999; 37(3): 152-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10581849

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Clinico-pathological analysis of pilocytic astrocytomas and gangliogliomas. Author(s): Fiks T, Jesionek-Kupnicka D, Zakrzewski K, Polis L, Liberski PP. Source: Pol J Pathol. 2001; 52(1-2): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11505680

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Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas. Author(s): Gutmann DH, Hedrick NM, Li J, Nagarajan R, Perry A, Watson MA. Source: Cancer Research. 2002 April 1; 62(7): 2085-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929829

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Comparison between mitochondrial DNA sequences in low grade astrocytomas and corresponding blood samples. Author(s): Kirches E, Krause G, Weis S, Mawrin C, Dietzmann K. Source: Molecular Pathology : Mp. 2002 June; 55(3): 204-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032233

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Comparison of MR spectroscopy and MR imaging with contrast agent in children with cerebral astrocytomas. Author(s): Dezortova M, Hajek M, Cap F, Babis M, Tichy M, Vymazal J. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 August; 15(8): 408-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10447614

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Complete surgical resection in children with low-grade astrocytomas after neoadjuvant chemotherapy. Author(s): Valera ET, Serafini LN, Machado HR, Tone LG. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 February; 19(2): 86-90. Epub 2003 February 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607025

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Computer- and robot-assisted resection of thalamic astrocytomas in children. Author(s): Drake JM, Joy M, Goldenberg A, Kreindler D. Source: Neurosurgery. 1991 July; 29(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1870684

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Conformal proton radiation therapy for pediatric low-grade astrocytomas. Author(s): Hug EB, Muenter MW, Archambeau JO, DeVries A, Liwnicz B, Loredo LN, Grove RI, Slater JD. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2002 January; 178(1): 10-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977386

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Correlation of bFGF, FGFR-1 and VEGF expression with vascularity and malignancy of human astrocytomas. Author(s): Bian XW, Du LL, Shi JQ, Cheng YS, Liu FX. Source: Anal Quant Cytol Histol. 2000 June; 22(3): 267-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10872046

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Correlation of myo-inositol levels and grading of cerebral astrocytomas. Author(s): Castillo M, Smith JK, Kwock L. Source: Ajnr. American Journal of Neuroradiology. 2000 October; 21(9): 1645-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11039343

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Correlation of the expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1 (TNFR 1) and c-Myc with the clinical course in the treatment of malignant astrocytomas with recombinant mutant human tumor necrosis factor-alpha (TNFSAM2). Author(s): Yamamoto M, Fukushima T, Hayashi S, Ikeda K, Tsugu H, Kimura H, Soma G, Tomonaga M. Source: Anticancer Res. 2000 January-February; 20(1C): 611-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10769704

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C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting with a new gastrin binding site. Author(s): Pannequin J, Oiry C, Morel C, Kucharczak J, Camby I, Kiss R, Gagne D, Galleyrand JC, Martinez J. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 July; 302(1): 274-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065727

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Cyclooxygenase-2, Bcl-2, and chromosome 1p analysis in protoplasmic astrocytomas. Author(s): Prayson RA. Source: Human Pathology. 2004 March; 35(3): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017587

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Cytogenetics in pediatric low-grade astrocytomas. Author(s): Orr LC, Fleitz J, McGavran L, Wyatt-Ashmead J, Handler M, Foreman NK. Source: Medical and Pediatric Oncology. 2002 March; 38(3): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836716

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Deletion of chromosome arm 17p DNA sequences in pediatric high-grade and juvenile pilocytic astrocytomas. Author(s): Willert JR, Daneshvar L, Sheffield VC, Cogen PH. Source: Genes, Chromosomes & Cancer. 1995 March; 12(3): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7536455

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Deregulation of the TP53/p14ARF tumor suppressor pathway in low-grade diffuse astrocytomas and its influence on clinical course. Author(s): Watanabe T, Katayama Y, Yoshino A, Komine C, Yokoyama T. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 October 15; 9(13): 4884-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581362

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Detection of a novel point mutation in the p53 gene in grade II astrocytomas by PCRSSCP analysis with additional Klenow treatment. Author(s): Chawengchao B, Petmitr S, Ponglikitmongkol M, Chanyavanich V, Sangruji T, Theerapuncharoen V, Hayashi K, Thangnipon W. Source: Anticancer Res. 2001 July-August; 21(4A): 2739-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11724349

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Detection of apoptotic cells in archival tissue from diffuse astrocytomas using a monoclonal antibody to single-stranded DNA. Author(s): Korkolopoulou PA, Konstantinidou AE, Patsouris ES, Christodoulou PN, Thomas-Tsagli EA, Davaris PS. Source: The Journal of Pathology. 2001 March; 193(3): 377-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241419

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Detection of chromosomal changes by interphase cytogenetics in biopsies of recurrent astrocytomas and oligodendrogliomas. Author(s): Rosso SM, van Dekken H, Krishnadath KK, Alers JC, Kros JM. Source: Journal of Neuropathology and Experimental Neurology. 1997 October; 56(10): 1125-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9329456

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Detection of TNF inhibitors (soluble receptors) in the sera and tumor cyst fluid of patients with malignant astrocytomas of the brain. Author(s): Ammirato M, Rao S, Granger G. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2001 October 1; 6: B17-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11578951

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Diagnosis and management of astrocytomas, oligodendrogliomas and mixed gliomas: a review. Author(s): Walker DG, Kaye AH. Source: Australasian Radiology. 2001 November; 45(4): 472-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903181

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Diagnostic and prognostic role of Ki67 immunostaining in human astrocytomas using four different antibodies. Author(s): Torp SH. Source: Clin Neuropathol. 2002 November-December; 21(6): 252-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489673

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Diagnostic difficulties in childhood bilateral thalamic astrocytomas. Author(s): Gudowius S, Engelbrecht V, Messing-Junger M, Reifenberger G, Gartner J. Source: Neuropediatrics. 2002 December; 33(6): 331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571791

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Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Author(s): Perilongo G, Carollo C, Salviati L, Murgia A, Pillon M, Basso G, Gardiman M, Laverda A. Source: Cancer. 1997 July 1; 80(1): 142-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9210720

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Differences in vasculature between pilocytic and anaplastic astrocytomas of childhood. Author(s): Gesundheit B, Klement G, Senger C, Kerbel R, Kieran M, Baruchel S, Becker L. Source: Medical and Pediatric Oncology. 2003 December; 41(6): 516-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595708

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Differential expression between pilocytic and anaplastic astrocytomas: identification of apolipoprotein D as a marker for low-grade, non-infiltrating primary CNS neoplasms. Author(s): Hunter S, Young A, Olson J, Brat DJ, Bowers G, Wilcox JN, Jaye D, Mendrinos S, Neish A. Source: Journal of Neuropathology and Experimental Neurology. 2002 March; 61(3): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895042

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Differential expression of sst1, sst2A, and sst3 somatostatin receptor proteins in lowgrade and high-grade astrocytomas. Author(s): Mawrin C, Schulz S, Pauli SU, Treuheit T, Diete S, Dietzmann K, Firsching R, Schulz S, Hollt V. Source: Journal of Neuropathology and Experimental Neurology. 2004 January; 63(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748557

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Differential expression of tenascin-C and tenascin-X in human astrocytomas. Author(s): Hasegawa K, Yoshida T, Matsumoto K, Katsuta K, Waga S, Sakakura T. Source: Acta Neuropathologica. 1997 May; 93(5): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9144580

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Differentiation of glioblastoma multiforme from astrocytomas by in vitro 1H MRS analysis of human brain tumors. Author(s): Carpinelli G, Carapella CM, Palombi L, Raus L, Caroli F, Podo F. Source: Anticancer Res. 1996 May-June; 16(3B): 1559-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8694526

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Diffuse bilateral thalamic astrocytomas as examined serially by MRI. Author(s): Yoshida M, Fushiki S, Takeuchi Y, Takanashi M, Imamura T, Shikata T, Morimoto A, Konishi K, Miyazaki A, Sawada T. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 August; 14(8): 384-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753406

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Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastomas. Author(s): Camby I, Decaestecker C, Gordower L, DeDecker R, Kacem Y, Lemmers A, Siebert HC, Bovin NV, Wesseling P, Danguy A, Salmon I, Gabius HJ, Kiss R. Source: Journal of Neuropathology and Experimental Neurology. 2001 January; 60(1): 75-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11202177

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Distinct pattern of PCR-SSCP analysis of p53 mutations in human astrocytomas. Author(s): Thangnipon W, Mizoguchi M, Kukita Y, Inazuka M, Iwaki T, Fukui M, Hayashi K. Source: Cancer Letters. 1999 July 1; 141(1-2): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10454262

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DNA ploidy and S-phase in recurrent astrocytomas: a retrospective study by flow cytometry of deparaffinized specimens. Author(s): Vavruch L, Nordenskjold B, Carstensen J, Enestrom S. Source: Journal of Neuro-Oncology. 1996 October; 30(1): 37-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865001

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Dynamic contrast-enhanced MRI: differentiating melanoma and renal carcinoma metastases from high-grade astrocytomas and other metastases. Author(s): Kremer S, Grand S, Berger F, Hoffmann D, Pasquier B, Remy C, Benabid AL, Bas JF. Source: Neuroradiology. 2003 January; 45(1): 44-9. Epub 2002 December 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525954

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Early genetic events in the formation of astrocytomas. Author(s): Henson JW. Source: Current Opinion in Neurology. 2000 December; 13(6): 613-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11148659

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Early mental changes in patients with astrocytomas with special reference to anxiety and epilepsy. Author(s): Lilja A, Salford LG. Source: Psychopathology. 1997; 30(6): 316-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9444700

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Early outcomes after stereotactic radiosurgery for growing pilocytic astrocytomas in children. Author(s): Somaza SC, Kondziolka D, Lunsford LD, Flickinger JC, Bissonette DJ, Albright AL. Source: Pediatric Neurosurgery. 1996 September; 25(3): 109-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9144708

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Effect of surgery on tumor progression and malignant degeneration in hemispheric diffuse low-grade astrocytomas. Author(s): Kilic T, Ozduman K, Elmaci I, Sav A, Necmettin Pamir M. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 September; 9(5): 549-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383413

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EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas. Author(s): Varela M, Ranuncolo SM, Morand A, Lastiri J, De Kier Joffe EB, Puricelli LI, Pallotta MG. Source: Journal of Surgical Oncology. 2004 April 1; 86(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15048678

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Epigenetic changes in pilocytic astrocytomas and medulloblastomas. Author(s): Gonzalez-Gomez P, Bello MJ, Lomas J, Arjona D, Alonso ME, Aminoso C, De Campos JM, Vaquero J, Sarasa JL, Casartelli C, Rey JA. Source: International Journal of Molecular Medicine. 2003 May; 11(5): 655-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684707

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Epigenetics in high-grade astrocytomas: opportunities for prevention and detection of brain tumors. Author(s): Debinski W, Gibo D, Mintz A. Source: Annals of the New York Academy of Sciences. 2003 March; 983: 232-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724228

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Evaluation of molecular markers in low-grade diffuse astrocytomas: loss of p16 and retinoblastoma protein expression is associated with short survival. Author(s): Hilton DA, Penney M, Evans B, Sanders H, Love S. Source: The American Journal of Surgical Pathology. 2002 April; 26(4): 472-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914625

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Evidence for a high free radical state in low-grade astrocytomas. Author(s): Louw DF, Bose R, Sima AA, Sutherland GR. Source: Neurosurgery. 1997 November; 41(5): 1146-50; Discussion 1151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9361070

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Exophytic juvenile pilocytic astrocytomas of the posterior fossa. Author(s): Martin DS, Geller TJ, Falbo S, Pittman T. Source: Journal of Child Neurology. 2000 April; 15(4): 262-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10805195

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Expression and activation of signal regulatory protein alpha on astrocytomas. Author(s): Chen TT, Brown EJ, Huang EJ, Seaman WE. Source: Cancer Research. 2004 January 1; 64(1): 117-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729615

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Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas. Author(s): Ulbricht U, Brockmann MA, Aigner A, Eckerich C, Muller S, Fillbrandt R, Westphal M, Lamszus K. Source: Journal of Neuropathology and Experimental Neurology. 2003 December; 62(12): 1265-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692702

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Expression and hypoxic regulation of angiopoietins in human astrocytomas. Author(s): Ding H, Roncari L, Wu X, Lau N, Shannon P, Nagy A, Guha A. Source: Neuro-Oncology. 2001 January; 3(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11305411

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Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas. Author(s): Kunkel P, Muller S, Schirmacher P, Stavrou D, Fillbrandt R, Westphal M, Lamszus K. Source: Neuro-Oncology. 2001 April; 3(2): 82-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296484

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Expression and regulation of neuropilin-1 in human astrocytomas. Author(s): Ding H, Wu X, Roncari L, Lau N, Shannon P, Nagy A, Guha A. Source: International Journal of Cancer. Journal International Du Cancer. 2000 November 15; 88(4): 584-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11058875

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Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: specific increase in interleukin-6 mRNA expression. Author(s): Sayah S, Ischenko AM, Zhakhov A, Bonnard AS, Fontaine M. Source: Journal of Neurochemistry. 1999 June; 72(6): 2426-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10349852

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Expression of fascin, an actin-bundling protein, in astrocytomas of varying grades. Author(s): Peraud A, Mondal S, Hawkins C, Mastronardi M, Bailey K, Rutka JT. Source: Brain Tumor Pathol. 2003; 20(2): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756441

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Expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1, and c-Myc in human astrocytomas. Author(s): Hayashi S, Yamamoto M, Ueno Y, Ikeda K, Ohshima K, Soma G, Fukushima T. Source: Neurol Med Chir (Tokyo). 2001 April; 41(4): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11381677

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Expression of p57(KIP2) potently blocks the growth of human astrocytomas and induces cell senescence. Author(s): Tsugu A, Sakai K, Dirks PB, Jung S, Weksberg R, Fei YL, Mondal S, Ivanchuk S, Ackerley C, Hamel PA, Rutka JT. Source: American Journal of Pathology. 2000 September; 157(3): 919-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980131

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Expression of the Ets-1 transcription factor in human astrocytomas is associated with Fms-like tyrosine kinase-1 (Flt-1)/vascular endothelial growth factor receptor-1 synthesis and neoangiogenesis. Author(s): Valter MM, Hugel A, Huang HJ, Cavenee WK, Wiestler OD, Pietsch T, Wernert N. Source: Cancer Research. 1999 November 1; 59(21): 5608-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10554042

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Failure of accelerated neutron therapy to control high grade astrocytomas. Author(s): Saroja KR, Mansell J, Hendrickson FR, Cohen L, Lennox A. Source: International Journal of Radiation Oncology, Biology, Physics. 1989 December; 17(6): 1295-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2557308

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False-negative CT in astrocytomas. Author(s): Weintraub MI. Source: Neurology. 1983 May; 33(5): 671. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6682512

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False-negative CTs in astrocytomas: the value of repeat scanning. Author(s): Wulff JD, Proffitt PQ, Panszi JG, Ziegler DK. Source: Neurology. 1982 July; 32(7): 766-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6283426

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Familial clustering of malignant astrocytomas. Author(s): Lossignol D, Grossman SA, Sheidler VR, Griffin CA, Piantadosi S. Source: Journal of Neuro-Oncology. 1990 October; 9(2): 139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2175769

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Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? Author(s): Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Source: In Vivo. 1999 July-August; 13(4): 357-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586378

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Fast neutron and mixed (neutron/photon) beam teletherapy for grades III and IV astrocytomas. Author(s): Laramore GE, Griffin TW, Gerdes AJ, Parker RG. Source: Cancer. 1978 July; 42(1): 96-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=96933

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Fast neutron boost for the treatment of grade IV astrocytomas. Author(s): Breteau N, Destembert B, Favre A, Pheline C, Schlienger M. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 1989 April; 165(4): 320-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2540541

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Fast neutron therapy for malignant astrocytomas. A review. Author(s): Kurup PD, Pajak TF, Nelson JS, Mansell J, Hendrickson FR, Cohen L, Griffin TW. Source: Journal of Neuro-Oncology. 1986; 4(2): 123-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3537221

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Fast neutrons and misonidazole for malignant astrocytomas. Author(s): Kurup PD, Pajak TF, Hendrickson FR, Nelson JS, Mansell J, Cohen L, Awschalom M, Rosenberg I, Ten Haken RK. Source: International Journal of Radiation Oncology, Biology, Physics. 1985 April; 11(4): 679-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2984151

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Fast neutrons in the treatment of grade IV astrocytomas. Author(s): Breteau N, Schlienger M, Favre A, Lescrainier J, Touboul E, Stecken J, Heitzmann A. Source: Bulletin Du Cancer. Radiotherapie : Journal De La Societe Francaise Du Cancer : Organe De La Societe Francaise De Radiotherapie Oncologique. 1996; 83 Suppl: 135S41S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8949766

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Ferritin in astrocytomas. Author(s): Liu YF, Li Q, Yang P, Wang WL, Liu JA. Source: Chinese Medical Journal. 1991 April; 104(4): 326-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1648465

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Fibroblast growth factor receptor (FGFR) 4 correlated with the malignancy of human astrocytomas. Author(s): Yamada SM, Yamada S, Hayashi Y, Takahashi H, Teramoto A, Matsumoto K. Source: Neurological Research. 2002 April; 24(3): 244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958417

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Fibronectin in human astrocytomas grown in tissue culture. Author(s): Sherbet GV, Tindle ME, Stidolph S. Source: Anticancer Res. 1982 July-August; 2(4): 251-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6293369

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Flow cytometric analysis of cellular DNA content in human astrocytomas and oligodendrogliomas. Author(s): Ahyai A. Source: Neurosurgical Review. 1988; 11(2): 177-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3244416

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Flowcytometric and cytogenetic analysis of human cultured cell lines derived from high- and low-grade astrocytomas. Author(s): Shitara N, McKeever PE, Whang-Peng J, Knutsen T, Smith BH, Kornblith PL. Source: Acta Neuropathologica. 1983; 60(1-2): 40-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6880621

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Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. Author(s): Edwards MS, Wara WM, Ciricillo SF, Barkovich AJ. Source: Journal of Neurosurgery. 1994 January; 80(1): 20-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8271016

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Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors. Author(s): Plathow C, Schulz-Ertner D, Thilman C, Zuna I, Lichy M, Weber MA, Schlemmer HP, Wannenmacher M, Debus J. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 November 15; 57(4): 996-1003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575830

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Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration. Author(s): Camby I, Belot N, Rorive S, Lefranc F, Maurage CA, Lahm H, Kaltner H, Hadari Y, Ruchoux MM, Brotchi J, Zick Y, Salmon I, Gabius HJ, Kiss R. Source: Brain Pathology (Zurich, Switzerland). 2001 January; 11(1): 12-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145198

