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

CHILDHOOD CANCER 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., 1960Childhood Cancer: 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: 0-497-00228-0 1. Childhood Cancer-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 childhood cancer. 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 CHILDHOOD CANCER .............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Childhood Cancer.......................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 55 The National Library of Medicine: PubMed ................................................................................ 56 CHAPTER 2. NUTRITION AND CHILDHOOD CANCER ..................................................................... 99 Overview...................................................................................................................................... 99 Finding Nutrition Studies on Childhood Cancer......................................................................... 99 Federal Resources on Nutrition ................................................................................................. 101 Additional Web Resources ......................................................................................................... 101 CHAPTER 3. ALTERNATIVE MEDICINE AND CHILDHOOD CANCER ............................................ 103 Overview.................................................................................................................................... 103 National Center for Complementary and Alternative Medicine................................................ 103 Additional Web Resources ......................................................................................................... 107 General References ..................................................................................................................... 107 CHAPTER 4. DISSERTATIONS ON CHILDHOOD CANCER .............................................................. 109 Overview.................................................................................................................................... 109 Dissertations on Childhood Cancer............................................................................................ 109 Keeping Current ........................................................................................................................ 110 CHAPTER 5. BOOKS ON CHILDHOOD CANCER ............................................................................. 111 Overview.................................................................................................................................... 111 Book Summaries: Federal Agencies............................................................................................ 111 Book Summaries: Online Booksellers......................................................................................... 112 Chapters on Childhood Cancer................................................................................................... 113 CHAPTER 6. PERIODICALS AND NEWS ON CHILDHOOD CANCER ............................................... 117 Overview.................................................................................................................................... 117 News Services and Press Releases.............................................................................................. 117 Newsletter Articles .................................................................................................................... 120 Academic Periodicals covering Childhood Cancer ..................................................................... 120 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 125 Overview.................................................................................................................................... 125 NIH Guidelines.......................................................................................................................... 125 NIH Databases........................................................................................................................... 127 Other Commercial Databases..................................................................................................... 129 APPENDIX B. PATIENT RESOURCES ............................................................................................... 131 Overview.................................................................................................................................... 131 Patient Guideline Sources.......................................................................................................... 131 Associations and Childhood Cancer........................................................................................... 133 Finding Associations.................................................................................................................. 134 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 137 Overview.................................................................................................................................... 137 Preparation................................................................................................................................. 137 Finding a Local Medical Library................................................................................................ 137 Medical Libraries in the U.S. and Canada ................................................................................. 137 ONLINE GLOSSARIES................................................................................................................ 143 Online Dictionary Directories ................................................................................................... 143 CHILDHOOD CANCER DICTIONARY .................................................................................. 145

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INDEX .............................................................................................................................................. 195

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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 childhood cancer 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 childhood cancer, 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 childhood cancer, 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 childhood cancer. 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 childhood cancer, 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 childhood cancer. 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 CHILDHOOD CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on childhood cancer.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and childhood cancer, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “childhood cancer” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Disturbances in Oral and Dental Structures in Patients with Pediatric Lymphoma After Chemotherapy: A Preliminary Report Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 87(3): 317-321. March 1999. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Summary: This article reports on a study undertaken to evaluate the effects of chemotherapy on oral and dental structures and craniofacial growth in 30 survivors of childhood lymphoma (cancer). Eruption status, root malformations, premature apexification (closure of the tooth root), agenesis (lack of a tooth or teeth), crown anomalies, soft tissue abnormalities, gingival and periodontal status, enamel defects and

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Childhood Cancer

discolorations, and craniofacial growth status of the subjects were documented and compared with findings in 20 healthy children who served as controls. Statistically significant differences between the study and control groups were found for plaque index, enamel hypoplasia, discolorations, and agenesis. The authors conclude that antineoplastic therapy and or childhood cancer can result in a higher prevalence of various malformations in teeth. Children treated in the early years of their lives displayed the most severe dental defects, suggesting that immature teeth are at a greater risk of developmental disturbances than fully developed teeth. 1 figure. 3 tables. 22 references. (AA-M).

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

Project Title: A MUTATIONAL MODEL FOR CHILDHOOD CANCER Principal Investigator & Institution: Strong, Louise C.; Professor; Pediatrics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 30-APR-2004 Summary: Overall Description (Applicant's Description) We have developed a multidisciplinary program to investigate genetic susceptibility to childhood and associated cancer using genetic epidemiologic, cellular, and molecular techniques. The hypotheses are based on a multi-stage model for cancer, and are tested in two model familial syndromes of childhood and adolescent cancers, sarcomas and Li Fraumeni syndrome and its variants and Wilms' tumor of the kidney. or each tumor type, genetic loci have been identified that may be altered both as germline mutations and as tumor-specific mutations. There is also significant evidence for genetic heterogeneity, or involvement of additional cancer susceptibility loci. The underlying themes of the program include characterization of the underlying characterization of the underling cancer susceptibility, determination of the heritable contribution to each tumor, determination of the role and nature of genomic instability and genes that confer genomic instability in familial cancer syndromes, analysis of germline and somatic mutations by type and mechanism, development of animal models for human cancer susceptibility syndromes

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).

Studies

5

to explore evidence for modifier genes and developmental effects, and determination of the implications of germline mutations for the patients and their families. The findings from this program should provide insights into the mechanisms of carcinogenesis as well as guidelines for clinical programs for patients at high risk of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTICANCER DRUG EFFLUX TRANSPORTERS IN DEVELOPMENT Principal Investigator & Institution: Sartorelli, Alan C.; Professor; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Resistance of tumor cells to multiple chemotherapeutic agents (MDR) is a major obstacle to the treatment of most human cancers. The phenomenon of MDR confers upon malignant cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. Multidrug resistance has been characterized by the overexpression of membrane-associated glycoproteins; the two most studied of these ATP-binding cassette (ABC) transporters which have a role in drug efflux are the P-glycoprotein (P-gly) and the multidrug resistance (-associated) protein (MRP1). Little is known about the expression of the ABC transporters during ontogeny and how their development impacts the host response to therapeutic agents in utero and in early postnatal life. Similarly, little information is available on their role in the toxicity of cancer chemotherapeutic agents to normal tissues and their importance to the treatment of malignant diseases during childhood. Accordingly, we plan to determine the murine development patterns of the P-gly (mdr1a/1b) and the multidrug resistance protein family (mrps 1-7) by examining the tissue distribution of these ABC transporters prenatally and postnatally at 1, 3, and 10-12 weeks of age, corresponding approximately to the fetal, newborn, childhood and adulthood developmental periods. As model systems we will employ wild-type and genetically deficient mrp1 (-/-); mdr1a/1b(-/-); and mrp1 (- /-), mdr1a/1b(-/-) mice and embryonic fibroblast cell lines derived therefrom (a) to evaluate the role of these ABC transporters in protecting normal tissue from several anticancer agents, particularly stressing their relationships to vincristine and methotrexate, including their impact on the metabolism and pharmacokinetic disposition of these drugs; (b) to determine the impact of the absence of one or more of the ABC transporters, as well as determine the presence of possible compensatory mechanisms; and (c) to ascertain the involvement of the P-gly and the MRP family of transporters (MRPs 1-6) in the prediction of response of childhood cancers to antineoplastic agents. Thus, we will obtain information on the utility of measurements of the ABC transporters in childhood cancers in selecting therapeutic agents with the greatest potential to induce response and on the use of knockout mice and cell lines as model systems to estimate the role of the ABC transporters on the toxicity to and disposition of anticancer agents in normal tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MILLENNIUM

C.O.G.--NURSES

WORKING

TOGETHER

IN

THE

NEW

Principal Investigator & Institution: Ettinger, Alice G.; National Childhood Cancer Foundation Suite 402 Arcadia, Ca 91066 Timing: Fiscal Year 2003; Project Start 27-JUN-2001; Project End 31-MAR-2006 Summary: Pediatric oncology is a dynamic field with ever changing research protocols, chemotherapeutic regimens, radiation and surgical techniques, and ethical consideration

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for the professionals, families, and the patient. The pediatric oncology nurse is the consistent caregiver serving the patient and family in the inpatient arena, in the ambulatory setting, and in the patient's home. The nurse is called upon to answer questions, assist with procedures, administer therapies, and support the family and child throughout the treatment trajectory. The nurse must remain on the leading edge of knowledge in order to perform these functions. Therefore, continuing education is essential to the ongoing knowledge and expertise of these nurses. The Children's Cancer Group and the Pediatric Oncology Group have combined to form The Children's Oncology Group (C.O.G.). The Nursing Committee of the C.O.G. is sponsoring its first combined workshop to educate nurses caring for children on clinical trials. There has been a long-standing history of successful workshops sponsored by these groups and the C.O.G. Nursing Discipline believes that there should be a continuation of these efforts at least every 18 months. The planned workshop, to be held on April 20th and 21st, 2001 in Chicago, IL will bring together nurses from all over the United States and Canada in order to learn about new protocols, techniques, and research within the C.O.G. Recent improvements in survival after childhood cancer have been achieved with complex multimodal treatment protocols. Unless nurses understand these protocols and have the requisite skills, clinical trials cannot be performed safely and correctly. Achievement of clinical trials' competencies by nurses demands high quality organized and continuous educational effort using a variety of communication channels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER IN CHILDREN Principal Investigator & Institution: Whitlock, James A.; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-1981; Project End 30-NOV-2002 Summary: The long-range objective of this proposal is further improvement in the treatment of cancer in children through the participation of investigators at the Vanderbilt University School of Medicine in Children Cancer Group (CCS). The multidisciplinary team of investigators from Vanderbilt are pooling resources with comparable teams from other institutions to investigate the biology, treatment, and epidemiology of the childhood cancers. Specific aims can be summarized in terms of Vanderbilt's contributions to the Group's scientific endeavors and administrative leadership. These include the following: 1. Through participation in disease-specific Strategy Groups, establish research priorities and develop new strategies for therapeutic studies of acute lymphocytic leukemia (ALL), Hodgkin's disease, neuroblastoma, bone sarcomas, and brain tumors. 2. Through Study Committee chairmanships, provide leadership in the development, conduct, analysis, and reporting of investigation dealing with the treatment of ALL, neuroblastoma, and brain tumors. 3. Through participation as Study Committee members, assist in the conduct of studies concerned with the treatment of ALL, Hodgkin's disease, astrocytoma, and brain stem tumors. 4. Provide leadership in the development and interpretation of studies that assess the developmental and neuropsychologic sequelae of curative therapy for ALL. 5. Through committee participation, contribute to the development and analyses of investigational drugs. 6. Provide administrative leadership through participation on the Executive Committee, the Officers Committee, and the Affiliate Activities Steering Committee. In addition, investigators will continue to enlist the participation of Vanderbilt patients in CCG research protocols so as to facilitate the expeditious conduct and timely conclusion of Group studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

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Project Title: CARDIAC RISK FACTORS IN PEDIATRIC CANCER SURVIVORS Principal Investigator & Institution: Lipshultz, Steven E.; Professor and Chairman of Pediatrics; Pediatrics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 02-SEP-1998; Project End 30-JUN-2004 Summary: (Applicant's Description) Although subclinical cardiac abnormalities are common and often progressive in long-term survivors of childhood cancer who have been treated with anthracycline chemotherapy or mediastinal irradiation, a comprehensive assessment of risk factor for premature symptomatic cardiovascular disease has never been performed. The relationship between emerging late effects of treatment (lipid abnormalities, obesity, and cardiomyopathy) warrants further study. In this application, the investigators will study and identify a comprehensive cardiac risk factor profile on all eligible long-term survivors of childhood cancer within the catchment area of upstate New York. The primary hypothesis is that these patients will have more risk factors for subsequent symptomatic cardiovascular disease than two control populations that will be studied. The first will be matched siblings of treated patients, and the second will be long-term survivors of childhood cancer who have not been treated with therapy known to be cardiotoxic. The investigators will be able to determine whether there are increased risk factors and whether these risk factors are related to prior oncologic therapy. The second hypothesis is that there are differences in the number of cardiac risk factors for three groups of long-term survivors: those treated with anthracyclines alone, those treated with radiation to the heart alone, and those treated with both. The applicants will specifically determine the presence of depressed left ventricular (LV) function, thin LV wall, elevated LV afterload, increased body fat, elevated blood pressure, abnormal endothelial function, and abnormal lipid profiles. These will be compared to the control populations. Other secondary risk factors will be determined. Longitudinal changes in study and control patients will be determined as well to chart the trajectory over time in risk factors in different populations. If the hypotheses are true, this should enable more rational recommendations for preventive cardiology in long-term survivors to be made and to standardize care and management for this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOVASCULAR IRRADIATION

RISK

50

YEARS

AFTER

THYMIC

Principal Investigator & Institution: Adams, Michael J.; Community and Prev Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The purpose of this K-23 grant proposal is to develop a didactic training and research program that will enable Dr. Adams to become an independent investigator in the epidemiology of cardiovascular disease. Dr. Adams is particularly interested in the epidemiology of cardiovascular disease in survivors of childhood cancer and would like to expand his knowledge and skill in order to look at the precursors of cardiovascular disease in general. The specific aims of this proposal are: 1) To establish a comprehensive training program in field techniques of epidemiology, follow-up study design and advanced statistical techniques including mathematical model building and survival analysis; 2) To analyze data from an ongoing study at the University of Rochester evaluating cardiovascular functioning in childhood cancer survivors treated with high-dose mediastinal irradiation; 3) To design a non-concurrent prospective study to assess the association between chest irradiation during infancy and coronary artery

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Childhood Cancer

disease in adulthood; 4) To design and carry out a pilot study to assess the association between chest irradiation during infancy and subclinical cardiovascular disease. This program takes advantage of expertise in preventive cardiology, pediatrics, and radiation-associated heart disease found within the University of Rochester Medical Center. Additionally, a previously well followed cohort in the Rochester area of nearly 2800 individuals exposed to low-dose irradiation to the thymus as infants and 4800 of their siblings provides a unique opportunity to assess the potential association between low-dose chest irradiation during infancy and cardiovascular disease later in life. The major project of this proposal evaluating this cohort is in fact two studies: 1) the followup of the entire cohort evaluating the risk of clinical coronary artery disease events associated with radiotherapy and 2) a pilot study clinically evaluating CAD risk factors and cardiac function. At the end of the training program, Dr. Adams will be an independent investigator in the field of preventive cardiology with experience in several study designs. The clinical and public health significance of this proposal is based on the fact that much remains unknown about the epidemiology and pathophysiology of atherosclerosis in special subpopulations such as those exposed to irradiation during childhood. This group of individuals, if shown to be at high risk, constitutes a potentially huge number of persons who may benefit from additional preventive measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZING THE OBESITY OF LONG-TERM CANCER SURVIVORS Principal Investigator & Institution: Nunez, Susan B.; Attending Physician; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2004; Project Start 25-JUN-2004; Project End 31-MAY-2006 Summary: (provided by applicant) We have more than 1000 long-term survivors of childhood cancer followed in our Late Effects and Neuro-Oncology Clinics. With improved treatment modalities, more patients diagnosed with childhood cancer are surviving into adulthood. Endocrine and cardiovascular late effects have been described by our group and others in long-term survivors of childhood cancer. This includes obesity and the Metabolic Syndrome (1-8). The atherosclerotic cardiovascular disease component of the Metabolic Syndrome continue to be one of the leading cause of death in the general population and may occur earlier and with increased frequency in survivors of childhood cancer. Obesity is major component of the Metabolic Syndrome. There is little information on the mechanism of obesity in long-term cancer survivors. This project is a pilot study to determine the role of neuropeptides in the development of obesity in cancer survivors treated with cranial irradiation with or without surgery. We plan to enroll obese cancer survivors and perform a 2-hr oral glucose tolerance test (OGTT) measuring glucose, insulin and obesity-related peptides levels. We hypothesize that childhood cancer survivors exposed to cranial irradiation and/or cranial surgery experience disruption in the hypothalamus that increases the risk for the development of hypothalamic obesity and insulin resistance, both components of the Metabolic Syndrome many years after completion of therapy. Obese survivors with these treatments will have abnormal levels of obesity-related peptides compared to obese survivors without those treatments. Among obese survivors, the proportion of insulin resistant patients is higher among those who had cranial irradiation and/or cranial surgery and who also have abnormal levels of the obesity-related peptides. A successful conclusion to this project will not only result in the development of preventive and intervention therapy to minimize the cardiovascular risks in these patients but also open

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9

the way to more focused studies of neuropeptide involvement in the pathogenesis of osteopenia/osteoporosis, a less well-described but recently recognized to have a higher incidence in long-term survivors of childhood cancers (22). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDHOOD CANCER GENE PROGRAM PROJECT GRANT Principal Investigator & Institution: Downing, James R.; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAY-2006 Summary: The long-range goal of this program project is to improve our understanding of the pathogenesis and pathophysiology of childhood cancers, and to capitalize on the insights gained from these basic studies to device new means of assessing prognosis and improving therapy. This broad objective is being pursued through four interactive projects whose goal is to define the mechanisms by which chimeric transcription factors and altered tumor suppressors contribute to the pathogenesis of childhood cancer. Specifically, this program will examine the translocation-encoded fusion oncoprotein AML1-ETO and Pax3-FKHR and the ARF/Mdm2/p53 tumor suppressor pathway. Together, these genetic abnormalities represent the underlying lesions in a variety of common pediatric malignancies, including leukemias, soft tissue sarcomas, and epithelial tumors. The focus of Project 1 (M. Roussel) is to understand how p16/INK4a and ARF mediate tumor suppressive functions in different physiologic contexts, by studying their regulation, downstream targets and genetic modifier. Project 2 (J. Downing) seeks to define the molecular pathway by which alterations of AML1 leads to leukemia, by defining the spectrum of mutations that cooperate with the t(8;21)encoded AML1-ETO oncoprotein to induce leukemia, and determine how point mutations in AML1 predispose hematopoietic stem cells to leukemic transformation. Project 3 (G. Grosveld) will use biochemical, cell biological and mouse experiments to determine how Pax3-FKHR acts as an activated oncogene in alveolar rhabdomyosarcoma, and to identify the secondary genetic alterations that are required to cooperate with Pax3-FKHR to induce a full tumor phenotype. In Project 4 (G. Zambetti) will directly examine the biochemical and biophysical properties of a novel germline p53 mutation (p53R337H) that has identified in a cluster of pediatric patients in Southern Brazil with adrenal cortical carcinoma (ACC). These patients lack features of Li-Fraumenia syndrome, suggesting that p53R337H is predisposing patients to ACC. To test this hypothesis, Dr. Zambetti will directly examine the biochemical and biophysical properties of this mutant p53 protein, and will develop mice that contain this mutation in the germline. The proposed research is supported by an Administrative Core and three scientific Core's that provide assistance in the generation of genetically modified mice and the subsequent analysis of these animals through a Pathology Core and a Microarray Gene Expression Laboratory. Through this coordinated program of research, we anticipate substantial progress toward the ultimate goal of improving the treatment of children with cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDHOOD CANCER SURVIVOR STUDY Principal Investigator & Institution: Robison, Leslie L.; Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 20-JUL-1993; Project End 31-MAY-2005

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Childhood Cancer

Summary: The resource represented by the Childhood Cancer Survivor Study (CCSS) is the result of a multi-institutional collaborative project, which has established and followed a retrospectively ascertained cohort of over 14,000 five year survivors of childhood cancer diagnosed between 1970 and 1986 and over 6000 sibling controls. Members of the cohort, currently ranging in age from 11 to 48 years (median age 26 years) have provided information encompassing over 200,000 person-years of followup since diagnosis of the original cancer. This population represents a large and heterogenous group of childhood cancer survivors treated in a fashion that has direct relevance to most current heterogenous group of childhood cancer survivors treated in a fashion that has direct relevance to most current therapeutic strategies. This characteristic, in combination with the high rate of participation, the extensive characterization of participants' prior therapy, and attention to collection of high quality data, makes the CSS an outstanding and, indeed, unique national resource for the conduct of innovative research. The objectives of this competitive renewal application, which reflects a conversion from a U01 to U24, are to (1) expand the research questions posed in the original grant application by extending the length of follow-up of this unique population with questions posed in the original grant application by extending the length of follow-up of this unique population with approximately 65,000 additional person-years; (b) strengthen the resource by establishing repositories for biological specimens to facilitate future molecular biologic investigations; (c) maintain the current consortium of investigators from specimens to facilitate future molecular biologic investigations; (c) maintain the current consortium of investigations from the 25 participating centers in the United States and Canada, who provide scientific expertise and facilitate ongoing activities; (d) serve as a source of ongoing education for the survivor population; and (3) continue to be a resource for innovative investigatorinitiated studies of childhood cancer survivors. These objectives will be achieved through specific aims: (1) continued follow-up and interaction with members of the cohort to educate and ascertain key outcomes; (2) collection and storage of biologic specimens consisting of tumor specimens from subsequent neoplasms, buccal cells as a source of genomic DNA on all members of the cohort, a and peripheral blood for establishment of lymphoblastoid cell lines for survivors who develop a subsequent neoplasm or have a known genetic condition associated with cancer risk; and (3) facilitate the use of the CCSS resource to address important questions related to cancer survivorship including the development and testing of intervention strategies. The CCSS provides a dynamic framework and resource in which to investigate current and future questions regarding consequences of therapy, genetic associations, disease processes and causation, interventions, and quality of life among childhood cancer survivors. 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 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

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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: Fallon, Robert J.; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 11-MAR-1994; Project End 30-NOV-2002 Summary: This is a proposal for the continued support of Indiana University's participation in the Children's Cancer Group (CCG) activities. Indiana University has been a funded member of CCG since 1971. The Indiana University childhood cancer program has recruited substantial numbers of patients into CCG studies and consistently has ranked in the top 10 of 35 of CCG institutions. This should continue as this program remains the major referral center for the State of Indiana and is committed to CCG participation. This application supports the efforts of 41 Indiana University investigators and support staff. Additional strengths of the Indiana program which serve the interests of CCG include basic and translational research. Funding from the NIH/NCI for childhood cancer research at the Indiana University program was 2.9M dollars for 1995-1996. Areas of expertise are in basic hematopoiesis, DNA repair and gene therapy. Translational efforts include the use of peripheral blood progenitor cells for hematopoietic support, and gene therapy and DNA repair proteins to off-set hematopoietic toxicity of chemotherapy. These efforts have already lead to Drs. Jakacki and Kreissman acting as study chairs for novel translational studies within the CCG targetted for brain tumors and neuroblastoma. Similar efforts in gene therapy at the institutional level may be ready for limited institutional CCG trials in 3-5 years. The Indiana program can be expected to feed the CCG with pilot data for these novel translational studies. This should greatly aid efforts directed toward the development of

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Childhood Cancer

scientifically-based, hypothesis-driven research aims within the CCG. Indiana investigators chair 6 scientific committees, 7 serve on disease strategy groups, and have chaired 11 studies during the 1992-1997 period. Finally, multidisciplinary expertise is represented in the areas of cytogenetics (Heerema), local tumor control (Rescorla), and tumor imaging (Cohen). The Indiana group remains dedicated to the understanding and development of better treatment for children with cancer through its participation in the CCG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Geyer, J R.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 30-NOV-2002 Summary: The specific research interests are: 1) To participate fully in the clinical studies of the CCG by enrolling as many eligible children with primary or recurrent malignant disorders on CCG studies as possible, including Phase I, II and III studies; 2) To continue to provide scientific and administrative expertise to CCG through active participation in Strategy groups, Scientific and Discipline Committees and study committees; 3) To enhance fundamental understanding of biology and treatment of childhood cancer, focusing particularly on the areas of bone marrow transplantation, AML, bone and soft tissue sarcomas, brain tumors, and new agent development; 4) To conduct pilot biologic and therapeutic studies in hematopoietic stem cell transplantation and peripheral blood stem cell support of intensive chemotherapy to provide preliminary data for consideration of these approaches by the CCG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Gaynon, Paul S.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 900276062 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 30-NOV-2002 Summary: The project proposes continuation of a comprehensive pediatric oncology program at Childrens Hospital Los Angeles (CHLA). This program is designed to improve the treatment of children with cancer by conducting clinical investigations as a member of the Childrens Cancer Group (CCG) and by independently conducting other research which is directly related to the mission of CCG. CHLA is a major pediatric referral center for the Pacific Southwest and has one of the largest pediatric oncology services in the nation. An interdepartmental program has developed which involves basic and clinical scientists and has evolved into a multidisciplinary model for the management of pediatric cancers. CHLA is one of the major contributors of patients to CCG studies and the multidisciplinary staff at this institution participate in all activities of CCG. Participation of CHLA investigators in CCG enables quantitative comparative clinical investigations aimed at establishing the best mode of any cancer therapy. The unique resources of CHLA permit development of new therapeutic approaches for Group-wide application. These include participation in the Leukemia/Lymphoma, Neuro-Oncology, Bone and Soft Tissue Tumor, and Long-Term Followup Programs; the evaluation of new dose schedules and combinations of established agents predicted by in vitro and in vivo pharmacological studies; investigation of mechanisms of drug resistance; bone marrow peripheral blood and umbilical cord stem cell transplantation; immunological characterization of selected neoplasms; effects of cancer and its

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treatment on hematopoiesis optimum nutritional support in childhood malignancies; approaches to psychosocial rehabilitation of the pediatric cancer patient and family; education of caregivers and patients/families; epidemiology of childhood malignancies; preclinical studies in molecular and cellular pharmacology; tumor cell biology; carcinogenesis and chemoprevention; cytogenetics; and in vitro and in vivo tumor model systems. A network of community physicians participate in the CCG under the sponsorship of CHLA which enables the use of optimal therapy in children who are not referred for initial cancer care. The project also provides continuation of entry of minority patients on CCG clinical trials. Through the proposed renewal, the comprehensive program at CHLA will seek as its ultimate goal an integrated and investigative approach to childhood cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Rausen, Aaron R.; Pediatrics; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 10-JUN-1999; Project End 30-NOV-2002 Summary: The objectives of this proposal are to support and enhance the current and future activities of New York University Medical Center (NYUMC) as a principal member of the Children's Cancer Group (CCG) by: (1) Improving the outcome for children with cancer through, a) continued patient entries at an increasing level to active CCG protocols, b) participation in leadership positions on CCG Strategy Groups and Discipline Committees so as to develop improved methods of treating childhood cancer, c) collaborating in the development of new studies by NYUMC investigators. 2) Developing new methodologies for the treatment of childhood cancer by, a) participation and leadership roles in Phase II studies and New Agent Phase I studies, b) piloting studies that have potential for incorporation into future CCG trials in selected disease entities such as brain tumors. 3) Improving the quality of life for survivors of childhood cancer and their families by, a) participating in CCG long-term effects studies, b) evaluating quality of life issues in children being treated for cancer, c) placing all eligible patients on open supportive care studies, d) continued participation in the cardiac intervention study conducted by the Children's Hospital of Philadelphia. 4) Active participation in biology studies by, a) timely and complete submission of biology samples and data, b) participation of NYUMC scientists and laboratories in studies involving cytogenetics, molecular biology and other laboratory disciplines. 5) Increasing the network of affiliated institutions relating to NYUMC so as to recruit patients for study who are currently not available for clinical trials. This includes the affiliation with Brooklyn Hospital and the recent affiliation with Maimonides Hospital- both caring for urban minority populations not otherwise participating in clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Dinndorf, Patricia A.; Principal Investigator; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 30-NOV-2002 Summary: The objective of this proposal is to enable investigators at Children's National Medical Center (CNMC) to conduct investigations of the therapy, biology, and causes of malignant disease in infants, children and adolescents through participation in the Children's Cancer Group (CCG) and to provide scientific and administrative leadership

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Childhood Cancer

of such studies. We propose to enter all eligible patients on Groupwide studies of multimodality therapy of acute leukemia and solid tumors. We propose to develop and conduct limited institution pilot (toxicity and/or feasibility) studies incorporating novel treatment strategies for childhood ALL, and dose-intensified treatments incorporating hematopoietic growth factors and stem cell transplantation. We propose to develop and conduct limited institution pilot studies of new agents and novel therapeutic approaches for the management of brain tumors and will continue to design and conduct clinical trials which pose questions of CNS pharmacologic interest. CNMC will continue as the most active CCG institution in the evaluation of new agents, both cytotoxic and biologic. We will participate in correlative pharmacology and biology studies. We will comply with protocol-specified therapy as well as required evaluations and will submit complete and accurate data to the Operations Office in a timely fashion. CNMC will continue as a performance site of the CCG ALL Biology Reference Laboratory for the identification of appropriate patients for biotherapeutic studies incorporating monoclonal antibodies to leukemia cell associated antigens to identify specific immunotoxins for immunotherapeutic classes of disease. This laboratory will lead the effort to evaluate the efficacy of new classes of agents in acute lymphoblastic leukemia using a variety of preclinical models. Laboratory studies of the significance of the expression of the mdr-1 gene at diagnosis and correlation with functional assessment of multidrug resistance and clinical outcome will continue in homogeneously treated patient groups. We propose to continue investigation of the biological significance of shed tumor gangliosides in neuroblastoma, as well as the evaluation of differences in neuroblastoma membrane ganglioside patterns between patients identified through screening programs and patients with overt clinical disease. We propose to participate in case controlled epidemiologic studies of childhood cancer to investigate the possible relationship between genetic predisposition and pre- and post-natal environmental factors on the development of specific malignancies. We will participate in the formulation and conduct of quality of life evaluations to examine the long-term impact of successful anticancer therapy on all aspects of growth and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Neglia, Joseph P.; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 30-NOV-2002 Summary: Dramatic gains have been made in childhood cancer including markedly more effective therapy, insights into the biology of these diseases, a clearer definition of etiologic factors, and a new focus on the outcomes of the survivors of these diseases. These gains have largely been facilitated by the cooperative clinical trials groups. This grant will facilitate the continued involvement of the investigators at the University of Minnesota in the multi-institutional cooperative therapeutic and non- therapeutic studies conducted by the Children's Cancer Group (CCG). Minnesota investigators have been at the forefront of all of these venues over the past grant cycle and are poised to continue this productive relationship into the future. In 1997, the Minnesota consortium registered 162 patients on therapeutic trials (phase I, II, and III) and, in addition, registered patients on almost 100 non-therapeutic (biology, epidemiology) studies. The combination of strong patient accrual, data management, group leadership, and authorship of CCG publications resulted in Minnesota being ranked first among all group institutions in 1995, 1996, and 1997. Minnesota investigators have continued strong leadership roles in Epidemiology and Cancer Control, Hematopoetic Stem Cell