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Gamma knife radiosurgery for low-grade astrocytomas: results of long-term follow up. Author(s): Kida Y, Kobayashi T, Mori Y. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 42-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11143261

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Gamma knife radiosurgery for pilocytic astrocytomas. Author(s): Boethius J, Ulfarsson E, Rahn T, Lippittz B. Source: Journal of Neurosurgery. 2002 December; 97(5 Suppl): 677-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507119

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Gangliosides as diagnostic markers of human astrocytomas and primitive neuroectodermal tumors. Author(s): Sung CC, Pearl DK, Coons SW, Scheithauer BW, Johnson PC, Yates AJ. Source: Cancer. 1994 December 1; 74(11): 3010-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7954264

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Gemistocytic astrocytomas: a reappraisal. Author(s): Krouwer HG, Davis RL, Silver P, Prados M. Source: Journal of Neurosurgery. 1991 March; 74(3): 399-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1993905

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Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. Author(s): Huang H, Colella S, Kurrer M, Yonekawa Y, Kleihues P, Ohgaki H. Source: Cancer Research. 2000 December 15; 60(24): 6868-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11156382

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Gene therapy for the treatment of recurrent pediatric malignant astrocytomas with in vivo tumor transduction with the herpes simplex thymidine kinase gene/ganciclovir system. Author(s): Raffel C, Culver K, Kohn D, Nelson M, Siegel S, Gillis F, Link CJ, Villablanca JG, Anderson WF. Source: Human Gene Therapy. 1994 July; 5(7): 863-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981311

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Genetic alterations in pediatric high-grade astrocytomas. Author(s): Cheng Y, Ng HK, Zhang SF, Ding M, Pang JC, Zheng J, Poon WS. Source: Human Pathology. 1999 November; 30(11): 1284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10571506

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Genetic and biologic progression in astrocytomas and their relation to angiogenic dysregulation. Author(s): Brat DJ, Castellano-Sanchez A, Kaur B, Van Meir EG. Source: Advances in Anatomic Pathology. 2002 January; 9(1): 24-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756757

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Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas. Author(s): Reis RM, Hara A, Kleihues P, Ohgaki H. Source: Acta Neuropathologica. 2001 November; 102(5): 422-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11699553

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Genetic heterogeneity in human astrocytomas: spatial distribution of P16 and TP53 deletions in biopsies. Author(s): Steilen-Gimbel H, Steudel WI, Feiden W, Moringlane JR, Henn W, Zang KD. Source: Cancer Genetics and Cytogenetics. 1999 September; 113(2): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10484976

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Genetic subgroups of anaplastic astrocytomas correlate with patient age and survival. Author(s): Kunwar S, Mohapatra G, Bollen A, Lamborn KR, Prados M, Feuerstein BG. Source: Cancer Research. 2001 October 15; 61(20): 7683-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11606412

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Genotype-phenotype correlation in gemistocytic astrocytomas. Author(s): Kosel S, Scheithauer BW, Graeber MB. Source: Neurosurgery. 2001 January; 48(1): 187-93; Discussion 193-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11152345

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Glycolipid markers of astrocytomas and oligodendrogliomas. Author(s): Yates AJ, Comas T, Scheithauer BW, Burger PC, Pearl DK. Source: Journal of Neuropathology and Experimental Neurology. 1999 December; 58(12): 1250-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10604750

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Grade II astrocytomas are subgrouped by chromosome aberrations. Author(s): Hirose Y, Aldape KD, Chang S, Lamborn K, Berger MS, Feuerstein BG. Source: Cancer Genetics and Cytogenetics. 2003 April 1; 142(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660025

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Grading and therapy monitoring of astrocytomas with 1H-spectroscopy: preliminary study. Author(s): Speck O, Thiel T, Hennig J. Source: Anticancer Res. 1996 May-June; 16(3B): 1581-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8694530

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Grading brain tumors other than astrocytomas. Author(s): Alvord EC Jr, Shaw CM. Source: Neurosurg Clin N Am. 1994 January; 5(1): 43-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8124093

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Grading of diffusely infiltrating astrocytomas by quantitative histopathology, cell proliferation and image cytometric DNA analysis. Comparison of 133 tumours in the context of the WHO 1979 and WHO 1993 grading schemes. Author(s): Sallinen PK, Sallinen SL, Helen PT, Rantala IS, Rautiainen E, Helin HJ, Kalimo H, Haapasalo HK. Source: Neuropathology and Applied Neurobiology. 2000 August; 26(4): 319-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931365

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Granular cell astrocytomas show a high frequency of allelic loss but are not a genetically defined subset. Author(s): Castellano-Sanchez AA, Ohgaki H, Yokoo H, Scheithauer BW, Burger PC, Hamilton RL, Finkelstein SD, Brat DJ. Source: Brain Pathology (Zurich, Switzerland). 2003 April; 13(2): 185-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744472

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Guanidinobenzoatase and UPA in high-grade human astrocytomas and after xenografting cell suspensions into the rat cerebral cortex: proteases for metastasis and disease progression. Author(s): Bernstein LJ, Tonn JC, Goldbrunner RH, Vince GH, Wagner S, Goldberg WJ. Source: Anticancer Res. 1998 July-August; 18(4A): 2583-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9703913

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High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin. Author(s): Albrecht KW, de Witt Hamer PC, Leenstra S, Bakker PJ, Beijnen JH, Troost D, Kaaijk P, Bosch AD. Source: Journal of Neuro-Oncology. 2001 July; 53(3): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718259

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High cyclin E/low p27Kip1 expression is associated with poor prognosis in astrocytomas. Author(s): Tamiya T, Mizumatsu S, Ono Y, Abe T, Matsumoto K, Furuta T, Ohmoto T. Source: Acta Neuropathologica. 2001 April; 101(4): 334-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11355304

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High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM1) in astrocytomas. Author(s): Araki K, Nozaki K, Ueba T, Tatsuka M, Hashimoto N. Source: Journal of Neuro-Oncology. 2004 March-April; 67(1-2): 53-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072448

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High frequency of p53 protein accumulation without p53 gene mutation in human juvenile pilocytic, low grade and anaplastic astrocytomas. Author(s): Lang FF, Miller DC, Pisharody S, Koslow M, Newcomb EW. Source: Oncogene. 1994 March; 9(3): 949-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8108140

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High frequency of TP53 mutations in juvenile pilocytic astrocytomas indicates role of TP53 in the development of these tumors. Author(s): Hayes VM, Dirven CM, Dam A, Verlind E, Molenaar WM, Mooij JJ, Hofstra RM, Buys CH. Source: Brain Pathology (Zurich, Switzerland). 1999 July; 9(3): 463-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416986

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High grade astrocytomas in children: Hartford Hospital experience. Author(s): Hall AJ, Wagle VG, Voytek T. Source: Conn Med. 1991 March; 55(3): 135-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1647288

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High-dose chemotherapy with autologous bone marrow transplantation in the treatment of high grade astrocytomas in adults: therapeutic rationale and clinical experience. Author(s): Fine HA, Antman KH. Source: Bone Marrow Transplantation. 1992 October; 10(4): 315-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1330152

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High-grade astrocytomas in children: radiologically complete resection is associated with an excellent long-term prognosis. Author(s): Campbell JW, Pollack IF, Martinez AJ, Shultz B. Source: Neurosurgery. 1996 February; 38(2): 258-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8869052

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High-grade astrocytomas. Author(s): Wen PY, Fine HA, Black PM, Shrieve DC, Alexander E 3rd, Loeffler JS. Source: Neurologic Clinics. 1995 November; 13(4): 875-900. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8584002

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High-grade astrocytomas: resource use, clinical outcomes, and cost of care. Author(s): Silverstein MD, Cascino TL, Harmsen WS. Source: Mayo Clinic Proceedings. 1996 October; 71(10): 936-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8820767

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High-throughput molecular profiling of high-grade astrocytomas: the utility of fluorescence in situ hybridization on tissue microarrays (TMA-FISH). Author(s): Fuller CE, Wang H, Zhang W, Fuller GN, Perry A. Source: Journal of Neuropathology and Experimental Neurology. 2002 December; 61(12): 1078-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484570

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Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. Author(s): Labrousse F, Daumas-Duport C, Batorski L, Hoshino T. Source: Journal of Neurosurgery. 1991 August; 75(2): 202-5. Erratum In: J Neurosurg 1992 March; 76(3): 563. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1649271

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Histologically confirmed changes on CT of reoperated low-grade astrocytomas. Author(s): Afra D, Osztie E. Source: Neuroradiology. 1997 November; 39(11): 804-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9406207

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Histone mRNA in-situ hybridization in astrocytomas: a comparison with PCNA, MIB-1 and mitoses in paraffin-embedded material. Author(s): Rautiainen E, Haapasalo H, Sallinen P, Rantala I, Helen P, Helin H. Source: Histopathology. 1998 January; 32(1): 43-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9522215

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HLA-Dr expression by tumor cells compared with survival in high grade astrocytomas. Author(s): Rossi ML, Jones NR, Karr GF, Esiri MM, Havas L, Coakham HB. Source: Tumori. 1991 April 30; 77(2): 122-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1646510

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Homozygous deletions of the multiple tumor suppressor gene 1 in the progression of human astrocytomas. Author(s): Walker DG, Duan W, Popovic EA, Kaye AH, Tomlinson FH, Lavin M. Source: Cancer Research. 1995 January 1; 55(1): 20-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7805033

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Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. Author(s): Desbaillets I, Tada M, de Tribolet N, Diserens AC, Hamou MF, Van Meir EG. Source: International Journal of Cancer. Journal International Du Cancer. 1994 July 15; 58(2): 240-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7517920

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Human astrocytomas co-expressing Fas and Fas ligand also produce TGFbeta2 and Bcl-2. Author(s): Frankel B, Longo SL, Ryken TC. Source: Journal of Neuro-Oncology. 1999; 44(3): 205-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10720200

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Human-specific c-neu proto-oncogene protein overexpression in human malignant astrocytomas before and after xenografting. Author(s): Bernstein JJ, Anagnostopoulos AV, Hattwick EA, Laws ER Jr. Source: Journal of Neurosurgery. 1993 February; 78(2): 240-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8093625

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Identification of allelic loss on chromosome arm 6p in human astrocytomas by arbitrarily primed polymerase chain reaction. Author(s): Saitoh Y, Bruner JM, Levin VA, Kyritsis AP. Source: Genes, Chromosomes & Cancer. 1998 July; 22(3): 165-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9624527

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Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas. Author(s): Ezer R, Alonso M, Pereira E, Kim M, Allen JC, Miller DC, Newcomb EW. Source: Journal of Neuro-Oncology. 2002 September; 59(2): 123-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241105

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Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: an index of malignancy in astrocytomas. Author(s): Yamaguchi F, Morrison RS, Gonatas NK, Takahashi H, Sugisaki Y, Teramoto A. Source: International Journal of Oncology. 2003 May; 22(5): 1045-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684670

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Immunohistochemical detection of lactoferrin in human astrocytomas and multiforme glioblastomas. Author(s): Tuccari G, Giuffre G, Crisafulli C, Barresi G. Source: Eur J Histochem. 1999; 43(4): 317-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10682270

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Immunohistochemical detection of parathyroid hormone-related protein in human astrocytomas. Author(s): de Miguel F, Sarasa JL, Lopez-Ferro O, Esbrit P. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1998 February; 46(2): 277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9527553

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Immunohistochemical detection of the DNA repair enzyme O6-methylguanine-DNA methyltransferase in formalin-fixed, paraffin-embedded astrocytomas. Author(s): McLendon RE, Cleveland L, Pegram C, Bigner SH, Bigner DD, Friedman HS. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1998 May; 78(5): 643-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9605190

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Immunohistochemical markers for prognosis of anaplastic astrocytomas. Author(s): Korshunov A, Golanov A, Sycheva R. Source: Journal of Neuro-Oncology. 2002 July; 58(3): 203-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187956

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Impact of tumor stage, operative down-staging, tumor grade and radioresponsitivity of the tumor on survival in supratentorial astrocytomas. Author(s): Erkurt E, Tunali C, Erkisi M, Boyer B, Burgurt R. Source: J Exp Clin Cancer Res. 1998 December; 17(4): 471-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10089070

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In situ expression of angiopoietins in astrocytomas identifies angiopoietin-2 as an early marker of tumor angiogenesis. Author(s): Zagzag D, Hooper A, Friedlander DR, Chan W, Holash J, Wiegand SJ, Yancopoulos GD, Grumet M. Source: Experimental Neurology. 1999 October; 159(2): 391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10506510

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In situ hybridization with single-stranded RNA probes to demonstrate infrequently elevated gli mRNA and no increased ras mRNA levels in meningiomas and astrocytomas. Author(s): Salgaller M, Pearl D, Stephens R. Source: Cancer Letters. 1991 May 24; 57(3): 243-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1827754

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Incidence of p14ARF gene deletion in high-grade adult and pediatric astrocytomas. Author(s): Newcomb EW, Alonso M, Sung T, Miller DC. Source: Human Pathology. 2000 January; 31(1): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10665922

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Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study. Author(s): Klein R, Roggendorf W. Source: Acta Neuropathologica. 2001 March; 101(3): 245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307624

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Indocyanine green angiography of retinal astrocytomas associated with tuberous sclerosis. Author(s): Koak N, Saatci AO, Kaynak S, Ergin MH, Ingil GC. Source: Korean J Ophthalmol. 2003 December; 17(2): 145-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717494

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Infiltrative astrocytomas with granular cell features (granular cell astrocytomas): a study of histopathologic features, grading, and outcome. Author(s): Brat DJ, Scheithauer BW, Medina-Flores R, Rosenblum MK, Burger PC. Source: The American Journal of Surgical Pathology. 2002 June; 26(6): 750-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023579

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Influence of growth hormone therapy on pituitary and lumbar spine astrocytomas. A clinical observation. Author(s): Mohn A, di Ricco L, de Santis A, Tartaro A, Capanna R, Chiarelli F. Source: Hormone Research. 2003; 59(3): 156-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637796

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Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas. Author(s): Hirano H, Lopes MB, Laws ER Jr, Asakura T, Goto M, Carpenter JE, Karns LR, VandenBerg SR. Source: Neuro-Oncology. 1999 April; 1(2): 109-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11550306

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Interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor type I, IL-1 receptor antagonist, and TGF-beta 1 mRNAs in pediatric astrocytomas, ependymomas, and primitive neuroectodermal tumors. Author(s): Ilyin SE, Gonzalez-Gomez I, Gilles FH, Plata-Salaman CR. Source: Mol Chem Neuropathol. 1998 February; 33(2): 125-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565970

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Intramedullary low-grade astrocytomas: long-term outcome following radical surgery. Author(s): Jallo GI, Danish S, Velasquez L, Epstein F. Source: Journal of Neuro-Oncology. 2001 May; 53(1): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678433

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Isotype-specific Ras.GTP-levels predict the efficacy of farnesyl transferase inhibitors against human astrocytomas regardless of Ras mutational status. Author(s): Feldkamp MM, Lau N, Roncari L, Guha A. Source: Cancer Research. 2001 June 1; 61(11): 4425-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11389071

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IV ventricle astrocytomas in childhood: clinicopathological features in 21 cases. Author(s): Tomita T, Chou P, Reyes-Mugica M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 October; 14(10): 537-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840376

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Juvenile astrocytomas with subarachnoid spread. Author(s): McLaughlin JE. Source: The Journal of Pathology. 1976 February; 118(2): 101-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1255303

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Juvenile pilocytic astrocytomas: CT and MR characteristics. Author(s): Lee YY, Van Tassel P, Bruner JM, Moser RP, Share JC. Source: Ajr. American Journal of Roentgenology. 1989 June; 152(6): 1263-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2718863

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Keratin expression in astrocytomas: an immunofluorescent and biochemical reassessment. Author(s): Kriho VK, Yang HY, Moskal JR, Skalli O. Source: Virchows Archiv : an International Journal of Pathology. 1997 August; 431(2): 139-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9293896

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Ki-67 antigen expression as a prognostic factor in primary and recurrent astrocytomas. Author(s): Enestrom S, Vavruch L, Franlund B, Nordenskjold B. Source: Neuro-Chirurgie. 1998 March; 44(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9757314

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Ki-67 immunoreactivity, basic fibroblastic growth factor (bFGF) expression, and microvessel density as supplementary prognostic tools in low-grade astrocytomas. An immunohistochemical study with special reference to the reliability of different Ki-67 antibodies. Author(s): Torp SH, Alsaker M. Source: Pathology, Research and Practice. 2002; 198(4): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049334

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Leptomeningeal dissemination of cerebellar malignant astrocytomas. Author(s): Endo H, Kumabe T, Jokura H, Shirane R, Ariga H, Takai Y, Yoshimoto T. Source: Journal of Neuro-Oncology. 2003 June; 63(2): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825824

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Local invasion and intraparenchymal metastasis of astrocytomas. Author(s): Bernstein JJ. Source: Neuropathology and Applied Neurobiology. 1996 October; 22(5): 421-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8930952

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Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): report of 110 consecutive cases. Author(s): Due-Tonnessen BJ, Helseth E, Scheie D, Skullerud K, Aamodt G, Lundar T. Source: Pediatric Neurosurgery. 2002 August; 37(2): 71-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145515

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Long-term survival in treated anaplastic astrocytomas. A report of combined RTOG/ECOG studies. Author(s): Fischbach AJ, Martz KL, Nelson JS, Griffin TW, Chang CH, Horton J, Nelson DF. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1991 October; 14(5): 365-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1659173

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Loss of DCC expression in astrocytomas: relation to p53 abnormalities, cell kinetics, and survival. Author(s): Hara A, Saegusa M, Mikami T, Okayasu I. Source: Journal of Clinical Pathology. 2001 November; 54(11): 860-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11684721

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Loss of neurofibromatosis 1 (NF1) gene expression in NF1-associated pilocytic astrocytomas. Author(s): Gutmann DH, Donahoe J, Brown T, James CD, Perry A. Source: Neuropathology and Applied Neurobiology. 2000 August; 26(4): 361-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931370

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Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas. Author(s): Kluwe L, Hagel C, Tatagiba M, Thomas S, Stavrou D, Ostertag H, von Deimling A, Mautner VF. Source: Journal of Neuropathology and Experimental Neurology. 2001 September; 60(9): 917-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11556548

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Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Author(s): Henske EP, Wessner LL, Golden J, Scheithauer BW, Vortmeyer AO, Zhuang Z, Klein-Szanto AJ, Kwiatkowski DJ, Yeung RS. Source: American Journal of Pathology. 1997 December; 151(6): 1639-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9403714

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Low density lipoprotein receptor related protein gene amplification and 766T polymorphism in astrocytomas. Author(s): Baum L, Dong ZY, Choy KW, Pang CP, Ng HK. Source: Neuroscience Letters. 1998 October 30; 256(1): 5-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9832203

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Low expression of p27 indicates a poor prognosis in patients with high-grade astrocytomas. Author(s): Kirla RM, Haapasalo HK, Kalimo H, Salminen EK. Source: Cancer. 2003 February 1; 97(3): 644-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548606

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Low grade astrocytomas in the West of Scotland 1987-96: treatment, outcome, and cognitive functioning. Author(s): Yule SM, Hide TA, Cranney M, Simpson E, Barrett A. Source: Archives of Disease in Childhood. 2001 January; 84(1): 61-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124789

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Low grade astrocytomas: controversies in management. Author(s): Kaye AH, Walker DG. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2000 November; 7(6): 475-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11029226

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Low grade supratentorial astrocytomas: management and prognostic factors. Author(s): Kreth FW, Warnke PC, Ostertag CB. Source: Cancer. 1994 December 15; 74(12): 3247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7982190

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Low-grade astrocytomas arising from the pineal gland. Author(s): Barnett DW, Olson JJ, Thomas WG, Hunter SB. Source: Surgical Neurology. 1995 January; 43(1): 70-5; Discussion 75-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7701429

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Low-grade astrocytomas in children: evolving management strategies. Author(s): Freeman CR, Farmer JP, Montes J. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 July 15; 41(5): 979-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9719106

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Low-grade astrocytomas of childhood. Author(s): Rekate HL, Rakfal SM. Source: Neurologic Clinics. 1991 May; 9(2): 423-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1944108

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Low-grade astrocytomas: prognosis factors and elements of management. Author(s): Loiseau H, Dartigues JF, Cohadon F. Source: Surgical Neurology. 1995 September; 44(3): 224-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8545772

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Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era. Author(s): Bahary JP, Villemure JG, Choi S, Leblanc R, Olivier A, Bertrand G, Souhami L, Tampieri D, Hazel J. Source: Journal of Neuro-Oncology. 1996 February; 27(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8699240

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Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. Author(s): Guo AC, Cummings TJ, Dash RC, Provenzale JM. Source: Radiology. 2002 July; 224(1): 177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091680

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MAGE-1, a cancer/testis-antigen, expression in childhood astrocytomas as an indicator of tumor progression. Author(s): Bodey B, Siegel SE, Kaiser HE. Source: In Vivo. 2002 November-December; 16(6): 583-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494904

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Malignant cerebellar astrocytomas in childhood. Experience with four cases. Author(s): Bristot R, Raco A, Vangelista T, Delfini R. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 October; 14(10): 532-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840375

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Malignant cerebellar astrocytomas: clinico-pathological remarks on 10 cases. Author(s): Bristot R, Santoro A, Raco A, Salvati M, Puzzilli F, Delfini R, Cantore G. Source: Journal of Neurosurgical Sciences. 1999 December; 43(4): 271-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10864389

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Malignant supratentorial astrocytomas of late childhood. Our experience with 25 cases. Author(s): Raco A, Bristot R, Salvati M, Delfini R. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 June; 13(6): 341-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272287

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Management of optic chiasmatic/hypothalamic astrocytomas in children. Author(s): Steinbok P, Hentschel S, Almqvist P, Cochrane DD, Poskitt K. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2002 May; 29(2): 132-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035834

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Matrix metalloproteinase expression in childhood astrocytomas. Author(s): Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Source: Anticancer Res. 2000 September-October; 20(5A): 3287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11062755

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Mdr1 mRNA expression differs between grade III astrocytomas and glioblastomas. Author(s): Kirches E, Oda Y, Von Bossanyi P, Diete S, Schneider T, Warich-Kirches M, Dietzmann K. Source: Clin Neuropathol. 1997 January-February; 16(1): 34-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9020393

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MIB-1 and p53 immunocytochemistry for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas in children and young adults. Author(s): Matsumoto T, Fujii T, Yabe M, Oka K, Hoshi T, Sato K. Source: Histopathology. 1998 November; 33(5): 446-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839169

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Microtubule-associated protein 2 (MAP-2) is expressed in low and high grade diffuse astrocytomas. Author(s): Wharton SB, Chan KK, Whittle IR. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 March; 9(2): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11922706

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Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. Author(s): Besson A, Yong VW. Source: Journal of Neuro-Oncology. 2001 February; 51(3): 245-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407596

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Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1. Author(s): Gutmann DH, James CD, Poyhonen M, Louis DN, Ferner R, Guha A, Hariharan S, Viskochil D, Perry A. Source: Neurology. 2003 November 25; 61(10): 1397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638962

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Molecular genetic alterations in radiation-induced astrocytomas. Author(s): Brat DJ, James CD, Jedlicka AE, Connolly DC, Chang E, Castellani RJ, Schmid M, Schiller M, Carson DA, Burger PC. Source: American Journal of Pathology. 1999 May; 154(5): 1431-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10329596

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Molecular markers that identify human astrocytomas and oligodendrogliomas. Author(s): Popko B, Pearl DK, Walker DM, Comas TC, Baerwald KD, Burger PC, Scheithauer BW, Yates AJ. Source: Journal of Neuropathology and Experimental Neurology. 2002 April; 61(4): 32938. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939588

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MR characteristics of malignant spinal cord astrocytomas in children. Author(s): Kulkarni AV, Armstrong DC, Drake JM. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1999 November; 26(4): 290-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10563214

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MR imaging characteristics of pilomyxoid astrocytomas. Author(s): Arslanoglu A, Cirak B, Horska A, Okoh J, Tihan T, Aronson L, Avellino AM, Burger PC, Yousem DM. Source: Ajnr. American Journal of Neuroradiology. 2003 October; 24(9): 1906-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561626

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Multidisciplinary management of adult anaplastic astrocytomas. Author(s): Chang S, Theodosopoulos P, Sneed P. Source: Seminars in Radiation Oncology. 2001 April; 11(2): 163-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11285554

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Multimodal target point assessment for stereotactic biopsy in children with diffuse bithalamic astrocytomas. Author(s): Messing-Junger AM, Floeth FW, Pauleit D, Reifenberger G, Willing R, Gartner J, Coenen HH, Langen KJ. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 August; 18(8): 445-9. Epub 2002 July 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192504

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Mutational and expression analysis of the NF1 gene argues against a role as tumor suppressor in sporadic pilocytic astrocytomas. Author(s): Wimmer K, Eckart M, Meyer-Puttlitz B, Fonatsch C, Pietsch T. Source: Journal of Neuropathology and Experimental Neurology. 2002 October; 61(10): 896-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387455

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Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas. Author(s): Biernat W, Debiec-Rychter M, Liberski PP. Source: Pol J Pathol. 1998; 49(4): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323080

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Neoangiogenesis in human astrocytomas: expression and functional role of angiopoietins and their cognate receptors. Author(s): Zadeh G, Guha A. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 January 1; 8: E12837. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456344

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Neuroimaging of juvenile pilocytic astrocytomas. Author(s): Lamki LM. Source: Radiology. 1994 April; 191(1): 288. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8134591

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Neuroimaging of juvenile pilocytic astrocytomas: an enigma. Author(s): Fulham MJ, Melisi JW, Nishimiya J, Dwyer AJ, Di Chiro G. Source: Radiology. 1993 October; 189(1): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8372197

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Neurological assessment of high grade astrocytomas following high dose radiotherapy as sole treatment. Author(s): Grant P. Source: Clin Oncol (R Coll Radiol). 1996; 8(1): 64-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8688367

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Neurological assessment of high grade astrocytomas following high dose radiotherapy as sole treatment. Author(s): Peat IM, Madden FJ. Source: Clin Oncol (R Coll Radiol). 1995; 7(4): 273. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8845333

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Neurological assessment of high grade astrocytomas following high dose radiotherapy as sole treatment. Author(s): Fuentes R, Izquierdo AX, Canals E, Vayreda J, Dorca J, Beltran M, Viladiu P. Source: Clin Oncol (R Coll Radiol). 1995; 7(2): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7619760

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Neuropeptide Y, somatostatin, and cholecystokinin neurone preservation in anaplastic astrocytomas. Author(s): Przedborski S, Goldman S, Schiffmann SN, Vierendeels G, Depierreux M, Levivier M, Hildebrand J, Vanderhaeghen JJ. Source: Acta Neuropathologica. 1988; 76(5): 507-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2903606

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Neuroradiological studies of JCV-induced astrocytomas in nonhuman primates. Author(s): Houff SA, London WT, DiChiro G, Padgett BL, Walker DL, Zu Rhein GM, Sever JL. Source: Prog Clin Biol Res. 1983; 105: 253-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6304762

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Neurosurgical management of cerebral astrocytomas in children. Author(s): Ciurea AV, Vasilescu G, Nuteanu L, Silveanu-Vladu M, Teodorescu I, Lisievici M. Source: Annals of the New York Academy of Sciences. 1997 September 17; 824: 237-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9382451

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No chromosomal imbalances detected by comparative genomic hybridisation in subependymal giant cell astrocytomas. Author(s): Rickert CH, Paulus W. Source: Acta Neuropathologica. 2002 August; 104(2): 206-8. Epub 2002 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111364

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Non-enhancing supratentorial malignant astrocytomas: MR features and possible mechanisms. Author(s): Mihara F, Numaguchi Y, Rothman M, Kristt D, Fiandaca M, Swallow L. Source: Radiat Med. 1995 January-February; 13(1): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7597198

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Nonoccupational risk indicators for astrocytomas in adults. Author(s): Ahlbom A, Navier IL, Norell S, Olin R, Spannare B. Source: American Journal of Epidemiology. 1986 August; 124(2): 334-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3728449

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Nonrandom chromosomal gains in pilocytic astrocytomas of childhood. Author(s): White FV, Anthony DC, Yunis EJ, Tarbell NJ, Scott RM, Schofield DE. Source: Human Pathology. 1995 September; 26(9): 979-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672798

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Numerical aberrations of chromosomes 1, 2, and 7 in astrocytomas studied by interphase cytogenetics. Author(s): Wernicke C, Thiel G, Lozanova T, Vogel S, Witkowski R. Source: Genes, Chromosomes & Cancer. 1997 May; 19(1): 6-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9135989

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Numerical grading of astrocytomas. Author(s): Schad LR, Schmitt HP, Oberwittler C, Lorenz WJ. Source: Med Inform (Lond). 1987 January-March; 12(1): 11-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3035294

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Occupational factors associated with astrocytomas: a case-control study. Author(s): Olin RG, Ahlbom A, Lindberg-Navier I, Norell SE, Spannare B. Source: American Journal of Industrial Medicine. 1987; 11(6): 615-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3037895

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On the treatment of subependymal giant cell astrocytomas and associated hydrocephalus in tuberous sclerosis. Author(s): Di Rocco C, Iannelli A, Marchese E. Source: Pediatric Neurosurgery. 1995; 23(3): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8751291

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Oncogene abnormalities in astrocytomas: EGF-R gene alone appears to be more frequently amplified and rearranged compared with other protooncogenes. Author(s): Burgart LJ, Robinson RA, Haddad SF, Moore SA. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1991 March; 4(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1675468

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Operated low grade astrocytomas: a long term PET study on the effect of radiotherapy. Author(s): Roelcke U, von Ammon K, Hausmann O, Kaech DL, Vanloffeld W, Landolt H, Rem JA, Gratzl O, Radu EW, Leenders KL. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 May; 66(5): 644-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209179

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Operation and permanent low activity 125I brachytheraphy for recurrent high-grade astrocytomas. Author(s): Halligan JB, Stelzer KJ, Rostomily RC, Spence AM, Griffin TW, Berger MS. Source: International Journal of Radiation Oncology, Biology, Physics. 1996 June 1; 35(3): 541-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8655378

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Optic chiasm astrocytomas of childhood. 1. Long-term follow-up. Author(s): Medlock MD, Madsen JR, Barnes PD, Anthony DS, Cohen LE, Scott RM. Source: Pediatric Neurosurgery. 1997 September; 27(3): 121-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9548522

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Optic chiasm astrocytomas of childhood. 2. Surgical management. Author(s): Medlock MD, Scott RM. Source: Pediatric Neurosurgery. 1997 September; 27(3): 129-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9548523

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Osteoblastic metastases from astrocytomas: a report of two cases. Author(s): Longee DC, Friedman HS, Phillips PC, Burger PC, Oakes WJ, Heffez D, Wharam M, Strauss L, Fuller GN, Schold SC. Source: Medical and Pediatric Oncology. 1991; 19(4): 318-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2056977

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Outcome and patterns of failure following limited-volume irradiation for malignant astrocytomas. Author(s): Garden AS, Maor MH, Yung WK, Bruner JM, Woo SY, Moser RP, Lee YY. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 1991 February; 20(2): 99-110. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1851573

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Overexpression of cyclin A and cyclin B1 proteins in astrocytomas. Author(s): Allan K, Jordan RC, Ang LC, Taylor M, Young B. Source: Archives of Pathology & Laboratory Medicine. 2000 February; 124(2): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656729

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Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling. Author(s): Khatua S, Peterson KM, Brown KM, Lawlor C, Santi MR, LaFleur B, Dressman D, Stephan DA, MacDonald TJ. Source: Cancer Research. 2003 April 15; 63(8): 1865-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702575

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Pharmacotherapy of malignant astrocytomas of children and adults: current strategies and future trends. Author(s): Jennings MT, Iyengar S. Source: Cns Drugs. 2001; 15(9): 719-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11580310

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Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Author(s): Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P, Ohgaki H. Source: Acta Neuropathologica. 2002 March; 103(3): 267-75. Epub 2001 November 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907807

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Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Author(s): Komotar RJ, Burger PC, Carson BS, Brem H, Olivi A, Goldthwaite PT, Tihan T. Source: Neurosurgery. 2004 January; 54(1): 72-9; Discussion 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683543

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Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases. Author(s): Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paz Paredes A, Lena G. Source: Neurosurgery. 2003 September; 53(3): 544-53; Discussion 554-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943571

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Pilocytic astrocytomas with leptomeningeal dissemination: biological behavior, clinical course, and therapeutical options. Author(s): Buschmann U, Gers B, Hildebrandt G. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 June; 19(5-6): 298-304. Epub 2003 May 22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12761643

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Preirradiation ifosfamide, carboplatin, and etoposide (ICE) for the treatment of highgrade astrocytomas in children. Author(s): Rueda-Franco F. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 December; 19(12): 824. Epub 2003 November 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614569

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Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1. Author(s): Tada K, Kochi M, Saya H, Kuratsu J, Shiraishi S, Kamiryo T, Shinohima N, Ushio Y. Source: Neuro-Oncology. 2003 October; 5(4): 228-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565158

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Progesterone receptor isoforms expression pattern in human astrocytomas. Author(s): Gonzalez-Aguero G, Ondarza R, Gamboa-Dominguez A, Cerbon MA, Camacho-Arroyo I. Source: Brain Research Bulletin. 2001 September 1; 56(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11604247

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Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. Author(s): Desai KI, Nadkarni TD, Muzumdar DP, Goel A. Source: Pediatric Neurosurgery. 2001 December; 35(6): 311-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786699

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Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade II astrocytomas and oligoastrocytomas. Author(s): Peraud A, Kreth FW, Wiestler OD, Kleihues P, Reulen HJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 May; 8(5): 1117-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006527

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Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas. Author(s): Kuriyama H, Lamborn KR, O'Fallon JR, Iturria N, Sebo T, Schaefer PL, Scheithauer BW, Buckner JC, Kuriyama N, Jenkins RB, Israel MA. Source: Neuro-Oncology. 2002 July; 4(3): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084348

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Prognostic value of loss of heterozygosity around three candidate tumor suppressor genes on chromosome 10q in astrocytomas. Author(s): Terada K, Tamiya T, Daido S, Kambara H, Tanaka H, Ono Y, Matsumoto K, Ito S, Ouchida M, Ohmoto T, Shimizu K. Source: Journal of Neuro-Oncology. 2002 June; 58(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164681

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Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas. Author(s): Ribom D, Andrae J, Frielingsdorf M, Hartman M, Nister M, Smits A. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 June; 72(6): 782-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023424

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Proliferative activity as measured by MIB-1 labeling index and long-term outcome of cerebellar juvenile pilocytic astrocytomas. Author(s): Roessler K, Bertalanffy A, Jezan H, Ba-Ssalamah A, Slavc I, Czech T, Budka H. Source: Journal of Neuro-Oncology. 2002 June; 58(2): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164686

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PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas. Author(s): Idoate MA, Soria E, Lozano MD, Sola JJ, Panizo A, de Alava E, Manrique M, Pardo-Mindan FJ. Source: Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B. 2003 September; 12(3): 160-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960698

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PTEN, DMBT1, and p16 alterations in diffusely infiltrating astrocytomas. Author(s): Fan X, Munoz J, Sanko SG, Castresana JS. Source: International Journal of Oncology. 2002 September; 21(3): 667-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12168116

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Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14. Radiation Therapy Oncology Group. Author(s): Choucair AK, Scott C, Urtasun R, Nelson D, Mousas B, Curran W. Source: International Journal of Radiation Oncology, Biology, Physics. 1997 April 1; 38(1): 9-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9211998

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Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligoastrocytomas. Author(s): Decaestecker C, Lopes BS, Gordower L, Camby I, Cras P, Martin JJ, Kiss R, VandenBerg SR, Salmon I. Source: Journal of Neuropathology and Experimental Neurology. 1997 April; 56(4): 391402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9100670

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Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas. Author(s): De Witte O, Levivier M, Violon P, Brotchi J, Goldman S. Source: Neurosurgery. 1998 August; 43(2): 398-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9696102

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Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas. Author(s): Kowalczuk A, Macdonald RL, Amidei C, Dohrmann G 3rd, Erickson RK, Hekmatpanah J, Krauss S, Krishnasamy S, Masters G, Mullan SF, Mundt AJ, Sweeney P, Vokes EE, Weir BK, Wollman RL. Source: Neurosurgery. 1997 November; 41(5): 1028-36; Discussion 1036-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9361056

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Radiological and clinical outcome following stereotactic biopsy and radiotherapy for low-grade insular astrocytomas. Author(s): Shankar A, Rajshekhar V. Source: Neurology India. 2003 December; 51(4): 503-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742933

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Rap1 activity is elevated in malignant astrocytomas independent of tuberous sclerosis complex-2 gene expression. Author(s): Lau N, Uhlmann EJ, Von Lintig FC, Nagy A, Boss GR, Gutmann DH, Guha A. Source: International Journal of Oncology. 2003 January; 22(1): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469204

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Ras p21 expression in brain tumors: elevated expression in malignant astrocytomas and glioblastomas multiforme. Author(s): Arvanitis D, Malliri A, Antoniou D, Linardopoulos S, Field JK, Spandidos DA. Source: In Vivo. 1991 July-August; 5(4): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1667267