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Transplantation, acute lymphoblastic and acute myeloid leukemia, biology, and experimental therapeutics. Over the past grant cycle, Minnesota investigators have chaired fourteen group therapeutic or scientific committees and served as vice-chairs on an additional twenty four. Minnesota has consistently led the group in first- authorship of group publications. Institutional research in stem cell transplantation, epidemiology and cancer control, experimental therapeutics, and biology has been applied to group studies and future investigations of all of these areas are under development. This grant requests support for the personnel critical to our future group activities. It will assure continued excellence in data management, allow travel by investigators and other key personnel to group meetings, and supply the funds needed for expenses generated by the accrual of patients to group studies. This funding will assure the continued leadership of Minnesota investigators in all aspects of the Children's Cancer Group over the coming five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Arndt, Carola A.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-JAN-1981; Project End 30-NOV-2002 Summary: The primary objective of this proposal is to continue to support and expand Mayo Clinic's participation in the activities of Children's Cancer Group through: 1.) Evaluating new cancer chemotherapeutic agents and developing new approaches to treatment of children with cancer by, a) maintaining a leadership role in CCG Phase II and New Agent Study Committees, b) performing pilot studies for potential incorporation into future randomized CCG trials, c) entering patients on new agent studies, d) utilizing the resources in Doctor Ames' pharmacology laboratory to evaluate the pharmacology and pharmacokinetics of cancer chemotherapy. 2.) Improving treatment and potential for cure of various childhood cancers and leukemias by, a) continuing to enter patients into CCG treatment protocols with the expectation that study entries will increase as new studies for various tumor systems are activated, b) playing a leadership role in CCG Strategy Groups in order to develop new approaches to the treatment of childhood cancer, c) participating in the development of new randomized trials for the treatment of specific diseases and maintaining active participation in CCG study committees by Mayo investigators currently assigned to study committees, d) studying long-term effects of treatment. 3.) Studying the biology and epidemiology of childhood cancer by, a) active participation in regional and CCG case-control epidemiology studies, b) making available to CCG the skills and resources of Mayo investigators in Pathology, Immunology, Molecular Biology, cytogenetics and other areas of basic and applied laboratory research. 4.) Improving supportive care of children with cancer by, a) continued participation in CCG supportive care studies, b) standardization of drug administration procedures for various chemotherapeutic agents, c) development and evaluation of methods for controlling cancer- related and procedure-related side-effects. 5.) Providing access for patients in outlying areas to these clinical research programs through affiliates in Des Moines, Iowa; Fargo, North Dakota; Duluth, Minnesota; Regina and Saskatoon, Sasketchewan; Sioux Falls, South Dakota; and Green Bay, Wisconsin. 6.) Active participation in CCG administrative activities by continuing to chair and participate in appropriate committees, including Membership, Data Monitoring, and Constitution and By-Laws. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDRENS CANCER GROUP Principal Investigator & Institution: Ruymann, Frederick B.; Children's Research Institute 700 Children's Dr Columbus, Oh 432052664 Timing: Fiscal Year 2002; Project Start 01-MAR-1994; Project End 30-NOV-2002 Summary: Columbus Children's Hospital (CCH) is a 313-bed fully capable children's hospital, which has been a funded Childrens Cancer Group (CCG) institution since 1958. Dr. Frederick B. Ruymann has been the Principal Investigator (PI) and CCG representative to the Intergroup Rhabdomyosarcoma Study (IRS) since November 1982. The Division of Hematology/Oncology is the pediatric component of the OSU-NCI funded Comprehensive Cancer Center and has an approved hematology/oncology fellowship with 60 residents in pediatrics. CCH serves as the CCG-Pathology Center, which is under the direction of Dr. Stephen Qualman (Co-Investigator), a member of the CCG Pathology Steering Committee. The CCH/CCG Network, which includes three other institutions in Ohio, The Medical College of Ohio (Toledo), the Children's Medical Center/Wright Patterson AFB (Dayton), and The Cleveland Clinic Foundation (Cleveland), saw 241 children and adolescents with newly diagnosed malignancy in 1996. In November 1997, the Cabell Huntington Hospital in Huntington, West Virginia became the fourth affiliate in the CCH/CCG network. From 1992 through 1996 an average of 87 patients were placed annually on CCG therapeutic (Phase I/II) studies; 56 cases per year were placed on non-therapeutic studies. From 1992-1996, there were 437 therapeutic and 282 non-therapeutic CCG entries by the CCH/CCG Network. CCH/CCG Network follows 561 long-term survivors of childhood cancer and an additional 213 survivors on Intergroup studies. CCH is an approved CCG Phase I/II (1990) and bone marrow transplant (1992) institution under the direction of Drs. Kathryn Klopfenstein and Alfred Grovas (Co-Investigators), respectively. CCH was approved by the National Marrow Donor Program for the performance of matched unrelated transplants in July 1997. CCH's resident scientist, M. Sue O'Dorisio, MD, PhD (Co-Investigator) is a world expert on the neuropeptide regulation of neuroblastoma and a member of the CCG Neuroblastoma Strategy Committee. Other Co-Investigators on this grant include Dr. Allan Yates (neuropathology), and Dr. Amanda Rauck (pediatric oncology) who both have major roles in CCG science and leadership. CCH has made major contributions in diagnosis, treatment, and biology of leukemia, rhabdomyosarcoma, brain tumors, and neuroblastoma, through CCG pilot and preclinical investigations. Current protocols or proposals include escalating cyclophosphamide in intermediate risk rhabdomyosarcoma, neuropeptide imaging in neuroblastoma and peripheal neural ectodermal tumors, high-dose rate brachytherapy in soft tissue sarcomas, and bone marrow transplant in brain tumors. The status of each of these protocols is discussed in the text of this competing renewal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDRENS CANCER GROUP (CCG) Principal Investigator & Institution: Rogers, Paul C.; University of British Columbia 2075 Wesbrook Pl Vancouver, Bc Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 30-NOV-2002 Summary: The Pediatric Oncology Division of the University of British Columbia, Department of Pediatrics, has a long established record of commitment to CCG. The Division has enjoyed full membership since 1974 and NCI funding support since 1980. The Division actively participates in CCG Trials as well as being involved in strategic planning, trial design, lab-based research, outcome analysis and administrative

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responsibilities within the CCG network. During the next 5 year grant cycle, the Division will continue to participate in all aspects of CCG activities. Specific aims: Commitment to continue to enter as many patients as possible into CCG Trials; Actively participate in new proposals specifically in the field of high risk acute lymphatic leukemia (Dr. K. Schultz), Hodgkin's Disease (Dr. C. Fryer), radionucleotide imaging studies- Thallium (Dr. H. Nadel), radiotherapy aspects of CCG (Dr. C. Fryer); Investigate prognostic markers specifically the significance of molecular abnormalities in sarcomas (Dr. P. Sorensen); Continue to develop new therapies for poor prognostic patients, specifically to continue Phase II Pilot work on marrow ablative therapy and PBSC rescue in patients presenting with metastatic disease utilizing molecular genetic techniques to detect minimal residual disease and contamination of PBSC; To continue our laboratory research into understanding mechanisms of graft-versus-host disease and graft-versus-leukemia effect to gain further understanding of the host response to malignant disease; To expand our molecular biology research into the genetic changes associated with childhood cancers; and to investigate the cytolytic T-cell therapy for Hodgkin's Disease directed against EB viral antigens (Dr. K. Schultz and Dr. Ru Tan). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILDREN'S ONCOLOGY GROUP CHAIR'S GRANT Principal Investigator & Institution: Reaman, Gregory H.; Professor of Pediatrics/ Chairman; National Childhood Cancer Foundation Suite 402 Arcadia, Ca 91066 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 28-FEB-2008 Summary: The Children's Oncology Group (COG) is a new multidisciplinary clinical trials group resulting from the unification of the four pediatric cooperative groups. It is the largest childhood cancer research organization in the world and encompasses approximately 238 pediatric cancer programs as clinical trial sites throughout all of North America, Australia, and several institutions in Europe. It is exclusively well poised to translate basic biology studies into clinical investigations and to develop translational approaches through human proof of principle, toxicity assessment, identification of efficacy, and ultimately, incorporation into established treatments to improve outcome and/or decrease toxicity. COG represents the legacy of four groups, the oldest of which existed for nearly 50 years. Currently, 48,259 patients accrued to clinical trials are in active follow-up; over 2,500,000 person years of life have been saved. Although childhood cancer mortality has decreased by 50% in the last two decades and by 25% inthe past decade, nearly 2,500 children and adolescents die from cancer annually inthe U.S. alone. The majority of these deaths can be attributed to specific pediatric cancers for which new therapeutic approaches must be devised. Improvement in the cure rates for these high-risk cancers is more likely to emerge as a result of the identification of biologic features which predict resistance and, more importantly, by the identification of new anti-cancer agents with novel mechanisms of action, whose efficacy might be predicted on the basis of specific unique molecular abnormalities detected in cancer cells. COG is also uniquely able to establish for the first time a North America-wide population-based registry of childhood cancer to investigate, utilizing case control studies, potential epidemiologic associations, including genetic alterations and ultimately interactions of genes with the environment. COG, through a series of hypothesis-driven research studies, seeks to maximize cure rates for children with cancer; to achieve an expanded understanding of tumor and host biology; to elucidate new therapeutic strategies and to build on the concept of risk-adjusted therapy; and to reduce treatment-related toxicity and morbidity, thereby optimize quality of life and survival.The proposed research is aimed at reducing deaths from childhood cancer by

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20% and increasing 5-year disease-free survival (cure) rates to >85% during the study period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURVIVORS

COGNITIVE

REMEDIATION

FOR

CHILDHOOD

CANCER

Principal Investigator & Institution: Butler, Robert W.; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 26-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from investigator's abstract): As a result of central nervous system involvement or treatment, many survivors of childhood cancer suffer from significant attentional deficits. The proposed project will investigate the efficacy of a multi-modal Cognitive Remediation Program (CRP) specifically designed to improve survivors attentional deficits which occurred, presumably, as a consequence of cancer and its treatment. For this study, survivors are further defined as having been treated or prophylaxed for a central nervous system cancer (leukemia, brain tumor, non-Hodgkin's lymphoma). A randomized design will be used to evaluate the effectiveness of a 4-to-5 month CRP on attention and other cognitive skills in school-aged children/adolescents 6 to 17 years of age. The stability of achieved change will be evaluated six months later. Childhood cancer survivors who are at least one year off treatment will be screened for an attentional deficit and if it is detected, they will be randomized to receive CRP (n=112) or no treatment (n=56). CRP consists of 20 two-hour sessions of attention training. Subjects will be evaluated pre-treatment, post-treatment (or at a 5 month interval for the control subjects), and for the treatment group at six-month follow-up. Measures of focused attention, working memory, memory recall, learning, vigilance, academic achievement, school behavior, and self-esteem will be administered. Statistical analyses will assess individual and group changes in attention and other cognitive skills, and these changes will be related to changes in academic achievement, school behavior, and self-esteem. To evaluate the mothers' role in influencing the child's compliance with CRP, they will be evaluated pre-treatment with measures of problem-solving skills, parenting skills, and emotional stability. Secondary and exploratory analyses will examine the influences of maternal factors on CRP adherence and effectiveness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONDITIONAL RHABDOMYOSARCOMA

MOUSE

MODEL

OF

ALVEOLAR

Principal Investigator & Institution: Keller, Charles; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 07-SEP-2001; Project End 31-JUL-2006 Summary: Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer associated with significant morbidity and mortality. Eighty-five percent of alveolar rhabdomyosarcomas demonstrate a common genetic alteration, the translocationmediated fusion of a developmentally regulated Pax transcription factor (either Pax3 or Pax7) to the Forkhead transcription factor, Fkhr. An understanding of the molecular events underlying the development of alveolar rhabdomyosarcomas will improve our ability to stratify patients to risk-based therapies and to develop new therapies. The goals of this project are to investigate whether the postembryonic, translocationmediated fusion of Pax3 to Fkhr initiates an aberrant embryonic muscle development program which is involved in the genesis of alveolar rhabdomyosarcoma, and to

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investigate whether the early and intermediate steps in the activation of oncogenic properties contributing to the genesis of alveolar rhabdomyosarcoma occur in a predictable sequence. The specific aims of this proposal are (I) to examine whether a genomic single copy-number of Pax3:Fkhr is sufficient and necessary to cause both aberrant Pax3 pathway activation and the initiation of alveolar rhabdomyosarcoma, (II) to study whether genetic, transcriptional, or translational contributions to common oncogenic mechanisms (eg. insensitivity to antigrowth signals, evasion of apoptosis) occur in a predictable sequence in alveolar rhabdomyosarcomas, and (III) to determine whether Cre recombinase-mediated translocations between heterologous chromosomes can be induced somatically at a frequency sufficient for the initiation of alveolar rhabdomyosarcoma. For the first and second aims, a conditional, knock-in mouse model of alveolar rhabdomyosarcoma will be created which initially harbors two functionally normal Pax3 alleles. Conditional, somatic expression of the site-specific DNA recombinase Cre will mediate a genomic rearrangement converting a single Pax3 allele to a single Pax3:Fkhr allele in skeletal muscle only. Animals will be serially sacrificed to analyze the ensuing sequence of intracellular changes in cells harboring Pax3:Fkhr. Analysis will be performed at the genomic, mRNA, and protein level with an emphasis on known markers of tumor progression. For the final aim, a conditional, somatic translocation between the Pax3 and Fkhr loci will be attempted using Cre-mediated rearrangement of heterologous chromosomes. Dr. Keller's research training with Dr. Capecchi and the support of the NCI will prepare Dr. Keller for an independent research career investigating developmental aspects of pediatric cancer. Ultimately, a detailed knowledge of dysregulated developmental pathways in pediatric malignancies may improve our ability to treat childhood cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--HIGH RISK PATIENTS AND FAMILIES Principal Investigator & Institution: Li, Frederick P.; Chief; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Women differ in their risk of developing breast cancer. Studies of individuals and families with exceptionally high risk have led to the identification of inherited breast cancer susceptibility genes, including BRCA1, BRCA2, p53, and recently, chk2. These and other cancer- predisposing genes were identified through studies of unusual patients with multiple primary cancers, early-onset cancers, precancerous lesions or cancers associated with malformation syndromes. Within this SPORE, the High Risk Core will identify patients at high risk of breast cancer who are likely to be informative in future cancer research. Our Core recruitment criteria include: families carrying one of the high penetrance breast cancer predisposing genes; early onset breast cancer particularly with a family history of either breast or ovarian cancer, family cluster of three or more first and second-degree relatives with either breast or ovarian cancer; breast cancer diagnosed before age 45 with family history of childhood cancers; breast cancer under 45, associated with major malformations or another primary cancer; or precancerous lesions (ADH, DCIS or LCIS) at any age. Our Core staff will consent eligible individuals and families to respond to a standard questionnaire and donate blood samples and their fresh or fixed tumor tissues for research. All tissue samples will be delivered to the Tissue and Pathology Core under Drs. Harris and Schnitt for processing, storage and future distribution. After replacing personal identifiers with codes, data on biospecimen availability and questionnaire information will be entered into a searchable database that can be accessed by approved SPORE investigators. Blood

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sample and tumor specimens will also be made available with approval. The High Risk Core will also facilitate re-contact of patients and families for additional collection of specimens and data, including mortality and the occurrences of new cancers on followup. Based on the proposed personnel, we will enroll at least 1,000 breast cancer cases over the next 5 years and at least 4,000 of their affected and at-risk relatives (total 5,000 family members). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TRANSGENIC/GENE KNOCKOUT SHARED RESOURCE Principal Investigator & Institution: Grosveld, Gerard C.; Chair; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 24-JUN-2002; Project End 28-FEB-2007 Summary: (provided by applicant): The Transgenic/Gene Knockout Facility was established in 1993 and transitioned into the Cancer Center in 1995. Under the directorship of Gerard Grosveld, Ph.D., the facility provides genetically modified mice to the members of St. Jude Cancer Center. These animals are created by transgenic and gene targeting technology. The investigators provide the core facility with targeted ES cells or injectionready DNA constructs and in turn, the core provides the investigators with transgenic or chimeric offspring. During the past 4 years the core facility produced 84 different knockout and 83 different transgenic lines, respectively. To keep up with the increasing demand for genetically modified mice, due to our expanding research effort, our facility will move to the Integrated Research Center in the fall of 2001. This will increase the available space from the present 1,235 net sq. ft. (900 sq. ft. holding space; 335 sq. ft. laboratory space) to 5,100 net sq. ft. (4,500 sq. ft. holding space; 600 sq. ft. laboratory space). We will increase the number of injection stations from the present 3, manned by three Transgenic Research Specialists, to 5 in the first year of occupancy, adding a sixth in the second year. The increase in injection stations will lead to the hiring and training of three additional Transgenic Research Technologists. The projected total budget for this Shared Resource in year 25 of this grant is approximately $800,000, of which 26% ($207,969) is requested from the CCSG; the remainder of the budget ( 74%; $892,031) will be provided by SJCRH institutional funds, by chargeback to individual investigators and by funds from the Childhood Cancer Gene program project. More than 90% of the usage of this Shared Resource is by Cancer Center members for peerreviewed funded projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYSTATHIONINE B SYNTHASE AND ARA C THERAPY FOR LEUKEMIA Principal Investigator & Institution: Taub, Jeffrey W.; Pediatrics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The goal of this project is to better understand the biology of acute myeloid leukemia (AML) in Down syndrome (DS) children related to the association of the chromosome 21-localized gene, cystathionine-beta- synthase (CBS) and response to cytosine arabinoside (ara-C)-based therapy. Childhood AML has the worst prognosis of all major childhood cancers with five year relative survival rates of approximately 37%. In contrast, DS children with AML represent an unique group of leukemia patients in view of having significantly higher event-free survival (EFS) rates (70-100% with relapse rates < 15%) compared to non-DS children when treated with ara-C-based protocols.

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Thus, identifying the biological basis for the extremely high cure rates of DS AML patients can have very important implications and potentially can lead to improvements in AML therapy for all patients. Our previous results have begun to shed light on the underlying mechanisms responsible for the striking increased EFS in DS AML patients. Our results demonstrating i) significantly increased CBS transcript levels in DS myeloblasts and a correlation with in vitro ara-C sensitivity and ara-CTP generation, ii) dramatic increased in ara-C metabolism to ara-CTP in vitro in leukemia cell lines transfected with the CBS cDNA, associated with increased in vitro and in vivo ara-C sensitivity, and iii) significant differences in frequency of the 844ins68 CBS gene polymorphism in DS myeloblasts, provide compelling evidence of an integral relationship between CBS gene expression and ara-C metabolism. This mechanisms is likely a major factor that accounts for the increased chemotherapy sensitivity and high cure rates of pediatric DS AML patients. This study will continue to examine over novel hypothesis and laboratory observations which bridge basic research (e.g., understanding the transcriptional regulation of CBS, determining the relation of CBS mutations/polymorphisms and ara-C metabolism) and apply this work to translational studies using clinical leukemia samples. These findings may ultimately be applied clinically to improve the treatment and cure of AML. The specific aims of the study are: 1) To characterize the transcriptional regulation of the CBS gene in leukemia cell lines and clinical leukemia samples; 2) To develop CBS-transfected AML cell models and to determine the mechanistic basis for the effects of CBS on ara-C metabolism and sensitivity; 3) To determine the relationships between CBS gene expression and ara-C sensitivities in patient myeloblasts with wild-type CBS and with the T833C, G919A, 844ins68 CBS gene variants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUG METABOLISM, DNA REPAIR & SECOND CANCERS Principal Investigator & Institution: Friedman, Debra L.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Candidate: Dr. Friedman is a pediatric oncologist with research training and interest in cancer epidemiology, prevention and long-term health-related outcomes of therapy. Environment: The Fred Hutchinson Cancer Research Center (FHCRC), University of Washington (UW) and Children's Hospital and Regional Medical Center (CHRMC) comprise the Seattle Cancer Care Alliance (SCCA), which facilitates sharing of research resources. This research will be performed in the FHCRC Cancer Prevention Research Program under the mentorship of Dr. John Potter. Research Plan: The hypothesis to be tested is that genetic differences in the metabolism of chemotherapeutic agents, in the provision of nucleotides for DNA synthesis, and in DNA repair modify risk of SMN development. To address this hypothesis, we will examine allelic variants of genes involved in these processes in two well-defined cohorts at high risk of SMN. These are patients treated for childhood cancer with conventional therapy, and patients treated with hematopoietic stem cell transplant. The genes chosen for study include methylenetetrahydrofolate reductase (MTHFR), Glutathione-Stransferase (GST), GSTT1, GSTM1, GSTM3, GSTP1, Cytochrome P-450 (CYP) CYP2C9, CYP2C19, CYP3A4, thiopurine methyltransferase, methylguanine DNA methyltransferase, ERCC1, XPD, XRCC1, XRCC2, XRCC3, XRCC4 and XRCC5. Nested case-control methodology will be used, in each of the cohorts, to examine the association of specific allelic variants with SMN development. Career Plan and Development: Dr. Friedman's career goal is to be a translational researcher with a focus on cancer control,

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prevention, and long-term outcomes of therapy. This award will provide continued mentored training in molecular biology, cancer genetics and epidemiology and biostatistics. Educational opportunities will be provided to Dr. Friedman in the Division of Public Health Sciences at Fred Hutchinson Cancer Research center and in the School of Public Health at the University of Washington. The findings of this research can be applied to the development of preventive strategies of second malignant neoplasms and other adverse long-term health-related outcomes for cancer survivors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL EXPOSURES, HOST FACTORS, AND HUMAN DISEASE Principal Investigator & Institution: Peters, John M.; Professor and Director; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 03-MAR-2006 Summary: This application is to continue our Southern California Environmental Health Services Center whose main purposes are 1) to study the effects of environmental exposures on humans; 2) to determine host factors (genetic and other) influencing response to these exposures; and 3) to inform the public. To accomplish these goals we bring together an interdisciplinary team of investigators from 2 major Souther California universities: USC and UCLA. The research of our Center features interdisciplinary cornerstones: detained exposure assessment, including toxicokinetics and biomarkers; cutting edge study design, including the most powerful statistical and epidemiologic approaches; and the basic sciences, including physiology, molecular biology, genetics, chemistry and engineering. The foci of the Center cover a wide range of problems and address environmental exposures of public health importance including indoor and outdoor air pollution, pesticides, alflatoxins, radiation, passive smoking, bioaerosols and nitrites. The 5 Research Cores consist of: Respiratory Effects; Exposure Assessment; Childhood Cancer, Adult Cancer Study Design and Statistical Methodology. The 3 Facility Cores consist of: the Molecular Biology, Sample Processing and Storage Core; the Analytic Chemistry, Exposure Assessment and Aerosol Sciences Core; and the Biostatistics Core. The Center also features a separate core for Community Outreach and Education (COEP). The Center is structured to promote interdisciplinary research and linkage between the research and the COEP. Processes creating these interactions include the seminar series, pilot projects, research focus groups, workshops and retreats. The first 4 years of support for this Center have resulted in recruitment of new investigators, more investigators working on environmental health problems, doubling of funding support, more interaction between researchers from different disciplines and a greater production of research findings relevant to answering critical public health questions. The Center also developed research initiatives for the next 5 years that focus the interdisciplinary team of investigators on important environmental health problems involving genetic-environmental interactions as asthma and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN IN THE ESTABLISHMENT OF PEAK BONE MASS Principal Investigator & Institution: Mulder, Jean E.; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-SEP-1999; Project End 30-JUN-2004

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Summary: Advances in the treatment of childhood cancers have resulted in markedly improved survival rates for many patients. These advancements in therapy, however, have led to new problems, namely, long-term consequences of effective tretments such as the premature loss of gonadal function. Premature ovarian failure (POF) places women at great risk for osteoporosis. The issues raised in this research project, however, differ from usual considerations of age-related menopausal ovarian failure and the accelerated bone loss that ensues. This more typical clinical event follows well after the establishment of peak bone mass. The young women to be investigated in this research project have become estrogen deficient before achieving peak bone mass in this setting. The skeletal profile of young women cancer survivors with ovarian failure will be characterized first. Other potential contributing factors, such as androgen deficiency, growth hormone deficiency, chemotherapeutic agents, nutritional, and other metabolic parameters will be evaluated. The dosage of estrogen required to establish peak bone mass optimally will then be determined. In this prospective, longitudinal study, young cancer survivors with POF will be randomized to one of two estrogen replacement regimens (high dose versus conventional dose). Patients will be monitored every three months for 2 years. Evaluations will include peripheral and central measurements of bone density, indices of bone turnover, and endocrine studies. We anticipate that these studies will yield new information regarding the sufficiency of estrogen replacement therapy in establishing peak bone density in young amenorrheic women. My goal is to become an independent investigator in the field of metabolic bone disease. This award will enable me to obtain new skills in clinical research methods, as well as a greater understanding of the relationship between estrogen and bone modeling in young women. The proposal is particularly fitting for a research career award because it sets the groundwork for future studies, which are essential to my development as an independent investigator. My environment is ideally suited for achieving my goals. My sponsor, Dr. Bilezikian, is an internationally recognized investigator in the field of metabolic bone disease and is committed to providing me with the support I need to pursue my research plans as I make my transition to independent investigator. Through my collaboration with Dr. Sklar, I have access to a large number of young female cancer survivors with ovarian failure. Our Metabolic Bone Unit, with its distinguished tradition in metabolic bone research and education, is an excellent environment in which to develop my career as a clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVOLUTION OF AXIAL SPECIFICATION IN CAENORHABDITIS Principal Investigator & Institution: Baird, Scott E.; Associate Professor; Biological Sciences; Wright State University Colonel Glenn Hwy Dayton, Oh 45435 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Axial specification in bilateral organisms is regulated by the expression of homeotic cluster/homeobox-containing (HOM-C/Hox) genes. Changes in HOM-C/Hox expression patterns have been correlated with changes in vertebrate and invertebrate body plans. In humans and other mammals, altered cervical vertebrae specification due to defects in HOM-C/Hox gene expression patterns is associated with thoracic outlet syndrome and early childhood cancer. Despite the overwhelming evidence for the role of HOM-C/Hox genes in axial specification, little is known about the evolutionary mechanisms that lead to altered HOM-C/Hox gene expression patterns and hence to altered body plans. The research proposed in this application will address the evolution of axial specification in the nematode genus Caenorhabditis. In Caenorhabditis, the pattern of sensory rays in the male tail and the

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size of the vulval equivalence group are determined by positional information imparted from HOM-C/Hox genes. Both of these characters have changed during the evolution of C. briggsae. The overall goal of the research proposed in this application is to determine the genetic basis of these changes. Specific aims are: 1. to determine the number of genes involved in the evolution of these characters; 2. to determine if changes in ray pattern and in the vulval equivalence group have a common genetic basis; and 3. to map and identify those genes responsible for ray pattern and vulva equivalence group evolution. These aims will be achieved through genetic analyses of C. briggsae variant strains that exhibit ancestral phenotypes for ray pattern and for specification of cell fates in the vulval equivalence group. Gene number will be determined from the frequency with which parental strains are recovered following crosses between C. briggsae variants that express ancestral and derived characters. Cosegregation of ray pattern and vulval equivalence group phenotypes will be evidence of a common genetic basis. Genes will be mapped and identified using multifactor data from such crosses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPOSURE INSIGHTS USING GIS IN A CASE-CONTROL STUDY Principal Investigator & Institution: Reynolds, Peggy; Cheif; Impact Assessment, Inc. 2166 Avenida De La Playa, Ste F La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): The proposed geographic information system-based study of the causes of childhood leukemia is not only designed to advance the state-ofthe-art in epidemiologic methods, but also to lead to greater understanding of the etiologic role of environmental pollutants. The study employs an innovative application of GIS analytic capability to address some of the fundamental shortcomings of traditional epidemiology. It will build on one of the first large-scale GIS studies of patterns of childhood cancer, and one of the most extensive case-control studies of childhood leukemia undertaken in the US. As such, it represents an important direction in the evolution of GIS as an analysis tool. A key objective is to solve the problem of characterizing the spectrum of exposure opportunity to individuals, especially for the range of chemical agents potentially encountered in residential settings from environmental sources. The proposed study is organized around the hypothesis that perinatal or early life exposures to environmental chemicals are associated with increased risk of developing childhood leukemia. Primary exposure sources of concern for this project include agricultural pesticides, motor vehicle emissions, and other sources of air toxicants. The project will create individualized geographically-based estimates of exposure constructed from residential and school history data collected in the first five years of an ongoing UC Berkeley/California Department of Health Services case-control study, calibrated by measured air monitoring data and validated by means of laboratory analyses of household dust and air samples. These exposure estimates will be applied to the full case-control study (an estimated total of 660 cases and 1052 controls accessioned by year-2 of this project) to assess risk relationships, with adjustment for important covariables. The study offers sufficient power to detect even modest changes in environmental risk factors associated with the chemical agents of concern. The proposed project presents an unusual opportunity to extend the capabilities of GIS tools to assist epidemiologists in attributing population exposures, to validate generated exposure attributes, and to integrate these estimates with individual measures for a more comprehensive assessment of the role of environmental risk factors in the etiology of these little understood diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GIS-BASED EXPOSURE FOR CHILDHOOD CANCER STUDIES Principal Investigator & Institution: Sussman, Nancy B.; Environ & Occupational Health; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The overall objectives of the proposed research are (1) to refine models of potential exposures for use in environmental epidemiology that are derived from Geographical Information Systems (GIS) and (2) to assess the feasibility of application of the novel exposure indices to a case-control study of childhood cancers in the Southwestern Pennsylvania region. The proposed research will be accomplished under the following specific aims: (1) a GIS-based, index of potential exposure from hazardous sources will be refined for use in new and ongoing environmental epidemiology studies. The novel approach uses directionally-dependent wind rose frequencies and wind velocity in various combinations with toxic emission quantities, emission toxicities and frequencies to calculate an index of potential exposure from hazardous sources. (2) The potential exposure indices will be calculated for administrative regions (census tracts and blocks) in Southwestern Pennsylvania and compared with the indices calculated for iso-density population centers and randomly distributed regions. (3) Stand -alone algorithms will be created for use with GIS databases centered on other regions of interest identified using the GIS-based Atlas of Cancer. (4) A concurrent feasibility study for childhood cancer in a six-county region of Southwestern Pennsylvania will be performed. This portion of the study will determine the accessibility of relevant information for hospital-based cases and controls in the sixcounty region and develop the necessary mechanisms for mounting a full-scale casecontrol study using the novel potential exposure indices. The GIS-derived potential exposure indices derived in this research can be geographically referenced for use in GIS-based health studies in general and also directly linked with the coordinates of individual cases and controls in specific studies of disease. When the exposure estimates are coupled with geographically-reference health data, such as published in the Atlas of Cancer, this will crate an effective tool for (1) screening studies linking environmental exposures with disease and (2) providing a relative exposure measure for individuals in case-control studies of disease. Overall, the simplified potential exposure indices will improve both environmental epidemiological studies and the monitoring for purposes of disease control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEALTH BEHAVIORS IN ADOLESCENT CANCER SURVIVORS Principal Investigator & Institution: Ford, Jennifer S.; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2003; Project Start 27-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Healthy People 2010 (USDHHS, 2000), highlights critical health objectives for adolescents, including the importance of reducing tobacco use, reducing the proportion who are overweight or obese, increasing the proportion who engage in regular physical activity, and increasing the proportion who engage in sun protection. Given adolescent cancer survivors' increased risk for physical late-effects and their increased vulnerability to additional chronic conditions, these health behaviors are even more critical. Advances in pediatric cancer care have resulted in a growing population of childhood cancer survivors. However, little research to date has investigated the mechanisms that promote or hinder a healthy lifestyle among adolescent cancer survivors. Guided by the Theory of Planned Behavior, and