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Reader shares additional resources for astrocytomas. Author(s): Tufel R. Source: Clinical Journal of Oncology Nursing. 2000 September-October; 4(5): 198. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11899760

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Recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2) immunotherapy with ranimustine chemotherapy and concurrent radiation therapy for malignant astrocytomas. Author(s): Fukushima T, Yamamoto M, Oshiro S, Tsugu H, Hirakawa K, Soma G. Source: Anticancer Res. 2003 November-December; 23(6A): 4473-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666736

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Regulation of secretion of PTHrP by Ca(2+)-sensing receptor in human astrocytes, astrocytomas, and meningiomas. Author(s): Chattopadhyay N, Evliyaoglu C, Heese O, Carroll R, Sanders J, Black P, Brown EM. Source: American Journal of Physiology. Cell Physiology. 2000 September; 279(3): C6919. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10942719

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Relationship between the expression of E-, N-cadherins and beta-catenin and tumor grade in astrocytomas. Author(s): Utsuki S, Sato Y, Oka H, Tsuchiya B, Suzuki S, Fujii K. Source: Journal of Neuro-Oncology. 2002 May; 57(3): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125981

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Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. Author(s): Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 April 15; 19(8): 2189-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11304771

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Role of early radiotherapy in the treatment of supratentorial WHO Grade II astrocytomas: long-term results of 97 patients. Author(s): Hanzely Z, Polgar C, Fodor J, Brucher JM, Vitanovics D, Mangel LC, Afra D. Source: Journal of Neuro-Oncology. 2003 July; 63(3): 305-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892238

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Role of surgery for high-grade astrocytomas. Author(s): Gaspar LE, Schold SC Jr, Cairncross JG. Source: Journal of Neurosurgery. 1991 June; 74(6): 1027-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2033442

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Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas. Author(s): Chen B, Ahmed T, Mannancheril A, Gruber M, Benzil DL. Source: Cancer. 2004 May 15; 100(10): 2201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139065

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Spinal cord astrocytomas: presentation, management and outcome. Author(s): Houten JK, Cooper PR. Source: Journal of Neuro-Oncology. 2000 May; 47(3): 219-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11016738

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Spinal cord malignant astrocytomas. Clinicopathologic features in 36 cases. Author(s): Santi M, Mena H, Wong K, Koeller K, Olsen C, Rushing EJ. Source: Cancer. 2003 August 1; 98(3): 554-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879473

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Spontaneous regression of low-grade astrocytomas: an underrecognized condition? Author(s): Zizka J, Elias P, Jakubec J. Source: European Radiology. 2001; 11(12): 2638-40. Epub 2001 July 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734972

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Stereotactic radiosurgery for well-circumscribed fibrillary grade II astrocytomas: an initial experience. Author(s): Hadjipanayis CG, Niranjan A, Tyler-Kabara E, Kondziolka D, Flickinger JC, Lunsford LD. Source: Stereotactic and Functional Neurosurgery. 2002; 79(1): 13-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677101

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Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents. Author(s): Bowers DC, Gargan L, Kapur P, Reisch JS, Mulne AF, Shapiro KN, Elterman RD, Winick NJ, Margraf LR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 2968-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885817

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Supratentorial astrocytomas and oligodendrogliomas treated in the MRI era. Author(s): Sakata K, Hareyama M, Komae T, Shirato H, Watanabe O, Watarai J, Takai K, Yamada S, Tsuchida E, Sakai K. Source: Japanese Journal of Clinical Oncology. 2001 June; 31(6): 240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11463800

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Surgical resection of grade II astrocytomas in the superior frontal gyrus. Author(s): Peraud A, Meschede M, Eisner W, Ilmberger J, Reulen HJ. Source: Neurosurgery. 2002 May; 50(5): 966-75; Discussion 975-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11950399

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Surgical treatment of patients with low-grade astrocytomas and medically intractable seizures. Author(s): Gunnarsson T, Olafsson E, Sighvatsson V, Hannesson B. Source: Acta Neurologica Scandinavica. 2002 April; 105(4): 289-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939941

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Targeting the Tie2/Tek receptor in astrocytomas. Author(s): Zadeh G, Qian B, Okhowat A, Sabha N, Kontos CD, Guha A. Source: American Journal of Pathology. 2004 February; 164(2): 467-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742253

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Temodar offers promise for treating astrocytomas. Author(s): Armstrong T, Hancock C. Source: Clinical Journal of Oncology Nursing. 2000 July-August; 4(4): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261095

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Temozolomide. A new option for high-grade astrocytomas. Author(s): Schwenka J, Ignoffo RJ. Source: Cancer Practice. 2000 November-December; 8(6): 311-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11898150

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Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal. Author(s): Steiger HJ, Gotz C, Schmid-Elsaesser R, Stummer W. Source: Acta Neurochirurgica. 2000; 142(12): 1327-36; Discussion 1336-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214625

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The clinical significance of cathepsin S expression in human astrocytomas. Author(s): Flannery T, Gibson D, Mirakhur M, McQuaid S, Greenan C, Trimble A, Walker B, McCormick D, Johnston PG. Source: American Journal of Pathology. 2003 July; 163(1): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819022

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The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas. Author(s): Oz B, Karayel FA, Gazio NL, Ozlen F, Balci K. Source: Pathology Oncology Research : Por. 2000; 6(2): 118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936787

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The rationale for rational surgery for fibrillary astrocytomas. Author(s): Lunsford LD, Niranjan A. Source: Clin Neurosurg. 2001; 48: 20-36. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11692641

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Treatment of malignant astrocytomas with repetitive resections: a longitudinal study. Author(s): Azizi A, Black P, Miyamoto C, Croul SE. Source: Isr Med Assoc J. 2001 April; 3(4): 254-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344836

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Tuberin and hamartin expression is reduced in the majority of subependymal giant cell astrocytomas in tuberous sclerosis complex consistent with a two-hit model of pathogenesis. Author(s): Jozwiak S, Kwiatkowski D, Kotulska K, Larysz-Brysz M, Lewin-Kowalik J, Grajkowska W, Roszkowski M. Source: Journal of Child Neurology. 2004 February; 19(2): 102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072102

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Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after radiation therapy. Author(s): Fuss M, Wenz F, Essig M, Muenter M, Debus J, Herman TS, Wannenmacher M. Source: International Journal of Radiation Oncology, Biology, Physics. 2001 October 1; 51(2): 478-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11567824

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Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease. Author(s): Lowe J, Blanchard A, Morrell K, Lennox G, Reynolds L, Billett M, Landon M, Mayer RJ. Source: The Journal of Pathology. 1988 May; 155(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2837558

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Up-regulation of specific NF 1 gene transcripts in sporadic pilocytic astrocytomas. Author(s): Platten M, Giordano MJ, Dirven CM, Gutmann DH, Louis DN. Source: American Journal of Pathology. 1996 August; 149(2): 621-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8702000

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Use of a portable CT scanner during resection of subcortical supratentorial astrocytomas of childhood. Author(s): Gwinn R, Cleary K, Medlock M. Source: Pediatric Neurosurgery. 2000 January; 32(1): 37-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765137

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Use of fluorescence in situ hybridization to detect loss of chromosome 10 in astrocytomas. Author(s): Dalrymple SJ, Herath JF, Ritland SR, Moertel CA, Jenkins RB. Source: Journal of Neurosurgery. 1995 August; 83(2): 316-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7616278

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Usefulness of motor functional MRI correlated to cortical mapping in Rolandic lowgrade astrocytomas. Author(s): Roux FE, Boulanouar K, Ranjeva JP, Tremoulet M, Henry P, Manelfe C, Sabatier J, Berry I. Source: Acta Neurochirurgica. 1999; 141(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10071689

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Variation of the magnetic relaxation rate 1/T1 of water protons with magnetic field strength (NMRD profile) of untreated, non-calcified, human astrocytomas: correlation with histology and solids content. Author(s): Spiller M, Kasoff SS, Lansen TA, Rifkinson-Mann S, Valsamis MP, Koenig SH, Tenner MS. Source: Journal of Neuro-Oncology. 1994; 21(2): 113-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7861187

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Variations in the natural history and survival of patients with supratentorial lowgrade astrocytomas. Author(s): Piepmeier J, Christopher S, Spencer D, Byrne T, Kim J, Knisel JP, Lacy J, Tsukerman L, Makuch R. Source: Neurosurgery. 1996 May; 38(5): 872-8; Discussion 878-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8727811

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Why do benign astrocytomas become malignant in NF1? Author(s): Ruggieri M, Packer RJ. Source: Neurology. 2001 April 10; 56(7): 827-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294917

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CHAPTER 2. NUTRITION AND ASTROCYTOMAS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and astrocytomas.

Finding Nutrition Studies on Astrocytomas 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 “astrocytomas” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 “astrocytomas” (or a synonym): •

Agonists of the retinoic acid- and retinoid X-receptors inhibit hepatocyte growth factor secretion and expression in U87 human astrocytoma cells. Author(s): Endocrine-Hypertension Division and Membrane Biology Program, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, MA 02115, Boston, USA. [email protected] Source: Chattopadhyay, N Butters, R R Brown, E M Brain-Res-Mol-Brain-Res. 2001 February 19; 87(1): 100-8 0169-328X

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Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions. Author(s): Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan. Source: Nishio, S Morioka, T Takeshita, I Shono, T Inamura, T Fujiwara, S Fukui, M Clin-Neurol-Neurosurg. 1995 November; 97(4): 300-6 0303-8467

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Cisplatin/vincristine chemotherapy for hypothalamic/visual pathway astrocytomas in young children. Author(s): Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan. Source: Kato, T Sawamura, Y Tada, M Ikeda, J Ishii, N Abe, H J-Neurooncol. 1998 May; 37(3): 263-70 0167-594X

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Effects of mycophenolic acid on detection of glial filaments in human and rat astrocytoma cultures. Source: Lipsky, R H Silverman, S J Cancer-Res. 1987 September 15; 47(18): 4900-4 00085472

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Exposure to 60-Hz magnetic fields and proliferation of human astrocytoma cells in vitro. Author(s): Department of Environmental Health, University of Washington, Seattle, Washington, 98105, USA. Source: Wei, M Guizzetti, M Yost, M Costa, L G Toxicol-Appl-Pharmacol. 2000 February 1; 162(3): 166-76 0041-008X

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High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence. Author(s): Division of Oncology and Bone Marrow Transplantation, Children's Hospital, Philadelphia, University of Pennsylvania School of Medicine. Source: Finlay, J L August, C Packer, R Zimmerman, R Sutton, L Freid, A Rorke, L Bayever, E Kamani, N Kramer, E et al. J-Neurooncol. 1990 December; 9(3): 239-48 0167594X

•

Immunophenotyping of childhood astrocytomas with a library of monoclonal antibodies. Author(s): Childrens Hospital, Los Angeles, CA 90054. Source: Bodey, B Zeltzer, P M Saldivar, V Kemshead, J Int-J-Cancer. 1990 June 15; 45(6): 1079-87 0020-7136

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Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. Author(s): Department of Neurosurgery, Children's Hospital of Philadelphia, Pennsylvania, USA.

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Source: Sutton, L N Molloy, P T Sernyak, H Goldwein, J Phillips, P L Rorke, L B Moshang, T Lange, B Packer, R J J-Neurosurg. 1995 October; 83(4): 583-9 0022-3085 •

Neurofibromatosis type 1-associated unusual pleomorphic astrocytoma displaying continual malignant progression. Author(s): First Department of Pathology, Gunma University School of Medicine, Maebashi, Japan. [email protected] Source: Yokoo, H Kamiya, M Sasaki, A Hirato, J Nakazato, Y Kurachi, H Pathol-Int. 2001 July; 51(7): 570-7 1320-5463

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Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of anaplastic astrocytomas and glioblastoma multiforme: a phase II study. Author(s): Departamentos de Oncologia, Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico, D.F., Mexico. Source: Lopez Aguilar, E Sepulveda Vildosola, A C Rivera Marquez, H Cerecedo Diaz, F Hernandez Contreras, I Ramon Garcia, G Diegoperez Ramirez, J Santacruz Castillo, E Arch-Med-Res. 2000 Mar-April; 31(2): 186-90 0188-4409

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Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alphahydroxycholecalciferol. Author(s): Neurology service, H pital Neurologique, Lyon, France. [email protected] Source: Trouillas, P Honnorat, J Bret, P Jouvet, A Gerard, J P J-Neurooncol. 2001 January; 51(1): 57-66 0167-594X

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Spontaneous sister chromatid exchange in metastatic variants of the murine B16 melanoma and human astrocytomas in culture. Author(s): Cancer Research Unit, University of Newcastle upon Tyne, UK. Source: Lakshmi, M S Hunt, G Sherbet, G V Invasion-Metastasis. 1988; 8(4): 205-16 02511789

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Stereotactic radiosurgery for pilocytic astrocytomas when multimodal therapy is necessary. Author(s): Department of Neurological Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA. [email protected] Source: Hadjipanayis, Constantinos G Kondziolka, Douglas Gardner, Paul NiranJanuary, Ajay Dagam, Shekhar Flickinger, John C Lunsford, L Dade J-Neurosurg. 2002 July; 97(1): 56-64 0022-3085

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The farnesyltransferase inhibitor L-744,832 inhibits the growth of astrocytomas through a combination of antiproliferative, antiangiogenic, and proapoptotic activities. Author(s): Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. Source: Feldkamp, M M Lau, N Guha, A Ann-N-Y-Acad-Sci. 1999; 886257-60 0077-8923

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Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy. Author(s): Division of Neoplastic Diseases, University Hospital Medical Center, Stony Brook, New York 11794-8174, USA. Source: Madajewicz, S Chowhan, N Tfayli, A Roque, C Meek, A Davis, R Wolf, W Cabahug, C Roche, P Manzione, J Iliya, A Shady, M Hentschel, P Atkins, H Braun, A Cancer. 2000 May 15; 88(10): 2350-6 0008-543X

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Treatment of cystic astrocytomas with intracavitary phosphorus 32. Author(s): Department of Surgery, University of Michigan Hospitals, Ann Arbor 48109.

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Source: Hood, T W Shapiro, B Taren, J A Acta-Neurochir-Suppl-(Wien). 1987; 3934-7 0065-1419

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/

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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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ASTROCYTOMAS

ALTERNATIVE

MEDICINE

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to astrocytomas. 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 astrocytomas 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 “astrocytomas” (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 astrocytomas: •

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404. Author(s): Prados MD, Scott C, Sandler H, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. Source: International Journal of Radiation Oncology, Biology, Physics. 1999 December 1; 45(5): 1109-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10613302

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Adjuvant chemotherapy with VM 26 and CCNU after operation and radiotherapy of high-grade supratentorial astrocytomas. Author(s): Seiler RW, Zimmermann A, Markwalder H.

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Source: Surgical Neurology. 1980 January; 13(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6244679 •

Astrocytoma cell interaction with elastin substrates: implications for astrocytoma invasive potential. Author(s): Jung S, Hinek A, Tsugu A, Hubbard SL, Ackerley C, Becker LE, Rutka JT. Source: Glia. 1999 January 15; 25(2): 179-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890632

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BUdR radiosensitization in anaplastic astrocytoma. Author(s): Yung WK. Source: International Journal of Radiation Oncology, Biology, Physics. 1999 December 1; 45(5): 1105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10613300

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Chemotherapeutic trials on human malignant astrocytomas in organ culture. Author(s): Saez RJ, Campbell RJ, Laws ER Jr. Source: Journal of Neurosurgery. 1977 March; 46(3): 320-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=190361

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Chemotherapy for aggressive or anaplastic high grade oligodendrogliomas and oligoastrocytomas: better than a salvage treatment. Author(s): Bouffet E, Jouvet A, Thiesse P, Sindou M. Source: British Journal of Neurosurgery. 1998 June; 12(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11013683

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Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions. Author(s): Nishio S, Morioka T, Takeshita I, Shono T, Inamura T, Fujiwara S, Fukui M. Source: Clinical Neurology and Neurosurgery. 1995 November; 97(4): 300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8599896

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Chemotherapy for spinal cord astrocytoma: can natural history be modified? Author(s): Lowis SP, Pizer BL, Coakham H, Nelson RJ, Bouffet E. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 July; 14(7): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9726582

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Chemotherapy in recurrent noncystic low-grade astrocytomas of the cerebrum in children. Author(s): Sumer T, Freeman AI, Cohen M, Bremer AM, Thomas PR, Sinks LF.

Alternative Medicine 85

Source: Journal of Surgical Oncology. 1978; 10(1): 45-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=628217 •

Cisplatin/vincristine chemotherapy for hypothalamic/visual pathway astrocytomas in young children. Author(s): Kato T, Sawamura Y, Tada M, Ikeda J, Ishii N, Abe H. Source: Journal of Neuro-Oncology. 1998 May; 37(3): 263-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9524084

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Combined intra-arterial chemotherapy followed by radiation in astrocytomas. Author(s): Watne K, Hannisdal E, Nome O, Hager B, Wester K, Heier M, Hirschberg H. Source: Journal of Neuro-Oncology. 1992 September; 14(1): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1469466

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Combined surgery, radiation, and PCV chemotherapy for astrocytomas compared to oligodendrogliomas and oligoastrocytomas WHO grade III. Author(s): Kristof RA, Neuloh G, Hans V, Deckert M, Urbach H, Schlegel U, Simon M, Schramm J. Source: Journal of Neuro-Oncology. 2002 September; 59(3): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241120

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Concomitant chemoradiotherapy for incompletely resected supratentorial low-grade astrocytoma in children: preliminary report. Author(s): Strojan P, Petric-Grabnar G, Zupancic N, Jereb B. Source: Medical and Pediatric Oncology. 1999 February; 32(2): 112-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9950199

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Concurrent modified PCV chemotherapy and radiotherapy in newly diagnosed grade IV astrocytoma. Author(s): Murphy C, Pickles T, Knowling M, Thiesse B. Source: Journal of Neuro-Oncology. 2002 May; 57(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125984

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Cyclophosphamide for the treatment of progressive low-grade astrocytoma: a Pediatric Oncology Group phase II Study. Author(s): Kadota RP, Kun LE, Langston JW, Burger PC, Cohen ME, Mahoney DH, Walter AW, Rodman JH, Parent A, Buckley E, Kepner JL, Friedman HS. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 May-June; 21(3): 198-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10363852

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Development of secondary anaplastic oligoastrocytoma after matched unrelated bone marrow transplantation in a child with acute myeloid leukemia. Author(s): Panigrahi S, Das M, Stagler D, Konstantini S, Gmori M, Slavin S, Nagler A. Source: Acta Haematologica. 2003; 109(4): 196-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853693

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Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with highdose irradiation on malignant astrocytomas. Author(s): Genka S, Shitara N, Nakamura H, Takakura K. Source: Neurol Med Chir (Tokyo). 1993 May; 33(5): 295-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7687035

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Epidermal growth factor receptor 425 monoclonal antibodies radiolabeled with iodine-125 in the adjuvant treatment of high-grade astrocytomas. Author(s): Snelling L, Miyamoto CT, Bender H, Brady LW, Steplewski Z, Class R, Emrich J, Rackover MA. Source: Hybridoma. 1995 April; 14(2): 111-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7590764

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Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes. Author(s): Vartak S, McCaw R, Davis CS, Robbins ME, Spector AA. Source: British Journal of Cancer. 1998 May; 77(10): 1612-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635836

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High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence. Author(s): Finlay JL, August C, Packer R, Zimmerman R, Sutton L, Freid A, Rorke L, Bayever E, Kamani N, Kramer E, et al. Source: Journal of Neuro-Oncology. 1990 December; 9(3): 239-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1964962

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Histologic evidence of a radiosensitizing effect of Taxol in patients with astrocytomas. Author(s): Wehbe T, Glantz M, Choy H, Glantz L, Cortez S, Akerley W 3rd, Mills P, Cole B. Source: Journal of Neuro-Oncology. 1998 September; 39(3): 245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9821110

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Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS Consortium. Author(s): Hochberg F, Grossman SA, Mikkelsen T, Glantz M, Fisher JD, Piantadosi S.

Alternative Medicine 87

Source: Neuro-Oncology. 2000 January; 2(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302251 •

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial. Author(s): Ron IG, Gal O, Vishne TH, Kovner F. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 June; 25(3): 296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040293

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Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. Author(s): Sutton LN, Molloy PT, Sernyak H, Goldwein J, Phillips PL, Rorke LB, Moshang T Jr, Lange B, Packer RJ. Source: Journal of Neurosurgery. 1995 October; 83(4): 583-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7674005

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Mitogen activated protein kinase activation and oxidant signaling in astrocytoma cells. Author(s): Kuruganti PA, Wurster RD, Lucchesi PA. Source: Journal of Neuro-Oncology. 2002 January; 56(2): 109-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11995811

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Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas. Author(s): Bauman GS, Cairncross JG. Source: Seminars in Radiation Oncology. 2001 April; 11(2): 170-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11285555

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Neurofibromatosis type 1-associated unusual pleomorphic astrocytoma displaying continual malignant progression. Author(s): Yokoo H, Kamiya M, Sasaki A, Hirato J, Nakazato Y, Kurachi H. Source: Pathology International. 2001 July; 51(7): 570-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472572

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Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas. Author(s): Glantz MJ, Choy H, Kearns CM, Cole BF, Mills P, Zuhowski EG, Saris S, Rhodes CH, Stopa E, Egorin MJ.

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Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 February; 14(2): 600-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8636777 •

Phase II study of DTIC, ACNU, and vincristine combination chemotherapy for supratentorial malignant astrocytomas. Author(s): Ikeda J, Aida T, Sawamura Y, Abe H, Kaneko S, Kashiwaba T, Kawamoto T, Mitsumori K, Saitoh H. Source: Neurol Med Chir (Tokyo). 1996 August; 36(8): 555-8; Discussion 558-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8831197

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Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. Author(s): Buckner JC, Gesme D Jr, O'Fallon JR, Hammack JE, Stafford S, Brown PD, Hawkins R, Scheithauer BW, Erickson BJ, Levitt R, Shaw EG, Jenkins R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 15; 21(2): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525516

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Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Author(s): Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. Source: International Journal of Radiation Oncology, Biology, Physics. 2004 March 15; 58(4): 1147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001257

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Pre-irradiation carboplatin and etoposide and accelerated hyperfractionated radiation therapy in patients with high-grade astrocytomas: a phase II study. Author(s): Jeremic B, Shibamoto Y, Grujicic D, Milicic B, Stojanovic M, Nikolic N, Dagovic A, Aleksandrovic J. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 1999 April; 51(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10386714

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Preirradiation ifosfamide, carboplatin and etoposide (ICE) for the treatment of highgrade astrocytomas in children. Author(s): Lopez-Aguilar E, Sepulveda-Vildosola AC, Rivera-Marquez H, CerecedoDiaz F, Valdes-Sanchez M, Delgado-Huerta S, Wanzke-del Angel V, Ramon-Garcia G, Rodriguez-Jimenez H, Hernandez-Contreras I, Santacruz-Castillo E, Romo-Rubio HA.

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Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 December; 19(12): 818-23. Epub 2003 November 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614568 •

Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of anaplastic astrocytomas and glioblastoma multiforme: a phase II study. Author(s): Lopez-Aguilar E, Sepulveda-Vildosola AC, Rivera-Marquez H, CerecedoDiaz F, Hernandez-Contreras I, Ramon-Garcia G, Diegoperez-Ramirez J, SantacruzCastillo E. Source: Archives of Medical Research. 2000 March-April; 31(2): 186-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10880725

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Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. Author(s): Prados MD, Scott C, Curran WJ Jr, Nelson DF, Leibel S, Kramer S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 November; 17(11): 3389-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10550132

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Procarbazine, lomustine, and vincristine (PCV) chemotherapy for grade III and grade IV oligoastrocytomas. Author(s): Kim L, Hochberg FH, Thornton AF, Harsh GR 4th, Patel H, Finkelstein D, Louis DN. Source: Journal of Neurosurgery. 1996 October; 85(4): 602-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8814163

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Radiographic response at end of therapy with carboplatin and vincristine as a prognostic indicator in children with low-grade astrocytoma. Author(s): Wendorf K, Townsend N, Foreman NK, Fenton L. Source: Medical and Pediatric Oncology. 2003 December; 41(6): 566-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595718

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Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. Author(s): Medical Research Council Brain Tumor Working Party. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 January 15; 19(2): 509-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208845

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Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas. Author(s): Chamberlain MC, Kormanik P.

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Source: Journal of Neuro-Oncology. 1999 May; 43(1): 71-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448874 •

Screening of transcriptionally regulated genes following iron chelation in human astrocytoma cells. Author(s): Ye Z, Connor JR. Source: Biochemical and Biophysical Research Communications. 1999 November 2; 264(3): 709-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543996

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Spinal cord astrocytoma: response to PCV chemotherapy. Author(s): Henson JW, Thornton AF, Louis DN. Source: Neurology. 2000 January 25; 54(2): 518-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668731

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Stereotactic radiosurgery for pilocytic astrocytomas when multimodal therapy is necessary. Author(s): Hadjipanayis CG, Kondziolka D, Gardner P, Niranjan A, Dagam S, Flickinger JC, Lunsford LD. Source: Journal of Neurosurgery. 2002 July; 97(1): 56-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134933

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Successful combination chemotherapy (vincristine, procarbazine, etoposide, and prednisolone) in the treatment of inoperable, radioresistant low grade astrocytoma: a case report. Author(s): Maipang MVasiknanonte P, Janjindamai SHirunpat S. Source: J Med Assoc Thai. 2000 December; 83(12): 1525-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11253894

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Successful high-dose chemotherapy for widespread neuroaxis dissemination of an optico-hypothalamic juvenile pilocytic astrocytoma in an infant: a case report. Author(s): Kageji T, Nagahiro S, Horiguchi H, Watanabe T, Suzuya H, Okamoto Y, Kuroda Y. Source: Journal of Neuro-Oncology. 2003 May; 62(3): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777080

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Taxol, vincristine or nocodazole induces lethality in G1-checkpoint-defective human astrocytoma U373MG cells by triggering hyperploid progression. Author(s): Hong FD, Chen J, Donovan S, Schneider N, Nisen PD. Source: Carcinogenesis. 1999 July; 20(7): 1161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10383885

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The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy. Author(s): Glass J, Hochberg FH, Gruber ML, Louis DN, Smith D, Rattner B. Source: Journal of Neurosurgery. 1992 May; 76(5): 741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1564535

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The use of chemotherapy to facilitate surgical resection in pleomorphic xanthoastrocytoma: experience in a single case. Author(s): Cartmill M, Hewitt M, Walker D, Lowe J, Jaspan T, Punt J. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2001 September; 17(9): 563-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11585332

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Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy. Author(s): Madajewicz S, Chowhan N, Tfayli A, Roque C, Meek A, Davis R, Wolf W, Cabahug C, Roche P, Manzione J, Iliya A, Shady M, Hentschel P, Atkins H, Braun A. Source: Cancer. 2000 May 15; 88(10): 2350-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10820358

•

Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy. Author(s): Sweet DL, Hendler FJ, Hanlon K, Hekmatpanah J, Griem ML, Duda EE, Mulligan B, Wollman RL. Source: Cancer Treat Rep. 1979 November-December; 63(11-12): 1707-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=230893

•

Treatment of recurrent malignant supratentorial astrocytomas with carboplatin and etoposide combined with recombinant mutant human tumor necrosis factor-alpha. Author(s): Yamamoto M, Oshiro S, Tsugu H, Hirakawa K, Ikeda K, Soma G, Fukushima T. Source: Anticancer Res. 2002 July-August; 22(4): 2447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174942

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

•

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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WebMDHealth: 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/

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. PATENTS ON ASTROCYTOMAS 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.8 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 “astrocytomas” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on astrocytomas, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Astrocytomas By performing a patent search focusing on astrocytomas, 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 8Adapted

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 astrocytomas: •

2-Halo-2'-deoxyadenosines as therapeutic agents against malignant astrocytoma Inventor(s): Piro; Lawrence D. (La Jolla, CA), Saven; Alan (San Diego, CA) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 5,424,296 Date filed: April 15, 1993 Abstract: A process for the treatment of malignant astrocytoma in mammals is disclosed that utilizes a 2-halo-2'-deoxyadenosine derivative as the active treating agent. Excerpt(s): This invention relates to a novel treatment for malignant astrocytoma. More particularly, this invention relates to a process for the treatment of malignant astrocytoma involving the administration of a 2-halo-2'-deoxyadenosine. Histologically and prognostically, cerebral astrocytomas can be divided into low-grade and high-grade subtypes. Glioblastoma multiforme is a most malignant form of astrocytoma. The median survival time for patients with malignant astrocytomas is dismal, usually being less than six months. Surgery and radiation therapy remain the mainstays of therapy. Aggressive surgical resection has been associated with an improved clinical outcome. Re-operation for recurrence can also be efficacious. Postoperative radiation therapy is of value for incompletely resected lesion, however, median survival duration remains less than 12 months. Web site: http://www.delphion.com/details?pn=US05424296__

•

Cell surface antigens of human astrocytoma Inventor(s): Albino; Anthony P. (New York, NY), Beresford; H. Richard (Centre Island, NY), Cairncross; J. Gregory (London, CA), Houghton; Alan N. (New York, NY), Lloyd; Kenneth O. (Bronx, NY), Mattes; M. Jules (Jamaica Estates, NY), Old; Lloyd J. (New York, NY) Assignee(s): Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 4,642,291 Date filed: September 1, 1982 Abstract: Method of forming an antibody producing hybridoma cell line by fusing a myeloma cell line with splenocytes derived from BALB/c mice immunized with human astrocytoma tumor cells, the hybridoma cell line formed, and the monoclonal antibodies generated by said hybridoma cell line. A method of phenotyping astrocytoma tumor cells comprising determining the reaction of said cells to various monoclonal antibodies to astrocytoma tumor cells is also provided. Excerpt(s): The present invention is concerned with various surface antigens of human cancer identified by mouse monoclonal antibodies and more particularly, with mouse monoclonal antibodies recognizing various antigens expressed by human malignant astrocytoma. Astrocytoma tumors are normally found only in the brain and are difficult to diagnose in a manner wherein a useful prognosis can be generated and the most effective treatment predicted. The present invention provides monoclonal antibodies which may be used in identifying or phenotying astrocytoma tumors whereby the

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course of the disease can be predicted and suitable therapy, e.g. chemotherapy versus radiotherapy--can be accomplished. Furthermore, the present invention provides monoclonal antibodies which may be coupled with various side or toxic agents which then may be used for actual treatment or containment of astrocytoma tumors. Imaging of the tumor may also be possible using various radio labels; however, other means which are believed to be more practical, are available for this purpose. Web site: http://www.delphion.com/details?pn=US04642291__ •

Method for treating pediatric high grade astrocytoma including brain stem glioma Inventor(s): Dugan; Margaret H. (Woodside, NY) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,942,247 Date filed: July 29, 1997 Abstract: There is disclosed a method for treating high grade astrocytoma, especially brain stem glioma, in a child by administering to a child in need of such treating an amount of temozolomide sufficient to achieve a clinical response. Preferred dosing schedules are provided. Excerpt(s): Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another study a clinical response was achieved in 21% of patients with advanced melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910-913). Treatment of high grade glioma in adults with temozolomide is also known, Eur. J. Cancer 1993; 29A:940. However treating cancers in children with temozolomide is not well known. This invention is predicated on the discovery that temozolomide is effective in treating a very difficult type of cancer in children--high grade astrocytoma, including brain stem glioma. This invention may be summarized as a method for treating high grade astrocytoma, including brain stem glioma, in a child in need of such treating comprising administering temozolomide in an amount sufficient to achieve a clinical response. Preferred dosing schedules are listed below. As used herein the term children and child is intended to mean a human being of age 18 years or less. As used herein the term patient or patients is intended to mean a child or children. Web site: http://www.delphion.com/details?pn=US05942247__

•

Method of diagnosing and treating gliomas Inventor(s): Sontheimer; Harald W. (Birmingham, AL), Ullrich; Nicole (Fairfield, CT) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 5,905,027 Date filed: December 26, 1996 Abstract: The present invention provides a recombinant toxin and monoclonal antibody which specifically binds to glial-derived or meningioma-derived tumor cells. Also provided are various methods of screening for malignant gliomas and meningiomas. Further provided are methods of treating malignant gliomas, including glioblastoma multiforme and astrocytomas.

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Excerpt(s): The present invention relates generally to the fields of cell physiology, neurology and neuro-oncology. More specifically, the present invention relates to a novel method of diagnosing and treating gliomas and meningiomas. Glial cells comprise a large proportion of the total cell population in the CNS. Unlike neurons, glial cells retain the ability to proliferate postnatally, and some glial cells still proliferate in the adult or aged brain. Uncontrolled glial proliferation can lead to aggressive primary intracranial tumors, the vast majority of which are astrocytomas, and therefore, of glial origin. Tumors of astrocytic origin vary widely in morphology and behavior, and, according to the 1993 WHO classification schema, can be separated into three subsets. Astrocytomas, the lowest grade tumors, are generally well-differentiated and tend to grow slowly. Anaplastic astrocytomas are characterized by increased cellularity, nuclear pleomorphism, and increased mitotic activity. They are intermediate grade tumors and show a tendency to progress to a more aggressive grade. Glioblastomas are considered the most aggressive, with poorly differentiated cells, vascular proliferation, and necrosis. Due to the common morphological heterogeneity of cells within a single tumor, such classification is not clear-cut and is somewhat unsatisfactory. The term "astrocyte-derived tumors" as used herein refers to astrocytomas. Meningiomas are tumor originating in the meninges. Significant progress has been made in identifying physiologically important growth factors, receptors, and signal transduction pathways that control normal and malignant cell proliferation. It is now commonly accepted that growth factor binding leads to activation of oncogenes such as the ras/raf pathway, and ras in turn regulates gene expression through at least two mitogen-activated protein kinases. Interestingly, the ras/raf pathway is in crosstalk with the cAMP signaling cascade which is activated by numerous hormones and neurotransmitters. Web site: http://www.delphion.com/details?pn=US05905027__

Patent Applications on Astrocytomas As of December 2000, U.S. patent applications are open to public viewing.9 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 astrocytomas: •

Methods for diagnosis of low grade astrocytoma Inventor(s): Imam, S. Ashraf; (North Hollywood, CA), Malhotra, Sudarshan; (Glendale, CA) Correspondence: Christie, Parker & Hale, Llp; P.O. Box 7068; Pasadena; CA; 91109-7068; US Patent Application Number: 20030073146 Date filed: October 10, 2002 Abstract: A method for identifying low grade astrocytoma cells in a sample is provided, wherein the method distinguishes between low grade astrocytoma cells and normal astrocytes, thus permitting early diagnosis of astrocytoma. The method uses antibody directed against JI-31 to test astrocytes in the sample for the presence or absence of JI-31 polypeptide, the low grade astrocytoma cells being characterized by the absence of JI-31 while normal astrocytes are characterized by the presence of JI-31.

9

This has been a common practice outside the United States prior to December 2000.

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Excerpt(s): This application claims the benefit of U.S. Provisional Application, Ser. No. 60/328,917, filed Oct. 11, 2001, the content of which is hereby incorporated by reference in its entirety. The subject of the present invention is a method for using an antibody to detect the presence of a disease, and more specifically to distinguish low grade astrocytomas from normal reactive astrocytes. Astrocytomas are members of the glioma family of tumors; that is, tumors arising from glial cells. In the case of astrocytomas, the tumors arise from a type of glial cell called astrocytes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel method of diagnosing and treating gliomas Inventor(s): Sontheimer, Harald W.; (Birmingham, AL), Ullrich, Nicole; (Fairfield, CT) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20020065216 Date filed: October 4, 2001 Abstract: The present invention provides a recombinant toxin and monoclonal antibody which specifically binds to glial-derived or meningioma-derived tumor cells. Also provided are various methods of screening for malignant gliomas and meningiomas. Further provided are methods of treating malignant gliomas, including glioblastoma multiforme and astrocytomas. Excerpt(s): The present invention relates generally to the fields of cell physiology, neurology and neuro-oncology. More specifically, the present invention relates to a novel method of diagnosing and treating gliomas and meningiomas. Glial cells comprise a large proportion of the total cell population in the CNS. Unlike neurons, glial cells retain the ability to proliferate postnatally, and some glial cells still proliferate in the adult or aged brain. Uncontrolled glial proliferation can lead to aggressive primary intracranial tumors, the vast majority of which are astrocytomas, and therefore, of glial origin. Tumors of astrocytic origin vary widely in morphology and behavior, and, according to the 1993 WHO classification schema, can be separated into three subsets. Astrocytomas, the lowest grade tumors, are generally well-differentiated and tend to grow slowly. Anaplastic astrocytomas are characterized by increased cellularity, nuclear pleomorphism, and increased mitotic activity. They are intermediate grade tumors and show a tendency to progress to a more aggressive grade. Glioblastomas are considered the most aggressive, with poorly differentiated cells, vascular proliferation, and necrosis. Due to the common morphological heterogeneity of cells within a single tumor, such classification is not clear-cut and is somewhat unsatisfactory. The term "astrocyte-derived tumors" as used herein refers to astrocytomas. Meningiomas are tumor originating in the meninges. Significant progress has been made in identifying physiologically important growth factors, receptors, and signal transduction pathways that control normal and malignant cell proliferation. It is now commonly accepted that growth factor binding leads to activation of oncogenes such as the ras/raf pathway, and ras in turn regulates gene expression through at least two mitogen-activated. protein kinases. Interestingly, the ras/raf pathway is in crosstalk with the cAMP signaling cascade which is activated by numerous hormones and neurotransmitters. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with astrocytomas, 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 “astrocytomas” (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 astrocytomas. You can also use this procedure to view pending patent applications concerning astrocytomas. 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 5. BOOKS ON ASTROCYTOMAS Overview This chapter provides bibliographic book references relating to astrocytomas. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on astrocytomas 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: 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 “astrocytomas” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “astrocytomas” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “astrocytomas” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Proceedings of the German Society for Neurosurgery: I. Biomechanics in the pathogenesis. II. Astrocytomas of the cerebrum. III. The neurosurgical intensive care unit. IV. Varia by Deutsche Gesellschaft für Neurochirurgie; ISBN: 0444150366; http://www.amazon.com/exec/obidos/ASIN/0444150366/icongroupinterna

Chapters on Astrocytomas In order to find chapters that specifically relate to astrocytomas, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and astrocytomas 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

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and language you prefer, and the format option “Book Chapter.” Type “astrocytomas” (or synonyms) into the “For these words:” box.