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empirically supported cancer-related variables, this study will identify the patterns and covariates of health-protective and health-damaging behavioral intentions and behaviors among adolescent cancer survivors. Specifically, we will investigate survivors' tobacco use, regular exercise, nutritional habits, and sun protection intentions. We will assess 200 adolescents (14-19 years of age), who were diagnosed with cancer during late childhood to early adolescence (8-14 years of age), have no evidence of disease (NED) and are at least 1 year post-treatment. No studies to date have examined theoreticallydriven covariates of adolescent survivors' health behavior intentions that may influence their future risk of disease. There is evidence to suggest that life-threatening illness may increase health behavior change among adults, however, the study of health risk behaviors among pediatric cancer survivors is an area that has received little attention. The proposed study will fill a research gap in a high priority area and the findings are likely to have both clinical and theoretical implications. The study findings will address a national priority and advance behavioral science by identifying theory-driven covariates that impact the health-protective and health-damaging behaviors of adolescent cancer survivors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEALTH PROMOTION IN CHILDHOOD CANCER SURVIVORS Principal Investigator & Institution: Cox, Cheryl L.; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-AUG-2005 Summary: (provided by applicant): The health and long-term survival of the growing population of childhood cancer survivors is threatened by late sequelae of therapy: cardiovascular complications, obesity, osteoporosis, and new malignancies. This application proposes a re-examination of a methodologically sophisticated clinical trial data set that has the potential to generate new hypotheses about the antecedents of health-risk behavior and health-promotion behavior in adolescent survivors of childhood cancer. The analysis will use a tested, broad-based, middle range theory of health behavior to identify potential new determinants of these behaviors in previously unexplored and/or reconfigured variables from the parent clinical trial. Unlike the parent trial, the proposed study will examine the health risk behaviors and health protective behaviors as 10 separate behaviors and as two multidimensional constructs, rather than as a single, unidimensional construct. This economical investigative approach maximizes the probability of identifying new targets for interventions aimed at reducing survivors' risk of late sequelae. Specifically, this study will: (1) define the relationships between selected demographic, social, psychological, and resource variables and the health risk behaviors and health promotion behaviors of adolescent survivors of childhood cancer; (2) specify two separate structural equation models (health risk behavior and health promotion behavior) in adolescent survivors of childhood cancer by using the Interaction Model of Client Health behavior (IMCHB); and (3) compare the explanatory power of the cognitive processing theory (Health Belief Model, which directed the parent clinical trial) with that of the IMCHB, which will direct the proposed study. This study will afford an established investigator (PI) an opportunity to enter a newly targeted high-priority area (health promotion and quality of life in people with chronic illness) with a self-contained research project that uses novel methods of analysis (reconceptualization of measures, logistic and multiple regression, item response theory, and structural equation model development). This study has the potential to make a major conceptual contribution to childhood cancer

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research and to provide the conceptual basis for prospective clinical trials of health promotion interventions for survivors of childhood cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATITIS C IN CHILDHOOD CANCER SURVIVORS Principal Investigator & Institution: Hudson, Melissa M.; Associate Professor of Pediatrics; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 15-SEP-1999; Project End 30-JUN-2004 Summary: The broad, long-term objective of this proposal is to conduct a prospective, longitudinal natural history study of hepatitis C (HCV) infection in a well-defined cohort of childhood cancer survivors. The specific aims of this proposal are (1) to assemble a cohort of survivors of childhood cancer who were infected with HCV by transfusion during childhood, and (2) to develop predictive models for the subsequent development of cirrhosis, chronic active hepatitis, fibrosis, liver decompensation, hepatoma, hepatocellular carcinoma, and other HCV-related hepatic sequelae. This cohort is unique in comparison with other groups with chronic HCV infection in that these patients acquired the infection when they were young and were receiving immunosuppressive or hepatotoxic therapy. Thus, studies of this cohort should advance the understanding of clinical risk factors that predispose patients to clinically significant liver disease. So far, 1,441 of 3,767 (38.3 percent) patients who received transfusions at St. Jude Children's Research Hospital between 1962 and July 1992 have been screened for HCV by enzyme immunoblot assay. Of these, 110 (7.6 percent) patients have detectable HCV antibodies; 59 of these patients have been enrolled, and the remaining 51 are potentially eligible for participation in a longitudinal study of the natural history of HCV. Based on the prevalence of HCV infection in our currently screened cohort, we estimate that 293 transfused, but untested patients will be HCV seropositive. After adjusting for the anticipated rates of survival and study participation, we estimate that we will enroll a total of 268 HCV seropositive cancer survivors in a prospective epidemiologic study. As the ultimate aims of this proposal are to define the risk of progression to clinically significant liver disease in this cohort and to elucidate the impact of age, immunosuppression, and hepatotoxic cancer therapy on the outcome of chronic HCV infection, the histologic findings of these study patients will be correlated with clinical, laboratory, and diagnostic imaging variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVED DIAGNOSIS IN ALL Principal Investigator & Institution: Stephan, Dietrich A.; Assistant Professor; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and the second leading cause of deaths from childhood cancer in the United States: 1. Approximately 3000 cases a year, representing 75 percent of all pediatric leukemias, are diagnosed in children in the United States, and the incidence continues to increase steadily 2. Despite dramatic progress in treating this disease, the absolute number of patients who relapse (who are initially defined as 'standard' risk) is greater than the number of children diagnosed with AML, neuroblastoma, or Wilms tumor 2. These patients appear to have a different class of disease, which cannot be differentiated using available clinical/pathological approaches (such as white blood celI count) at the time of diagnosis. The goal of this proposal is to

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define a diagnostic system, derived from gene expression profiles, which would differentiate between tumors initially classified as 'standard risk' which are amenable to therapy (achieve long-term disease free survival (LTDFS)) and those which are not (relapse within 2 years). Salvage therapy for this poor outcome group is currently ineffectual (LTDFS in less than 10 percent of cases) but there is evidence that intensification of treatment at the time of diagnosis for these cases would be highly effective. Expression profiling and analysis, blinded to clinical data, has previously been shown to easily discriminate between different types of leukemia tumors (ALL vs. AML) 3. We hypothesize that similar techniques will enable us to identify tumor subtypes with increased propensity to rapidly relapse within the 'standard' risk group. Our team consists of the Chairman of the Children's Oncology Group (Dr. Reaman), CNMC (one of 11 sites in the country to receive a $14,000,000 NHLBI PGA grant for profiling clinical samples)(Dr. Stephan), and several of the most experienced groups in the field of expression array statistics and bioinformatics in the community (Drs. Butte, Golub, Trent). In the R21 portion of this proposal we will first develop, as a proof-of-principle, a cDNA array-based system that can, in a single step, provide prognostic fusion transcript information, which is currently obtained by cytogenetics. We have an in-house tissue bank of greater than 3000 leukemia bone marrow aspirates (extremely high tissue homogeneity) which have been flash frozen which will be used as the resource for the entire proposal. Secondly, we will expression profile 50 tumors of the 'standard' risk - no relapse and 50 closely matched tumors of 'standard' risk which relapse rapidly after therapy to define a set of predictor gene candidates using both supervised and unsupervised techniques. In the R33 phase, this set of predictor gene candidates will be validated by profiling an additional 100 ALL samples blinded to relapse status. These samples will simultaneously be genotyped for the known prognostic indicators using the cDNA array to validate our ability to detect translocation status (specificity and sensitivity determined by comparison with the COG database). Finally, both the oligos which are able to detect translocation status from tumor RNA, as well as the validated predictor gene set will be incorporated onto a custom Affymetrix array for use as a rapid, one-step, inexpensive molecular diagnostic tool. The future goal of this proposal is to prospectively diagnose relapse so that therapy can be intensified at the time of presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING INFORMED CONSENT IN CHILDHOOD CANCER TRIALS Principal Investigator & Institution: Kodish, Eric D.; Director; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 21-JAN-1999; Project End 28-FEB-2007 Summary: (provided by applicant): Informed consent requires further study, and pediatric oncology is the ideal context for the conduct of such research. The primary goal of this study is to improve the quality of informed consent for childhood cancer trials. The project will take place as a limited-institution study within the Children's Oncology Group, the single pediatric member of the NCI's Clinical Trials Cooperative Group Program. The long-term objective will be to capitalize on our understanding of consent to yield generalizable findings that can be implemented to improve consent in clinical trials across various diseases and all age groups. The research plan is based on the premise that specific outcome measures and rigorous scientific methodology are required to accurately study the complex interaction that is informed consent. The work accomplished to date has allowed us to refine this methodology, select key outcome

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measures, and develop rational intervention plans; it is the foundation upon which this competitive renewal proposal is based. The Specific Aims of the project are: 1) To utilize our scientific understanding of the informed consent process in childhood leukemia trials to further develop, test and implement two databased interventions to improve informed consent: a) a physician-directed intervention based on teaching improved management of the informed consent conference, and b) a parent-directed intervention based on the model of anticipatory guidance for informed consent; 2) To conduct a clinical trial to test the effect of each intervention on three specific outcomes: a) parental comprehension of choice and alternative to clinical trial participation, b) parental understanding of randomization, and c) parental participation during the informed consent process as measured by the number and quality of questions asked by parents, and; 3) To determine if either intervention is superior to a control group, and how the two interventions compare to one another. This clinical trial of two rational, data-driven interventions will allow us to act on what we have learned, to determine whether we can improve informed consent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRATHECAL CAMPTOTHECIN ANALOGS FOR NEOPLASTIC MENINGITIS Principal Investigator & Institution: Friedman, Henry S.; Professor; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002 Summary: Primary brain tumors, including malignant gliomas and ependymomas, are second only to leukemia as a cause of childhood cancer. Advances in chemotherapy and combined modality regimens, though dramatically successful in the treatment of other pediatric malignancies, have not been translated into effective therapy for most pediatric brain tumors. Although the role of chemotherapy in the treatment of malignant gliomas and ependymomas remains poorly defined, recent clinical and laboratory studies support the activity of the classical bifunctional alkylating agents against these tumors. Nevertheless, substantial increases in patient survival as a result of adjuvant use of these agents remain to be demonstrated, and an understanding of the mechanisms responsible for drug failure is critical for the design of optimal chemotherapeutic intervention. Successful establishment of cell line and xenograft models of childhood high grade glioma and ependymoma now provide the biological tools to facilitate an understanding of alkylator resistance in these tumors. Resistance to alkylating agents, including cyclophosphamide and melphalan, is multifactorial, with a diverse spectrum of mechanisms observed in murine and human neoplasia. Mechanisms of resistance to cyclophosphamide include increased aldehyde dehydrogenase activity., increased glutathione-S- transferase activity, elevated levels of glutathione, and a presently undefined mechanism in medulloblastoma. Similarly, mechanisms of resistance to malphalan include decreased cellular transport, increased intracellular glutathione levels protective of critical cellular targets, cellular detoxification and enhanced capacity to repair damaged DNA. These studies may not be relevant to the mechanisms of resistance operational in childhood malignant glioma and ependymoma. The hypothesis of this proposal is: definition and modulation/bypass of alkylator resistance in childhood high grade glioma and ependymoma will allow selection of alkylator regimens active in the treatment of these tumors and increase survival of children with these neoplasms. The specific aims of this proposal are: 1) To continue to establish childhood high grade glioma and ependymoma cell lines and transplantable xenografts in athymic mice with de novo clinical, acquired clinical and laboratory-generated

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cyclophosphamide and melphalan resistance. 2) To define the mechanisms of resistance to cyclophosphamide and melphalan of childhood high grade glioma and ependymoma cell lines and xenografts with de novo, acquired clinical, and laboratory-generated resistance. 3) To define modulation effective in bypassing/reversing cyclophosphamide and melphalan resistance in childhood high grade glioma and ependymoma cell lines and xenografts and 4) To define the role of L- amino acid oxidase-mediated depletion of plasma large neutral amino acids to enhance delivery and activity of melphalan in the treatment of subcutaneous and intracranial childhood high grade glioma and ependymoma xenografts in athymic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISOLATION OF THE NEUROBLASTOMA PREDISPOSITION GENE Principal Investigator & Institution: Maris, John M.; Assistant Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2003; Project Start 14-AUG-1998; Project End 30-APR-2007 Summary: (provided by applicant): Neuroblastoma remains an important pediatric disease that results in 15% of overall childhood cancer mortality. Several chromosomal aberrations that contribute to the malignant phenotypes are known, but the genetic events essential to initiate neuroblastoma tumorigenesis have not been discovered. We have shown that hereditary predisposition to develop neuroblastoma is genetically linked to the distal short arm of chromosome 16. In addition, we have demonstrated that hemizygous deletions of the same locus are a common somatically acquired event in sporadic neuroblastomas. Thus, we hypothesize that hereditary neuroblastoma is due to mutations in a tumor suppressor gene (HNB1) located at 16p12-13. We also predict that functional inactivation of this gene is responsible for the initiation of many nonfamilial human neuroblastomas, and perhaps other cancers. Accordingly, we propose to first localize HNB1 to within a one megabase region at 16p12-13 and identify candidates for mutation analysis. This will be accomplished using a multifaceted approach including high-density SNP genotyping, array-based comparative genomic hybridization, and gene expression profiling using oligonucleotide arrays. Second, we will identify HNB1 and characterize the spectrum of germline and somatically acquired mutations in familial and sporadic neuroblastomas. We will also survey a large panel of sporadic neuroblastoma primary tumor samples, as well as other human cancers with particular emphasis on neural crest derived tumors, for HNB1 mutations and loss of functional protein expression. Third, we will characterize HNB1 as a tumor suppressor and reintroduce wild-type HNB1 into HNB1-null neuroblastoma cell lines to determine effect on proliferation in vitro and tumorigenicity in vivo. Fourth, we will describe the phenotype of mice harboring heterozygous inactivation of one allele of the murine HNB1 homologue, with particular attention to neural crest tumor formation. Successful completion of these experiments will determine if inactivation of HNB1 is the seminal initiating event for human neuroblastomas, or if genetic heterogeneity exists. Successful completion of this project should dramatically improve our understanding of the fundamental genetic basis of neuroblastoma, and perhaps other human cancers. We also expect that this project will result in a valuable mouse model of this enigmatic pediatric disease. Ultimately, these experiments should lead to the identification of a common pathway to neuroblastoma tumorigenesis that will be an outstanding target for rationally designed therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KNOWLEDGE EMPOWERMENT FOR YOUTH WITH SOLID TUMORS Principal Investigator & Institution: Jones, Judith K.; President and Ceo; Degge Group, Ltd. 1616 N Fort Meyer Dr, Ste 1430 Arlington, Va 22209 Timing: Fiscal Year 2003; Project Start 01-AUG-2000; Project End 31-JAN-2005 Summary: (provided by investigator): Childhood cancer is the number one disease killer of children and adolescents in North America. For adolescents, a diagnosis of cancer comes at a particularly vulnerable developmental stage in their lives. Phase I focus group interviews indicated that these adolescents are adamant about wanting to know and learn about all aspects of their disease and how it will impact their lives. Unfortunately, few educational tools exist for these young cancer patients, particularly those with solid tumors, and none are in an interactive format. This application seeks funding to complete and evaluate a multimedia CD-ROM for 12-18 year-olds with solid tumors to teach them about their disease, treatment, and coping strategies. A combination of text, videos, animations/graphics, voice-overs, music, and games will creatively relay important information in an interactive and non-threatening manner. This innovative product is the first of its kind, focusing on solid tumors. It will be evaluated in a randomized pre-post design against a "usual care" print handbook to determine its effect on coping skills, feelings of control over health, knowledge about solid tumors and their treatment, satisfaction, and acceptability. Once developed, the CD-ROM will be marketed so that it will be available to all adolescents with solid tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LAB RESEARCH TRAINING IN HEMATOLOGY

PEDIATRIC

ONCOLOGY-

Principal Investigator & Institution: Civin, Curt I.; Professor of Cancer Research; Oncology Center; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 31-MAY-2008 Summary: (provided by applicant): To continue to make progress in Pediatric OncologyHematology (POH), we need to perpetuate the pool of talented and trained POH physician-scientists and Ph.D. scientists who will make POH-relevant discoveries and provide investigative leadership. Nevertheless, in the field of POH, there continues to be a shortage of young investigators with extensive laboratory research expertise. In the current funding period (1998-2003), this grant has already supported superb laboratory research training for an outstanding group of 17 physician-scientists and 12 Ph.D. scientists who have demonstrated a high degree of productivity and commitment to careers in cancer research. Selection of the 2002-2003 trainees is in progress. In addition, these trainees have strengthened the laboratory research base in the POH in the Johns Hopkins Medical Institutions (JHMI). This application now seeks support for 10 interdisciplinary postdoctoral research fellowship positions per year to fund the research training that is the major ingredient of the recently combined Johns Hopkins University/National Cancer Institute (NCI) Subspecialty Fellowship Training Program in POH (JHU/NCISFTP). Two groups of postdoctoral fellows will be supported by the grant proposed herein. The major group of trainees will be composed of physicianscientists, since the laboratory research training of academic POH physician-scientists is the primary objective of this training program. These highly selected physician-scientists will have completed the clinical year of their fellowships in the JHU/NCISFTP. The second (smaller) group of trainees will be composed of Ph.D. postdoctoral scientists

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working at JHMI on projects highly relevant to the biology of childhood cancer and blood diseases. These strongly qualified postdoctoral trainees will be provided intensive 3-year research experiences that will prepare them for careers in cancer research. Trainees will work on projects relevant to the biology of childhood cancer and blood diseases, in the laboratories of leading scientists in the field. The trainees and their mentors will participate in an interactive, dynamic research environment bridging the JHMI and the National Institutes of Health (NIH), with an emphasis on translational research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LANGUAGE AND INFORMED CONSENT IN CHILDHOOD CANCER Principal Investigator & Institution: Simon, Christian M.; Cancer Center; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Communication is the fabric of medical care. Nevertheless, it has recently been estimated that more than 31 million people in the United States are unable to communicate in the same language as their health care providers. Pressure to recruit interpreters in order to facilitate communication between clinicians and patients has followed, a factor that introduces into health care communication such issues as interpreter inaccuracy, role conflict, and other complexities of language interpretation. This two-year study investigates language interpretation in the context of informed consent for cancer clinical trials, where effective communication is vital to the optimal disclosure and understanding of information, and the decision-making competency of patients and their families. It focuses on informed consent discussions involving parents with children who were newly diagnosed with leukemia. The study's objectives are to: 1. Examine how interpreters function during informed consent discussions for cancer clinical trials, and how their behaviors shape the consent process; 2. Assess the impact of interpreter behaviors on parental understanding of informed consent; and, 3. Tie the above findings to first-hand data on the concerns and needs of key stakeholders in interpreted informed consent. The study plans to meet the first two objectives through a structured, sentenceby-sentence analysis of the English and Spanish portions of a sample of audiotaped informed consent discussions. Structured questionnaires will be used to meet the third objective. These will be administered to a sample of interpreters, parents, and clinicians who have previously participated in multilingual informed consent discussions for cancer clinical trials. Little research exists on the use of interpreter services in informed consent for cancer trials, even though it is clear that informed consent obtained without competent language interpretation is unlikely to be truly informed. The proposed study will identify aspects of language interpretation that may require improvement, or that may serve as a model for enhanced communication and understanding in informed consent discussions for cancer trials, both within and beyond the pediatric setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LATE TRANSPLANTATION

EFFECTS

IN

SURVIVORS

OF

STEM

CELL

Principal Investigator & Institution: Baker, Kevin S.; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006

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Summary: (Applicant's Description) K. Scott Baker, M.D. is a pediatric oncologist in the Blood and Marrow Transplant Program at the University of Minnesota, and holds an appointment as an Assistant Professor in the Department of Pediatrics. The candidates career goals are: 1) to develop clinical research expertise which has a solid foundation in clinical research methodology, epidemiology, and biostatistics, 2) to focus these activities on patient oriented research in the field of hematopoietic stem cell transplantation (SCT), specifically transplant related complications and late effects, 3) to utilize these newly acquired skills in order to achieve the status as an independent clinical investigator. The proposed career development plan will provide a comprehensive, multidisciplinary, closely mentored, patient oriented research experience. This will be accomplished in conjunction with formal didactic training in Clinical Research obtained by the candidate enrolling in the master's degree program in clinical research in the Division of Epidemiology. Under the mentorship of Dr. Leslie Robison and Dr. Norma Ramsay, the candidate will initiate investigations into the late effects seen in long-term survivors after SCT. The proposed research will establish prospective and retrospective, long-term follow-up studies of SCT survivors at the University of Minnesota for the systematic, protocol driven, evaluation of the incidence, risk factors, and characteristics of cardiopulmonary, renal, endocrine and reproductive late effects, quality of life outcomes, and second malignant neoplasms. Hypothesis driven investigations will also be undertaken in the current population of 1226 longterm survivors. These will include studies of the impact of different transplant conditioning regimens (total body irradiation, total lymphoid irradiation, and chemotherapy only) on subsequent late effects in children, an analysis of the spectrum and severity of treatment related sequelae which develop in the second decade of longterm follow-up, and an analysis of the impact that chronic graft-versus-host disease has on late effects and quality of life in SCT survivors. The candidate will also utilize data frorn the ongoing, multi-institutional, Childhood Cancer Survivor Study (Dr. Robison is Principal Investigator) for a comparative analysis of patients in that cohort receiving standard chemotherapy versus those who have undergone SCT as part of their therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEARNING IMPAIRMENTS AMONG SURVIVORS OF CHILDHOOD CANCER Principal Investigator & Institution: Mulhern, Raymond K.; Director of the Department of Behavioral; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 12-JUL-1999; Project End 30-APR-2004 Summary: (adapted from investigator's abstract): Children surviving some types of cancer, particularly acute lymphoblastic leukemia (ALL) and brain tumors, have an increased incidence of learning impairments compared to their healthy peers in the general population. These impairments, for which there is no known effective treatment, are of sufficient severity to inhibit normal academic achievement, vocational attainment, and quality of life. Previous investigations have suggested a model in which treatmentinduced lesions of the brain, especially in the white matter, are an underlying cause of learning difficulties that are frequently manifested as deficits in the ability to sustain attention. The goal of this research proposal is to test the validity of this model by defining the neuroanatomic substrates of problems with attention and learning and by assessing the behavioral response of these problems to pharmacological intervention. To accomplish this goal, quantitative magnetic resonance imaging (qMRI) of the brain and neuropsychological testing will be conducted on 625 participating children treated for ALL or malignant brain tumors at 3 pediatric cancer centers. It is hypothesized that

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Childhood Cancer

volumes of normal white matter in patients will be: a) significantly reduced compared to healthy peers, b) directly associated with the intensity of their central nervous system treatment, and c) positively correlated with their performance on measures of sustained attention and learning. A second study hypothesis is that methylphenidate will be effective in reducing their problems with attention and learning. This hypothesis will be tested with 200 children selected from the larger screened sample on the basis of objective problems with sustained attention and learning with regard to: (a) immediate (1-1/2 hr) behavioral benefits in our laboratory and (b) short-term (3 week) benefits at home and school in randomized, placebo-controlled, crossover designs, and then (c) long-term (12 month) maintenance benefits at home and school. The results of these studies will have a potentially important impact on childhood cancer by reducing the cognitive morbidities of cancer and cancer treatment and by furthering our knowledge of their biological basis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG-TERM COMPLICATIONS OF CHILDREN/ADOLESCENTS & CANCER Principal Investigator & Institution: Green, Daniel M.; Associate Chief; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to hold a two-day conference on June 28-29, 2002 at Queen's Landing Inn (Niagara-on-the-Lake, Ontario, Canada). The program will be of interest to pediatric hematologists/oncologists, pediatric nurse practitioners, pediatric psychologists, pediatric oncology social workers, medical oncologists, fellows, residents, interns, clinical research associates and other primary care providers. The topic of bone complications following treatment of children and adolescents for cancer will be addressed. The goals of the 7th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer will be to: 1) Review the biology of the basic multicellular unit; 2) review the role of the kidney in the regulation of calcium metabolism; 3) review the effect of cis-platinum on renal function and calcium metabolism; 4) review the late effects of ifosfamide on the kidney; 5) review the issues involved in the measurement of bone density; 6) review the effects of radiation therapy effects on bone density; 7) review the effects of glucocorticoid hormones on bone density; 8) review the roles of androgen and estrogen in skeletal physiology; 9) review the issues involved in the management of osteoporosis due to ovarian failure; 10) review the role of growth hormone in the regulation of bone density; and 11) review the issues involved in the duration of treatment with growth hormone replacement therapy. The conference will include presentations by nationally and internationally recognized experts in these areas. The conference will facilitate subsequent discussions among the investigators of the Childhood Cancer Survivor Study, most of whom attend this conference, regarding future research on bone complications among participants in the Childhood Cancer Survivor Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MATERNAL PROBLEM-SOLVING TRAINING IN CHILDHOOD CANCER Principal Investigator & Institution: Sahler, Olle Jane Z.; Pediatrics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2007

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Summary: (provided by applicant): Research and experience document that caregivers, especially, mothers of children with cancer encounter extraordinary stresses during the child's illness. These stresses are particularly severe during diagnosis and induction therapy and can interfere significantly with caregivers' ability to make reasoned and timely decisions on their children's behalf. With increasing survivor rates, it has become evident that decisions made in the early stages of cancer management can have profound, long-term effects, adding to the distress caregivers feel trying to make the "right" decisions. To help mothers of newly diagnosed children cope more effectively with these challenges, we conducted two randomized trials as part of our previous work (R25-CA65520) to develop, field test, and evaluate the efficacy of problem-solving skills training (PSST), a cognitive behavioral therapy shown to decrease anxiety and depression --- two symptoms of post-traumatic stress commonly experienced among this group of mothers. We also pilot tested a multimedia, technology-based PSST enhancement, Carmen's Bright IDEAS. Our findings clearly show that PSST significantly increases problem-solving skills (primary effect) and decreases negative affectivity (secondary effect) in mothers from a variety of racial, ethnic, and socioeconomic backgrounds. Particularly powerful and long-lasting effects were noted in Spanishspeaking mothers, an especially underserved population. At this stage, it is essential that we investigate PSST as rigorously as possible by testing its clinical effectiveness against an active control and that we intensify the intervention to extend its duration of action among all users. These goals are the basis for the 4-5 aims of the proposed project. Aim 1" To develop a time-and-attention control condition to better assess the direct and mediational effects of PSST independent of social support (placebo). Aim 2: To develop a personal digital assistant hand-held supplement to standard PSST to provide real-time training, reinforcement, and on-the-spot documentation of PSST usage. Aim 3 A, B: To develop independent measures of the application of problem-solving strategies in everyday life. Aim 4: To measure utilization of and satisfaction with other resources accessed by mothers as independent indicators of the usefulness and cost-effectiveness of PSST. (Aim 5) To incorporate a maintenance phase into the PSST protocol to promote longer term change. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC EFFECTS OF BRAIN RADIATION IN CHILDREN Principal Investigator & Institution: Horska, Alena; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Brain radiation therapy (RT) has contributed positively to long term disease-free survival from childhood cancer. Despite its therapeutic benefit, RT has been associated with a spectrum of acute, early-delayed, and late-delayed toxicities to the central nervous system. As a consequence, children treated with brain radiation often develop neurological and neurocognitive deficits manifesting as behavioral or learning disabilities. It is unclear whether the neurocognitive deficits are due mainly to damage to the white matter or if cortical areas are also involved. Are there markers that could be measured non-invasively that reflect the degree of brain injury? Could these markers predict early in the course of treatment if brain damage will occur? Could these markers be used to evaluate sensitivity of different brain regions to radiation? Can the temporal course of regional changes due to radiation be mapped in the brain, non-invasively? We intend to answer these questions using non-invasive methods based on magnetic resonance (MR): magnetic resonance spectroscopy, diffusion tensor imaging, and volumetric MRI. Methods using MR have been

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Childhood Cancer

demonstrated to be promising tools for detection of radiation damage. However, their ability to explain neuropsychological deficits in children remains to be evaluated. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism, damage to tissue microstructure, and loss of brain tissue. Concurrent neuropsychological assessments will further enhance our understanding of the relationship between neuropsychological status and parameters measured by the proposed MR methods. The broad objectives of our research are to determine a) how brain function and integrity, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentrations, water diffusion characteristics, and lobar gray and white volumes) can be used as surrogate markers to predict the neuropsychological outcome from RT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NORTHERN CALIFORNIA COOPERATIVE FAMILY REGISTRY Principal Investigator & Institution: John, Esther M.; Director; Northern California Cancer Center 32960 Alvarado Niles Rd, Ste 600 Union City, Ca 94587 Timing: Fiscal Year 2004; Project Start 30-SEP-1995; Project End 30-NOV-2005 Summary: This project proposes to establish a Family Registry for Breast Cancer (FRBC) as part of an NCl-funded cooperative registry. The FRBC will be population-based (in the Greater San Francisco Bay Area), include many racial/ethnic minorities, and use a cost-efficient design to: 1) collect pedigree information, epidemiologic data, and biologic specimens from breast cancer cases with a family history of breast, ovarian and/or childhood cancers; 2) identify a population at high- risk for breast cancer that could be examined for inherited BRCA1 and p53 mutations, and facilitate cloning and analysis of other susceptibility genes; and 3) identify and obtain biologic specimens from Greater Bay Area families with Li-Fraumeni syndrome and a select subset of Dr. Li's established Li-Fraumeni families to broaden the resource for characterizing genetic susceptibility to breast cancer. Data included in the FRBC will be available to approved investigators to further genetic and translational research for breast cancer. Cases included in the FRBC will be identified by the Northern California Cancer Center's (NCCC) population-based Greater Bay Area Cancer Registry (GBACR), which covers six million residents. During a 3-year ascertainment period, 8047 female cases (< age65) and 78 male cases (< age 80), diagnosed from 1/1/95 through 12/31/97, will be identified. Cases will be asked to complete a brief screening questionnaire about their family history of cancer. Based on the reported cancer patterns of breast, ovarian and childhood cancers in their families, we will classify cases as "exceptional," "ordinary," or "sporadic" probands. "Exceptional" and a sample of "ordinary" probands (n=875), the groups reporting positive family histories, will be sent a family pedigree and a brief risk-factor questionnaire. A racestratified sample of "exceptional" and "ordinary" probands who complete the questionnaires (N= 424) will be asked to provide a blood sample and access to archived tissue. Affected relatives of probands from these high-risk families whose diagnoses have been verified by review of pathology and medical records will be asked to complete a family pedigree, donate blood, and provide access to archived tissue (N=648). Blood collected as part of the FRBC will be processed and stored at NCCC. Archived tissue will be prepared for storage by a Co- Investigator at Stanford University. With the proposed sampling strategy, racial/ethnic minorities will comprise one-half of the high-risk probands and affected family members. Cases will be followed using GBACR methods to obtain survival and recurrence data. Genetic counseling will be provided as needed using trained oncology nurse/genetic counselor pairs and