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CHAPTER 6. PERIODICALS AND NEWS ON ASTROCYTOMAS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover astrocytomas.

News Services and Press Releases One of the simplest ways of tracking press releases on astrocytomas 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 “astrocytomas” (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 astrocytomas. 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 “astrocytomas” (or synonyms). The following was recently listed in this archive for astrocytomas: •

Marker predicts progression of pilocytic astrocytoma after resection Source: Reuters Medical News Date: July 29, 2003

•

Gamma-linolenic acid selectively toxic to rat astrocytoma cells Source: Reuters Medical News Date: June 11, 1998

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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 “astrocytomas” (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 “astrocytomas” (or synonyms). If you know the name of a company that is relevant to astrocytomas, 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/. 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 “astrocytomas” (or synonyms).

Academic Periodicals covering Astrocytomas Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to astrocytomas. In addition to

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these sources, you can search for articles covering astrocytomas 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 7. 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 astrocytomas. 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).

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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.

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 astrocytomas 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 “astrocytomas” (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

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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 astrocytomas: •

IL-4 Pseudomonas Toxin Fusion Protein (IL-4(38-37) http://www.rarediseases.org/nord/search/nodd_full?code=1038

•

Iodine I-131 radiolabeled chimeric MAb tumor necro (trade name: 131IchTNT-1) http://www.rarediseases.org/nord/search/nodd_full?code=967

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 Institute10: •

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/

10

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.11 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:12 •

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

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “astrocytomas” (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 15228 26 545 9 35 15843

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “astrocytomas” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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.

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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 astrocytomas 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 astrocytomas. 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 astrocytomas. 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 “astrocytomas”:

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Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Spinal Cord Diseases http://www.nlm.nih.gov/medlineplus/spinalcorddiseases.html Tuberous Sclerosis http://www.nlm.nih.gov/medlineplus/tuberoussclerosis.html 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 astrocytomas. 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 options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

An Introduction to TSC Source: Tuberous Sclerosis Alliance. March 2003. 30 p. Contact: Available from Tuberous Sclerosis Alliance. 801 Roeder Road, Suite 750, Silver Spring, MD 20110. (301) 562-9820 or (800) 225-6872. Fax: (301) 562-9870. Website: www.tsalliance.org. Summary: This brochure presents an overview of tuberous sclerosis complex (TSC), a genetic disorder that causes benign tumors in the skin, brain, eyes, heart, kidney, and lungs. Skin manifestations include hypomelanotic macules characterized by flat, light areas of skin sometimes appearing in an 'ash leaf' shape; shagreen patches which appear as tough and dimpled skin usually found on the lower back and nape of the neck; periungal or subungal fibromas (fibrous growths found around the fingernails or toenails); facial angiomas characterized by small red bumps across the cheeks and nose; and forehead plaques that are similar to shagreen patches but found on the scalp and forehead. Diagnosis is made using a Wood's lamp. The types of brain lesions associated with TSC include cortical tubers, subendymal nodules, and subendymal giant cell astrocytomas. The most common neurological problems associated with TSC are epilepsy, mental disorders, and behavioral problems. Benign renal angiomyolipomas are the most common type of lesion in patients with TSC. Benign lesions also occur in

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the heart, eye, and kidney. Fibromas also appear in the gums. Cysts and angiomyolipomas also occur in the adrenal gland, liver, ovary, and pancreas. A glossary of terms is included. Numerous illustrations. •

Clinical Manifestations of Tuberous Sclerosis: A Publication for Professionals Source: Silver Spring, MD: Tuberous Sclerosis Alliance (TSA). 2000. 24 p. Contact: Available from Tuberous Sclerosis Alliance. 801 Roeder Road, Suite 750, Silver Spring, MD 20910. (800) 225-6872 or (301) 562-9890. Fax (301) 562-9870. E-mail: [email protected]. Website: www.tsalliance.org. PRICE: Contact for pricing. Summary: This brochure provides community service professionals, the general public, and people who have tuberous sclerosis (TS) with information on this genetic disease that affects multiple organs and causes tumors in various organ systems. The severity of TS can range from mild to severe. Skin manifestations include hypomelanotic macules, the shagreen patch, periungual or subungual fibromas, and facial angiofibromas. TS can present as benign angiomyolipomas, cysts, malignant angiomyolipomas, oncocytomas, and renal cell carcinoma in the kidneys. Several types of brain lesions are seen in people who have TS, including cortical tubers, cortical hypoplasia, subependymal nodules, and subependymal giant cell astrocytomas. The most frequently observed neurologic problems in TS are epilepsy, mental disabilities, and psychiatric and behavioral problems. Tumors may also appear in the heart, the eyes, the lungs, and gums. The brochure describes all of these clinical manifestations; presents the diagnostic criteria for TS; and discusses diagnostic screening, treatment, and follow up treatment for each clinical manifestation. In addition, the brochure explains the genetics of TS and identifies sources of additional information about TS. 15 figures and 2 tables. 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 astrocytomas. 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 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

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

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•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: 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 astrocytomas. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with astrocytomas. 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 astrocytomas. 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 “astrocytomas” (or a synonym), and you will receive information on all relevant organizations listed in the database. 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 “astrocytomas”. 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

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option “Organization Resource Sheet.” Type “astrocytomas” (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 “astrocytomas” (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.21

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

21

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)22: •

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/

22

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

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

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

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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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

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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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).

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

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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ASTROCYTOMAS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] 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] 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] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [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] 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] 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] 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

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synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] 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] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [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] 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] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as 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] Alpha Particles: Positively charged particles composed of two protons and two neutrons,

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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] 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] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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] Aminocamptothecin: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [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] 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] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angina: Chest pain that originates in the heart. [NIH] 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]

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Angiography: Radiography of blood vessels after injection of a contrast medium. [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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] 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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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-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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing 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] 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]

Antiproliferative: Counteracting a process of proliferation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to

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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] Arginine: An essential amino acid that is physiologically active in the L-form. [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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aseptic: Free from infection or septic material; sterile. [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] 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] 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] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Avian: A plasmodial infection in birds. [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 toxin: A toxic substance, made by bacteria, that can be modified to kill specific

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tumor cells without harming normal cells. [NIH] 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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] 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] 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] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to 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] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [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] 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 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

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capillaries and the brain tissue. [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, 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 Transplantation: The transference of bone marrow from one human or animal to another. [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] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain stem glioma: A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor. [NIH] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU]

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Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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 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 Division: The fission of a cell. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH]

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Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chiasmatic: A subarachnoid space between the pituitary body and the optic chiasm. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Choroid plexus tumor: A rare type of cancer that occurs in the ventricles of the brain. It usually occurs in children younger than 2 years. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone

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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] Chromosome Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [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] 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] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [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] 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] Colloidal: Of the nature of a colloid. [EU] Combination chemotherapy: Treatment using more than one anticancer drug. [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

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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 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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] 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] 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] Conjugated: Acting or operating as if joined; simultaneous. [EU] 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] 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] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues,

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allows radiographic visualization of the structure. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [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 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] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Irradiation: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions). [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] 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]

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Cyst: A sac or capsule filled with fluid. [NIH] Cyst Fluid: Liquid material found in epithelial-lined closed cavities or sacs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [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] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU]

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Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxyadenosines: Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [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] 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] Distemper: A name for several highly contagious viral diseases of animals, especially canine distemper. In dogs, it is caused by the canine distemper virus (distemper virus, canine). It is characterized by a diphasic fever, leukopenia, gastrointestinal and respiratory inflammation and sometimes, neurologic complications. In cats it is known as feline panleukopenia. [NIH] Distemper Virus, Canine: A species of morbillivirus causing distemper in dogs, wolves, foxes, raccoons, and ferrets. [NIH] Diuretic: A drug that increases the production of urine. [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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [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

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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] 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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] 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] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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]

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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Ependymal: It lines the cavities of the brain's ventricles and the spinal cord and slowly divides to create a stem cell. [NIH] Ependymal tumors: A type of brain tumor that usually begins in the central canal of the spinal cord. Ependymomas may also develop in the cells lining the ventricles of the brain, which produce and store the special fluid (cerebrospinal fluid) that protects the brain and spinal cord. Also called ependymomas. [NIH] Ependymomas: Brain tumors that usually begin in the central canal of the spinal cord. Ependymomas may also develop in the cells lining the ventricles of the brain, which produce and store the special fluid (cerebrospinal fluid) that protects the brain and spinal cord. Also called ependymal tumors. [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] 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 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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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 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]

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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] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [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] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH]

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Fast Neutrons: Neutrons, the energy of which exceeds some arbitrary level, usually around one million electron volts. [NIH] Fat: Total lipids including phospholipids. [NIH] Feline Panleukopenia: A highly contagious DNA virus infection of the cat family and of mink, characterized by fever, enteritis and bone marrow changes. It is also called feline ataxia, feline agranulocytosis, feline infectious enteritis, cat fever, cat plague, show fever. [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] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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] Fold: A plication or doubling of various parts of the body. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

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Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [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 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] 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] 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]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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. [NIH]

Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g.,

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fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [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 (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [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] 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [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]

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Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [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] 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] Hamartoma: A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area. [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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematologic Neoplasms: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of leukemia, of lymphoma, and of the progressive, life-threatening forms of the myelodysplastic syndromes. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [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]

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Herpes Zoster: Acute vesicular inflammation. [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]

Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [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] 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] 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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of

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hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] 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] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamic: Of or involving the hypothalamus. [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] Hypoxic: Having too little oxygen. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [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] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] 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

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with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] 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] 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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] 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] Infant, Newborn: An infant during the first month after birth. [NIH] 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

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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]

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 intravenous infusion. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoperable: Not suitable to be operated upon. [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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [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-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds,

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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] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial tumors: Tumors that occur in the brain. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

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] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA

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fragments are up to 50 kilobases long. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] 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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] 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] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkages: 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] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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]

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Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [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 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] 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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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 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] 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] 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] Macroglia: A type of neuroglia composed of astrocytes. [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] 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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to

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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 fibrous histiocytoma: A sarcoma that usually begins in soft tissue. It usually appears as an enlarging, painful mass that can cause fracture due to destruction of the bone by a spreading tumor. [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]

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] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Mechlorethamine: A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median survival time: The point in time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH]

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Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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 Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [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 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] 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] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [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] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] 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]

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Misonidazole: A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic. [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] 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] Mixed gliomas: Brain tumors that occur in more than one type of brain cell, including astrocytes, ependymal cells, and oligodendrocytes. [NIH] 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] 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] Monocyte Chemoattractant Protein-1: A chemokine that is a chemoattractant for human monocytes and may also cause cellular activation of specific functions related to host

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defense. It is produced by leukocytes of both monocyte and lymphocyte lineage and by fibroblasts during tissue injury. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [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] 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] Mutagenic: Inducing genetic mutation. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] 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] Neoplastic Processes: The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity. [NIH] 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] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neuroectodermal tumor: A tumor of the central or peripheral nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

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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] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [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] Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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

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prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oligodendroglial tumors: Rare, slow-growing tumors that begin in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglioma. [NIH] Oligodendroglioma: A rare, slow-growing tumor that begins in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglial tumor. [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] Oncogenic Viruses: Viruses that produce tumors. [NIH] Oncology: The study of cancer. [NIH] Oncology nurse: A nurse who specializes in treating and caring for people who have cancer. [NIH]

Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [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] 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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to

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form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [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 by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [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] Overexpress: An excess of a particular protein on the surface of a cell. [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]

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] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch

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over the eye. [NIH] 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 (= 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]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Peduncle: A narrow supporting part, a stem. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [NIH] 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] 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] Perivascular: Situated around a vessel. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived

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from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [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] 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] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [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] Pilocytic: Made up of cells that look like fibers when viewed under a microscope. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [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] Planning Techniques: Procedures, strategies, and theories of planning. [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] 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] 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

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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] 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-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Pneumonia: Inflammation of the lungs. [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] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [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]

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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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [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] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal 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] Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. [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]

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Promoter: A chemical substance that increases the activity of a carcinogenic process. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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]

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

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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] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [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] 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]

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] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [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] Quiescent: Marked by a state of inactivity or repose. [EU] 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]

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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] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] 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] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign 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] 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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] 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

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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] Renal cell carcinoma: A type of kidney cancer. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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 (= cell respiration). [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] 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]

Retinoid: Vitamin A or a vitamin A-like compound. [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] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU]

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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] 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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] 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] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [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] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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]

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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] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] Shock: The general bodily disturbance following a severe injury; an emotional or moral 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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sister Chromatid Exchange: An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in Bloom syndrome. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spasmogenic: Capable of producing convulsions. [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] Spectroscopic: The recognition of elements through their emission spectra. [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] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [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] 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

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of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] 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] 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]

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 biopsy: A biopsy procedure that uses a computer and a three-dimensional scanning device to find a tumor site and guide the removal of tissue for examination under a microscope. [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] Sterile: Unable to produce children. [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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU]

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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] Subependymal: Below the ependyma (the membrane that lines the ventricles of the brain and the central canal of the spinal cord). [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [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] Subungual: Beneath a nail. [NIH] 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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supratentorial: Located in the upper part of the brain. [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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Teletherapy: Radiotherapy with a souce-skin distance that is large compared to the dimensions of the irradiated tissue being treated. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to

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the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [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] 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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] 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] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tissue: A group or layer of cells that are alike in type and work together to perform a

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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] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] 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] 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] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell

Dictionary 181

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 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]

Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [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 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 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] 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] 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] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases.

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[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] 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] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [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] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [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] 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 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] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new

Dictionary 183

infectious particle. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] 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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] 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]

185

INDEX A Abdominal, 131, 165 Aberrant, 7, 18, 22, 33, 131 Acceptor, 131, 165, 179 Acid Phosphatase, 29, 131 Acidity, 131, 166 Actin, 11, 46, 131, 160 Actinin, 11, 131 Acute myelogenous leukemia, 131 Acute myeloid leukemia, 86, 131 Acute nonlymphocytic leukemia, 131 Adaptability, 131, 138 Adenosine, 31, 131, 144, 167 Adenovirus, 27, 131, 173 Adjuvant, 18, 83, 86, 89, 131 Adjuvant Therapy, 18, 131 Adolescence, 12, 80, 86, 131 Adrenergic, 30, 31, 131, 132, 146 Adrenergic Agonists, 30, 132 Adverse Effect, 132, 175 Aerosol, 132, 178 Afferent, 132, 147 Affinity, 25, 132, 135 Age Groups, 8, 17, 132 Aged, 80 and Over, 132 Agonist, 31, 132 Albumin, 4, 132, 167 Algorithms, 14, 132, 136 Alkaline, 14, 132, 137, 179 Alkalosis, 14, 132, 179 Alkylating Agents, 132, 138, 179 Alleles, 19, 59, 132, 158 Allergen, 132, 144 Alpha Particles, 132, 172 Alternative medicine, 102, 133 Amino Acid Sequence, 18, 133, 134 Aminocamptothecin, 86, 133 Amino-terminal, 26, 133 Amplification, 19, 27, 28, 64, 133 Amygdala, 133, 179 Anaesthesia, 133, 154 Anal, 39, 133, 158 Analog, 133, 149 Analogous, 133, 180 Anaphylatoxins, 46, 133, 141 Anaplastic, 6, 7, 9, 10, 12, 16, 20, 21, 27, 29, 36, 42, 43, 49, 51, 53, 56, 59, 62, 63, 65, 81, 83, 84, 86, 87, 88, 89, 96, 97, 133

Anatomical, 133, 135, 139, 154, 160, 174 Angina, 133, 163 Angiogenesis, 6, 11, 22, 26, 56, 68, 76, 133, 159 Angiography, 57, 134 Animal model, 10, 17, 25, 134 Anions, 132, 134 Annealing, 134, 168 Antiangiogenic, 81, 134 Antibiotic, 134, 176, 179 Antibodies, 18, 30, 41, 58, 94, 134, 146, 151, 153, 158, 161, 167, 172 Anticoagulant, 134, 170 Antigen, 13, 18, 24, 58, 61, 132, 134, 141, 144, 146, 152, 153, 154, 159, 160, 173 Antigen-presenting cell, 134, 144 Antihypertensive, 134, 163 Anti-infective, 134, 156 Anti-inflammatory, 134, 142, 150, 165, 169 Antimetabolite, 134, 137 Antineoplastic, 132, 134, 137, 142, 159, 161, 163, 165, 168, 169, 182 Antineoplastic Agents, 132, 134, 163, 182 Antiproliferative, 81, 134 Antiviral, 134, 137, 155 Anxiety, 44, 134 Aorta, 134, 182 Apolipoproteins, 134, 157 Apoptosis, 10, 11, 22, 27, 31, 32, 35, 70, 135, 138 Arginine, 133, 135, 152, 164, 171 Arterial, 85, 135, 139, 170 Arteries, 134, 135, 136, 142, 158, 160 Arterioles, 135, 136, 137 Artery, 135, 142, 171 Aseptic, 135, 164 Astrocytes, 6, 10, 11, 14, 19, 20, 21, 24, 28, 30, 72, 86, 96, 97, 135, 158, 160, 161 Ataxia, 20, 135, 148, 152 Atrium, 135, 182 Attenuated, 20, 135, 181 Attenuation, 20, 135 Autologous, 53, 73, 135 Autologous bone marrow transplantation, 53, 135 Avian, 25, 135