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existing community resources. An Operations Core will track all aspects of the project, record pedigrees, and make FRBC data accessible electronically; this unit also will conduct quality-control measures at all steps of data collection. Four pilot studies using the FRBC are proposed. FRBC Investigators will serve on NCl's Steering Committee and develop common policies for quality and distribution of data from the FRBC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUDR--A POTENTIAL TUMOR SUPPRESSOR OF CHILDHOOD CANCERS Principal Investigator & Institution: Huggenvik, Jodi I.; Physiology; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: NUDR is a mammalian transcription factor with homology to Drosophila DEAF-1, a developmental cofactor of Hox and homeodomain proteins. NUDR will regulate target genes in adults and during fetal development, and may influence the process of genomic imprinting. NUDR behaves as a transcriptional repressor by binding to CpG containing motifs found in target genes that include its own promoter and hnRNP A2/B1, an early biomarker of lung cancer. NUDR has sequence or structural homology to known and putative oncoproteins (c-myc, AML1/MTG8, SP100). NUDR is cell-cycle regulated and may recruit the corepressor N-CoR to produce chromatin remodeling. Mutations in NUDR cDNAs from tumor tissues have been identified that will produce truncated and altered proteins. Human ovarian and breast tumors show variable expression of a NUDR anti-sense gene, Nopps, which is encoded on the opposite strand as NUDR and may affect the expression of NUDR. Mutations in NUDR result in transformed cell phenotypes that produce tumors in athymic nude mice, thus mutated NUDR acts as an oncogene. Normal NUDR and Nopps produce strong tumor suppression of the childhood cancer cell line, RD. NUDR maps to the precise chromosomal region (11 p15.5) harboring multiple tumor suppressors for lung, liver, Wilms', and possibly many other cancers. Loss of imprinting at 11 p15.5 is likely to be an underlying mechanism for a number of pediatric and adult cancers, and based upon its profile, NUDR is the most likely candidate for the WT2 tumor suppressor. To investigate the normal physiological role of NUDR and Nopps, and to determine the role that NUDR functional domains may contribute to childhood cancers, we propose the following: 1) Establish stable cell lines expressing Nopps or NUDR functional domains. 2) Determine if the functional domains promote or inhibit tumor formation. 3) Eliminate the NUDR gene by homologous recombination in mouse and determine the physiological phenotypes. and 4) Determine if the Nopps tumor suppressor is expressed in mice and assess the feasibility for gene targeting. These studies will provide an understanding of how NUDR and Nopps act as tumor suppressors, how mutations in NUDR contribute to the development of childhood malignancies and adult cancers, and how global changes in chromosome function may affect oncogenic processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPTIMIZING IMMUNOTHERAPY FOR NEUROBLASTOMA AFTER BMT Principal Investigator & Institution: Johnson, Bryon D.; Associate Professor; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2004; Project Start 15-JUN-2004; Project End 31-MAY-2009

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Childhood Cancer

Summary: (provided by applicant): Neuroblastoma remains a serious childhood malignancy, accounting for 8-10% of all childhood cancers. Prognosis for patients with advanced disease remains poor, with a 2-year disease-free survival of only 10-30%. Recent clinical research has shown that for patients with advanced disease, bone marrow transplantation (BMT) with purged autologous marrow improves event-free survival. However, the majority of patients still relapse within 2 years after transplant. Immune intervention early after transplant might improve survival of these patients. Our preliminary data in an experimental model indicates that T cells capable of responding to a neuroblastoma tumor vaccine are required for induction of anti-tumor immunity after BMT. Immune regulatory T cells (CD4+CD25+) have been found to play a key role in regulating self-non-self recognition by the immune system, and it appears that these cells can be recruited or induced by tumors to prevent immune activation and tumor elimination. The presence of these regulatory cells in the diseased host may in part explain the low degree of success with tumor vaccines. The time period early after BMT, before regulatory T cells have reestablished dominant peripheral tolerance, offers a unique setting to induce effective anti-tumor immunity by combining T cell add-back and tumor vaccination with the inhibition of CD4+25+ T cell-mediated tolerance. Utilizing a mouse model for neuroblastoma, Neuro-2a, we hypothesize that: (1) Using a novel technology, nucleofection, neuroblastoma can be genetically engineered with DNA plasmid vectors to rapidly and efficiently express costimulatory/accessory molecules (CDS0, CD86, ICAM-1, and/or 4-1BBL), and that these engineered cells can serve as a potent tumor vaccine; (2) CD25+ cells suppress anti-neuroblastoma immunity, and depletion of these regulatory T cells augments immunity during tumor vaccination by increasing the contribution of multiple immune effector populations; and (3) Optimal T cell immunity to neuroblastoma can be induced early post-BMT by combining T cell addback with novel tumor vaccines in a setting where cellular mediators of tolerance induction (to tumor) have been removed. The goal of these studies is to provide preclinical data that will lead to the testing of novel immunotherapeutic strategies to prevent neuroblastoma relapse after BMT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY CLINICAL RESEARCH TRAINING PROGRAM Principal Investigator & Institution: Poplack, David G.; Director, Texas Children's Cancer Center; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The development of pediatric oncologists and pediatric oncology nurses who are highly trained in clinical research is essential for continued progress to be made in the treatment of childhood cancer. This proposal describes a Pediatric Oncology Clinical Research Training Program, developed by Baylor College of Medicine's Texas Children's Cancer Center, that is structured to provide a formal, comprehensive, multidisciplinary clinical research educational program that will train board eligible pediatric oncologists who have completed a three year fellowship and Ph.D.-prepared ontology nurses in the design, implementation and analysis of all phases of clinical research trials. Trainees will spend a portion of their first year participating in a core curriculum in clinical research and spend the remainder of that and subsequent year(s) receiving further clinical research training in their choice of one of five specialized training tracks (clinical pharmacology, neuro-oncology cell and gene therapy, leukemia or solid tumors). This carefully mentored training program will take advantage of BCM's funded (NIH-K30 award) Clinical Scientist Training Program

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to provide a comprehensive, didactic clinical research core curriculum that will serve as a foundation for further training within one of the five specialized areas of research. The research experience within each of these areas will be tailored to meet the individual trainee's long-term research goals. It will provide mentorship by both a laboratory and clinical mentor' while providing in depth exposure to the most important facets of the clinical research process. Trainees will be instructed in clinical trial design, statistical analysis, research ethics and regulatory requirements and guidelines. In addition, under the tutelage of experienced mentors, trainees will design and conduct clinical trials in their respective areas of focus and will learn by mentor modeling the uniquely interactive, collaborative skills necessary to successfully develop effective clinical trials. Because trainees who complete this program will be well-grounded in both in the basic biology of their particular specialty areas and translational research skills, they will be well suited to become future leaders in pediatric oncology clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Luchtman-Jones, Lori; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2002 Summary: The Washington University Medical Center in St. Louis is one of the 39 full member institutions, 48 affiliate, 12 consortia and 9 CCOP institutions of the Pediatric Oncology Group who has pooled their patient resources and scientific expertise to study the natural history of childhood cancer, develop and compare effective therapeutic regimens and investigate the toxicity and effectiveness of new anticancer agents in the treatment of children with cancer. Additionally tumor specimens and occasionally normal tissue and blood samples are collected to determine more about the basic cancer biology and pathology of the disease. Group studies are ongoing in epidemiology, cancer control, pharmacology and pharmacokinetics. The investigators at the Washington University Medical Center include pediatric oncologists, radiologists, radiation oncologists, cytogenetists, neurologists, surgeons, and pathologists. All children with malignant disease are placed on cooperative group protocols if they are eligible and if informed consent is obtained. Data accessioned at the time the patient is placed on study protocol, during the study, and when off therapy is submitted to the Group Statistical Office for data analysis, interpretation and eventual publication. The investigators at Washington University Medical Center serve in multiple administrative and research capacities for the Group. The diagnostic studies, pathological findings, surgical procedure and therapeutic plan for all new patients and patients who relapse are discussed at the weekly Tumor Board Conference. The Principal Investigator has a phase I contract and works with 16 other POG institutions to establish the maximum tolerated dose of a new agent along with the pharmacology and, if indicated, the biologic response of the agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Cohn, Susan L.; Associate Professor of Pediatrics; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 01-DEC-1978; Project End 31-DEC-2002 Summary: The objectives of this project are to enroll children with cancer in clinical trials, to develop clinical trials and study the biologic behaviors of childhood cancer,

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Childhood Cancer

and to improve and evaluate the disease- free survival of patients enrolled in these clinical trials. In order to achieve these goals, the member institutions of the Pediatric Oncology Group (POG) meet biannually to discuss, develop, and implement clinical trials for the most common childhood malignancies and to supply the reference research laboratories of the proper material or tissue necessary for the research. Since 1989, CMH has been one of the member institutions of POG who is actually involved in the accrual of children with cancer to clinical trials. CMH's faculty is also involved in the coordination of studies either as the Principal Investigator or co-Investigator. These protocols are POG 9443, POG 9240/41/42, POG 9135/6, POG 9410, NTWS #5. Participation in administrative activities within POG include the POG Chairperson, the POG Executive Officer, the Head of the Neuroblastoma Biology Committee, the Head of the Neuroblastoma Bone Marrow Transplant Working Group, along with members of the following committees: Non- Hodgkin's Lymphoma, Neuroblastoma, Bone Marrow Transplantation, Hodgkin's Disease, New ALL, Wilms' Tumor, Nursing, and Surgery, Radiotherapy, and Pathology Disciplines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Steuber, C P.; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2002 Summary: The concept of the pediatric cooperative cancer group was introduced over 30 years ago because of the rarity of pediatric malignant diseases and the vital importance of controlled trials to improve the outcome for such patients. For such a group to succeed, the collaborative contributions of individuals from a large variety of specialties and fields of research are absolutely essential. This multimodal organized approach to the treatment of childhood cancer through the cooperative group has welldemonstrated its value. The Section of Pediatric Hematology-Oncology at Baylor College of Medicine has been involved in the genesis of this kind of clinical research and has participated in the activities at even level. The current goals of the Section regarding cancer prevention, treatment, and research have lead to the recent development of the Texas Children's Cancer Center. The Center is a joint effort of Texas Children's Hospital and Baylor College of Medicine and is committed to providing the finest possible patient care, education and research in the areas of pediatric and adolescent cancer and hematological disorders. Major expansion of the clinic and research lab facility is underway. New faculty are being recruited to expand the current research program in the areas of gene therapy, bone marrow transplantation, molecular biology, clinical pharmacology, and experimental therapeutics. Additional personnel including data managers, pediatric nurse practitioners, and research personnel have been recruited to support the new faculty members and the expanded programs. In addition, outreach efforts are making the Center known to communities in Texas that would benefit from a service dedicated to the treatment of children with cancer. The development of the Texas Children's Cancer Center will enhance Baylor's contributions to the Pediatric Oncology Group (POG) by expanding the research and treatment programs that have so successfully contributed to POG throughout the years, by developing new and innovative treatment and research programs, and by increasing study populations for those programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Meyer, William H.; Pediatrics; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2002 Summary: Children's Hospital of Oklahoma (CHO) at the University of Oklahoma is a member institution of the Pediatric Oncology Group. One of our primary goals is the enrollment of the majority of pediatric patients with cancer in the state of Oklahoma in a cooperative cancer program (POG). Participation in group studies guarantees optimal care for these patients and the opportunity to study in depth the natural history of childhood cancer, develop effective therapeutic regimens, and evaluate the toxicity. and effectiveness of new anti-cancer agents in the treatment of childhood cancer. In addition to the POG studies, institutional non- therapeutic protocols have been developed, i.e., evaluation of leukemic therapy on the central nervous system of newly diagnosed leukemic patients and longitudinal evaluation of coping mechanisms with stress among patients and parents of children with cancer. For all these programs, patient resources and scientific expertise are available in Children's Hospital of Oklahoma. The team at the University of Oklahoma is multidisciplinary. It consists of pediatric hematologistsoncologists, radiation therapists, radiologists, pediatric surgeons, immunologists, pathologists and psychologists. All protocols are reviewed by the Institutional Review Board and informed consent is obtained on all patients entered into these protocols. Protocol compliance remains a high priority. The evaluability rate for the last four years averaged 92.5%. St. Francis Hospital of Tulsa was previously considered a branch of CHO. At the request of the POG Operations Office, Tulsa has applied to become an affiliate institution. The University of New Mexico is also affiliated with the University of Oklahoma. It serves an economically disadvantaged population (native American Indians) which needs to be included in the population studied by cooperative cancer groups. The Pathology Department at the University of New Mexico has special expertise in molecular diagnostic hematopathology and in solid tumors which can benefit the research efforts of the Pediatric Oncology Group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC ONCOLOGY GROUP MEMBERSHIP Principal Investigator & Institution: Schwartz, Cindy L.; Associate Professor; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-1980; Project End 31-DEC-2002 Summary: The aim of this research is to improve the treatment of childhood cancer through participation in organized clinical trials with fellow members of the Pediatric Oncology Group. In addition, we intend to expand our understanding of these diseases by collaborative laboratory investigations. Multiple projects are described which reflect the intense commitment of our faculty to work within the Pediatric Oncology Group. Our faculty are leaders of the POG commitments in ALL phenotyping, Neuropathology, Bone Tumors, Hodgkins disease, Rhabdomyosarcoma, Radiation Oncology, Bone Marrow Transplantation, Myeloid disease, Germ Cell Tumors, Late Effects of Childhood Cancer Therapy, and Multiple Drug Resistance. Pediatrics is the program that describes patient accrual and protocol activity within the division of Pediatric Oncology at Johns Hopkins under the supervision of Dr. Cindy Schwartz as POG PI. The disciplines of Radiation Oncology, Pathology, Pediatric Surgery, Orthopedic Surgery, Neurosurgery and Nursing also play a major role in patient accrual and protocol activity. In addition, Fairfax Hospital under the direction of Dr. Jay Greenberg

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is an active affiliate of our institution. With the limited numbers of children admitted with any single oncologic diagnosis to an individual institution, it is clear that cooperative clinical research is required if significant advances are to be made. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP PARTICIPATION Principal Investigator & Institution: Pui, Ching-Hon; Acting Chairman; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-JAN-1982; Project End 31-DEC-2002 Summary: We propose continued participation in the Pediatric Oncology Group (POG). Our goals are as follows: (1) to improve cure rates for children with cancer through participation in Phase I, II, and III clinical trials designed to test new agents or concepts; and (2) to participate in laboratory-based research aimed at clarifying the basis of drug resistance and pathogenetic mechanisms of childhood cancers. We are committed to Group participation because we believe: (1) that collaborative efforts are both desirable and necessary for study of childhood cancers, since all are relatively rare; and (2) that well-designed randomized clinical trials provide the most definitive test of efficacy and general applicability of new therapies and that pooled intellectual resources are advantageous as well. Our contribution to the Group can be categorized as follows: (1) contribution of selected patients (those with rare tumors or less common stages of other cancers, n approximately 80-100/year) to Group studies; (2) administrative and scientific leadership (e.g., disease or discipline committee chairs, and protocol coordinators); (3) provision of multiple reference laboratories (flow cytometry analyses of leukemia and solid tumors, cell bank, AML cytogenetics, pharmacokinetics/pharmacodynamics, molecular genetics of leukemia and solid tumor); (4) regular presentation of results of in-house research to the group. Since our center has an unusually large number of patients and staff (both clinical and basic), the latter contribution assumes unusual importance. We have an extensive in-house developmental therapeutics program which is independent of, but complementary to, the Group's clinical research programs. We also have extensive programs in basic research. The aim of these programs, to determine the pathogenesis of pediatric neoplasia, is expected to positively influence the Group's central goal -- curing children with cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER CTR

PEDIATRIC

ONCOLOGY

GROUP--MIDWEST

CHILDREN'S

Principal Investigator & Institution: Camitta, Bruce M.; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JAN-1983; Project End 31-DEC-2002 Summary: The primary objective of the Midwest Children's Cancer Center is to reduce the incidence of and mortality from childhood cancers. This is approached by: 1) providing the best possible patient care (diagnostic and therapeutic; 2) education of medical and nonmedical groups as to the types of, treatments for, and availability of care for different childhood cancers; and 3) clinical and laboratory research. Investigators at the Cancer Center include specialists in pediatric oncology, surgery, orthopedic surgery, neurosurgery, radiology, radiation therapy, pathology, neurology, psychology and nursing. All new patients are discussed at a multidisciplinary Tumor Board. The children are then treated on Pediatric Oncology Group (POG) or institutional

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protocols. Results are analyzed and reported regularly. The purpose for the Midwest Children's Cancer Center's participation in POG are: l) to enhance the probability of achieving the above objectives by collaboration with other institutions in the design and execution of clinical protocols; and 2) to evaluate, through laboratory investigations, aspects of tumor biology which result in successful and unsuccessful therapy. Pediatric tumors are relatively rare. The POG is composed of more than 50 member institutions. By pooling resources, biologic and therapeutic studies on these uncommon tumors are facilitated. Similar collaboration permits more rapid development of new drugs. In addition, participation in a common milieu promotes dissemination of information between institutions and investigators. If all children with cancer receive the best possible care, morbidity and mortality will be minimized. The Midwest Children's Cancer Center has been a major contributor to POG by: 1) patient accrual; 2) coordination of POG protocols; 3) institutional pilot studies that were advanced to POG studies; and 4) participation in POG disease and administrative committees. In the next grant period we will continue each of these activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PESTICIDE DISPERSION IN TEXAS WATERSHEDS IN CHILD CANCER Principal Investigator & Institution: Thompson, James A.; None; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Cancer is the second leading cause of fatalities among U.S. children under the age of fifteen. Exposure to pesticides is potentially an important cause of childhood cancer. Contaminated drinking water is suspected as a source of such exposure. However, there is no direct evidence that implicates pesticidecontaminated water as a risk factor. The objective of this application is to estimate the risk of specific childhood cancers with each watershed in Texas and the role that 'local' cropping practices have in contaminating water supplies. The central hypothesis is that childhood cancers have incidence patterns that correspond to the agricultural use of pesticides and that a proportion of the risk is attributable to watershed-mediated exposure to agricultural pesticides. This hypothesis will be tested by three specific aims, which are strongly supported by preliminary analysis of the Texas Cancer Database. 1) Estimate the cancer risks attributable to cropping practices. The product of this aim will be a GIS layer of cancer risk based on county-level crop production. 2) Estimate the risk for specific childhood cancers in each watershed in Texas. The GIS layer of cancer risk produced here will be based on risk estimates for discrete watersheds. 3) Estimate the extent that the risk surfaces for watersheds and cropping practice are correlated. This aim will utilize formal Bayesian analysis of homology of the two GIS layers. The approach is innovative, because it capitalizes on recently developed Bayesian mapping and analytical techniques. The proposed research is significant, because we expect to estimate the potential for contaminated watersheds to mediate childhood exposure to pesticide agricultural carcinogens. Data acquired will be useful in further study design to select sampling sites that will optimize environmental and biomarker testing. It is anticipated that the results produced will provide the preliminary data needed to continue definitive investigations under the auspices of subsequent R01 funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Childhood Cancer

Project Title: PILOT--CANCER GENETICS AND VIROLOGY Principal Investigator & Institution: Fearon, Eric R.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: Established in 1998, the Cancer Genetics and Virology Program is an interdisciplinary group of 34 scientists pursuing basic and translational research to advance understanding of the nature and role of mutations, gene expression changes, and viruses in the development and behavior of cancer. This research is supported by over $6.4 million in annual direct support. The Cancer Genetics Group focuses on studies of germline and somatic mutations in oncogenes and tumor suppressor genes in cancer cells as well as efforts to define critical gene expression changes in the cancer cell and the specific epigenetic mechanisms that underlie the changes. The Virology Group is focused on the investigation of mechanisms which regulate DNA and RNA tumor virus replication and gene expression, as well as the effects of such viruses on infected host cells, including the role of viruses in cancer pathogenesis. Due to the complementary nature of the research, and the overlapping research interests and goals of the two groups, investigators in the two groups work together in a single program. Program members have primary and joint appointments in more than 12 departments at the School of Medicine and Public Health. Investigators in other programs in the Basic Science, Clinical Science, and Prevention Divisions of the Cancer Center, including the Programs in Cancer Cell Biology, Tumor Immunology, Experimental Therapeutics, Breast Oncology, Childhood Cancer, Cutaneous Oncology, Gastrointestinal Oncology, Prostate Cancer/Urological Oncology, and Cancer Prevention/Biomedical Research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--CHILDHOOD CANCER Principal Investigator & Institution: Boxer, Laurence A.; Professor of Pediatrics; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The Program in Childhood Cancer has three goals: to develop a better understanding of the biology and molecular defects responsible for pediatric cancer, train postdoctoral level physicians for independent research in the field of pediatric oncology; and to develop new approaches to the treatment of pediatric cancers. The Program is based on the clinical and research interests and expertise of twenty members from eight departments. The Program has 19 members with a total of $2.3 million in annual direct funding. The areas of scientific investigation include: Molecular Studies in Pediatric Solid Tumors; Biology and Therapeutics of Pediatric Solid Tumors; and the Biology of Hematopoiesis. The members of the Childhood Cancer Program (CCP) utilize all of the Cancer Center cores to accomplish their research mission. The members of the CCP have established extensive collaborations with members of the Basic Science, Clinical Science, and the Cancer Prevention and Control Programs. The members of the CCP participate in the Children's Cancer Group (CCG) and serve as the principal site for CCG and our five affiliate institutions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--TUMOR IMMUNOLOGY Principal Investigator & Institution: Mule, James J.; Associate Center Director; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The main objective of the Tumor Immunology Program is to investigate the immunologic interactions between the host and tumor and to translate these findings into novel clinical trials in patients with cancer. The Program's membership includes basic and clinical investigators from the Departments pf Surgery, Internal Medicine, Pediatrics, Radiology, Pathology, and Microbiology. In addition, the Program has established formal scientific and clinical interactions with the Breast Oncology, Leukemia/Lymphoma, Gastrointestinal Oncology, Childhood Cancers, Head and Neck, and Urological/Prostate Programs to investigate the elicitation of immune responses to these tumors and the use of immune- based therapies in these settings. The Tumor Immunology Program relies heavily on the functions of several Cores, including Biostatistics, Flow Cytometry, Molecular Biology and Protein Chemistry, Experimental Irradiation, Vector, Animal, and the Clinical Trials Office. The Program has also played a key organizational role in the new Immunological Monitoring Core and has initiated studies involving the new Microarray Core. The research component of the Program focuses on efforts to improve tumor immunotherapy by developing novel vaccine adoptive T cell, and gene therapy tumor immunotherapy by developing novel vaccine adoptive T cell, and gene therapy approaches through the use of well-defined in vivo animal models, in vitro tissue culture systems, and state-of-the-art immunologic assays. In addition, the Program's investigators are actively involved in studies of the induction and breaking of immune tolerance as well as actively involved in studies of the induction and breaking of immune tolerance as well as immune reconstitution following hematopoietic stem cell transplantation as critical areas in tumor immunology. By doing so, the basic research component of the Program focuses on efforts to improve cancer immunotherapy. The clinical research component actively enrolls advanced to improve cancer immunotherapy. The clinical research component actively enrolls advanced cancer patients in novel clinical trials as a direct outcome of Program. Current and planned future clinical trials include: the use of tumor-pulsed dendritic cells, recombinant vaccinia viruses, and gene-modified tumor cells in vaccine strategies; the adoptive transfer of immune effector T cells and gene-modified hematopoietic stem cells; and the systemic delivery of recombinant cytokines. In the area of education, the Program has spearheaded the formal establishment of a new Ph.D. degree granting Graduate Program in Immunology administered through the University of Michigan's Rackham Graduate School and the Medical School. This new graduate program is directed by the Tumor Immunology Program's current director (J. Mule) with additional oversight by an operating committee in which the majority of seats are currently held by members of the Tumor Immunology Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREMATURE MENOPAUSE IN SURVIVORS OF CHILDHOOD CANCER Principal Investigator & Institution: Sklar, Charles A.; Attending Pediatrician; SloanKettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 05-SEP-1998; Project End 31-JUL-2003

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Childhood Cancer

Summary: (Applicant's Description) Advances in the treatment of childhood cancer have resulted in markedly improved survival rates. However, with these advancements, cancer survivors now face the long-term consequences of treatment with intensive, multimodality therapies. While the majority of prepubertal girls and adolescent females retain or recover ovarian function during or immediately after completing cancer therapy, preliminary data indicate that many of these young women are at risk for premature menopause in the future. We propose to study, in a cohort of young adult survivors of cancer diagnosed during childhood/adolescence, the prevalence of early menopause, risk factors for the development of early menopause, the impact of an early menopause on quality of life and psychosexual functioning. The study cohort will consist of 5,500 young adult female survivors of cancer diagnosed during childhood and adolescence, selected from a larger population of survivors of childhood cancer, the Childhood Cancer Survivor Study (CCSS), and 3,000 sibling controls. Data will be collected using a self-administered questionnaire and will include the following topics: menstrual history and menopause status, covariates of menopause, health-related outcomes associated with premature menopause, and standardized instruments which measure quality of life and psychosexual functioning. Detailed information concerning cancer diagnosis and treatment, including cumulative drug dosages and radiation fields/doses, will be known for all study participants, facilitating the study of endpoints of interest. The large size of the study population, the heterogeneity of diagnoses and exposures, combined with the extensive treatment data, will allow assessment of interaction between the major risk factors of interest. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURVIVORS

PSYCHOSOCIAL

OUTCOMES

IN

CHILDHOOD

CANCER

Principal Investigator & Institution: Zebrack, Bradley J.; Assistant Professor; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 08-FEB-2002 Summary: The purpose of this proposal is to further understanding of the prevalence, characteristics and predictors of the psychosocial health status, health risk behaviors and neurological sequelae of long-term survivors of childhood cancer. The research proposed in this application will make use of the Childhood Cancer Survivor Study, a multi-institutional collaborative project that has established and followed a retrospectively-ascertained cohort of long-term survivors of childhood cancer and 6,000 sibling controls. This is the largest sample of well-characterized childhood cancer survivors and sibling controls known to date. Previous work suggests that certain subsets of childhood cancer survivors are vulnerable to a variety of physical and psychosocial problems, but the generalizability of these findings are limited by small sample sizes, data derived from single institutions, and lack of a control group. Furthermore, study in this field has yet to identify critical variables that influence (1) long-term survivors' psychosocial problems, but the generalizability of these findings are limited by small sample sizes, data derived from single institutions, and lack of a control group. Furthermore, study in this field has yet to identify critical variables that influence (1) long-term survivors' psychosocial status/quality of life, including their experiences with pain, and (2) behaviors that place them at risk for future health problems. The work to be conducted during the period of this functioning, and health behaviors. Physical, psychological, social and neurological factors that potentially influence these outcomes will be investigated. Specific hypotheses related to these

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outcomes are proposed and potentially moderating and mediating factors will be investigated. Psychosocial support interventions throughout a continuum of care- from diagnosis through treatment and into long-term survivorship-will be suggested. Plans for intervention research will be forthcoming. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTITATIVE MR MEASURE OF MTX NEUROTOXICITY IN CHILDREN Principal Investigator & Institution: Reddick, Wilburn E.; Assistant Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer with approximately 3,500 new cases each year in the United States. When cancer treatment specifically targets the immature brain, as is the case for children with ALL, treatment efficacy must be balanced against the potential for chronic neurotoxicity. With estimated three-year event-free survival for children with ALL now at approximately 90 percent, increasing attention is directed toward minimizing late neurotoxicity in this particularly vulnerable population. The most common method of CNS prophylaxis for pediatric ALL includes high-dose methotrexate (HDMTX). However, several studies have shown a significant association between HDMTX and neurotoxicity. Thus, treatment-induced neurotoxicity is an important and clinically relevant problem in pediatric oncology. Our own studies have confirmed that leukoencephalopathy can be observed in as many as 75 percent of patients during treatment with HDMTX, even those without seizures or other symptoms of acute neurotoxicity. Our research builds on the hypothesis that leukoencephalopathy resulting from HDMTX spans a continuum of severity that can be probed reliably using noninvasive MR technology. More than 300 children will be treated for ALL on a five-year protocol at our institution with therapy that includes five courses of either 2.5 or 5.0 g/m2 of HDMTX during the induction and consolidation phases. The proposed project will be the first to use quantitative imaging-based measures (hybrid neural network segmentation; T1 and T2 relaxation times) to investigate treatment-induced leukoencephalopathy during therapy in a group of subjects sufficiently large to adequately test the following hypotheses: 1) that leukoencephalopathy early in therapy is predictive of later white matter changes; 2) that leukoencephalopathy during therapy is proportionate to exposure to HDMTX; and 3) that leukoencephalopathy during therapy is predictive of treatment-induced neurocognitive outcome will have a direct impact on the design of future clinical trials for pediatric ALL. The ultimate goal is to use these quantitative MR imaging measures to detect early therapy-induced neurotoxicity, which is potentially reversible through therapy adjustments of other neurobehavioral and pharmacological interventions for individual children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK AGRICULTURAL *

OF

CHILDHOOD

CANCERS

ASSOCIATED

WITH

Principal Investigator & Institution: Carozza, Susan E.; Assistant Professor; Epidemiology and Biostatistics; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006

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Childhood Cancer

Summary: The overall goal of the proposed case-control study is to estimate the risk of specific childhood cancers associated with in utero exposure to pesticides (fungicides, herbicides and insecticides) used in agricultural settings, with particular emphasis on differential risk by race/ethnicity. In the process of addressing the study goal, we will be developing two tools which will have wider applications for public health research in Texas populations: 1) a geographic information system (GIS) capable of producing historical agricultural land use maps for a majority of Texas counties; and 2) a cropspecific Pesticide Exposure Index (PEI) for use in evaluating exposure to agricultural pesticides based on cropping and pesticide use patterns. These data applications will be of particular use in evaluating public health outcomes in rural populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP, FATIGUE, AND DEXAMETHOSONE IN CHILDHOOD CANCER Principal Investigator & Institution: Hinds, Pamela S.; Director of Nursing Research; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 30-JUN-2004 Summary: Mounting evidence indicates that adding dexamethasone to the therapy for children and adolescents diagnosed with lymphoblastic leukernia contributes to more positive long-term outcomes such as lower rates of meningeal leukemia. The significant positive contributions of dexamethasone have not occurred without adverse effects including avascular necrosis. mania and psychosis, and aberrant sleep and fatigue. These adverse effects could be related to inter-individual variability in the systemic exposure to dexamethasone and if so, the adverse effects could serve as behavioral indicators of patient sensitivity to the dosing schedule. To determine whether dexamethasone dosing schedules need to be individualized to minimize adverse effects while maintaining antileukernic effects, the relationship between inter-individual variability and adverse effects must be established. The overall purpose of this two-site study is to determine the relationship between systemic exposure to dexamethasone and patients' sleep and fatigue by comparing multiple indicators of patient sleep and fatigue in two consecutive 5-day periods during Continuation therapy off and on dexatnethasone. Approximately 134 children and adolescents with low or standard fisk ALL will wear a wnist actigraph for the two consecutive 5-day study periods and will complete a self-report fatigue questionnaire during a telephone interview on Days 2 and 5 of both study periods. Their parents will complete a sleep diary and a fatigue questionnaire on Days 2 and 5 of both study periods regarding their child's sleep and fatigue patterns. In addition, on Day I of the on dexamethasone 5-day study period, patients will-have sequential blood samples collected pre- and post- the morning dose of dexamethasone. These samples will be analyzed for dexamethasone pharmacokinetics and genetic polymorphism. Using these data, we will test the hypothesis that dexamethasone contributes to aberrant sleep and increased fatigue in children and adolescents with ALL, and that the altered sleep and fatigue are related to the pharmacokinetics of the drug. Our study findings will explicate the relationship between sleep efficiency and fatigue, and between sleep, fatigue, and systemic exposure to dexamethasone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURVIVORS

SMOKING

CESSATION

AMONG

CHILDHOOD

49

CANCER

Principal Investigator & Institution: Emmons, Karen M.; Deputy Director; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: Childhood cancer survivors represent a large and rapidly increasing group due to successes in cancer therapy over the last several decades. However, the treatments for childhood cancers tend to damage vital organs, and there is an increased risk of second cancers in childhood cancer survivors who may already have an innate susceptibility to neoplasia. Therefore, it is extremely important that preventable risk factors of cardiac, pulmonary, neoplastic, and other major diseases be minimized among this high-risk population. Interventions to reduce smoking prevalence among childhood cancer survivors are a critical component of efforts to reduce their preventable cancer morbidity and mortality. We recently completed Partnership for Health (PFH), the first large-scale smoking cessation intervention study to be conducted with childhood cancer survivors. The PFH intervention yielded a doubling of quit rates in the intervention group, compared to a self-help control group. PFH was conducted in the context of the Childhood Cancer Survivor Study (CCSS), a large epidemiologic cohort study of the late effects of treatment for childhood cancers. CCSS is a consortium of 22 cancer centers that enrolled over 14,000 patients into this surveillance program. The CCSS institutions are all members of the Children's Oncology Group (COG), which is our partner in this dissemination effort. As a result of the success of PFH, we plan to disseminate the intervention directly to the 235 COG institutions that provide on-going follow-up to the majority of childhood cancer survivors in the US and Canada. Our initial discussions with several COG members suggest that few of its member institutions currently offer smoking cessation services. The 235 COG institutions provide care to over 95% of North American children with cancer. The focus of this supplement will be on the process of dissemination of the PFH intervention to COG institutions, and the evaluation of the effectiveness of our dissemination efforts guided by a well-delineated theoretical framework. In addition to evaluating the relationship of organizational characteristics to program adoption, we will conduct a randomized control trial to determine whether providing assistance with the more labor-intensive aspects of implementation increases adoption and effective implementation. Outcomes include: intervention adoption (percent of cancer centers that adopt the program), quality of implementation (number of components implemented and level of implementation of each), and delivery of the intervention to survivors (number of survivors enrolled in the dissemination effort). COG's infrastructures and clinical trials network has resulted in dramatic improvements in cure rates for pediatric cancers. The proposed project will begin an effort to build on this success related to clinical therapeutic outcomes, and transfer it to cancer prevention outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOUTH TEXAS PEDIATRIC MINORITY BASED CCOP Principal Investigator & Institution: Infante, Anthony J.; Professor; Pediatrics; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-MAY-2004 Summary: The overall goal of the South Texas Pediatric Minority-Based Community Clinical Oncology Program (STP-MB-CCOP) is to reduce the incidence, morbidity and mortality of cancer among Mexican- American children and adolescents residing in the

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South Texas service area. The three specific aims of the STP-MB-CCOP are: 1) provide data management services to all pediatric oncology providers serving the region, 2) provide travel support for pediatric oncologists and support personnel to outreach clinics within the medically underserved areas along the Texas-Mexico border, and 3) increase awareness of cancer- related issues and available resources through a continuing medical education program aimed at primary care providers. The research plan involves the operation of a Clinical Research Office in San Antonio that coordinates the data management activities of the component institutions, including primary data collection and submission, IRB approval, Spanish translation, research base audits and sample collection. In addition, each site has an assigned clinical research associate (CRA). Each institution operates outreach clinics in the border counties to provide access to pediatric oncology services. The headquarters institution provides a CME program to promote the awareness of childhood cancer issues and resources. The program has an ongoing evaluation program, involving weekly meetings of the component institutions and quarterly meetings of the entire STP-MB-CCOP. The quarterly meetings specifically are directed at finding ways to implement and improve mechanisms for meeting MBCCOP accural target. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRESS, SUPPORT AND SURVIVAL--CHILDREN AT MEDICAL RISK Principal Investigator & Institution: Kazak, Anne E.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 30-JUN-2003 Summary: Our previous research on psychological sequelae of childhood cancer treatment indicates that symptoms of post traumatic stress are significant for many survivors and their mothers and fathers. Indeed, there are many aspects of cancer and its treatment which are potential traumatic stressors, including invasive medical procedures, life threat, and disruption of family relationships. These prior data support the importance of anxiety, beliefs about cancer and its treatment, social support and family functioning as both direct and indirect contributions to posttraumatic stress symptoms. This proposal expands research on child and family adjustment to long-term survival of childhood cancer by developing and examining an intervention for posttraumatic stress in childhood cancer survivors and their families. The intervention integrates cognitive behavioral and family intervention approaches for 11-18 year old adolescent survivors, at least one year from the completion of their cancer treatment, and their mothers and fathers, at The Children's Hospital of Philadelphia. Home-based pre (Time 1) and six-month post (Time 2) evaluations will be conducted. Families will be randomized to the intervention or wait list condition after Time 1. The wait list group will receive the intervention after Time 2. The intervention consists of two half-day weekend sessions, eight weeks apart, with the first half-day session focused individually on the recognition of the long-term psychological effects of cancer and its treatment and use of cognitive-behavioral strategies for reducing cancer-related distress, for survivors, mothers and fathers separately. The second half-day session is a family-oriented intervention directed towards helping families communicate more effectively about the impact of cancer and reframe the experiences for themselves as families. Eight families will participate in each intervention, for a total n of 128 families. Data analysis strategies address change in post traumatic stress symptoms with particular attention to anxiety, perceptions of life threat and perceived intensity of treatment, social support and family factors. To our knowledge, this project is unique in providing an empirical evaluation of

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an intervention combining cognitive behavioral and family intervention techniques to alleviate and prevent ongoing psychological distress in children who have survived cancer and their parents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF CHILDHOOD SOLID TUMORS Principal Investigator & Institution: Houghton, Peter J.; Member and Chairman; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-AUG-1978; Project End 30-JUN-2007 Summary: (provided by applicant): Our long-term goal is to advance cure rates for children with malignant solid tumors. The restructured program has an increased focus on developmental therapeutics, testing laboratory driven hypotheses developed from non-mammalian and mammalian experimental systems, in unique xenograft models of childhood cancers, with subsequent design of clinical trials that simulate schedules and systemic exposures found optimal in these models. This approach has been validated through our clinical project, where camptothecins, drugs that target DNA topoisomerase I, have demonstrated very significant activity in Phase I/II trials in pediatric patients. In this application we propose studies that will lead to a greater understanding of sensitivity or resistance to topoisomerase inhibitors, and will start of integrate cytotoxic agents with inhibitors of signal transduction pathways. Project 23 continues studies of mTOR signaling in growth, and survival of tumor cells. Studies will explore the therapeutic strategy of combining the mTOR inhibitor CCI-779, a rapamycin ester, in combination with IGF-I receptor antagonists and cytotoxic agents. Project 24 builds on the finding that hypomorphic alleles of genes that regulate cell cycle checkpoints in yeast confer dramatic hypersensitivity to camptothecin and rapamycin. Human homologues will be cloned, their function defined and their role in determining drug sensitivity in mammalian cells determined. Project 25 will focus on how know DNA damage response pathways determine cellular fate to camptothecins, and how hypoxia induced stress influences p53-directed cell fate. Project 26 will focus on how hypoxia or nutritional stress influences cellular sensitivity to topoisomerase II-targeted drugs and DNA cross-linking drugs through the unfolded protein response pathway. Project 27 builds on results showing that ZD1839 (an ErbB1 inhibitor) potently inhibits ABC transporters (BCRP/MRP4) that confer resistance to camptothecin drugs. The role of ZD1839 in reversing drug resistance, and altering the pharmacology of clinically used camptothecins will be explored. Project 10 comprises Phase I and II clinical trials with topotecan and irinotecan each of which is based on our laboratory and preclinical data. These protocols are supported by pharmacokinetic, and pharmacogenomic studies that ensure optimal systemic exposure, and biological studies designed to increase our understanding of parameters that determine therapeutic efficacy of camptothecin-based topoisomerase I inhibitors used alone or in combination. We will also evaluate the rapamycin ester, CCI-779, alone or in combination with vincristine, to test whether mTOR-targeted therapy will have therapeutic significance in children with solid malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: T-ALL STROMAL CELL INTERACTION AND PATIENT OUTCOME Principal Investigator & Institution: Larson, Richard S.; Pathology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005

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Summary: (provided by applicant): T-lineage acute lymphoblastic leukemia (T-ALL) accounts for 10-15% of childhood ALL, the most common form of childhood cancer. Prognostic indicators of patient outcome in T-ALL are few, and those currently identified are too weak or inappropriate for risk stratification. Since good biologic predictors of patient outcome in T-ALL do not exist, the utility of risk stratification strategies based on biologic predictors, a common and successful strategy for improving patient outcome in other types of leukemia, is not useful in T-ALL. In this R21 proposal, we hypothesize that ex vivo survival of T-ALL cells (T-lineage lymphoblasts) on bone marrow (BM) stromal cells is a discriminating predictor of patient outcome. Furthermore, we postulate that adhesion receptor defects alter survival of T-ALL cells on BM stroma and, when measured in a novel flow cytometry based assay, may also correlate with disease characteristics or patient outcome. In the first aim, we will test the hypothesis that ex vivo survival of T-lineage lymphoblasts predicts treatment outcome. We will use a novel cellular assay that we have recently established in our laboratory to examine ex vivo T-lineage lymphoblast survival. Ex vivo survival of T-lineage lymphoblasts will be correlated with event free survival (EFS, the primary endpoint) and slow early response (secondary endpoint, i.e. disappearance of blasts from the bone marrow during the first 14 days of therapy). In the second aim, we will test the hypothesis that adhesion receptor defects may correlate with T-ALL biology or patient outcome. The second aim is to employ a novel assay for detecting adhesion receptor activity on the surface of cells. This assay uses fluorescein-labeled small molecules that bind to the binding site of integrins LFA-1 or VLA-4. By using these compounds at a concentration equivalent to their affinity constant, we can detect the affinity state of the receptor as well as detect the affinity state conversion in real time, The affinity state of the receptor will be correlated with ex vivo survival, disease characteristics, and patient outcome as in Aim 1. Accomplishment of Aim 2 will provide an additional prognostic tool as well as provide novel insights into the biology of leukemia that can be pursued in future studies. Although aim 2 involves more risk than aim 1, its completion is likely to produce insightful and novel data about the importance of adhesion receptors in leukemia biology and cell survival. In addition, this novel assay format may be potentially valuable in a wide array of biologic and clinical studies. Identification of a strong predictor of patient outcome is important to improving therapy, since having good prognostic indicators will allow for risk-based treatment stratification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CREB IN LEUKEMOGENESIS Principal Investigator & Institution: Sakamoto, Kathleen M.; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 20-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Leukemia is the most common form of childhood cancer. Children with acute myeloid leukemia (AML) have less than 50% overall survival despite aggressive chemotherapy and bone marrow transplantation. Therefore, it is critical to understand the molecular pathogenesis of AML. We demonstrated that CREB is overexpressed in bone marrow cells from patients with AML but not in normal bone marrow or bone marrow from patients without active leukemia. Furthermore, CREB overexpression was associated with an increased risk of relapse and decreased event-free survival in patients with AML. Our preliminary results suggest that AML is a heterogeneous disease that is not well understood. We hypothesize that there is an uncoupling of differentiation and CREB expression in myeloid leukemia cells. We propose to study the role of CREB in normal and malignant myeloid cells to identify

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novel mechanisms of leukemogenesis and improve our understanding of the molecular pathways regulating myeloid cell proliferation and differentiation. In Specific Aim 1, we will characterize CREB expression and activation in primary normal myeloid cells and myeloid leukemia cells. Experiments are proposed to determine the expression of CREB in normal mouse embryos at different stages of hematopoietic development. We will also examine CREB expression in normal myeloid progenitor cells at different stages of myeloid differentiation. Finally, we will examine whether CREB is activated in primary leukemia cells. In Specific Aim 2, we will further characterize the biological phenotype of CREB overexpression and down regulation in myeloid leukemia cell lines and primary normal myeloid cells. Our preliminary results demonstrated that CREB overexpression leads to increased proliferation and survival of myeloid leukemia cells. CREB down regulation using RNA interference (RNAi) suppresses the growth and survival of leukemia cells. To study signaling pathways upstream of CREB, we will overexpress activated kinases and use RNAi technology to inhibit expression of kinases. In Specific Aim 3, we will characterize the phenotype of transgenic mice in which CREB overexpression is targeted to myeloid cells. Defects in hematopoiesis and development of leukemia will be determined in both CREB transgenic mice and a mouse bone marrow transplant model. These studies will define the role of CREB in both normal and malignant myelopoiesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDICTORS

THERAPY-RELATED

LEUKEMIA--CLINICAL/BIOLOGIC

Principal Investigator & Institution: Davies, Stella; Professor and Jacob G. Schmidlapp Endowe; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 20-SEP-2002 Summary: (Applicant's Abstract) Over the last 20 years marked improvements in survival from childhood cancer have been achieved, at least in part by significant increases in the dose intensity of chemotherapy administered. While this has improved survival from the primary malignancy, increases in dose intensity have been associated with a marked increase in the frequency of therapy-related acute myeloid leukemia or myelodysplasia (t-MDS/AML), with frequencies as high as 22% in a Children's Cancer Group (CCG) treatment protocol for children with Ewing's sarcoma. The applicant hypothesizes that it is possible to identify genetic markers of alkylator damage to predict risk of t-MDS/AML in children receiving high dose-alkylating agent chemotherapy for sarcoma. Additionally, she hypothesizes that host genetic polymorphisms in drug metabolizing enzymes will influence genetic susceptibility to tMDS/AML and could be used in the future to guide therapy. In this study she will investigate markers of genetic susceptibility and increased risk of t-MDS/AML in 321 children enrolled on CCG sarcoma treatment protocols. She will ask whether genetic susceptibility to alkylating agent damage can be measured prospectively (using analysis of glutathione-S-transferase genotype and glycophorin A mutation frequency). She will look for early signs of development of myeloid malignancy (clonal hematopoiesis), and for acquisition of later genetic events associated with myeloid malignancy (presence of ras gene mutations in peripheral blood leukocytes) in patients who have completed intensive chemotherapy. The identification of markers of genetic susceptibility to tMDS/AML will allow future modification of therapy for individual patients. The identification of markers of early progression to t-MDS/AML during or after therapy

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will also allow modification of therapy and/or the development of treatment with chemopreventive agents such as retinoids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF CHILDHOOD CANCER Principal Investigator & Institution: Brecher, Martin L.; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUL-1980; Project End 31-DEC-2002 Summary: Cooperative trials in pediatric cancer patients have played a major role in the remarkable improvement in cure of childhood cancers. Because most childhood cancers are rare, it is only through this mechanism that adequate numbers of patients can be accrued in reasonable lengths of time for randomized controlled studies. The Department of Pediatrics at Roswell Park Cancer Institute (RPCI) has actively participated in cooperative group trials via the Pediatric Oncology Group (POG) to answer treatment questions which would be impossible to answer were we to conduct only single institution studies. Some pediatric solid tumors are so rare that national intergroup studies are required. We also participate in these intergroup studies. RPCI investigators are coordinators for a number of POG protocols including front-line studies for the treatment of advanced Hodgkin's disease, advanced small non- cleaved cell lymphoma, non-rhabdomyosarcoma soft tissue sarcomas, acute lymphoblastic leukemia in relapse, the National Wilms Tumor Study, brain tumors in infants, and the Intergroup Ewing's Sarcoma Study. Roswell Park investigators have also developed POG phase II studies of continuous infusion 5-fluouracil and the combination of cisplatin, ifosfamide and etoposide. Roswell Park investigators chair the Wilms Tumor Committee, the Neuroscience Subcommittee of the Brain Tumor Committee, and cochair the Pathology Discipline Core Committee, as well as being active on a number of other POG Core Committees. They have made major contributions over the last few years in the areas of solid tumor oncology, neuro- oncology and the treatment of lymphoid malignancies. We are strongly committed to the interdisciplinary approach to pediatric cancer and have established collaboration with the necessary clinical specialties including Radiation Medicine, Pediatric Surgery, Pediatric Neurology, Neurosurgery, and Orthopedic Surgery, as well as with researchers in immunology, pharmacology and molecular biology. As more children are cured of their cancers, the identification and prevention, when feasible, of complications of therapy have become imperative. We have been a major contributor to the identification and understanding of the long-term medical and psychosocial effects of the treatment of leukemia, Hodgkin's disease, and a number of solid tumors, both through the cooperative group mechanism and through institutional studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UNIV. MICHIGAN COMPREHENSIVE CANCER CENTER SUPPORT GRANT Principal Investigator & Institution: Wicha, Max S.; Director; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 30-SEP-1988; Project End 31-MAY-2006 Summary: The University of Michigan Comprehensive Cancer Center (UWCCC) requests renewal of its core grant in support of senior leadership, programs and shared core facilities. A core grant to support the UMCCC was initially awarded by NCI in 1988

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and renewed for five years in 1991 and 1995. The Cancer Center received comprehensive designation in 1991. The Center provides an organizational framework to promote interdisciplinary research through the development of defined clinical, basic and prevention programs in cancer research, and the development and support of shared resources. The Cancer Center has experienced considerable growth over the current grant period with a 76% increase in NCI funding and a doubling of patient accruals to clinical therapeutic trials. In 1997 the Center moved to a new $88 million facility which houses the Center's outpatient clinics and four and one half floors of research laboratories. The Cancer Center's four basic research programs are: Cancer Genetics/Virology, Cancer Cell Biology, Tumor Immunology and, Experimental Therapeutics. The eight clinical research programs investigating the biology and therapeutics of disease sites are: Cancer Genetics/Virology, Cancer Cell Biology, Tumor Immunology, and Experimental Therapeutics. The eight clinical research programs investigating the biology and therapeutics of disease sites are: Breast, Prostrate, Leukemia/Lymphoma, GI, Cutaneous, Childhood Cancers, Head & Neck, and Connective Tissue. The two prevention programs are Biomedical and Socio-Behavioral. Support is requested for a total of 13 shared core facilities: 11 9ongoing in Clinical Trials, Biostatistics, Tissue Procurement, Tumor Imaging, DNA and Protein Analysis, Morphology Flow Cytometry, Experimental Radiation, Animal Facility, Transgenic Mouse and Vector cores, as well as two new cores in DNA Array Analysis and Immune Monitoring. The Cancer Center senior leadership is composed of the director and five associate directors. Funds are also requested for Development, Planning and Evaluation, and Administration to support Center goals. Over the past 10 years the University and Medical Center have made substantial commitments to the Cancer Center, totaling over $130 million. The UMCCC members receive nearly $66 million in research funding, including over $20 million in annual direct NCI support. 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 “childhood cancer” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for childhood cancer in the PubMed Central database: •

3 4

Inosiplex for Localized Herpes Zoster in Childhood Cancer Patients: Preliminary Controlled Study. by Feldman S, Hayes FA, Chaudhary S, Ossi M.; 1978 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352489

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

A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. United Kingdom Childhood Cancer Study Investigators. Author(s): Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. Source: Cancer Research. 1999 August 15; 59(16): 4095-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463613

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A psychometric analysis of the Quality of Life-Cancer Survivors (QOL-CS) in survivors of childhood cancer. Author(s): Zebrack BJ, Chesler MA. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2001; 10(4): 319-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11763245

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A reexamination of a childhood cancer stereotype. Author(s): Wiens BA, Gilbert BO. Source: Journal of Pediatric Psychology. 2000 April-May; 25(3): 151-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10780142

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Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. Author(s): Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, Greffe B, Wolden S, Robison L. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 September; 85(9): 3227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999813

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Adjustment of siblings to childhood cancer: a literature review. Author(s): Houtzager BA, Grootenhuis MA, Last BF. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 1999 September; 7(5): 302-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10483815

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Adult height and age at menarche in childhood cancer survivors. Author(s): Noorda EM, Somers R, van Leeuwen FE, Vulsma T, Behrendt H; Dutch Late Effects Study Group. Source: European Journal of Cancer (Oxford, England : 1990). 2001 March; 37(5): 605-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11290436

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Adult psychosocial functioning following childhood cancer: the different roles of sons' and daughters' relationships with their fathers and mothers. Author(s): Hill J, Kondryn H, Mackie E, McNally R, Eden T. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2003 July; 44(5): 752-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12831119

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After the cure. Long-term effects of childhood cancer. Author(s): Ruble K. Source: Adv Nurse Pract. 1999 September; 7(9): 48-51, 56. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10763613

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Agricultural pesticide use in California: pesticide prioritization, use densities, and population distributions for a childhood cancer study. Author(s): Gunier RB, Harnly ME, Reynolds P, Hertz A, Von Behren J. Source: Environmental Health Perspectives. 2001 October; 109(10): 1071-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689348

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Alexithymia in long-term survivors of childhood cancer. Author(s): van Dijk M, Grootenhuis MA, de Boer M, Bermond B, Last BF. Source: Pediatric Rehabilitation. 2002 October-December; 5(4): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745899

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An evaluation of a psychosocial intervention for survivors of childhood cancer: paradoxical effects of response shift over time. Author(s): Schwartz CE, Feinberg RG, Jilinskaia E, Applegate JC. Source: Psycho-Oncology. 1999 July-August; 8(4): 344-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10474852

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An examination of the dental utilization practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Author(s): Yeazel MW, Gurney JG, Oeffinger KC, Mitby PA, Mertens AC, Hudson MM, Robison LL. Source: J Public Health Dent. 2004 Winter; 64(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078062

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Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Author(s): Harrison RM, Leung PL, Somervaille L, Smith R, Gilman E. Source: Occupational and Environmental Medicine. 1999 November; 56(11): 774-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10658564

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Antenatal irradiation and childhood cancer: causation or coincidence? Author(s): Mole RH. Source: British Journal of Cancer. 1974 September; 30(3): 199-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4476218

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Aspects of childhood cancer during the Byzantine period. Author(s): Ramoutsaki IA, Dimitriou H, Galanakis E, Stiakaki E, Kalmanti M. Source: Pediatric Hematology and Oncology. 2001 April-May; 18(3): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293282

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Association of childhood cancer with factors related to pregnancy and birth. Author(s): Schuz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J. Source: International Journal of Epidemiology. 1999 August; 28(4): 631-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480689

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Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany. Author(s): Meinert R, Kaletsch U, Kaatsch P, Schuz J, Michaelis J. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1999 September; 8(9): 793-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498398

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Atonic seizures in survivors of childhood cancer. Author(s): Khan RB, Marshman KC, Mulhern RK. Source: Journal of Child Neurology. 2003 June; 18(6): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886974

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Attitudes and impressions of participants in a study of the causes of childhood cancer. Author(s): Jenkinson CM, Muir KM, Hawtin PG, Chilvers CE. Source: British Journal of Cancer. 2001 February 2; 84(3): 413-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11161409

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Bacteremia in childhood cancer. Author(s): Celkan T, Ozkan A, Apak H, Diren S, Can G, Yuksel L, Yildiz I. Source: Journal of Tropical Pediatrics. 2002 December; 48(6): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521283

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Behavioral responses of healthy Chinese siblings to the stress of childhood cancer in the family: a longitudinal study. Author(s): Wang RH, Martinson IM. Source: Journal of Pediatric Nursing. 1996 December; 11(6): 383-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8991339

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Bias in studies of parental self-reported occupational exposure and childhood cancer. Author(s): Schuz J, Spector LG, Ross JA. Source: American Journal of Epidemiology. 2003 October 1; 158(7): 710-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507608

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Binomial cokriging for estimating and mapping the risk of childhood cancer. Author(s): Oliver MA, Webster R, Lajaunie C, Muir KR, Parkes SE, Cameron AH, Stevens MC, Mann JR. Source: Ima Journal of Mathematics Applied in Medicine and Biology. 1998 September; 15(3): 279-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773520

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Birth characteristics of childhood cancer cases, controls, and their siblings. Author(s): Savitz DA, Ananth CV. Source: Pediatric Hematology and Oncology. 1994 November-December; 11(6): 587-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7857782

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Birth defects and childhood cancer in offspring of survivors of childhood cancer. Author(s): Green DM, Fiorello A, Zevon MA, Hall B, Seigelstein N. Source: Archives of Pediatrics & Adolescent Medicine. 1997 April; 151(4): 379-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9111437

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Birthweight and the risk of early childhood cancer among Chinese in Singapore. Author(s): Lee J, Chia KS, Cheung KH, Chia SE, Lee HP. Source: International Journal of Cancer. Journal International Du Cancer. 2004 June 20; 110(3): 465-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15095317

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Bleomycin and cyclophosphamide toxicity simulating metastatic nodules to the lungs in childhood cancer. Author(s): Ben Arush MW, Roguin A, Zamir E, el-Hassid R, Pries D, Gaitini D, Dale A, Postovsky S. Source: Pediatric Hematology and Oncology. 1997 July-August; 14(4): 381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9211543

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Bone mass and body composition after cessation of therapy for childhood cancer. Author(s): Nysom K, Molgaard C, Holm K, Hertz H, Michaelsen KF. Source: Int J Cancer Suppl. 1998; 11: 40-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876476

•

Bone mineral density in long-term survivors of childhood cancer. Author(s): Arikoski P, Voutilainen R, Kroger H. Source: J Pediatr Endocrinol Metab. 2003 March; 16 Suppl 2: 343-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729414

•

Bone mineral density in long-term survivors of childhood cancer. Author(s): Hesseling PB, Hough SF, Nel ED, van Riet FA, Beneke T, Wessels G. Source: Int J Cancer Suppl. 1998; 11: 44-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876477

•

Bone mineral density in young adult survivors of childhood cancer. Author(s): Aisenberg J, Hsieh K, Kalaitzoglou G, Whittam E, Heller G, Schneider R, Sklar C. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1998 May-June; 20(3): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9628436

•

Bone mineral status during and after therapy of childhood cancer: an increasing population with multiple risk factors for impaired bone health. Author(s): Kaste SC, Chesney RW, Hudson MM, Lustig RH, Rose SR, Carbone LD. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 December; 14(12): 2010-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10620059

Studies

61

•

Breast cancer screening in childhood cancer survivors. Author(s): Powers A, Cox C, Reintgen DS. Source: Medical and Pediatric Oncology. 2000 March; 34(3): 210-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696129

•

Breast masses in women treated for childhood cancer: incidence and screening guidelines. Author(s): Kaste SC, Hudson MM, Jones DJ, Fryrear R, Greenwald CA, Fleming ID, Pratt CB. Source: Cancer. 1998 February 15; 82(4): 784-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9477113

•

Breastfeeding and childhood cancer risks: OSCC data. Author(s): Lancashire RJ, Sorahan T; OSCC. Source: British Journal of Cancer. 2003 April 7; 88(7): 1035-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671700

•

Breastfeeding and childhood cancer. Author(s): UK Childhood Cancer Study Investigators. Source: British Journal of Cancer. 2001 November 30; 85(11): 1685-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742489

•

Brief report: assessment of body image in survivors of childhood cancer. Author(s): Kopel SJ, Eiser C, Cool P, Grimer RJ, Carter SR. Source: Journal of Pediatric Psychology. 1998 April; 23(2): 141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9585640

•

Brief report: does posttraumatic stress apply to siblings of childhood cancer survivors? Author(s): Alderfer MA, Labay LE, Kazak AE. Source: Journal of Pediatric Psychology. 2003 June; 28(4): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730285

•

Cardiovascular trials in long-term survivors of childhood cancer. Author(s): Lipshultz SE, Colan SD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 March 1; 22(5): 769-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990630

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Childhood Cancer

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Childhood cancer among Alaska Natives. Author(s): Lanier AP, Holck P, Ehrsam Day G, Key C. Source: Pediatrics. 2003 November; 112(5): E396. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595083

•

Childhood cancer and residential radon exposure - results of a population-based casecontrol study in Lower Saxony (Germany). Author(s): Kaletsch U, Kaatsch P, Meinert R, Schuz J, Czarwinski R, Michaelis J. Source: Radiation and Environmental Biophysics. 1999 September; 38(3): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525959

•

Childhood cancer in relation to cured meat intake: review of the epidemiological evidence. Author(s): Blot WJ, Henderson BE, Boice JD Jr. Source: Nutrition and Cancer. 1999; 34(1): 111-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453449

•

Childhood cancer in relation to infections in the community during pregnancy and around the time of birth. Author(s): Nyari TA, Dickinson HO, Parker L. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 10; 104(6): 772-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640686

•

Childhood cancer in Seascale. Author(s): Wakeford R. Source: Journal of Public Health Medicine. 2002 December; 24(4): 343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546218

•

Childhood cancer in Thailand: 1995-1997. Author(s): Wiangnon S, Kamsa-Ard S, Jetsrisuparb A, Sriplung H, Sontipong S, Sumitsawan Y, Martin N. Source: Asian Pac J Cancer Prev. 2003 August-December; 4(4): 337-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14728593

•

Childhood cancer in the classroom. Author(s): VanDenburgh K. Source: School Nurse News. 2003 March; 20(2): 28-33. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12683314

Studies

63

•

Childhood cancer incidence and arsenic exposure in drinking water in Nevada. Author(s): Moore LE, Lu M, Smith AH. Source: Archives of Environmental Health. 2002 May-June; 57(3): 201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507173

•

Childhood cancer incidence rates and hazardous air pollutants in California: an exploratory analysis. Author(s): Reynolds P, Von Behren J, Gunier RB, Goldberg DE, Hertz A, Smith DF. Source: Environmental Health Perspectives. 2003 April; 111(4): 663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676632

•

Childhood cancer patients' access to cooperative group cancer programs: a population-based study. Author(s): Liu L, Krailo M, Reaman GH, Bernstein L; Surveillance, Epidemiology and End Results Childhood Cancer Linkage Group. Source: Cancer. 2003 March 1; 97(5): 1339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599243

•

Childhood cancer registries in Ontario, Canada: lessons learned from a comparison of two registries. Author(s): Greenberg ML, Barr RD, DiMonte B, McLaughlin E, Greenberg C. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 20; 105(1): 88-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672035

•

Childhood cancer survival: the good news and the not-so-good news. Author(s): Schulmeister L. Source: Clinical Journal of Oncology Nursing. 2004 February; 8(1): 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983756

•

Childhood cancer survivors face long-term complications. Author(s): Nelson R. Source: Lancet. 2003 September 13; 362(9387): 884. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506811

•

Childhood cancer survivors--living beyond cure. Author(s): Kurkure P, Achrekar S, Dalvi N, Goswami S. Source: Indian J Pediatr. 2003 October; 70(10): 825-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14649480

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Childhood Cancer

•

Childhood cancer. Rapid changes in the last 40 years. Author(s): Wilkinson RW. Source: Hawaii Med J. 2003 April; 62(4): 84-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774677

•

Childhood cancer--a mother's story. Author(s): Pfeifer R. Source: European Journal of Cancer (Oxford, England : 1990). 2003 November; 39(17): 2427-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602128

•

Childhood cancer--challenges and opportunities. Author(s): Arya LS. Source: Indian J Pediatr. 2003 February; 70(2): 159-62. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661812