186

Astrocytomas

B Bacteria, 134, 135, 136, 147, 160, 167, 174, 176, 180, 181 Bacterial toxin, 13, 135 Bacteriophage, 136, 180 Basal Ganglia, 135, 136, 137, 150 Basement Membrane, 136, 147, 157 Benign, 10, 36, 59, 77, 118, 119, 136, 137, 151, 162, 165, 172 Benign tumor, 10, 118, 136 Bilateral, 41, 43, 136 Bile, 136, 152, 157 Bilirubin, 132, 136 Biochemical, 8, 16, 19, 24, 58, 90, 132, 134, 136, 148, 157 Biological therapy, 136, 151 Biopolymers, 12, 136 Biopsy, 8, 37, 136, 147, 177 Biosynthesis, 31, 136, 164, 175 Biotechnology, 29, 32, 102, 113, 136 Blood pressure, 134, 136, 161 Blood vessel, 25, 133, 134, 136, 139, 145, 158, 160, 166, 176, 179, 182 Blood-Brain Barrier, 4, 27, 136 Body Fluids, 132, 137, 181 Bone Marrow, 5, 53, 80, 86, 131, 135, 137, 148, 149, 151, 153, 158, 159, 176, 177 Bone Marrow Transplantation, 5, 53, 80, 86, 137 Brachytherapy, 37, 137, 156, 172, 183 Brain Neoplasms, 137, 152 Brain Stem, 95, 137, 139 Brain stem glioma, 95, 137 Bromodeoxyuridine, 54, 137 Buccal, 16, 137 C Cadherins, 72, 137 Calcium, 30, 137, 141, 159, 163, 165, 170, 179 Capillary, 22, 26, 137, 182 Carboplatin, 69, 81, 88, 89, 91, 137 Carcinogenesis, 90, 137, 167 Carcinogenic, 132, 137, 164, 170, 181 Carcinogens, 138, 164 Carcinoma, 29, 43, 137, 138, 144 Carmustine, 89, 138 Carotene, 138, 173 Case report, 90, 138, 140 Case series, 138, 140 Caspase, 15, 32, 138 Caudal, 138, 153, 169 Cell Adhesion, 137, 138

Cell Cycle, 7, 12, 18, 63, 138, 142, 146, 171 Cell Death, 14, 31, 135, 138, 146, 162 Cell Division, 135, 138, 142, 143, 146, 151, 156, 161, 167, 175 Cell motility, 11, 138, 151 Cell Physiology, 72, 96, 97, 138 Cell proliferation, 52, 96, 97, 138, 173 Cell Size, 138, 148 Cell Survival, 138, 151 Cell Transplantation, 138 Central Nervous System, 4, 21, 137, 138, 139, 145, 149, 150, 151, 152, 160, 164, 169 Central Nervous System Infections, 139, 151, 152 Cerebellar, 36, 38, 59, 61, 62, 69, 70, 76, 135, 139 Cerebellum, 137, 139, 148, 169 Cerebral, 4, 7, 8, 22, 28, 33, 35, 37, 38, 39, 52, 61, 65, 94, 135, 136, 137, 139, 146, 147, 148, 150, 152, 178 Cerebral Cortex, 52, 135, 139, 147 Cerebral hemispheres, 7, 136, 137, 139, 150, 178 Cerebrospinal, 15, 139, 146, 152 Cerebrospinal fluid, 15, 139, 146, 152 Cerebrum, 84, 99, 139, 167, 178, 181 Chelation, 90, 139 Chemotherapeutic agent, 4, 139 Chiasmatic, 68, 80, 87, 139 Chin, 139, 160 Cholesterol, 136, 139, 140, 157, 158 Cholesterol Esters, 139, 157 Chondrocytes, 139, 148 Choroid, 35, 139, 173 Choroid Plexus, 35, 139 Choroid plexus tumor, 35, 139 Chromatin, 71, 135, 139 Chromosomal, 7, 10, 41, 65, 66, 88, 133, 140, 152, 167, 174 Chromosome, 7, 23, 27, 28, 34, 40, 51, 55, 70, 76, 140, 149, 151, 157, 158, 175 Chromosome Aberrations, 23, 51, 140 Chronic, 140, 154, 177 Chylomicrons, 140, 157 CIS, 140, 173 Clinical Medicine, 140, 169 Clinical study, 14, 140 Clinical trial, 3, 13, 23, 34, 113, 140, 159, 166, 170, 172 Cloning, 136, 140, 155 Clot Retraction, 140, 168 Cofactor, 140, 170, 179

187

Colchicine, 140, 181 Collagen, 133, 136, 140, 147, 148, 159, 168 Colloidal, 132, 140, 178 Combination chemotherapy, 88, 90, 140 Complement, 133, 140, 141, 167 Complement Activation, 133, 141 Complementary and alternative medicine, 83, 92, 141 Complementary medicine, 83, 141 Computational Biology, 113, 141 Concomitant, 24, 85, 141 Cones, 141, 173 Conjugated, 141, 143 Connective Tissue, 137, 140, 141, 148, 149, 160, 174 Contraindications, ii, 141 Contralateral, 141, 164 Contrast medium, 134, 141 Coordination, 16, 139, 142 Coronary, 142, 160, 163 Coronary Thrombosis, 142, 160 Cortex, 4, 142 Cortical, 10, 19, 76, 118, 119, 142, 175 Corticosteroid, 142, 169 Cortisol, 132, 142 Cranial, 87, 139, 142, 147, 151, 156, 164, 166 Cranial Irradiation, 87, 142 Craniocerebral Trauma, 142, 151, 152 Crossing-over, 142, 172 Cultured cell line, 49, 142 Cultured cells, 19, 142 Curative, 142, 179 Cyclic, 30, 31, 142, 174 Cyclin, 34, 52, 68, 142 Cyclophosphamide, 85, 142, 153 Cyst, 41, 143 Cyst Fluid, 41, 143 Cytochrome, 15, 143 Cytogenetics, 5, 40, 41, 51, 66, 143 Cytokine, 13, 29, 143 Cytomegalovirus, 22, 30, 31, 143, 149 Cytomegalovirus Infections, 143, 149 Cytoplasm, 135, 143, 147, 174 Cytotoxic, 18, 86, 143, 161, 172 Cytotoxicity, 13, 23, 143 Cytotoxins, 13, 143 D Data Collection, 16, 143 De novo, 8, 10, 28, 143 Decarboxylation, 143, 152, 164, 171 Deletion, 7, 27, 40, 135, 143, 149, 158

Denaturation, 143, 168 Dendrites, 143, 163 Dendritic, 23, 143, 144, 159 Dendritic cell, 23, 144 Density, 21, 58, 60, 144, 148, 157, 164 Deoxyadenosines, 94, 144 DES, 133, 144 Desensitization, 31, 144 Diagnostic procedure, 93, 102, 144 Digestion, 136, 144, 157, 177 Digestive tract, 144, 175, 177 Dilation, 144, 152 Dimethyl, 144, 163 Diploid, 144, 167, 168 Direct, iii, 10, 140, 144, 172, 178 Dissociation, 132, 144 Distemper, 30, 144 Distemper Virus, Canine, 144 Diuretic, 14, 144, 176 Dorsal, 144, 169 Dose-dependent, 15, 144 Drug Interactions, 106, 144 Drug Resistance, 12, 144, 145 Drug Tolerance, 145, 180 E Effector, 22, 140, 145 Effector cell, 145 Efferent, 145, 147 Efficacy, 4, 22, 58, 73, 86, 88, 145, 181 Elasticity, 12, 145 Elastin, 84, 140, 145, 147 Electrons, 145, 156, 158, 165, 172 Electrophysiological, 4, 145 Elementary Particles, 145, 158, 163, 170 Embryo, 145, 154 Encapsulated, 145, 157 Endemic, 145, 177 Endogenous, 10, 145, 167 Endothelial cell, 4, 20, 22, 136, 145, 148, 179 Environmental Exposure, 145, 164 Environmental Health, 80, 112, 114, 145 Enzymatic, 133, 137, 138, 141, 146, 152, 168, 173 Ependyma, 146, 178 Ependymal, 146, 161 Ependymal tumors, 146 Ependymomas, 57, 146 Epidemic, 146, 177 Epidermal, 17, 18, 19, 21, 28, 86, 146, 159 Epidermal Growth Factor, 17, 18, 19, 21, 28, 146

188

Astrocytomas

Epidermis, 146 Epidermoid carcinoma, 146, 177 Epigastric, 146, 165 Epinephrine, 131, 146, 163, 181 Epithelial, 143, 146, 151, 157, 165 Epithelial Cells, 146, 151, 157 Epitopes, 43, 146 Erythrocytes, 137, 146 Etoposide, 69, 81, 88, 89, 90, 91, 146 Eukaryotic Cells, 147, 154 Evoke, 147, 177 Excisional, 9, 147 Excitation, 147, 148, 163 Exocrine, 147, 165 Exogenous, 145, 147 Exons, 28, 147 External-beam radiation, 147, 156, 172, 183 Extracellular, 13, 75, 135, 141, 147, 148, 159, 161, 179 Extracellular Matrix, 75, 141, 147, 148, 159 Extracellular Matrix Proteins, 75, 147, 159 Extracellular Space, 147 Extraction, 8, 147 Eye Infections, 131, 147 F Facial, 49, 118, 119, 147 Facial Expression, 147 Facial Nerve, 49, 147 Family Planning, 113, 147 Farnesyl, 58, 147 Fast Neutrons, 148, 163 Fat, 137, 138, 142, 148, 157, 176 Feline Panleukopenia, 144, 148 Fibrinogen, 148, 167, 168, 179 Fibroblast Growth Factor, 35, 148 Fibroblasts, 15, 148, 155, 162 Fibronectins, 147, 148 Fibrosis, 148, 174 Flow Cytometry, 43, 148 Fluorescence, 5, 54, 76, 148 Fluorescent Dyes, 148 Fold, 6, 20, 148 Fossa, 45, 139, 148 Fourth Ventricle, 139, 148 Fractionation, 33, 149 Functional magnetic resonance imaging, 17, 149 Fungi, 147, 149, 160, 181, 183 G Gamma Rays, 149, 172 Ganciclovir, 50, 149

Ganglia, 149, 162, 166, 178 Gas, 149, 153, 159, 163, 178 Gastric, 18, 146, 149, 152 Gastrin, 40, 149, 152 Gastrointestinal, 144, 146, 149, 159, 176, 178, 181 Gastrointestinal tract, 149, 176, 181 Gene Amplification, 29, 60, 149 Gene Deletion, 23, 56, 149 Gene Expression, 6, 9, 12, 17, 24, 30, 37, 38, 59, 71, 96, 97, 149 Gene Therapy, 50, 131, 149 Genetic testing, 150, 168 Genetics, 8, 9, 10, 16, 17, 51, 119, 143, 150 Genotype, 8, 12, 51, 68, 150, 166 Germ Cells, 150, 165, 179 Gland, 119, 150, 165, 167, 170, 175, 177, 178, 179 Glioblastoma, 6, 9, 10, 11, 12, 20, 21, 26, 27, 28, 42, 81, 86, 89, 94, 95, 97, 150 Glioblastoma multiforme, 6, 9, 10, 12, 20, 27, 28, 42, 81, 86, 89, 94, 95, 97, 150 Glioma, 8, 9, 10, 12, 13, 14, 16, 17, 21, 22, 25, 26, 27, 28, 95, 97, 150 Glucocorticoid, 150, 169 Glucokinase, 150, 152 Glucose, 150, 152, 155, 176 Glycine, 133, 150, 163, 175 Glycoprotein, 31, 148, 150, 157, 179, 181 Glycosaminoglycans, 147, 150 Governing Board, 150, 169 GP41, 30, 150 Grading, 8, 21, 39, 51, 52, 54, 57, 66, 150, 151 Graft, 151, 154 Graft Rejection, 151, 154 Grafting, 151, 154 Growth factors, 21, 96, 97, 151, 160 H Hamartoma, 19, 151 Haploid, 151, 167, 168 Haptens, 132, 151 Headache, 151, 152 Hematologic malignancies, 151, 158 Hematologic Neoplasms, 5, 151 Heme, 136, 143, 151 Hepatic, 132, 151 Hepatocyte, 45, 80, 151 Hepatocyte Growth Factor, 45, 80, 151 Hereditary, 151, 173 Heredity, 149, 150, 151 Herpes, 10, 20, 50, 151, 152

189

Herpes Zoster, 151, 152 Heterogeneity, 9, 51, 96, 97, 132, 152 Hexokinase, 14, 20, 152 Histamine, 31, 133, 152 Histamine Release, 133, 152 Histology, 19, 23, 77, 152, 165 Histones, 139, 152 Homeostasis, 25, 152 Homogeneous, 27, 152 Homologous, 132, 142, 149, 152, 175 Hormone, 22, 57, 131, 142, 144, 146, 149, 152, 155, 156, 159, 168, 174, 176, 179 Hormone therapy, 57, 131, 152 Humoral, 18, 151, 152 Humour, 152 Hybrid, 10, 12, 152 Hybridoma, 86, 94, 152 Hydrocephalus, 66, 152, 156 Hydrogen, 131, 143, 147, 153, 161, 163, 165, 166, 171 Hydrolysis, 153, 169, 170 Hydrophobic, 153, 157 Hydroxyproline, 133, 140, 153 Hypersensitivity, 132, 144, 153 Hyperthermia, 37, 153 Hypoplasia, 119, 153 Hypothalamic, 42, 62, 68, 80, 84, 85, 87, 90, 153 Hypothalamus, 137, 153, 167, 176 Hypoxia, 6, 20, 153 Hypoxic, 6, 45, 153, 161 I Ifosfamide, 69, 81, 88, 89, 153 Immune response, 18, 23, 131, 134, 142, 151, 153, 154, 178, 182 Immune Sera, 153 Immune system, 134, 136, 145, 153, 154, 158, 183 Immunization, 18, 153, 154 Immunodeficiency, 30, 31, 32, 153 Immunoglobulin, 134, 147, 153, 161 Immunohistochemistry, 32, 153 Immunologic, 153, 172 Immunology, 131, 132, 148, 154 Immunosuppressive, 142, 150, 153, 154 Immunosuppressive therapy, 154 Immunotherapy, 18, 23, 72, 136, 144, 154 Impairment, 6, 135, 147, 154, 160 Implant radiation, 154, 156, 172, 183 Implantation, 18, 154 In situ, 13, 54, 56, 76, 154 In Situ Hybridization, 54, 76, 154

In vitro, 4, 6, 12, 19, 20, 21, 22, 25, 26, 28, 29, 42, 54, 80, 149, 154, 168, 180 In vivo, 4, 6, 9, 10, 12, 13, 14, 20, 21, 22, 25, 26, 27, 28, 29, 50, 54, 149, 154 Incision, 154, 156 Incontinence, 152, 154 Incubated, 31, 154 Incubation, 154, 157 Incubation period, 154, 157 Induction, 18, 23, 30, 154, 172 Infant, Newborn, 132, 154 Infarction, 142, 153, 154, 160 Infection, 22, 25, 135, 136, 143, 147, 148, 153, 154, 157, 158, 178, 183 Inflammation, 132, 134, 144, 147, 148, 152, 155, 168 Infusion, 15, 155 Innervation, 147, 155 Inoperable, 90, 155 Inositol, 39, 155, 174 Insertional, 11, 155 Insulin, 57, 72, 155 Insulin-dependent diabetes mellitus, 155 Insulin-like, 57, 72, 155 Intensive Care, 99, 155 Interferon, 21, 155 Interferon-alpha, 155 Interleukin-6, 46, 155 Intermediate Filaments, 11, 155 Internal radiation, 155, 156, 172, 183 Interphase, 41, 66, 156 Interstitial, 137, 147, 156, 183 Intestines, 131, 144, 149, 156, 175 Intracellular, 4, 14, 154, 156, 159, 174, 182 Intracellular Membranes, 156, 159 Intracranial Hemorrhages, 152, 156 Intracranial Hypertension, 151, 152, 156 Intracranial tumors, 20, 96, 97, 156 Intrathecal, 10, 15, 156 Intravenous, 155, 156 Intrinsic, 20, 132, 136, 156 Invasive, 9, 21, 26, 27, 84, 156, 158 Involuntary, 156, 162, 179 Iodine, 86, 107, 156 Ion Channels, 135, 156 Ionizing, 133, 145, 156, 172, 175 Irradiation, 20, 37, 67, 86, 88, 156, 183 Isoenzyme, 152, 156 K Kb, 22, 28, 112, 156 Kinetics, 59, 157

190

Astrocytomas

L Lacrimal, 147, 157 Laminin, 136, 147, 157 Latency, 19, 157 Lectin, 157, 159 Lentivirus, 10, 157 Lesion, 94, 118, 157 Lethal, 9, 14, 17, 20, 157 Lethargy, 152, 157 Leukemia, 5, 150, 151, 157 Leukocytes, 137, 155, 157, 162, 181 Leukopenia, 144, 157 Life Expectancy, 14, 157 Ligands, 21, 157 Linkages, 9, 150, 152, 157 Lipid, 135, 155, 157 Lipoprotein, 21, 60, 157, 158 Liposomal, 52, 157 Liver, 10, 76, 119, 131, 132, 136, 142, 143, 151, 152, 157, 169, 181 Localization, 14, 33, 45, 153, 157 Localized, 9, 27, 28, 145, 154, 157, 167 Lomustine, 88, 89, 158 Longitudinal study, 75, 158 Loss of Heterozygosity, 70, 158 Low-density lipoprotein, 157, 158 Lumbar, 57, 158 Lymph, 145, 152, 158, 178 Lymphatic, 151, 155, 158, 160, 168, 176, 179 Lymphatic system, 158, 176, 179 Lymphocyte, 134, 158, 159, 162 Lymphoid, 134, 158 Lymphoma, 151, 158 M Macroglia, 158, 160 Macrophage, 30, 158 Magnetic Resonance Imaging, 158 Magnetic Resonance Spectroscopy, 8, 38, 158 Malformation, 151, 158 Malignancy, 13, 21, 28, 39, 48, 55, 158 Malignant fibrous histiocytoma, 15, 159 Malignant tumor, 27, 159 Malnutrition, 132, 159 Matrix metalloproteinase, 26, 62, 159 Measles Virus, 30, 31, 159 Mechlorethamine, 159, 169 Medial, 55, 159, 164 Median survival time, 94, 159 Mediate, 25, 30, 159 Mediator, 20, 159