•

Clusters and clustering of childhood cancer: a review. Author(s): Alexander FE. Source: European Journal of Epidemiology. 1999 October; 15(9): 847-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10608365

•

Continued parental attendance at a clinic for adult survivors of childhood cancer. Author(s): Ressler IB, Cash J, McNeill D, Joy S, Rosoff PM. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 November; 25(11): 868-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608196

•

Daunorubicin cardiotoxicity in childhood cancer. Author(s): Samuel L, Cummings J, Shaw P. Source: Lancet. 1998 October 3; 352(9134): 1150. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9798620

•

Deaths from childhood cancer in sibs. Author(s): Miller RW. Source: The New England Journal of Medicine. 1968 July 18; 279(3): 122-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5655197

•

Dental parameters in the long-term survivors of childhood cancer compared with siblings. Author(s): Duggal MS, Curzon ME, Bailey CC, Lewis IJ, Prendergast M. Source: Oral Oncology. 1997 September; 33(5): 348-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9415335

Studies

65

•

Description of a new computer wire coding method and its application to evaluate potential control selection bias in the Savitz et al. childhood cancer study. Author(s): Ebi KL, Kheifets LI, Pearson RL, Wachtel H. Source: Bioelectromagnetics. 2000 July; 21(5): 346-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899770

•

Detection of early anthracycline-induced cardiotoxicity in childhood cancer with dobutamine stress echocardiography. Author(s): Lenk MK, Zeybek C, Okutan V, Ozcan O, Gokcay E. Source: Turk J Pediatr. 1998 July-September; 40(3): 373-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9763901

•

Determinants of parental decisions on 'drop out' from cancer treatment for childhood cancer patients. Author(s): Yeh CH, Lin CF, Tsai JL, Lai YM, Ku HC. Source: Journal of Advanced Nursing. 1999 July; 30(1): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403996

•

Determinants of symptom interval in childhood cancer. Author(s): Saha V, Love S, Eden T, Micallef-Eynaud P, MacKinlay G. Source: Archives of Disease in Childhood. 1993 June; 68(6): 771-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8333770

•

Developing a measure of health outcomes in survivors of childhood cancer: a review of the issues. Author(s): Jenney ME, Kane RL, Lurie N. Source: Medical and Pediatric Oncology. 1995 March; 24(3): 145-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7838035

•

Developing strategies for long term follow up of survivors of childhood cancer. Author(s): Wallace WH, Blacklay A, Eiser C, Davies H, Hawkins M, Levitt GA, Jenney ME; Late Effects Committee of the United Kingdom Children's Cancer Study Group (UKCCSG). Source: Bmj (Clinical Research Ed.). 2001 August 4; 323(7307): 271-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485960

•

Diagnosing childhood cancer in primary care--a realistic expectation? Author(s): Feltbower RG, Lewis IJ, Picton S, Richards M, Glaser AW, Kinsey SE, McKinney PA. Source: British Journal of Cancer. 2004 May 17; 90(10): 1882-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15138465

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Childhood Cancer

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Diagnosis and treatment of childhood cancer. A statewide attack. Author(s): Talbert JL. Source: J Fla Med Assoc. 1971 November; 58(11): 21-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5117652

•

Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. Author(s): Rose SR, Lustig RH, Pitukcheewanont P, Broome DC, Burghen GA, Li H, Hudson MM, Kun LE, Heideman RL. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 December; 84(12): 4472-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10599705

•

Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Author(s): Shu XO, Jin F, Linet MS, Zheng W, Clemens J, Mills J, Gao YT. Source: British Journal of Cancer. 1994 September; 70(3): 531-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8080742

•

Diminished ovarian reserve in female childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l. Author(s): Larsen EC, Muller J, Rechnitzer C, Schmiegelow K, Andersen AN. Source: Human Reproduction (Oxford, England). 2003 February; 18(2): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571182

•

Disputed diagnoses: the cases of RSI and childhood cancer. Author(s): Arksey H, Sloper P. Source: Social Science & Medicine (1982). 1999 August; 49(4): 483-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414808

•

Dobutamine stress echocardiography in the evaluation of late anthracycline cardiotoxicity in childhood cancer survivors. Author(s): De Wolf D, Suys B, Maurus R, Benoit Y, Verhaaren H, Matthijs D, Otten J. Source: Pediatric Research. 1996 March; 39(3): 504-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8929873

•

Drug therapy and curability of childhood cancer. Author(s): Sutow WW. Source: Postgraduate Medicine. 1970 November; 48(5): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4320250

Studies

67

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Dual or single hepatitis B and C virus infections in childhood cancer survivors: longterm follow-up and effect of interferon treatment. Author(s): Utili R, Zampino R, Bellopede P, Marracino M, Ragone E, Adinolfi LE, Ruggiero G, Capasso M, Indolfi P, Casale F, Martini A, Di Tullio MT. Source: Blood. 1999 December 15; 94(12): 4046-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10590048

•

Early and late deaths after elective end of therapies for childhood cancer in Italy. Author(s): Haupt R, Valsecchi MG, Silvestri D, De Lorenzo P, Napoli S, Masera G, Terracini B, Jankovic M. Source: International Journal of Cancer. Journal International Du Cancer. 2000 May 1; 86(3): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10760828

•

Early deaths in childhood cancer. Author(s): Hamre MR, Williams J, Chuba P, Bhambhani K, Ravindranath Y, Severson RK. Source: Medical and Pediatric Oncology. 2000 May; 34(5): 343-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10797356

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Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964-1988 in Ontario, Canada. Author(s): Chiarelli AM, Marrett LD, Darlington G. Source: American Journal of Epidemiology. 1999 August 1; 150(3): 245-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430228

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Echocardiographic evaluation of patients cured of childhood cancer: a single center study of 117 subjects who received anthracyclines. Author(s): Bossi G, Lanzarini L, Laudisa ML, Klersy C, Raisaro A, Arico M. Source: Medical and Pediatric Oncology. 2001 June; 36(6): 593-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344489

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Economic effects of childhood cancer on families. Author(s): Dockerty JD, Skegg DC, Williams SM. Source: Journal of Paediatrics and Child Health. 2003 May-June; 39(4): 254-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755929

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Education, employment, insurance, and marital status among 694 survivors of pediatric lower extremity bone tumors: a report from the childhood cancer survivor study. Author(s): Nagarajan R, Neglia JP, Clohisy DR, Yasui Y, Greenberg M, Hudson M, Zevon MA, Tersak JM, Ablin A, Robison LL. Source: Cancer. 2003 May 15; 97(10): 2554-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733155

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Educational achievement, employment and living situation in long-term young adult survivors of childhood cancer in the Netherlands. Author(s): Langeveld NE, Ubbink MC, Last BF, Grootenhuis MA, Voute PA, De Haan RJ. Source: Psycho-Oncology. 2003 April-May; 12(3): 213-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673806

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Electronic telephone directory listings: preferred sampling frame for a populationbased study of childhood cancer in Australia. Author(s): Valery PC, Williams G, Mcwhirter W, Sleigh A, Scott D, Bain C. Source: Annals of Epidemiology. 2000 November; 10(8): 504-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11118929

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Elevated childhood cancer incidence proximate to U.S. nuclear power plants. Author(s): Mangano JJ, Sherman J, Chang C, Dave A, Feinberg E, Frimer M. Source: Archives of Environmental Health. 2003 February; 58(2): 74-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899207

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Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Author(s): Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, Stovall M, Yasui Y, Nicholson HS, Wolden S, McNeil DE, Mertens AC, Robison LL; Childhood Cancer Survivor Study. Source: Cancer. 2003 February 1; 97(3): 663-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548609

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Endocrine late effects of childhood cancer therapy. Author(s): Meacham L. Source: Current Problems in Pediatric and Adolescent Health Care. 2003 August; 33(7): 217-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902974

Studies

69

•

Endocrine sequelae in survivors of childhood cancer. Author(s): Oberfield SE, Sklar CA. Source: Adolescent Medicine (Philadelphia, Pa.). 2002 February; 13(1): 161-9, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11841962

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Environmental exposures and childhood cancer: our best may not be good enough. Author(s): Savitz DA. Source: American Journal of Public Health. 2001 April; 91(4): 562-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291365

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Epidemiologic studies in a population-based childhood cancer registry in Northeast Hungary. Author(s): Jakab Z, Balogh E, Kiss C, Olah E. Source: Medical and Pediatric Oncology. 2002 May; 38(5): 338-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979458

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Ethnic group and survival from childhood cancer: report from the UK Children's Cancer Study Group. Author(s): Stiller CA, Bunch KJ, Lewis IJ. Source: British Journal of Cancer. 2000 April; 82(7): 1339-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755411

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Event-related alpha synchronization/desynchronization in a memory-search task in adolescent survivors of childhood cancer. Author(s): Lahteenmaki PM, Krause CM, Sillanmaki L, Salmi TT, Lang AH. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 December; 110(12): 2064-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10616111

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Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology. Author(s): Eiser C, Hill JJ, Vance YH. Source: Journal of Pediatric Psychology. 2000 September; 25(6): 449-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980049

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Experiences of parents of childhood cancer survivors: a qualitative analysis. Author(s): Van Dongen-Melman JE, Van Zuuren FJ, Verhulst FC. Source: Patient Education and Counseling. 1998 July; 34(3): 185-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9791523

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Exposure to power frequency electric fields and the risk of childhood cancer in the UK. Author(s): Skinner J, Mee TJ, Blackwell RP, Maslanyj MP, Simpson J, Allen SG, Day NE, Cheng KK, Gilman E, Williams D, Cartwright R, Craft A, Birch JM, Eden OB, McKinney PA, Deacon J, Peto J, Beral V, Roman E, Elwood P, Alexander FE, Mott M, Chilvers CE, Muir K, Doll R, Taylor CM, Greaves M, Goodhead D, Fry FA, Adams G, Law G; United Kingdom Childhood Cancer Study Investigators. Source: British Journal of Cancer. 2002 November 18; 87(11): 1257-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439715

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Factors associated with childhood cancer in a national cohort study. Author(s): Golding J, Paterson M, Kinlen LJ. Source: British Journal of Cancer. 1990 August; 62(2): 304-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2386748

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Factors of importance for implantation and problems after treatment for childhood cancer. Author(s): Critchley HO. Source: Medical and Pediatric Oncology. 1999 July; 33(1): 9-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401491

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Families surviving childhood cancer: a comparison of posttraumatic stress symptoms with families of healthy children. Author(s): Barakat LP, Kazak AE, Meadows AT, Casey R, Meeske K, Stuber ML. Source: Journal of Pediatric Psychology. 1997 December; 22(6): 843-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9494321

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Family coping with childhood cancer. Author(s): Birenbaum LK. Source: Hosp J. 1990; 6(3): 17-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2276715

•

Family relationships in survivors of childhood cancer: resource or restraint? Author(s): Banner LM, Mackie EJ, Hill JW. Source: Patient Education and Counseling. 1996 July; 28(2): 191-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8852094

•

Fate of childhood cancer survivors comes under increasing scrutiny. Author(s): Raymond CA. Source: Jama : the Journal of the American Medical Association. 1988 December 9; 260(22): 3246-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3184406

Studies

71

•

Female reproductive potential post-treatment for childhood cancer. Author(s): Burton KA, Wallace WH, Critchley HO. Source: Hosp Med. 2002 September; 63(9): 522-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357853

•

Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. Author(s): Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, Orav EJ, Gelber RD, Colan SD. Source: The New England Journal of Medicine. 1995 June 29; 332(26): 1738-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7760889

•

Fifty-two forms of childhood cancer: United States mortality experience, 1960-1966. Author(s): Miller RW. Source: The Journal of Pediatrics. 1969 October; 75(4): 685-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4309282

•

Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. Author(s): Gurney JG, Ness KK, Stovall M, Wolden S, Punyko JA, Neglia JP, Mertens AC, Packer RJ, Robison LL, Sklar CA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 4731-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557448

•

Financial burden of childhood cancer. Author(s): Bodkin CM, Pigott TJ, Mann JR. Source: British Medical Journal (Clinical Research Ed.). 1982 May 22; 284(6328): 1542-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6805598

•

Follow-up and care of childhood cancer survivors. Author(s): Meadows AT. Source: Hosp Pract (Off Ed). 1991 February 15; 26(2): 99-102, 105-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1899257

•

Follow-up care for survivors of childhood cancer. Author(s): Fochtman D. Source: Nurse Pract Forum. 1995 December; 6(4): 194-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8547808

72

Childhood Cancer

•

Follow-up of survivors of childhood cancer. Author(s): Li FP. Source: Cancer. 1977 April; 39(4 Suppl): 1776-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=856455

•

Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy. Author(s): Smith MB, Xue H, Strong L, Takahashi H, Jaffe N, Ried H, Zietz H, Andrassy RJ. Source: Journal of Pediatric Surgery. 1993 October; 28(10): 1342-8; Discussion 1348-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8263699

•

Frequency-domain analysis of the QRS complex after treatment of childhood cancer with anthracycline cytostatics. Author(s): Mladosievicova B, Foltinova A, Luptak I, Petrasova H, Hulin I. Source: Pediatric Cardiology. 2001 November-December; 22(6): 478-82. Epub 2001 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11894149

•

From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action. Author(s): Sasco AJ, Vainio H. Source: Human & Experimental Toxicology. 1999 April; 18(4): 192-201. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333301

•

Future life expectations and self-esteem of the adolescent survivor of childhood cancer. Author(s): Overbaugh KA, Sawin K. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1992 January; 9(1): 8-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1596388

•

Gene transfer and the treatment of childhood cancer. Author(s): Brenner MK. Source: Cancer Investigation. 1998; 16(4): 269-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9589036

•

General anaesthesia or conscious sedation for painful procedures in childhood cancer: the family's perspective. Author(s): Crock C, Olsson C, Phillips R, Chalkiadis G, Sawyer S, Ashley D, Camilleri S, Carlin J, Monagle P. Source: Archives of Disease in Childhood. 2003 March; 88(3): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598395

Studies

73

•

Genetic effects of radiotherapy for childhood cancer. Author(s): Boice JD Jr, Tawn EJ, Winther JF, Donaldson SS, Green DM, Mertens AC, Mulvihill JJ, Olsen JH, Robison LL, Stovall M. Source: Health Physics. 2003 July; 85(1): 65-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12852473

•

Genetic epidemiology of childhood cancer. Author(s): Narod SA. Source: Biochimica Et Biophysica Acta. 1996 December 9; 1288(3): F141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9011177

•

Genetic implications for long-term survivors of childhood cancer. Author(s): Strong LC. Source: Cancer. 1993 May 15; 71(10 Suppl): 3435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8387878

•

Genetic implications for long-term survivors of childhood cancer. Author(s): Strong LC. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1991 April; 8(2): 57-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1675064

•

Genetic predispositions and childhood cancer. Author(s): Shannon K. Source: Environmental Health Perspectives. 1998 June; 106 Suppl 3: 801-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9646040

•

Genetics of childhood cancer. Author(s): Ganjavi H, Malkin D. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 75-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151885

•

Genetics of childhood cancer. Author(s): Pritchard-Jones K. Source: British Medical Bulletin. 1996 October; 52(4): 704-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039727

•

Geographic and ethnic variations in the incidence of childhood cancer. Author(s): Stiller CA, Parkin DM. Source: British Medical Bulletin. 1996 October; 52(4): 682-703. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039726

74

Childhood Cancer

•

Geographical and ethnic differences in the occurrence of childhood cancer. Author(s): Miller RW. Source: Iarc Sci Publ. 1988; (87): 3-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3058593

•

German cross-cultural adaptation of the Health Utilities Index and its application to a sample of childhood cancer survivors. Author(s): Felder-Puig R, Frey E, Sonnleithner G, Feeny D, Gadner H, Barr RD, Furlong W, Topf R. Source: European Journal of Pediatrics. 2000 April; 159(4): 283-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10789935

•

GH-deficient survivors of childhood cancer: GH replacement during adult life. Author(s): Murray RD, Darzy KH, Gleeson HK, Shalet SM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 January; 87(1): 12935. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788635

•

Gonadal and sexual function in men treated for childhood cancer. Author(s): Canning DA. Source: The Journal of Urology. 2001 July; 166(1): 377-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441830

•

Gonadal and sexual function in men treated for childhood cancer. Author(s): Relander T, Cavallin-Stahl E, Garwicz S, Olsson AM, Willen M. Source: Medical and Pediatric Oncology. 2000 July; 35(1): 52-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881008

•

Grading of late effects in young adult survivors of childhood cancer followed in an ambulatory adult setting. Author(s): Oeffinger KC, Eshelman DA, Tomlinson GE, Buchanan GR, Foster BM. Source: Cancer. 2000 April 1; 88(7): 1687-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10738228

•

Groups potentially at risk for making poorly informed decisions about entry into clinical trials for childhood cancer. Author(s): Simon C, Zyzanski SJ, Eder M, Raiz P, Kodish ED, Siminoff LA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2173-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775743

Studies

75

•

Growth and neuroendocrine dysfunction following therapy for childhood cancer. Author(s): Sklar CA. Source: Pediatric Clinics of North America. 1997 April; 44(2): 489-503. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9130931

•

Growth and pubertal development in survivors of childhood cancer. Author(s): Sklar CA. Source: Pediatrician. 1991; 18(1): 53-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1983862

•

Growth following therapy for childhood cancer. Author(s): Sklar CA. Source: Cancer Investigation. 1995; 13(5): 511-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7552819

•

Haemopoietic growth factors and childhood cancer. Author(s): Hann IM. Source: European Journal of Cancer (Oxford, England : 1990). 1995; 31A(9): 1476-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7577075

•

Health care for childhood cancer survivors: insights and perspectives from a Delphi panel of young adult survivors of childhood cancer. Author(s): Zebrack BJ, Eshelman DA, Hudson MM, Mertens AC, Cotter KL, Foster BM, Loftis L, Sozio M, Oeffinger KC. Source: Cancer. 2004 February 15; 100(4): 843-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14770443

•

Health care of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Author(s): Oeffinger KC, Mertens AC, Hudson MM, Gurney JG, Casillas J, Chen H, Whitton J, Yeazel M, Yasui Y, Robison LL. Source: Ann Fam Med. 2004 January-February; 2(1): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15053285

•

Health insurance access to young adult survivors of childhood cancer in North Carolina. Author(s): Vann JC, Biddle AK, Daeschner CW, Chaffee S, Gold SH. Source: Medical and Pediatric Oncology. 1995 November; 25(5): 389-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7674996

76

Childhood Cancer

•

Health issues in survivors of childhood cancer. Author(s): Castellino S, Hudson MM. Source: Southern Medical Journal. 2002 September; 95(9): 977-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356138

•

Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Author(s): Hudson MM, Mertens AC, Yasui Y, Hobbie W, Chen H, Gurney JG, Yeazel M, Recklitis CJ, Marina N, Robison LR, Oeffinger KC; Childhood Cancer Survivor Study Investigators. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1583-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506117

•

Health status of childhood cancer survivors: cure is more than the eradication of cancer. Author(s): Schwartz CL. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1641-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506124

•

Health-related behaviors of survivors of childhood cancer. Author(s): Mulhern RK, Tyc VL, Phipps S, Crom D, Barclay D, Greenwald C, Hudson M, Thompson EI. Source: Medical and Pediatric Oncology. 1995 September; 25(3): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7623724

•

Health-related quality of life in childhood cancer: discrepancy in parent-child reports. Author(s): Levi RB, Drotar D. Source: Int J Cancer Suppl. 1999; 12: 58-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679872

•

Health-related worries, self-image, and life outlooks of long-term survivors of childhood cancer. Author(s): Zebrack BJ, Chesler M. Source: Health & Social Work. 2001 November; 26(4): 245-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11758866

•

Helping the family cope with childhood cancer. Author(s): Johnson FL, Rudolph LA, Hartmann JR. Source: Psychosomatics. 1979 April; 20(4): 241, 245-7, 251. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=441238

Studies

77

•

Hepatitis C infection among survivors of childhood cancer. Author(s): Strickland DK, Riely CA, Patrick CC, Jones-Wallace D, Boyett JM, Waters B, Fleckenstein JF, Dean PJ, Davila R, Caver TE, Hudson MM. Source: Blood. 2000 May 15; 95(10): 3065-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807770

•

Hepatitis C infection and hepatocellular carcinoma after treatment of childhood cancer. Author(s): Strickland DK, Jenkins JJ, Hudson MM. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 November; 23(8): 527-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878782

•

Hepatitis C infection during treatment for childhood cancer: pitfalls in diagnosis and management. Author(s): Swilley S, Strickland DK, Davila R, Levstik M, Ribeiro R, Hudson MM. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 58-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12116084

•

Hepatitis C virus infection and long-term survivors of childhood cancer: issues for the pediatric oncology nurse. Author(s): Randall RJ. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2001 January-February; 18(1): 4-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172405

•

Hereditary factors in childhood cancer. Author(s): Lynch HT. Source: Paediatrician. 1982; 11(3-4): 205-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6804921

•

Hidden financial costs in the treatment for childhood cancer. Author(s): Barr RD, Sala A. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 November; 25(11): 842-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608192

•

Hidden financial costs in treatment for childhood cancer: an Australian study of lifestyle implications for families absorbing out-of-pocket expenses. Author(s): Cohn RJ, Goodenough B, Foreman T, Suneson J. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 November; 25(11): 854-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608194

78

Childhood Cancer

•

Home pesticide use and childhood cancer: a case-control study. Author(s): Leiss JK, Savitz DA. Source: American Journal of Public Health. 1995 February; 85(2): 249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7856787

•

Hypnosis as adjuvant antiemetic therapy in childhood cancer. Author(s): Hockenberry MJ, Cotanch PH. Source: Nurs Clin North Am. 1985 March; 20(1): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3844811

•

Identification of drinking water contaminants in the course of a childhood cancer investigation in Toms River, New Jersey. Author(s): Richardson SD, Collette TW, Price PC, Genicola FA, Jenks JW, Thruston AD Jr, Ellington JJ. Source: Journal of Exposure Analysis and Environmental Epidemiology. 1999 May-June; 9(3): 200-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10412669

•

Identity in adolescent survivors of childhood cancer. Author(s): Madan-Swain A, Brown RT, Foster MA, Vega R, Byars K, Rodenberger W, Bell B, Lambert R. Source: Journal of Pediatric Psychology. 2000 March; 25(2): 105-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10820948

•

Imaging investigation protocols for childhood cancer. Author(s): Hegarty SE, Fairhurst JJ. Source: Clin Oncol (R Coll Radiol). 1998; 10(5): 347. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848340

•

Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. Author(s): Thompson SJ, Leigh L, Christensen R, Xiong X, Kun LE, Heideman RL, Reddick WE, Gajjar A, Merchant T, Pui CH, Hudson MM, Mulhern RK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 March 15; 19(6): 1802-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251012

•

Impact of childhood cancer on religious life of Korean families. Author(s): Martinson PV, Martinson IM, Kim S. Source: European Journal of Cancer Care. 1996 December; 5(4): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9117063

Studies

79

•

Impact of childhood cancer on the mental health of parents. Author(s): Dockerty JD, Williams SM, McGee R, Skegg DC. Source: Medical and Pediatric Oncology. 2000 November; 35(5): 475-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070480

•

In vitro fertilization and childhood cancer. Author(s): Odone-Filho V, Cristofani LM, Bonassa EA, Braga PE, Eluf-Neto J. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 June-July; 24(5): 421-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12142799

•

Incidence and frequency rates of childhood cancer in Namibia. Author(s): Wessels G, Hesseling PB. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1997 July; 87(7): 885-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259725

•

Incidence of childhood cancer in Cuba (1986-1990). Author(s): Martin AA, Alert JA, Reno JS, Lonchong M, Grueiro S. Source: International Journal of Cancer. Journal International Du Cancer. 1997 August 7; 72(4): 551-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259390

•

Incidence of childhood cancer in Ho Chi Minh City, Vietnam, 1995-97. Author(s): Nguyen MQ, Nguyen CH, Kramarova E, Parkin DM. Source: Paediatric and Perinatal Epidemiology. 2000 July; 14(3): 240-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10949216

•

Incidence of childhood cancer in Stavropol territory, Russia. Author(s): Minaev SV. Source: Medical and Pediatric Oncology. 2001 August; 37(2): 140-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11496354

•

Increasing incidence of childhood cancer: report of 20 years experience from the greater Delaware Valley Pediatric Tumor Registry. Author(s): Bunin GR, Feuer EJ, Witman PA, Meadows AT. Source: Paediatric and Perinatal Epidemiology. 1996 July; 10(3): 319-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8822774

80

Childhood Cancer

•

Infant death and childhood cancer reductions after nuclear plant closings in the United States. Author(s): Mangano JJ, Gould JM, Sternglass EJ, Sherman JD, Brown J, McDonnell W. Source: Archives of Environmental Health. 2002 January-February; 57(1): 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12071357

•

Interim report: UICC international study of childhood cancer. Author(s): Miller RW. Source: International Journal of Cancer. Journal International Du Cancer. 1972 November; 10(3): 675-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4668499

•

Interpreting epidemiologic research: lessons from studies of childhood cancer. Author(s): Linet MS, Wacholder S, Zahm SH. Source: Pediatrics. 2003 July; 112(1 Pt 2): 218-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837914

•

Investigation of suppression of the hypothalamic-pituitary-gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer. Author(s): Thomson AB, Anderson RA, Irvine DS, Kelnar CJ, Sharpe RM, Wallace WH. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1715-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093829

•

Is KL-6 a serum indicator of early pulmonary fibrosis in childhood cancer patients? Author(s): Briassoulis G, Stefanaki K, Peristeri I, Endoh Y, Hatzis T. Source: Medical and Pediatric Oncology. 2003 January; 40(1): 44-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426686

•

Is posttraumatic stress a viable model for understanding responses to childhood cancer? Author(s): Stuber ML, Kazak AE, Meeske K, Barakat L. Source: Child Adolesc Psychiatr Clin N Am. 1998 January; 7(1): 169-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9894086

•

Is there any evidence for differential misclassification or for bias away from the null in the Swedish childhood cancer study? Author(s): Mezei G, Kheifets L. Source: Epidemiology (Cambridge, Mass.). 2001 November; 12(6): 750-2. Erratum In: Epidemiology 2002 January; 13(1): 116. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11679807

Studies

81

•

Issues in measuring quality of life in childhood cancer: measures, proxies, and parental mental health. Author(s): Vance YH, Morse RC, Jenney ME, Eiser C. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2001 July; 42(5): 661-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464970

•

Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Author(s): Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID. Source: Cancer. 2003 April 15; 97(8): 1991-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673729

•

Late effects of childhood cancer therapy. Author(s): Bottomley SJ, Kassner E. Source: Journal of Pediatric Nursing. 2003 April; 18(2): 126-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12720209

•

Late effects of childhood cancer therapy. Author(s): Friedman DL, Meadows AT. Source: Pediatric Clinics of North America. 2002 October; 49(5): 1083-106, X. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12430627

•

Late effects of the treatment of childhood cancer on the female reproductive system and the potential for fertility preservation. Author(s): Bath LE, Wallace WH, Critchley HO. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 February; 109(2): 107-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11905426

•

Late endocrine, metabolic and skeletal sequelae following treatment of childhood cancer. Author(s): Gleeson HK, Darzy K, Shalet SM. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2002 June; 16(2): 335-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064896

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Late reproductive sequelae following treatment of childhood cancer and options for fertility preservation. Author(s): Thomson AB, Critchley HO, Kelnar CJ, Wallace WH. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2002 June; 16(2): 311-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064895

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Childhood Cancer

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Lifestyle behaviours of young adult survivors of childhood cancer. Author(s): Larcombe I, Mott M, Hunt L. Source: British Journal of Cancer. 2002 November 18; 87(11): 1204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439706

•

Living beyond the sword of Damocles: surviving childhood cancer. Author(s): Zebrack BJ, Zeltzer LK. Source: Expert Review of Anticancer Therapy. 2001 August; 1(2): 163-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113014

•

Longitudinal risk-based health care for adult survivors of childhood cancer. Author(s): Oeffinger KC. Source: Current Problems in Cancer. 2003 May-June; 27(3): 143-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748583

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Long-term cause-specific mortality among five-year survivors of childhood cancer. Author(s): Cardous-Ubbink MC, Heinen RC, Langeveld NE, Bakker PJ, Voute PA, Caron HN, van Leeuwen FE. Source: Pediatric Blood & Cancer. 2004 June; 42(7): 563-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127410

•

Long-term effects of childhood cancer need to be documented, board says. Author(s): Marwick C. Source: Journal of the National Cancer Institute. 2003 October 15; 95(20): 1506-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559868

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Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. Author(s): Lipshultz SE, Lipsitz SR, Sallan SE, Simbre VC 2nd, Shaikh SL, Mone SM, Gelber RD, Colan SD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454107

•

Long-term follow-up of survivors of childhood cancer in the UK. Author(s): Taylor A, Hawkins M, Griffiths A, Davies H, Douglas C, Jenney M, Wallace WH, Levitt G. Source: Pediatric Blood & Cancer. 2004 February; 42(2): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752881

Studies

83

•

Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study. Author(s): Packer RJ, Gurney JG, Punyko JA, Donaldson SS, Inskip PD, Stovall M, Yasui Y, Mertens AC, Sklar CA, Nicholson HS, Zeltzer LK, Neglia JP, Robison LL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947060

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Long-term side effects of radiotherapy in survivors of childhood cancer. Author(s): Dieckmann K, Widder J, Potter R. Source: Front Radiat Ther Oncol. 2002; 37: 57-68. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764669

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Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer. Author(s): Davidson A, Tait DM, Payne GS, Hopewell JW, Leach MO, Watson M, MacVicar AD, Britton JA, Ashley S. Source: The British Journal of Radiology. 2000 April; 73(868): 421-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10844868

•

Male fertility following childhood cancer: current concepts and future therapies. Author(s): Brougham MF, Kelnar CJ, Sharpe RM, Wallace WH. Source: Asian Journal of Andrology. 2003 December; 5(4): 325-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695983

•

Managed care: the new context for social work in health care--implications for survivors of childhood cancer and their families. Author(s): Zebrack BJ, Chesler MA. Source: Social Work in Health Care. 2000; 31(2): 89-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081856

•

Managing side effects of childhood cancer treatment. Author(s): Bryant R. Source: Journal of Pediatric Nursing. 2003 April; 18(2): 113-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12720208

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Marriage in the survivors of childhood cancer: a preliminary description from the Childhood Cancer Survivor Study. Author(s): Rauck AM, Green DM, Yasui Y, Mertens A, Robison LL. Source: Medical and Pediatric Oncology. 1999 July; 33(1): 60-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401499

84

Childhood Cancer

•

Measuring health-related quality of life in childhood cancer: lessons from the workshop (discussion). Author(s): Guyatt GH. Source: Int J Cancer Suppl. 1999; 12: 143-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679886

•

Model for long-term follow-up of survivors of childhood cancer. Author(s): Jereb B. Source: Medical and Pediatric Oncology. 2000 April; 34(4): 256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10742062

•

Mouse models of childhood cancer of the nervous system. Author(s): Dyer MA. Source: Journal of Clinical Pathology. 2004 June; 57(6): 561-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15166259

•

Multi-component behavioral intervention to promote health protective behaviors in childhood cancer survivors: the protect study. Author(s): Hudson MM, Tyc VL, Srivastava DK, Gattuso J, Quargnenti A, Crom DB, Hinds P. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 2-1; Discussion 2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12116072

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Mutual concurrent validity of the child health questionnaire and the health utilities index: an exploratory analysis using survivors of childhood cancer. Author(s): Nixon Speechley K, Maunsell E, Desmeules M, Schanzer D, Landgraf JM, Feeny DH, Barrera ME. Source: Int J Cancer Suppl. 1999; 12: 95-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679879

•

National action plan for childhood cancer: report of the national summit meetings on childhood cancer. Author(s): Arceci R, Ettinger A, Forman E, Haase GM, Hammond GD, Hoffman R, Kupst MJ, Link MP, Lustig CP, Traynor DS. Source: Ca: a Cancer Journal for Clinicians. 2002 November-December; 52(6): 377-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469766

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NCI's childhood cancer monograph released on WEB. Author(s): Moulton G. Source: Journal of the National Cancer Institute. 1999 August 4; 91(15): 1279. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10433614

Studies

85

•

Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study. Author(s): Parker L, Cole M, Craft AW, Hey EN. Source: Bmj (Clinical Research Ed.). 1998 January 17; 316(7126): 189-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9468683

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No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer. Author(s): van Santen HM, Vulsma T, Dijkgraaf MG, Blumer RM, Heinen R, Jaspers MW, Geenen MM, Offringa MO, de Vijlder JJ, van den Bos C. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3657-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915651

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No excess fatigue in young adult survivors of childhood cancer. Author(s): Langeveld NE, Grootenhuis MA, Voute PA, de Haan RJ, van den Bos C. Source: European Journal of Cancer (Oxford, England : 1990). 2003 January; 39(2): 20414. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509953

•

No meeting of minds on childhood cancer. Author(s): Kaiser J. Source: Science. 1999 December 3; 286(5446): 1832-4. Erratum In: Science 2000 January 21; 287(5452): 429. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10610570

•

Nonclonal chromosomal aberrations induced by anti-tumoral regimens in childhood cancer: relationship with cancer-related genes and fragile sites. Author(s): Lopez de Mesa R, Sierrasesumaga L, Calasanz MJ, Lopez de Cerain AL, Patino-Garcia A. Source: Cancer Genetics and Cytogenetics. 2000 August; 121(1): 78-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958946

•

Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome. Author(s): De Vos M, Hayward BE, Picton S, Sheridan E, Bonthron DT. Source: American Journal of Human Genetics. 2004 May; 74(5): 954-64. Epub 2004 April 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15077197

86

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Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Author(s): Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M, Vik TA, Inskip PD, Robison LL; Childhood Cancer Survivor Study. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 1; 21(7): 1359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663727

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Observations from a survivor of childhood cancer. Author(s): Dorfman E. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1996 October; 13(4): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8908912

•

Ominous trend in childhood cancer mortality? Author(s): Parker L, Craft AW. Source: Medical and Pediatric Oncology. 2001 February; 36(2): 335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11452949

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On Joseph Mangano's response to "Critical assessment of opposing views on trends in childhood cancer". Author(s): Bukowski JA. Source: International Journal of Health Services : Planning, Administration, Evaluation. 2001; 31(1): 203-4; Discussion 204-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271645

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One fewer worry for survivors of childhood cancer. Author(s): Friedman JM. Source: American Journal of Human Genetics. 1998 January; 62(1): 25-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443886

•

Online exclusive: a model of health behavior to guide studies of childhood cancer survivors. Author(s): Cox CL. Source: Oncology Nursing Forum. 2003 September-October; 30(5): E92-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949602

•

Oral complications of childhood cancer and its treatment: current best practice. Author(s): Belfield PM, Dwyer AA. Source: European Journal of Cancer (Oxford, England : 1990). 2004 May; 40(7): 1035-41; Discussion 1042-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15093579

Studies

87

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Outcome of treatment for childhood cancer in black as compared with white children. The St Jude Children's Research Hospital experience, 1962 through 1992. Author(s): Pui CH, Boyett JM, Hancock ML, Pratt CB, Meyer WH, Crist WM. Source: Jama : the Journal of the American Medical Association. 1995 February 22; 273(8): 633-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7844873

•

Overall function in rural childhood cancer survivors. The role of social competence and emotional health. Author(s): Olson AL, Boyle WE, Evans MW, Zug LA. Source: Clinical Pediatrics. 1993 June; 32(6): 334-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8344043

•

Overcoming childhood cancer misconceptions among long-term survivors. Author(s): Everhart C. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1991 January; 8(1): 46-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2012694

•

Parental involvement and family-centered care in the diagnostic and treatment phases of childhood cancer: results from a qualitative study. Author(s): Holm KE, Patterson JM, Gurney JG. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2003 November-December; 20(6): 301-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738162

•

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study. Author(s): Pang D, McNally R, Birch JM. Source: British Journal of Cancer. 2003 February 10; 88(3): 373-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569379

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Paternal occupation and childhood cancer. Author(s): Olshan AF, van Wijngaarden E. Source: Advances in Experimental Medicine and Biology. 2003; 518: 147-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817683

•

Patterns of childhood cancer by ethnic group in Bradford, UK 1974-1997. Author(s): McKinney PA, Feltbower RG, Parslow RC, Lewis IJ, Glaser AW, Kinsey SE. Source: European Journal of Cancer (Oxford, England : 1990). 2003 January; 39(1): 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504664

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Childhood Cancer

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Population-based survival after childhood lymphoblastic leukaemia in time periods corresponding to specific clinical trials from 1979 to 1998--a report from the Childhood Cancer Registry of Piedmont (Italy). Author(s): Pastore G, Viscomi S, Gerov GL, Terracini B, Madon E, Magnani C. Source: European Journal of Cancer (Oxford, England : 1990). 2003 May; 39(7): 952-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706364

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Posttraumatic stress symptoms in adult survivors of childhood cancer. Author(s): Langeveld NE, Grootenhuis MA, Voute PA, de Haan RJ. Source: Pediatric Blood & Cancer. 2004 June; 42(7): 604-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127415

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Potential role of magnetic resonance spectroscopy in assessment of tumour response in childhood cancer. Author(s): Vaidya SJ, Payne GS, Leach MO, Pinkerton CR. Source: European Journal of Cancer (Oxford, England : 1990). 2003 April; 39(6): 728-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651196

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Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Author(s): Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, Pendergrass TW, Robison LL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 February 15; 21(4): 716-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586811

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Psychological outcomes in long-term survivors of childhood brain cancer: a report from the childhood cancer survivor study. Author(s): Zebrack BJ, Gurney JG, Oeffinger K, Whitton J, Packer RJ, Mertens A, Turk N, Castleberry R, Dreyer Z, Robison LL, Zeltzer LK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 March 15; 22(6): 999-1006. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15020603

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Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study. Author(s): Mertens AC, Yasui Y, Liu Y, Stovall M, Hutchinson R, Ginsberg J, Sklar C, Robison LL; Childhood Cancer Survivor Study. Source: Cancer. 2002 December 1; 95(11): 2431-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436452

Studies

89

•

Quality of life in adult survivors of childhood cancer. Author(s): Dolgin MJ, Somer E, Buchvald E, Zaizov R. Source: Social Work in Health Care. 1999; 28(4): 31-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425670

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Quality of life in childhood cancer survivors. Author(s): Zebrack BJ, Chesler MA. Source: Psycho-Oncology. 2002 March-April; 11(2): 132-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11921329

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Quality of life in survivors of childhood cancer after megatherapy with autologous bone marrow rescue. Author(s): Kanabar DJ, Attard-Montalto S, Saha V, Kingston JE, Malpas JE, Eden OB. Source: Pediatric Hematology and Oncology. 1995 January-February; 12(1): 29-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7703039

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Quality of life in young adult survivors of childhood cancer. Author(s): Langeveld NE, Stam H, Grootenhuis MA, Last BF. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2002 November; 10(8): 579-600. Epub 2002 October 24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436217

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Quality of life research in childhood cancer. The time is now. Author(s): Reaman GH, Haase GM. Source: Cancer. 1996 September 15; 78(6): 1330-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826958

•

Radiation therapy in childhood cancer. Author(s): Ruble K, Kelly KP. Source: Semin Oncol Nurs. 1999 November; 15(4): 292-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588033

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Radiotherapy at a young age reduces uterine volume of childhood cancer survivors. Author(s): Larsen EC, Schmiegelow K, Rechnitzer C, Loft A, Muller J, Andersen AN. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2004 January; 83(1): 96-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678092

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Radon and childhood cancer. Author(s): Henshaw DL. Source: British Journal of Cancer. 2002 November 18; 87(11): 1336-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439727

90

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Re: "Childhood cancer and population mixing". Author(s): Kinlen LJ. Source: American Journal of Epidemiology. 2004 April 1; 159(7): 716; Author Reply 717. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15033651

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Re: "Childhood cancer and population mixing". Author(s): Tucker MA. Source: American Journal of Epidemiology. 2004 April 1; 159(7): 716-7; Author Reply 717. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15033650

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Recent report in the etiology of childhood cancer: 'greatest hits'. Author(s): Ross JA, Davies SM. Source: Pediatric Blood & Cancer. 2004 January; 42(1): 3-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752788

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Recognition and management of childhood cancer syndromes: a systems approach. Author(s): Clericuzio CL. Source: American Journal of Medical Genetics. 1999 June 25; 89(2): 81-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559762

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Rehabilitation and development after childhood cancer: can the need for physical exercise be met? Author(s): Robertson AR, Johnson DA. Source: Pediatric Rehabilitation. 2002 October-December; 5(4): 235-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745903

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Residential exposure to traffic in California and childhood cancer. Author(s): Reynolds P, Von Behren J, Gunier RB, Goldberg DE, Hertz A. Source: Epidemiology (Cambridge, Mass.). 2004 January; 15(1): 6-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14712141

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Root surface areas in long-term survivors of childhood cancer. Author(s): Duggal MS. Source: Oral Oncology. 2003 February; 39(2): 178-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509972

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Seasonal variations in the diagnosis of childhood cancer in the United States. Author(s): Ross JA, Severson RK, Swensen AR, Pollock BH, Gurney JG, Robison LL. Source: British Journal of Cancer. 1999 October; 81(3): 549-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507784

Studies

91

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Second cancers in survivors of childhood cancer. Author(s): Bhatia S, Sklar C. Source: Nature Reviews. Cancer. 2002 February; 2(2): 124-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635175

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Second malignant neoplasms after treatment of childhood cancer. Author(s): Klein G, Michaelis J, Spix C, Wibbing R, Eggers G, Ritter J, Kaatsch P. Source: European Journal of Cancer (Oxford, England : 1990). 2003 April; 39(6): 808-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651207

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Second neoplasms after treatment of childhood cancer in Slovenia. Author(s): Jazbec J, Ecimovic P, Jereb B. Source: Pediatric Blood & Cancer. 2004 June; 42(7): 574-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127411

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Sense of humor, childhood cancer stressors, and outcomes of psychosocial adjustment, immune function, and infection. Author(s): Dowling JS, Hockenberry M, Gregory RL. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2003 November-December; 20(6): 271-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738160

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Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer. Author(s): Lando A, Holm K, Nysom K, Krogh Rasmussen A, Hoier Madsen M, FeldtRasmussen U, Muller J. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 November; 92(11): 1284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696848

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Sex ratio among offspring of childhood cancer survivors treated with radiotherapy. Author(s): Winther JF, Boice JD Jr, Thomsen BL, Schull WJ, Stovall M, Olsen JH. Source: British Journal of Cancer. 2003 February 10; 88(3): 382-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569380

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Sibling adaptation to the family crisis of childhood cancer. Author(s): Wilkins K. Source: Can Oncol Nurs J. 2003 Winter; 13(1): 46-52. Review. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754784

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Smoking among participants in the childhood cancer survivors cohort: the Partnership for Health Study. Author(s): Emmons KM, Butterfield RM, Puleo E, Park ER, Mertens A, Gritz ER, Lahti M, Li FP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 15; 21(2): 189-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525509

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Survival rates of childhood cancer patients in Osaka, Japan. Author(s): Ajiki W, Tsukuma H, Oshima A. Source: Japanese Journal of Clinical Oncology. 2004 January; 34(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15020664

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Testing of new agents in childhood cancer preclinical models: meeting summary. Author(s): Houghton PJ, Adamson PC, Blaney S, Fine HA, Gorlick R, Haber M, Helman L, Hirschfeld S, Hollingshead MG, Israel MA, Lock RB, Maris JM, Merlino G, Patterson W, Reynolds CP, Shannon K, Yu A, Yu J, Smith MA. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 December; 8(12): 3646-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473573

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The development of an off-therapy needs questionnaire and protocol for survivors of childhood cancer. Author(s): Nagel K, Eves M, Waterhouse L, Alyman C, Posgate S, Jamieson J, Metzger V, Wright M. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2002 November-December; 19(6): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444575

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The effect of childhood cancer on Hong Kong Chinese families at different stages of the disease. Author(s): Yin LK, Twinn S. Source: Cancer Nursing. 2004 January-February; 27(1): 17-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15108948

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The GEPETTO program for surveillance of long-term survivors of childhood cancer: preliminary report from a single institution in Brazil. Author(s): Rigon H, Lopes LF, do Rosario Latorre M, de Camargo B. Source: Medical and Pediatric Oncology. 2003 June; 40(6): 405-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692816

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The late endocrine effects of childhood cancer treatment. Author(s): Brougham MF, Kelnar CJ, Wallace WH. Source: Pediatric Rehabilitation. 2002 October-December; 5(4): 191-201. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745898

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The value of the PedsQLTM in assessing quality of life in survivors of childhood cancer. Author(s): Eiser C, Vance YH, Horne B, Glaser A, Galvin H. Source: Child: Care, Health and Development. 2003 March; 29(2): 95-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603354

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Treatment strategies in childhood cancer. Author(s): Alcoser PW, Rodgers C. Source: Journal of Pediatric Nursing. 2003 April; 18(2): 103-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12720207

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Trends in childhood cancer incidence and mortality in Catalonia, Spain, 1975-1998. Author(s): Gonzalez JR, Fernandez E, de Toledo JS, Galceran J, Peris M, Gispert R, Borras JM. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2004 February; 13(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075788

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Tumor vaccines--application to childhood cancer. Author(s): Roskrow MA, Zibert A, Souquet M, Dilloo D. Source: Klinische Padiatrie. 1999 July-August; 211(4): 336-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10472573

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U.S. childhood cancer deaths by cell type, 1960-68. Author(s): Miller RW, Dalager NA. Source: The Journal of Pediatrics. 1974 November; 85(5): 664-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4370569

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UKCCSG study of accelerated radiotherapy for pediatric brain stem gliomas. United Kingdom Childhood Cancer Study Group. Author(s): Lewis J, Lucraft H, Gholkar A. Source: International Journal of Radiation Oncology, Biology, Physics. 1997 July 15; 38(5): 925-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9276356

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Ultrasonography for thyroid screening after head and neck irradiation in childhood cancer survivors. Author(s): Crom DB, Kaste SC, Tubergen DG, Greenwald CA, Sharp GB, Hudson MM. Source: Medical and Pediatric Oncology. 1997 January; 28(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8950331

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Understanding sibling adaptation to childhood cancer. Author(s): Murray JS. Source: Issues in Comprehensive Pediatric Nursing. 2000 January-March; 23(1): 39-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11011662

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Understanding the psychosocial late effects of childhood cancer therapy. Author(s): Simms S. Source: Pediatric Hematology and Oncology. 1997 May-June; 14(3): 187-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9185202

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University of Newcastle Upon Tyne: epidemiological studies of childhood cancer. Author(s): Parker L. Source: Pediatric Hematology and Oncology. 2001 January-February; 18(1): 7-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11205843

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Use of a density equalizing map projection in analysing childhood cancer in four California counties. Author(s): Merrill DW. Source: Statistics in Medicine. 2001 May 15-30; 20(9-10): 1499-513. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343370

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Use of bisphosphonates in hypercalcemia associated with childhood cancer. Author(s): Tezer Kutluk M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 June; 17(6): 1960. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561239

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Utility of routine psychological screening in the childhood cancer survivor clinic. Author(s): Recklitis C, O'Leary T, Diller L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 787-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610175

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Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Author(s): Mitby PA, Robison LL, Whitton JA, Zevon MA, Gibbs IC, Tersak JM, Meadows AT, Stovall M, Zeltzer LK, Mertens AC; Childhood Cancer Survivor Study Steering Committee. Source: Cancer. 2003 February 15; 97(4): 1115-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569614

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Validation of the German version of the Pediatric Quality of Life Inventory (PedsQL) in childhood cancer patients off treatment and children with epilepsy. Author(s): Felder-Puig R, Frey E, Proksch K, Varni JW, Gadner H, Topf R. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2004 February; 13(1): 223-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15058802

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Vitamin K and childhood cancer. Author(s): Draper GJ, Stiller CA. Source: Journal of Paediatrics and Child Health. 1994 June; 30(3): 282-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8074920

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Vitamin K and childhood cancer. Author(s): Smith AL. Source: The Medical Journal of Australia. 1994 April 4; 160(7): 449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8007877

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Vitamin K and childhood cancer. Author(s): Henderson-Smart D. Source: The Medical Journal of Australia. 1994 January 17; 160(2): 91; Author Reply 92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8309375

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Vitamin K and childhood cancer. Author(s): Carmichael A. Source: The Medical Journal of Australia. 1994 January 17; 160(2): 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8166823

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Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany. Author(s): von Kries R, Gobel U, Hachmeister A, Kaletsch U, Michaelis J. Source: Bmj (Clinical Research Ed.). 1996 July 27; 313(7051): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8696195

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Vitamin K and childhood cancer: a report from the United Kingdom Childhood Cancer Study. Author(s): Fear NT, Roman E, Ansell P, Simpson J, Day N, Eden OB; United Kingdom Childhood Cancer Study. Source: British Journal of Cancer. 2003 October 6; 89(7): 1228-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520451

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Vitamin K and childhood cancer: analysis of individual patient data from six casecontrol studies. Author(s): Roman E, Fear NT, Ansell P, Bull D, Draper G, McKinney P, Michaelis J, Passmore SJ, von Kries R. Source: British Journal of Cancer. 2002 January 7; 86(1): 63-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857013

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Vitamin K prophylaxis and childhood cancer. Author(s): Ross JA, Davies SM. Source: Medical and Pediatric Oncology. 2000 June; 34(6): 434-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10842253

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Vitamin K regimens and incidence of childhood cancer in Denmark. Author(s): Olsen JH, Hertz H, Blinkenberg K, Verder H. Source: Bmj (Clinical Research Ed.). 1994 April 2; 308(6933): 895-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8173370

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What can be learned about childhood cancer from "Cancer statistics review 19731988". Author(s): Bleyer WA. Source: Cancer. 1993 May 15; 71(10 Suppl): 3229-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8490859

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What can we learn from differences in the patterns of occurrence of childhood cancer? Author(s): Parker L. Source: Pediatric Hematology and Oncology. 1998 January-February; 15(1): 3-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9509500

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What caused my child's cancer? Parents' response to epidemiology studies of childhood cancer. Author(s): Ruccione K, Waskerwitz M, Buckley J, Perin G. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1990 April; 7(2): 50-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2363874

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What caused my child's cancer? Parents' responses to an epidemiology study of childhood cancer. Author(s): Ruccione KS, Waskerwitz M, Buckley J, Perin G, Hammond GD. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1994 April; 11(2): 71-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8003264

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Wire codes, magnetic fields, and childhood cancer. Author(s): Kheifets LI, Kavet R, Sussman SS. Source: Bioelectromagnetics. 1997; 18(2): 99-110. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9084860

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With regard to the relative merits of contemporary measurements and historical calculated fields in the Swedish Childhood Cancer Study. Author(s): Feychting M, Ahlbom A. Source: Epidemiology (Cambridge, Mass.). 2000 May; 11(3): 357-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847714

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Workshop report. Behavioral and psychosocial research in childhood cancer. Author(s): Spinetta JJ, Lansky S. Source: Cancer. 1982 November 1; 50(9 Suppl): 1944-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7127271

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X rays and childhood cancer. Author(s): Jacobson LH. Source: Lancet. 1968 May 4; 1(7549): 980. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4171604

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X-rays and childhood cancer. Author(s): Stewart AM, Draper GJ. Source: Lancet. 1968 October 12; 2(7572): 828-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4175621

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X-rays and childhood cancer. Author(s): Russell JG. Source: Lancet. 1968 September 14; 2(7568): 632. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4175174

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X-rays in pregnancy and risk of childhood cancer. Author(s): Ennis J, Muirhead CR. Source: Lancet. 1985 November 23; 2(8465): 1185. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2865636

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X-rays in pregnancy and the risk of childhood cancer. Author(s): Hopton PA, McKinney PA, Cartwright RA, Mann JR, Birch JM, Hartley AL, Waterhouse JA, Johnston HE, Draper GJ, Stiller CA. Source: Lancet. 1985 October 5; 2(8458): 773. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2864498

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Young adult survivors of childhood cancer: attending to emerging medical and psychosocial needs. Author(s): Richardson RC, Nelson MB, Meeske K. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1999 July; 16(3): 136-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10444941

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CHAPTER 2. NUTRITION AND CHILDHOOD CANCER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and childhood cancer.

Finding Nutrition Studies on Childhood Cancer 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 “childhood cancer” (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 “childhood cancer” (or a synonym): •

Case-control studies of relation between childhood cancer and neonatal vitamin K administration. Author(s): Childhood Cancer Research Group, Oxford. Source: Passmore, S J Draper, G Brownbill, P Kroll, M BMJ. 1998 January 17; 316(7126): 178-84 0959-8138

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Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group. Author(s): Prince of Wales Children's Hospital, Randwick NSW, Sydney, Australia. Source: White, L McCowage, G Kannourakis, G Nayanar, V Colnan, L Kellie, S Shaw, P Seshadri, R Lockwood, L Tiedemann, K et al. J-Clin-Oncol. 1994 March; 12(3): 522-31 0732-183X

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Late problems faced by childhood cancer survivors. Author(s): Leukaemia Research Fund, Children's Hospital, Sheffield. Source: Davies, H A Br-J-Hosp-Med. 1993 July 14-August 17; 50(2-3): 137-40 0007-1064

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Nutritional management of the childhood cancer patient. Author(s): Clinica Pediatrica, Universita di Milano, Monza, Italy. Source: Rossi, M R Uderzo, C Recent-Results-Cancer-Res. 1988; 108198-204 0080-0015

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Postoperative chemotherapy without radiation in young children with malignant non-astrocytic brain tumours. A report from the Australia and New Zealand Childhood Cancer Study Group (ANZCCSG). Author(s): Prince of Wales Children's Hospital, Randwick, Australia. Source: White, L Johnston, H Jones, R Mameghan, H Nayanar, V McWhirter, W Kellie, S Waters, K Toogood, I Cancer-Chemother-Pharmacol. 1993; 32(5): 403-6 0344-5704

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Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. Author(s): Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. [email protected] Source: Sklar, Charles A Mertens, Ann C Mitby, Pauline Occhiogrosso, Glenn Qin, Jing Heller, Glenn Yasui, Yutaka Robison, Leslie L J-Clin-Endocrinol-Metab. 2002 July; 87(7): 3136-41 0021-972X

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Therapeutic effects and pharmacokinetics of recombinant human granulocytemacrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy. Author(s): Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101-0318. Source: Furman, W L Fairclough, D L Huhn, R D Pratt, C B Stute, N Petros, W P Evans, W E Bowman, L C Douglass, E C Santana, V M et al. J-Clin-Oncol. 1991 June; 9(6): 1022-8 0732-183X

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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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The following is a specific Web list relating to childhood cancer; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com

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Food and Diet Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND CHILDHOOD CANCER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to childhood cancer. 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 childhood cancer 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 “childhood cancer” (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 childhood cancer: •

A childhood cancer sibling's oral history. Author(s): Lehna CR. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1998 July; 15(3): 163-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9699453

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Alternative and complementary therapies in childhood cancer. Author(s): Anderson RA. Source: Medical and Pediatric Oncology. 2000 January; 34(1): 27-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10611581

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Alternative therapies for the treatment of childhood cancer. Author(s): Coppes MJ, Anderson RA, Egeler RM, Wolff JE.

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Source: The New England Journal of Medicine. 1998 September 17; 339(12): 846-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9750078 •

Alternative therapies in childhood cancer. Author(s): Fernandez C, Pyesmany A, Stutzer C. Source: The New England Journal of Medicine. 1999 February 18; 340(7): 569-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10026058

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Alternative therapies in childhood cancer. Author(s): Orbach O. Source: The New England Journal of Medicine. 1999 February 18; 340(7): 569. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10026055

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Burden of care and childhood cancer: experiences of parents in an Asian context. Author(s): Ow R. Source: Health & Social Work. 2003 August; 28(3): 232-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971287

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Common themes and ethnic differences in family caregiving the first year after diagnosis of childhood cancer: Part II. Author(s): Leavitt M, Martinson IM, Liu CY, Armstrong V, Hornberger L, Zhang JQ, Han XP. Source: Journal of Pediatric Nursing. 1999 April; 14(2): 110-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10337122

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Developmental therapeutics in childhood cancer. A perspective from the Children's Oncology Group and the US Food and Drug Administration. Author(s): Bernstein ML, Reaman GH, Hirschfeld S. Source: Hematology/Oncology Clinics of North America. 2001 August; 15(4): 631-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11676277

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Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group. Author(s): White L, McCowage G, Kannourakis G, Nayanar V, Colnan L, Kellie S, Shaw P, Seshadri R, Lockwood L, Tiedemann K, et al. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1994 March; 12(3): 522-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8120550

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Embracing uncertainty: an exploration of the experiences of childhood cancer survivors. Author(s): Parry C. Source: Qualitative Health Research. 2003 February; 13(2): 227-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643030

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Epipodophyllotoxins in the treatment of childhood cancer. Author(s): Rivera GK, Pui CH, Santana VM, Pratt CB, Crist WM. Source: Cancer Chemotherapy and Pharmacology. 1994; 34 Suppl: S89-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8070034

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Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer. Author(s): Hawkins MM, Wilson LM, Stovall MA, Marsden HB, Potok MH, Kingston JE, Chessells JM. Source: Bmj (Clinical Research Ed.). 1992 April 11; 304(6832): 951-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1581717

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Ethical issues in the treatment of childhood cancers. Author(s): Clark A. Source: Bioeth News. 1985 July; 4(4): 8-15. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11649642

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Needs and responses of parents following the diagnosis of childhood cancer. Author(s): Sloper P. Source: Child: Care, Health and Development. 1996 May; 22(3): 187-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8735673

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Non-conventional therapies in childhood cancer: guidelines for distinguishing nonharmful from harmful therapies: a report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology. Author(s): Jankovic M, Spinetta JJ, Martins AG, Pession A, Sullivan M, D'Angio GJ, Eden T, Ben Arush MW, X S, Punkko LR, Epelman C, Masera G; SIOP Working Committee on Psychosocial Issues in Pediatric Oncology. Source: Pediatric Blood & Cancer. 2004 January; 42(1): 106-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752802

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Postoperative chemotherapy without radiation in young children with malignant non-astrocytic brain tumours. A report from the Australia and New Zealand Childhood Cancer Study Group (ANZCCSG). Author(s): White L, Johnston H, Jones R, Mameghan H, Nayanar V, McWhirter W, Kellie S, Waters K, Toogood I.

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Source: Cancer Chemotherapy and Pharmacology. 1993; 32(5): 403-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8339393 •

Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer. Author(s): Davidson A, Payne G, Leach MO, McVicar D, Britton JM, Watson M, Tait DM. Source: Medical and Pediatric Oncology. 2000 July; 35(1): 28-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881004

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Sibling support in childhood cancer. Author(s): Simms S, Hewitt N, Vevers J, Ward F. Source: Paediatric Nursing. 2002 September; 14(7): 20-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12271871

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Surviving cancer competently intervention program (SCCIP): a cognitive-behavioral and family therapy intervention for adolescent survivors of childhood cancer and their families. Author(s): Kazak AE, Simms S, Barakat L, Hobbie W, Foley B, Golomb V, Best M. Source: Family Process. 1999 Summer; 38(2): 175-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407719

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The development of camptothecin analogs in childhood cancers. Author(s): Bomgaars L, Berg SL, Blaney SM. Source: The Oncologist. 2001; 6(6): 506-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743213

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The lived experience of childhood cancer: one sibling's perspective. Author(s): Murray JS. Source: Issues in Comprehensive Pediatric Nursing. 1998 October-December; 21(4): 21727. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10531888

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Views of childhood cancer survivors. Selected perspectives. Author(s): Lozowski SL. Source: Cancer. 1993 May 15; 71(10 Suppl): 3354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8490882

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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

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

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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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. DISSERTATIONS ON CHILDHOOD CANCER Overview In this chapter, we will give you a bibliography on recent dissertations relating to childhood cancer. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “childhood cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on childhood cancer, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Childhood Cancer ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to childhood cancer. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A study of the epidemiology of childhood cancer with special emphasis on smoking during pregnancy by Neutel, C. Ineke; ADVDEG from THE UNIVERSITY OF WESTERN ONTARIO (CANADA), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06349

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Functional MRI techniques to investigate cognitive deficits in childhood cancer survivors by Zou, Ping; PhD from THE UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3077418

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Impact of childhood cancer on the family by CORNMAN, BARBARA JANE, PHD from UNIVERSITY OF WASHINGTON, 1988, 161 pages http://wwwlib.umi.com/dissertations/fullcit/8810518

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Surviving childhood cancer the psychosocial impact on parents by Speechley, Kathy L. Nixon; PhD from THE UNIVERSITY OF WESTERN ONTARIO (CANADA), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL36062

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The psychosocial experiences of long-term survivors of childhood cancer across the lifespan by Parry, Carla; PhD from UNIVERSITY OF MICHIGAN, 2002, 178 pages http://wwwlib.umi.com/dissertations/fullcit/3058028

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. BOOKS ON CHILDHOOD CANCER Overview This chapter provides bibliographic book references relating to childhood cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on childhood cancer include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “childhood cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on childhood cancer: •

Communication Disorders in Childhood Cancer Source: London, United Kingdom: Whurr Publishers Ltd. 1999. 219 p. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: As the treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This book offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The treatments offered for these conditions, such as radiotherapy and chemotherapy, may have some long term adverse effects on brain

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structure and function leading to the development of a number of complications, including cognitive deficits as well as speech and language disorders. The book includes nine chapters, that cover the cancers themselves (leukemia and brain tumors), the effects of treatment for pediatric cancer on brain structure and function, language disorders in children treated for brain tumors, language recovery following treatment for pediatric brain tumors, variability in patterns of language impairment in children following treatment for posterior fossa tumor, language disorders in children treated for acute lymphoblastic leukemia, discourse abilities of children treated for neoplastic conditions, motor speech disorders in children treated for brain tumors, and the assessment and treatment of speech and language disorders occurring subsequent to cancer therapy in children. Each chapter includes extensive references and the textbook concludes with a subject index.