Medical Records, 159, 174 MEDLINE, 113, 159 Melanin, 159, 166, 181 Melanocytes, 159 Melanoma, 43, 81, 95, 159 Membrane Proteins, 25, 159 Meninges, 96, 97, 138, 139, 142, 159, 160 Meningioma, 9, 95, 97, 160 Mental, iv, 3, 19, 44, 112, 114, 118, 119, 139, 144, 160, 171, 175 Mental Disorders, 118, 160, 171 Mental Processes, 144, 160, 171 Mental Retardation, 19, 160 Mercury, 148, 160 Mesenchymal, 10, 146, 160 Metastasis, 25, 52, 59, 81, 159, 160 Metastatic, 81, 137, 160, 174 Methyltransferase, 32, 56, 160 MI, 47, 129, 160 Microbe, 160, 180 Microfilaments, 155, 160 Microglia, 57, 135, 160 Microorganism, 140, 160, 183 Microtubules, 155, 160, 163, 165 Migration, 4, 21, 22, 25, 49, 160 Misonidazole, 48, 161 Mitochondrial Swelling, 161, 162 Mitogen-Activated Protein Kinase Kinases, 161 Mitogen-Activated Protein Kinases, 96, 161 Mitosis, 135, 161 Mitotic, 96, 97, 146, 161, 182 Mixed gliomas, 41, 161 Modeling, 12, 161 Modification, 133, 161, 171 Molecule, 134, 141, 142, 144, 145, 147, 149, 153, 155, 157, 161, 165, 167, 168, 172, 180, 182 Monitor, 25, 161, 163 Monoclonal, 30, 41, 80, 86, 94, 95, 97, 156, 161, 172, 183 Monoclonal antibodies, 30, 80, 86, 94, 161 Monocyte, 32, 54, 161 Monocyte Chemoattractant Protein-1, 54, 161 Mononuclear, 162, 181 Morbillivirus, 144, 159, 162 Morphological, 8, 96, 97, 145, 159, 162 Morphology, 8, 96, 97, 162 Motility, 11, 40, 162 Mucositis, 162, 179

191

Mutagenic, 132, 162, 175 Myelin, 162, 164 Myeloma, 94, 152, 162 Myocardium, 160, 162 N Necrosis, 40, 96, 97, 135, 150, 154, 160, 162 Neoplasia, 15, 162 Neoplasm, 4, 151, 162, 165, 174, 181 Neoplastic, 5, 10, 21, 47, 50, 81, 158, 162 Neoplastic Processes, 5, 162 Nerve, 31, 131, 135, 139, 143, 145, 147, 155, 159, 162, 164, 174, 177, 180 Nerve Growth Factor, 31, 162 Networks, 11, 162 Neural, 10, 20, 132, 152, 160, 162 Neuroectodermal tumor, 162, 169 Neurologic, 6, 19, 53, 61, 119, 144, 150, 152, 162 Neuronal, 24, 33, 162 Neurons, 20, 24, 96, 97, 143, 149, 162, 163, 178 Neurotransmitter, 131, 133, 150, 152, 156, 163, 174, 176, 178 Neutrons, 48, 132, 148, 156, 163, 172 Nicardipine, 86, 163 Nitrogen, 142, 147, 163 Nocodazole, 90, 163 Norepinephrine, 131, 163 Nuclear, 40, 46, 96, 97, 136, 145, 147, 149, 150, 162, 163, 172, 173 Nuclei, 71, 133, 145, 147, 149, 152, 158, 161, 163, 164, 168, 170 Nucleic acid, 154, 163, 171, 176, 182 Nucleus, 49, 135, 140, 142, 143, 145, 147, 149, 155, 162, 163, 170, 177, 179 O Odds Ratio, 163, 173 Ointments, 164, 165 Oligo, 27, 71, 87, 164 Oligodendroglial, 27, 71, 164 Oligodendroglial tumors, 27, 164 Oligodendroglioma, 17, 88, 91, 164 Oncogene, 11, 15, 34, 53, 55, 67, 151, 164 Oncogenic, 5, 10, 17, 18, 157, 164, 171 Oncogenic Viruses, 5, 164 Oncology nurse, 5, 164 Opacity, 144, 164 Open Reading Frames, 157, 164 Opsin, 164, 173, 174 Optic Chiasm, 42, 62, 139, 153, 164 Optic Nerve, 164, 173, 174 Organ Culture, 84, 164, 180

Ornithine, 30, 164, 171 Ornithine Decarboxylase, 30, 164 Osmotic, 132, 161, 165 Outpatient, 87, 165 Ovary, 119, 165 Overall survival, 27, 44, 165 Overexpress, 15, 165 Oxidation, 131, 143, 165 P P53 gene, 36, 41, 53, 165 Paclitaxel, 87, 165 Palliative, 165, 179 Pancreas, 119, 131, 155, 165, 176, 181 Papilloma, 165, 173 Paraffin, 54, 56, 165 Parathyroid, 56, 165, 179 Parathyroid Glands, 165 Parathyroid hormone, 56, 165 Particle, 165, 180, 183 Patch, 119, 165 Pathogenesis, 10, 16, 17, 18, 60, 75, 99, 166 Pathologic, 10, 17, 135, 136, 142, 153, 166, 173 Pathologic Processes, 135, 166 Patient Education, 118, 124, 126, 129, 166 Patient Selection, 23, 166 Peduncle, 35, 166 Pelvis, 158, 166 Peptide, 18, 29, 133, 148, 166, 168, 169, 170 Performance status, 23, 166 Perfusion, 153, 166, 180 Peripheral Nervous System, 162, 163, 166, 176, 178 Perivascular, 160, 166 Petroleum, 165, 166 PH, 37, 40, 47, 166 Phagocytosis, 160, 166 Pharmacists, 5, 166 Pharmacologic, 166, 180 Phenotype, 11, 26, 30, 51, 68, 149, 166 Phenylalanine, 166, 181 Phospholipids, 148, 155, 157, 166, 170 Phosphorus, 38, 81, 137, 165, 167 Phosphorylation, 12, 161, 167, 170 Phosphotyrosine, 29, 167 Physiologic, 132, 136, 167, 172, 173 Physiology, 72, 145, 167 Pigment, 136, 159, 167 Pilot study, 23, 72, 167 Pineal Body, 167 Pineal gland, 60, 167 Pituitary Gland, 142, 148, 167

192

Astrocytomas

Planning Techniques, 32, 167 Plants, 143, 150, 157, 162, 163, 167, 180, 181 Plasma, 13, 29, 132, 134, 139, 148, 162, 167, 168, 170, 180 Plasma cells, 134, 162, 167 Plasma protein, 132, 167, 170 Plasmid, 149, 167, 182 Plasmin, 21, 167, 168 Plasminogen, 167, 168 Plasminogen Activators, 167, 168 Platelet Aggregation, 133, 168 Platelet-Derived Growth Factor, 30, 168 Platelets, 168 Pleomorphic, 81, 87, 91, 168 Plexus, 168 Ploidy, 43, 168 Pneumonia, 141, 168 Podophyllotoxin, 146, 168 Point Mutation, 41, 168 Polymerase, 55, 168 Polymerase Chain Reaction, 55, 168 Polymorphic, 12, 139, 168 Polymorphism, 12, 60, 168 Polypeptide, 96, 133, 140, 146, 148, 167, 169, 170, 176, 183 Polysaccharide, 134, 169, 170 Pons, 137, 148, 169 Posterior, 45, 133, 135, 139, 144, 165, 167, 169, 174 Postnatal, 169, 177 Postoperative, 87, 94, 169 Potentiate, 23, 169 Practicability, 169, 181 Practice Guidelines, 114, 169 Preclinical, 18, 19, 169 Precursor, 24, 142, 145, 146, 147, 163, 166, 168, 169, 170, 176, 181 Prednisolone, 90, 169 Prednisone, 169 Primary tumor, 21, 169 Primitive neuroectodermal tumors, 50, 57, 169 Probe, 11, 169 Procarbazine, 83, 88, 89, 90, 169 Prognostic factor, 49, 58, 60, 68, 69, 169 Progression, 7, 9, 11, 12, 18, 21, 25, 44, 50, 52, 54, 61, 74, 81, 87, 90, 101, 134, 169 Progressive, 80, 84, 85, 145, 151, 162, 169, 181 Promoter, 20, 22, 32, 170 Prospective study, 158, 170

Prostate, 170, 181 Protease, 22, 170 Protein C, 21, 31, 132, 133, 134, 136, 157, 170, 181 Protein Conformation, 133, 170 Protein Kinase C, 161, 170 Protein Kinases, 97, 161, 170 Protein S, 11, 136, 170, 174, 179 Protein-Serine-Threonine Kinases, 161, 170 Proteoglycans, 136, 147, 170 Proteolytic, 26, 141, 148, 168, 170 Prothrombin, 170, 179 Protocol, 5, 16, 169, 170 Protons, 77, 132, 153, 156, 158, 170, 172 Proto-Oncogene Proteins, 165, 171 Proto-Oncogene Proteins c-mos, 165, 171 Protozoa, 160, 171, 181 Psychiatric, 119, 160, 171 Psychiatry, 67, 70, 171 Psychic, 160, 171, 175 Psychology, 5, 144, 171 Public Policy, 113, 171 Publishing, 29, 171 Pulmonary, 136, 171, 182 Pulmonary Artery, 136, 171, 182 Pulse, 161, 171 Purines, 171, 175 Putrescine, 165, 171, 176 Pyridoxal, 164, 171 Pyrimidines, 171, 175 Q Quality of Life, 5, 171 Quiescent, 24, 171 R Race, 16, 160, 171 Radiation therapy, 14, 18, 20, 39, 72, 76, 81, 88, 89, 91, 94, 131, 147, 149, 156, 172, 177, 183 Radioactive, 153, 154, 155, 156, 161, 163, 164, 172, 181, 183 Radioactivity, 142, 172 Radioimmunotherapy, 172 Radiolabeled, 86, 107, 156, 172, 183 Radiology, 5, 9, 33, 38, 41, 61, 64, 67, 73, 88, 172 Radiosensitization, 84, 172 Radiotherapy, 20, 23, 32, 33, 49, 64, 65, 67, 71, 73, 83, 85, 87, 88, 95, 137, 156, 172, 177, 178, 183 Randomized, 83, 88, 89, 145, 172

193

Recombinant, 27, 31, 40, 72, 91, 95, 97, 172, 182 Recombination, 6, 149, 172 Recurrence, 4, 14, 16, 21, 94, 172 Refer, 1, 137, 140, 149, 151, 157, 163, 172, 180 Regeneration, 148, 172 Regimen, 145, 172 Relapse, 18, 29, 172 Relative risk, 16, 172 Reliability, 58, 173 Remission, 172, 173 Renal cell carcinoma, 10, 119, 173 Resected, 14, 85, 94, 173 Resection, 4, 14, 21, 25, 39, 53, 59, 71, 74, 76, 91, 94, 101, 173 Resorption, 152, 173 Respiration, 161, 173 Retina, 139, 141, 164, 173, 174 Retinal, 57, 164, 173, 174 Retinoblastoma, 45, 173 Retinoblastoma Protein, 45, 173 Retinoid, 80, 173 Retinol, 173, 174 Retraction, 4, 140, 173 Retrospective, 8, 43, 68, 89, 174 Retrospective study, 43, 68, 174 Retroviral vector, 25, 149, 174 Retrovirus, 10, 25, 174 Rhodopsin, 164, 173, 174 Ribose, 131, 144, 174 Ribosome, 174, 180 Rickettsiae, 174, 181 Risk factor, 170, 173, 174 Rods, 173, 174 S Salivary, 143, 147, 174, 178 Salivary glands, 143, 147, 174 Sarcoma, 159, 169, 174 Scatter, 45, 174 Sclera, 139, 174 Sclerosis, 19, 174 Screening, 90, 95, 97, 119, 140, 174 Second Messenger Systems, 174 Secondary tumor, 160, 174 Secretion, 29, 72, 80, 142, 146, 152, 155, 160, 174, 175 Sedimentation, 175, 181 Segmentation, 14, 175 Segregation, 172, 175 Seizures, 19, 74, 150, 175 Semisynthetic, 146, 175

Senescence, 46, 175 Sequencing, 168, 175 Serine, 21, 161, 170, 171, 175 Serum, 11, 30, 132, 133, 140, 141, 153, 158, 175, 181 Sex Characteristics, 131, 175 Shock, 35, 175, 181 Side effect, 105, 107, 132, 136, 142, 175, 180 Signs and Symptoms, 172, 173, 175 Sister Chromatid Exchange, 81, 175 Skeleton, 131, 175 Skull, 142, 175, 177 Small intestine, 140, 152, 156, 175, 182 Smooth muscle, 133, 152, 176, 178 Social Environment, 171, 176 Social Work, 5, 176 Soft tissue, 137, 159, 175, 176 Solid tumor, 5, 12, 27, 133, 158, 176 Somatic, 131, 152, 161, 166, 175, 176, 179 Somatostatin, 30, 42, 65, 176 Sorbitol, 152, 176 Spasmogenic, 133, 176 Specialist, 120, 144, 176 Species, 138, 140, 144, 146, 152, 157, 159, 160, 161, 162, 171, 176, 181, 182, 183 Specificity, 9, 13, 28, 29, 132, 137, 176, 180 Spectroscopic, 8, 158, 176 Spectrum, 160, 176 Sperm, 140, 176, 181 Spermidine, 165, 176 Spinal cord, 63, 73, 84, 90, 135, 137, 138, 139, 146, 156, 159, 160, 162, 163, 166, 176, 178 Spleen, 143, 152, 158, 176 Sporadic, 28, 38, 59, 64, 76, 173, 177 Squamous, 15, 29, 146, 177 Squamous cell carcinoma, 15, 146, 177 Squamous cells, 177 Staging, 56, 177 Stem cell transplantation, 5, 73, 177 Stem Cells, 11, 177 Stereotactic, 25, 44, 49, 64, 71, 73, 81, 90, 177 Stereotactic biopsy, 64, 71, 177 Stereotactic radiosurgery, 44, 73, 81, 90, 177 Sterile, 135, 165, 177 Stimulus, 6, 145, 147, 155, 156, 157, 177 Stomach, 131, 144, 149, 152, 156, 175, 177 Strand, 30, 168, 177 Stress, 142, 161, 177 Stromal, 26, 177

194

Astrocytomas

Subacute, 154, 177 Subarachnoid, 58, 139, 148, 151, 156, 177 Subclinical, 154, 175, 178 Subependymal, 10, 19, 28, 36, 60, 65, 66, 75, 119, 178 Submaxillary, 146, 178 Substance P, 175, 178 Substrate, 29, 178 Subungual, 119, 178 Sulfur, 147, 178 Suppression, 7, 142, 178 Supratentorial, 4, 8, 33, 34, 36, 43, 49, 56, 60, 62, 66, 69, 73, 74, 76, 77, 83, 85, 88, 91, 178 Survival Rate, 27, 165, 178 Suspensions, 52, 178, 181 Sympathetic Nervous System, 163, 178 Symptomatic, 17, 178 Synapse, 132, 178, 181 Synergistic, 178, 179 Systemic, 52, 134, 136, 146, 155, 156, 169, 172, 178, 180, 183 T Telencephalon, 136, 139, 178 Teletherapy, 47, 178 Telomerase, 6, 38, 178 Temozolomide, 74, 95, 179 Testis, 13, 61, 179 Tetany, 165, 179 Tetracycline, 10, 179 Thalamic, 39, 41, 43, 75, 135, 179 Therapeutics, 40, 106, 179 Thermal, 144, 163, 168, 179 Thorax, 158, 179 Threonine, 161, 170, 171, 175, 179 Thrombin, 30, 148, 168, 170, 179 Thrombomodulin, 170, 179 Thrombosis, 170, 179 Thymidine, 50, 137, 179 Thymidine Kinase, 50, 179 Thymus, 153, 158, 179 Thyroid, 156, 165, 179, 181 Thyroid Gland, 165, 179 Thyroxine, 132, 166, 179 Tic, 62, 179 Tissue Culture, 48, 180 Tissue Distribution, 137, 180 Tolerance, 20, 131, 180 Topical, 165, 180 Topoisomerase inhibitors, 133, 180 Toxic, iv, 13, 95, 101, 132, 135, 143, 145, 168, 171, 180

Toxicity, 16, 18, 20, 22, 29, 36, 144, 160, 180 Toxicology, 114, 180 Toxin, 95, 97, 107, 180 Transcriptase, 174, 178, 180 Transduction, 20, 23, 27, 50, 96, 97, 155, 167, 180 Transfection, 11, 136, 149, 180 Transfer Factor, 153, 180 Transgenes, 10, 180 Translating, 17, 180 Translation, 23, 133, 180 Translational, 5, 6, 17, 180 Transmitter, 135, 156, 159, 163, 180 Transplantation, 25, 153, 181 Trauma, 24, 162, 181 Treatment Outcome, 16, 181 Tropism, 20, 181 Tuberous Sclerosis, 10, 28, 57, 60, 66, 71, 75, 118, 119, 181 Tubulin, 33, 160, 181 Tumor marker, 9, 181 Tumor Necrosis Factor, 32, 40, 46, 72, 91, 181 Tumor suppressor gene, 7, 10, 22, 24, 27, 34, 54, 70, 158, 165, 173, 181 Tumorigenic, 6, 15, 181 Tumour, 29, 181 Tyrosine, 29, 45, 46, 167, 181 U Urea, 164, 181 Urinary, 152, 154, 181 Urine, 144, 146, 154, 181 Urokinase, 21, 181 V Vaccines, 18, 181, 182 Vascular, 10, 46, 96, 97, 139, 154, 155, 168, 179, 182 Vascular endothelial growth factor, 46, 182 Vasodilator, 152, 163, 182 Vector, 10, 20, 22, 155, 180, 182 Vein, 20, 156, 163, 182 Venoms, 143, 182 Venous, 170, 182 Ventricle, 58, 133, 153, 167, 171, 182 Ventricular, 153, 182 Venules, 136, 137, 182 Vertebrae, 176, 182 Veterinary Medicine, 113, 182 Villi, 152, 182 Villous, 139, 182 Vinblastine, 181, 182

195

Vinca Alkaloids, 182 Vincristine, 80, 83, 85, 86, 88, 89, 90, 169, 181, 182 Viral, 23, 28, 144, 148, 150, 164, 174, 180, 181, 182 Viral vector, 23, 182 Virulence, 135, 180, 182 Virus, 10, 20, 30, 31, 32, 136, 139, 144, 148, 155, 173, 174, 180, 182 Virus Replication, 30, 182 Visual field, 164, 183 Vital Statistics, 16, 183 Vitamin A, 155, 173, 183 Vitro, 20, 21, 22, 25, 183

Vivo, 4, 7, 8, 20, 21, 22, 25, 26, 28, 47, 61, 72, 183 W White blood cell, 134, 154, 157, 158, 161, 162, 167, 183 Wound Healing, 148, 159, 183 X Xenograft, 28, 29, 134, 183 X-ray, 141, 148, 149, 156, 163, 172, 177, 183 X-ray therapy, 156, 183 Y Yeasts, 149, 166, 183 Z Zymogen, 170, 183

196

Astrocytomas

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