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 “childhood cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “childhood cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “childhood cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Parent's Guide to Childhood Cancer (The Children's Hospital of Philadelphia) by Lisa J. Bain; ISBN: 0440506921; http://www.amazon.com/exec/obidos/ASIN/0440506921/icongroupinterna

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Epidemiology of Childhood Cancer (Iarc Scientific Publications, No.149) by Julian Little; ISBN: 9283221494; http://www.amazon.com/exec/obidos/ASIN/9283221494/icongroupinterna

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Family functioning and sibling adjustment following treatment of childhood cancer (SuDoc ED 1.310/2:414546) by Cindy L. Tucker; ISBN: B00010YF3M; http://www.amazon.com/exec/obidos/ASIN/B00010YF3M/icongroupinterna

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International Classification of Childhood Cancer 1996 (Iarc Technical Report , No 29) by E. Kramarova, et al; ISBN: 9283214439; http://www.amazon.com/exec/obidos/ASIN/9283214439/icongroupinterna

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International Incidence of Childhood Cancer (Iarc Scientific Publication, No 87) by D.M. Parkin; ISBN: 9283211871; http://www.amazon.com/exec/obidos/ASIN/9283211871/icongroupinterna

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Late Effects of Childhood Cancer (Arnold Publication) by W. Hamish B., Md. Wallace, Daniel M., Md. Green; ISBN: 0340808039; http://www.amazon.com/exec/obidos/ASIN/0340808039/icongroupinterna

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Chapters on Childhood Cancer In order to find chapters that specifically relate to childhood cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and childhood cancer using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “childhood cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on childhood cancer: •

Variability in Patterns of Language Impairment in Children Following Treatment for Posterior Fossa Tumour Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 89-125. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: An increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This chapter on patterns of language impairment in these children is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors summarize 20 cases reported by Murdoch and Hudson-Tennent (1994), to demonstrate the variability in language outcome following treatment for brain tumor. This approach also enables the authors to describe and discuss any observed language problem with reference to individual variables relating to personal details, medical conditions, and treatment factors. The authors stress that each of these individual factors must be taken into consideration as contributing to the overall outcome of posterior fossa tumor treatment. The results of their research indicate that the language skills of all children who experience tumor treatment should be monitored in the long term and the appropriate intervention provided. 7 figures. 54 references.

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Language Disorders in Children Treated for Brain Tumours Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 55-75. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: As the treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This chapter on language disorders is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors discuss a number of factors occurring secondary to the presence and removal of posterior fossa tumors that could conceivably lead to disturbances in language function. The authors

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review a number of case studies that demonstrate these postoperative complications in language. As yet, no characteristic language pattern has arise that could offer clinicians a starting point for patient management, or alert them to specific areas of language deficit. Rather, the data available to date indicate the presence of variable language abilities within the tumor population thereby necessitating the need for development and implementation of individualized therapy programs. The authors caution that neurological deterioration can occur in these children from months to years after the completion of treatment of brain tumors; postoperative baseline measurements of language abilities are highly recommended. 4 figures. 60 references. •

Discourse Abilities of Children Treated for Neoplastic Conditions Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 158-169. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: Language deficits have been identified as one of the adverse sequelae of treatment for various childhood cancer conditions including posterior fossa tumors and acute lymphoblastic leukemia (ALL). This chapter on the discourse abilities of children treated for neoplastic conditions is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors note that more recently the scope of language assessment has been broadened to encompass not only the structure and meaning of language (i.e., syntax and semantics) but also the use of language in naturalistic contexts (i.e., pragmatics). The authors discuss discourse units, which are defined as communication acts serving the needs of particular moments and audiences, and involve such situations as conversation, instruction and narrative. The authors summarize two studies that consider the discourse abilities of children treated for posterior fossa tumors and ALL. Topics include the procedures used for assessing the narrative abilities of these children, and the narrative abilities for the two different populations (those treated for posterior fossa tumors and those treated for ALL). The authors conclude that spontaneously generated narratives of children in both these populations were similar to those produced by age and sex matched control subjects. However, the authors caution that narrative abilities are only one component of discourse and other aspects should be examined. 34 references.

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Assessment and Treatment of Speech and Language Disorders Occurring Subsequent to Cancer Therapy in Children Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 187-205. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: This chapter on assessment and treatment is the final chapter in a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. Although dysarthria and language impairment are not inevitable outcomes, the authors stress that the evidence regarding the speech and language skills of the childhood cancer survivor points to the need for long term monitoring of these skills, based on

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thorough and ongoing assessment. Following treatment for cancer, a child may present with a motor speech disorder (MSD) in the form of dysarthria with or without developmental articulatory and phonatory features. The nature of the speech disorder is largely dependent on the timing and nature of the cancer and its treatment and the developmental status of the child's speech prior to this. The findings with regard to the language impairment following treatment for childhood cancer are much less clear cut than for speech. In addition, cognitive impairment must be considered in tandem with language impairment in children following treatment for cancer. The authors review assessment strategies, including perceptual assessment, physiological assessment, evaluation of respiration, laryngeal function, velpharyngeal function, the articulatory system, and assessment of language. Treatment considerations are briefly reviewed, for developmental disorders, dysarthria, and language disorders. One case report is provided to illustrate the details of these assessments. 64 references. •

Wilms Tumor Source: in Complete Directory for Pediatric Disorders. Millerton, NY: Grey House Publishing, Inc. 2002. p. 824-825. Contact: Available from Grey House Publishing, Inc. 185 Millerton Road, Millerton, NY 12546. Website: www.greyhouse.com. PRICE: $165.00 plus shipping and handling. ISBN: 1930956614. Summary: This entry, from a directory of pediatric disorders, describes Wilms tumor, a malignant tumor of the kidney that accounts for about eight percent of childhood cancers. The entry covers the incidence, epidemiology, symptoms, etiology (cause), and treatment of Wilms tumor. Wilms tumor typically becomes apparent by approximately three to five years of age. The most common sign is the presence of a smooth, firm mass in the abdominal area. Approximately 50 percent of affected children experience associated abdominal pain or vomiting (emesis) and about 10 to 25 percent have blood in their urine (microscopic or visible hematuria). In children with Wilms tumor in one kidney, treatment typically includes immediate surgical removal of the affected kidney (nephrectomy). During surgery, the remaining kidney is examined to exclude tumor development. After surgery, therapy may include the use of certain anticancer drugs (chemotherapy). In children with Wilms tumor in both kidneys, chemotherapy and radiation therapy may be considered before surgery. The entry concludes with a reference to organizations that may be helpful (listed in the General Resources Section of the book), the addresses of related websites, national associations and support groups, and the citations for related children's books.

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Language Disorders in Children Treated for Acute Lymphoblastic Leukaemia Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 126-157. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: Treatment of acute lymphoblastic leukemia (ALL) is aimed at inducing, consolidating, and maintaining remission of the disease, and involves multidrug chemotherapy and sometimes radiotherapy. As these treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This chapter on language disorders in

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children treated for ALL is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors review the literature on this population and present evidence from group studies that demonstrate language impairments following treatment for leukemia. The authors then present summaries of 23 case reports, focusing on the several factors that have the potential to influence language outcomes. These factors include the type and level of central nervous system (CNS) prophylaxis applied, the age at treatment, the time elapsed between treatment for ALL and language assessment, and the psychosocial effects of having a life threatening disease. The authors conclude that a large variation in the language abilities of children who have undergone treatment for leukemia can be expected, ranging from above normal to severely impaired language function. 70 references.

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

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

Hepatitis C common in some childhood cancer survivors Source: Reuters Medical News Date: April 30, 2004

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Better follow-up care urged for childhood cancer survivors in UK Source: Reuters Medical News Date: February 09, 2004

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Cancer screening practices among childhood cancer survivors suboptimal Source: Reuters Medical News Date: December 15, 2003

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Odds good for childhood cancer survivors: study Source: Reuters Health eLine Date: September 24, 2003

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Survivors of childhood cancer at increased risk for poor health as adults Source: Reuters Medical News Date: September 23, 2003

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Most childhood cancers do not raise the risk of future psychiatric disorders Source: Reuters Medical News Date: August 14, 2003

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Common childhood cancer can be cured Source: Reuters Health eLine Date: August 13, 2003

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Breastfeeding may not cut childhood cancer risk Source: Reuters Health eLine Date: April 08, 2003

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British study finds no radon, childhood cancer link Source: Reuters Health eLine Date: June 11, 2002

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Many survivors of childhood cancer lack information on diagnosis and treatment Source: Reuters Medical News Date: April 11, 2002

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Fertility preservation problematic for childhood cancer survivors Source: Reuters Medical News Date: April 19, 2001

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Late effects common in childhood cancer survivors Source: Reuters Medical News Date: April 03, 2000

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Female survivors of early childhood cancer at risk of early menopause, infertility Source: Reuters Medical News Date: August 02, 1999

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Study of childhood cancer survivors launched Source: Reuters Medical News Date: March 02, 1999

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Call for childhood cancer registry Source: Reuters Health eLine Date: May 07, 1998

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Cancer Risk In Childhood Cancer Survivors Source: Reuters Health eLine Date: February 13, 1998

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Psychological Adjustment By Families To Childhood Cancer Normalizes After One Year Source: Reuters Medical News Date: January 02, 1998

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Maternal Smoking Unrelated To Childhood Cancer Risk Source: Reuters Medical News Date: November 28, 1996 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 “childhood cancer” (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 “childhood cancer” (or synonyms). If you know the name of a company that is relevant to childhood cancer, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “childhood cancer” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “childhood cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on childhood cancer: •

Late Effect of Treatment to the Teeth Source: Candlelighters Childhood Cancer Foundation: The Quarterly Journal of the National Office. p. 3-4. Spring 2003. Contact: Available from Candlelighters Childhood Cancer Foundation (CCCF). P.O. Box 498, Kensington, MD 20895-0498. (800) 366-2223 or (301) 962-3520. Fax (301) 962-3521. Email: [email protected]. Website: www.candlelighters.org. Summary: The development and appearance of teeth are sometimes affected by treatment for childhood cancer. Survivors at highest risk for problems are those whose teeth and gums were in the radiation field. Treatment with chemotherapy during the time teeth are developing can also affect dental health. This article discusses the effects of cancer therapy on the teeth and how good dental care can help prevent these late effects from causing problems later in life. Abnormalities of the teeth that can develop include absent teeth, abnormally small teeth (microdontia), short or thin roots, small crowns, malocclusion (poor bite), poor enamel, incomplete calcification, frequent cavities, enlarged pulp chambers, and retained baby teeth. For many survivors, regular dental care and good home teeth care are all that is needed to maintain healthy teeth and gums. The authors also consider some special situations such as children with leaky heart valves and survivors who have an endoprosthesis. Readers are advised to visit one of two Web sites for additional information.

Academic Periodicals covering Childhood Cancer Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to childhood cancer. In addition to these sources, you can search for articles covering childhood cancer 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.”

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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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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 Institute8: •

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/

8

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.9 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:10 •

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

9

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). 10 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 Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “childhood cancer” (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 20077 198 1148 18 143 21584

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “childhood cancer” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

11

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

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15

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 Biologists16 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.17 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.18 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/.

16 Adapted 17

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. 18 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 childhood cancer 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 childhood cancer. 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 childhood cancer. 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 “childhood cancer”:

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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 Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.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. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Candlelighters Childhood Cancer Foundation: Just for Kids Summary: These are links to medical sites that can be used to explain cancer to children. Source: Candlelighters Childhood Cancer Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=8003 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 childhood cancer. 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.

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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

•

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

Associations and Childhood Cancer The following is a list of associations that provide information on and resources relating to childhood cancer: •

Candlelighters Childhood Cancer Foundation Telephone: (301) 962-3520 Toll-free: (800) 366-2223 Fax: (301) 962-3521 Email: [email protected] Web Site: http://www.candlelighters.org Background: The Candlelighter s Childhood Cancer Foundation (CCCF) is a 501c(3) nonprofit, tax exempt organization that provides support, information, and advocacy to children with cancer, their families, adult survivors of childhood cancer, and the professionals who care for them. Established in 1970 by concerned parents of children with cancer, the Foundation s membership now exceeds 45,000. Those dealing with childhood cancer and its effects, at any stage, are welcome as members. CCCF s major services include an information clearinghouse; publications, including four newsletters as well as books and reprints; and a network of support groups of childhood-cancer families, located in every state. Assistance is provided in starting and maintaining a group. Services that local groups provide often include camps, speakers, conferences, transportation, and one-to-one visitations. The Foundation does not provide direct financial assistance but has a financial aid list available ($1.00). CCCF is also a registered lobbyist and advocates on behalf of pediatric cancer patients and families.

•

Childhood Cancer Foundation - Candlelighters Canada Telephone: (416) 489-6440 Toll-free: (800) 363-1062 Fax: (416) 489-9812 Email: [email protected] Web Site: http://www.candlelighters.ca Background: The Candlelighters Childhood Cancer Foundation Canada (CCCFC), a national not-for-profit ' volunteer organization, is dedicated to serving families of

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children and adolescents with cancer by providing educational information, engaging in advocacy, and encouraging and assisting in the development of local parent support groups. Established in 1987, the Foundation has a network of over 50 local support groups across Canada for parents of children with cancer; promotes and supports the development of a long-term survivor network; offers individual and group assistance; and is developing a national financial assistance program. The Foundation's advocacy efforts include communicating the results of patient/family needs surveys to all levels of government; instituting task forces on professional and family issues; and forming coalitions with other organizations to address advocacy issues. The CCCFC also serves as a liaison with professionals and treatment centers, offers a speaker's bureau, and provides a wide variety of educational materials through its national resource library, which currently contains more than 300 books, pamphlets, and videos. In addition, the Foundation offers a school reentry resource kit and manual, provides supportive parent literature, and has several regular newsletters including a quarterly newsletter for families of children with cancer entitled 'CONTACT,' a quarterly newsletter with information for and by parents and professionals, and a youth newsletter with stories, art, and poetry by children with cancer and their siblings. •

National Childhood Cancer Foundation Telephone: (626) 447-1674 Toll-free: (800) 458-6223 Fax: (626) 447-6359 Email: [email protected] Web Site: http://www.nccf.org/nccf/ Background: The National Childhood Cancer Foundation (NCCF) is a charitable foundation which raises funds to support the research work of the Children's Oncology Group (COG) at over-235 hospitals throughout North America, and at sites in Australia and Europe. The physicians and scientists of COG not only conduct laboratory research, but also care for up to 90 percent of the children in the U.S. with cancer, providing expert diagnosis, state-of-the-art treatment and compassionate care. All members collaborate to standardize diagnostic, treatment and response criteria for each type of childhood cancer, and treat patients with the same cancer in exactly the same way. Treatment and research results from all hospitals are collated in the COG Patient Data Center so that advances in treatments can be discovered in a fraction of the time required for similar research at a single hospital. Effective new treatments are shared with members of the network and physicians throughout the world who treat children with cancer. NCCF also advocates on behalf of children with cancer and their families. The vision of NCCF is for a world free of the devastating impact of cancer upon infants, children and young adults. The National Childhood Cancer Foundation maintains a very comprehensive website that provides childhood cancer information and reports on the various activities of the Foundation.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to childhood cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with childhood cancer.

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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 childhood cancer. 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 “childhood cancer” (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 “childhood cancer”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “childhood cancer” (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 “childhood cancer” (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.19

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

19

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)20: •

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/

20

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

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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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

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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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

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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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

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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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/

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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

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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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

•

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

•

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

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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

•

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

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CHILDHOOD CANCER 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually

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referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adverse Effect: An unwanted side effect of treatment. [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] Afterload: The tension produced by the heart muscle after contraction. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

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] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [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] Air Pollutants: Substances which pollute the air. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as 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

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process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] 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 Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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] Anomalies: Birth defects; abnormalities. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier

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for white blood cells to destroy the antigen. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-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]

Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion

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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] Authorship: The profession of writing. Also the identity of the writer as the creator of a literary production. [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] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to 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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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

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technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blasts: Immature blood cells. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Groups: The classification systems (or schemes) of the different antigens located on erythrocytes.The antigens are the phenotypic expression of the genetic differences characteristic of specific blood groups. [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] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [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 Stem: The part of the brain that connects the cerebral hemispheres with the spinal

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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] Brain stem tumor: A tumor in the part of the brain that connects to the spinal cord (the brain stem). [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH]

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Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU]

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Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [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]

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Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH]

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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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] Conscious Sedation: An alternative to general anesthesia in patients for whom general anesthesia is refused or considered inadvisable. It involves the administering of an antianxiety drug (minor tranquilizer) and an analgesic or local anesthetic. This renders the patient free of anxiety and pain while allowing the patient to remain in verbal contact with the physician or dentist. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU]

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Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [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] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH]

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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] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [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] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or

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concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [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] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]

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Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [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] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Environmental Exposure: The exposure to potentially harmful chemical, physical, or

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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]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [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] 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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at

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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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Family Therapy: A form of group psychotherapy. It involves treatment of more than one member of the family simultaneously in the same session. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [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] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their

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opinions about topics, issues, or questions. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene 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., 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] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus,

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transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] 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] 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] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycophorin: The major sialoglycoprotein of the human erythrocyte membrane. It consists of at least two sialoglycopeptides and is composed of 60% carbohydrate including sialic acid and 40% protein. It is involved in a number of different biological activities including the binding of MN blood groups, influenza viruses, kidney bean phytohemagglutinin, and wheat germ agglutinin. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a

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microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [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] Haematemesis: The vomiting of blood. [EU] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Resources: Available manpower, facilities, revenue, equipment, and supplies to produce requisite health care and services. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology,

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and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematuria: Presence of blood in the urine. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [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

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arginine and lysine in each. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeodomain Proteins: Proteins encoded by homeobox genes that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (gene expression regulation, developmental). [NIH] Homeotic: Characterizes genes the mutations of which lead to inappropriate expressions of characteristics normally associated with another part of the organism (homeotic mutants). [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] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] 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 Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] 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]

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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 system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [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] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH]

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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 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] 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] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] 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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of

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crops, food products, or textile fabrics. [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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] 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] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU]

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Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH]

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Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes

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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 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 tumor: A tumor capable of metastasizing. [NIH] Mammogram: An x-ray of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medically Underserved Area: A geographic location which has insufficient health resources (manpower and/or facilities) to meet the medical needs of the resident population. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of

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the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [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 Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH]

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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [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] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [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] 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] 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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH]

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Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloid Progenitor Cells: One of the two stem cells derived from hematopoietic stem cells the other being the lymphoid progenitor cell. Derived from these myeloid progenitor cells are the erythroid progenitor cells and the myeloid cells (monocytes and granulocytes). [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic Processes: The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity. [NIH] Nephrectomy: Surgery to remove a kidney. Radical nephrectomy removes the kidney, the adrenal gland, nearby lymph nodes, and other surrounding tissue. Simple nephrectomy removes only the kidney. Partial nephrectomy removes the tumor but not the entire kidney. [NIH]

Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH]

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Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the 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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the 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] 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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH]

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Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [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] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Oncology nurse: A nurse who specializes in treating and caring for people who have cancer. [NIH]

Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [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]

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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] 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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [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

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gland that secretes digestive enzymes. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] 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] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [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

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increases and below it acidity increases. [EU] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived 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] 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] Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH]

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Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Power Plants: Units that convert some form of energy into electrical energy, such as hydroelectric or steam-generating stations, diesel-electric engines in locomotives, or nuclear power plants. [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

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health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary 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] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein 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]

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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [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 of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] 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] Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH]

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Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [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] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [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] 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] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly

Radon: A naturally radioactive element with atomic symbol Rn, atomic number 86, and atomic weight 222. It is a member of the noble gas family and released during the decay of

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radium and found in soil. There is a link between exposure to radon and lung cancer. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH]

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Relative survival rate: A specific measurement of survival. In cancer, the rate is calculated by adjusting the survival rate to remove all causes of death except cancer. The rate is determined at specific time intervals, such as 2 years and 5 years after diagnosis. [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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Personnel: Those individuals engaged in research. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [NIH] 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

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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] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Semantics: The relationships between symbols and their meanings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or

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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] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [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 Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [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] Soft tissue sarcoma: A sarcoma that begins in the 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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH]

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Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [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 of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Standardize: To compare with or conform to a standard; to establish standards. [EU] 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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclavian Artery: Artery arising from the brachiocephalic trunk on the right side and from the arch of the aorta on the left side. It distributes to the neck, thoracic wall, spinal cord, brain, meninges, and upper limb. [NIH]

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Subclavian Vein: The continuation of the axillary vein which follows the subclavian artery and then joins the internal jugular vein to form the brachiocephalic vein. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [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] 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] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the

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skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Outlet Syndrome: A neurovascular syndrome associated with compression of the brachial plexus; subclavian artery; and subclavian vein at the superior thoracic outlet. This may result from a variety of anomalies such as a cervical rib (cervical rib syndrome), anomalous fascial bands, and abnormalities of the origin or insertion of the anterior or medial scalene muscles. Clinical features may include pain in the shoulder and neck region which radiates into the arm, paresis or paralysis of brachial plexus innervated muscles, paresthesia, loss of sensation, reduction of arterial pulses in the affected extremity, ischemia, and edema. (Adams et al., Principles of Neurology, 6th ed, pp214-5). [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Thyroid Neoplasms: Tumors or cancer of the thyroid gland. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make

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permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [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] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] 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] Translocation: The movement of material in solution inside the body of the plant. [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

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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]

Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in

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nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [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] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [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] 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] 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 infectious particle. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH]

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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]

195

INDEX A Abdominal, 115, 145, 177 Abdominal Pain, 115, 145 Aberrant, 18, 48, 145 Acne, 145, 185 Acute leukemia, 14, 145 Acute lymphoblastic leukemia, 14, 27, 33, 47, 52, 54, 86, 112, 114, 115, 145 Acute lymphocytic leukemia, 6, 145 Acute myelogenous leukemia, 145 Acute myeloid leukemia, 15, 20, 52, 53, 145 Acute nonlymphocytic leukemia, 145 Adaptability, 145, 152 Adaptation, 74, 91, 94, 145, 175 Adenocarcinoma, 145, 165 Adjustment, 24, 50, 57, 91, 112, 119, 145 Adjuvant, 29, 78, 145 Adolescence, 26, 46, 145, 178 Adoptive Transfer, 45, 146 Adverse Effect, 48, 111, 146, 186 Affinity, 52, 146, 148 Afterload, 7, 146 Agar, 146, 179 Age Groups, 28, 146 Aged, 80 and Over, 146 Agenesis, 3, 146 Agonist, 146, 158 Air Pollutants, 63, 146 Aldehyde Dehydrogenase, 29, 146 Algorithms, 25, 146, 150 Alkaline, 146, 151, 183 Alkaloid, 146, 151 Alkylating Agents, 29, 105, 146 Alleles, 19, 51, 146 Allogeneic, 147, 164, 165 Alopecia, 147, 156 Alpha Particles, 147, 183 Alternative medicine, 119, 147 Amino Acid Sequence, 147 Amino Acids, 30, 147, 176, 178, 180, 182, 185, 191 Anaesthesia, 72, 147, 168 Anal, 22, 24, 147, 160, 171 Analgesic, 147, 155, 170 Anatomical, 147, 153, 159, 168 Anesthesia, 147, 155 Animal model, 4, 45, 147, 192

Anomalies, 3, 147, 190 Anthracycline, 7, 65, 66, 72, 81, 147, 157 Antibacterial, 147, 187 Antibiotic, 147, 157, 158, 187 Antibodies, 27, 147, 164, 167, 174, 179, 183 Antibody, 146, 147, 148, 154, 156, 164, 166, 167, 168, 170, 174, 183, 187, 194 Antiemetic, 78, 148 Antigen, 146, 147, 148, 154, 157, 166, 167, 168, 169 Antigen-presenting cell, 148, 157 Anti-inflammatory, 148, 157, 163 Antimetabolite, 148, 173 Antineoplastic, 4, 5, 146, 148, 156, 158, 172, 173, 180, 191, 193 Antineoplastic Agents, 5, 146, 148, 193 Antiviral, 148, 167, 169 Anus, 147, 148, 169 Anxiety, 35, 50, 148, 155 Aorta, 148, 164, 188, 193 Apoptosis, 19, 148 Applicability, 42, 148 Aqueous, 148, 149, 156 Arterial, 148, 166, 181, 190 Arteries, 148, 150, 155, 164, 175, 192 Artery, 7, 148, 188, 192 Articulation, 148, 159 Assay, 27, 52, 148 Astrocytes, 148, 149 Astrocytoma, 6, 149 Authorship, 14, 149 Autologous, 38, 89, 149, 165 Autologous bone marrow transplantation, 149, 165 B Bacteria, 147, 148, 149, 159, 174, 179, 187, 191, 192 Bacterial Physiology, 145, 149 Bacterium, 149, 154 Base, 31, 50, 149, 156, 170, 180, 189 Basophils, 149, 164 Benign, 149, 162, 175, 183 Bilateral, 23, 149, 178 Bile, 149, 162, 171 Biochemical, 9, 146, 148, 149, 161, 163, 179 Biological response modifier, 149, 169 Biological therapy, 149, 164, 172 Biological Transport, 149, 158

196

Childhood Cancer

Biomarkers, 22, 58, 149 Biotechnology, 55, 56, 119, 127, 149 Bladder, 150, 154, 181, 192 Blasts, 52, 150 Blood Coagulation, 150, 151 Blood Groups, 150, 163 Blood pressure, 7, 150, 152, 166, 174 Blood vessel, 150, 152, 153, 155, 170, 171, 173, 178, 187, 188, 190, 192 Body Composition, 60, 150 Body Fluids, 149, 150, 151, 161, 176, 192 Body Image, 61, 150 Body Mass Index, 71, 150, 177 Bone Density, 23, 34, 150 Bone Marrow Cells, 52, 150, 164, 172, 175 Bone Marrow Transplantation, 11, 12, 38, 40, 41, 52, 150 Bowel, 147, 150 Brachial, 150, 190 Brachial Plexus, 150, 190 Brachytherapy, 16, 150, 169, 170, 183, 194 Brain Stem, 6, 93, 150, 151 Brain stem glioma, 93, 151 Brain stem tumor, 6, 151 Buccal, 10, 151 Bypass, 29, 151 C Calcification, 120, 151 Calcium, 34, 151, 154, 166, 174, 186 Camptothecin, 51, 106, 151, 170 Carbohydrate, 151, 163 Carbon Dioxide, 151, 179, 185 Carcinogen, 151, 173 Carcinogenesis, 5, 13, 151, 153 Carcinogenic, 146, 151, 168, 177, 181 Carcinoma, 9, 151 Cardiac, 7, 8, 13, 49, 151, 157, 158 Cardiology, 7, 8, 72, 151 Cardiomyopathy, 7, 151 Cardiopulmonary, 33, 151 Cardiotonic, 151, 158 Cardiotoxic, 7, 71, 151 Cardiotoxicity, 64, 65, 66, 81, 151 Cardiovascular, 7, 8, 26, 61, 68, 152 Cardiovascular disease, 7, 8, 152 Case report, 115, 116, 152 Case-Control Studies, 24, 25, 96, 152, 160 Catecholamine, 152, 158 Caudal, 152, 166, 180 Causal, 152, 160 Cause of Death, 8, 27, 152 Cell Adhesion, 152, 169

Cell Cycle, 51, 152, 153, 160 Cell Death, 148, 152, 160, 175 Cell Differentiation, 152, 186 Cell Division, 149, 152, 156, 160, 164, 174, 179, 185 Cell proliferation, 53, 152, 186 Cell Respiration, 152, 185 Cell Size, 152, 161 Cell Survival, 52, 152, 164 Cell Transplantation, 12, 14, 15, 152, 165 Central Nervous System, 18, 34, 35, 41, 116, 152, 157, 162, 173, 180 Cerebral, 150, 152, 153, 190 Cerebral hemispheres, 150, 153 Cerebrovascular, 152, 153 Cervical, 23, 150, 153, 190 Cervix, 153, 185 Chemoprevention, 13, 153 Chemopreventive, 54, 153 Chemotherapeutic agent, 5, 15, 21, 23, 153 Chemotherapy, 3, 7, 11, 12, 15, 21, 29, 33, 52, 53, 85, 100, 105, 106, 111, 115, 120, 153, 172 Chin, 153, 173 Chromatin, 37, 148, 153, 171, 188 Chromosomal, 30, 37, 85, 153, 163, 165, 179 Chromosome, 20, 30, 37, 153, 171, 185 Chronic, 25, 26, 27, 33, 47, 153, 168, 170, 182, 183, 188 Chronic Disease, 153, 170 Cirrhosis, 27, 153 CIS, 34, 153 Cisplatin, 54, 153 Clinical Protocols, 43, 153 Clinical trial, 4, 6, 13, 14, 17, 26, 28, 32, 39, 41, 42, 45, 47, 49, 51, 74, 88, 127, 153, 155, 182, 184 Cloning, 36, 149, 153 Cofactor, 37, 154, 181 Cohort Studies, 154, 160 Combination Therapy, 154, 160 Compassionate, 134, 154 Competency, 32, 154 Complement, 154, 162, 169 Complementary and alternative medicine, 103, 107, 154 Complementary medicine, 103, 154 Complete remission, 154, 185 Compliance, 18, 41, 154 Computational Biology, 127, 155 Conception, 155, 161, 187, 188

197

Connective Tissue, 55, 150, 155, 161, 162, 171, 173, 185, 188 Conscious Sedation, 72, 155 Consolidation, 47, 155 Contamination, 17, 155 Continuous infusion, 54, 155 Continuum, 47, 155 Contraindications, ii, 155 Control group, 4, 29, 46, 49, 155, 181, 184 Cooperative group, 17, 39, 40, 54, 63, 155 Coordination, 40, 43, 155 Cornea, 155, 188 Coronary, 7, 152, 155, 175 Coronary heart disease, 152, 155 Cortex, 155, 156 Cortical, 9, 35, 156, 186 Corticosteroids, 156, 163 Cortisone, 156, 157 Cowpox, 156, 192 Cowpox Virus, 156, 192 Cranial, 8, 83, 156, 175 Cranial Irradiation, 8, 83, 156 Crossing-over, 156, 184 Cross-Sectional Studies, 156, 160 Crowns, 120, 156 Curative, 6, 156, 190 Cutaneous, 44, 55, 156, 178, 192 Cyclophosphamide, 16, 29, 60, 100, 104, 156, 167 Cytogenetics, 11, 12, 13, 15, 28, 42, 85, 156 Cytokines, 45, 156, 167 Cytoplasm, 148, 149, 156, 160, 171, 174, 185 Cytosine, 20, 156 Cytoskeleton, 156, 169 Cytotoxic, 14, 51, 156, 167, 183, 186 Cytotoxicity, 153, 156 D Data Collection, 37, 50, 157, 161 Daunorubicin, 64, 157, 158 De novo, 29, 157 Decompensation, 27, 157 Defense Mechanisms, 157, 169 Degenerative, 157, 165 Deletion, 148, 157 Delusions, 157, 182 Dendrites, 157 Dendritic, 45, 157 Dendritic cell, 45, 157 Dental Care, 120, 157 Depolarization, 157, 186 Desensitization, 157, 167

Detoxification, 29, 157 Dexamethasone, 48, 157 Dextroamphetamine, 157, 173 Diagnostic Imaging, 27, 157 Diagnostic procedure, 119, 157 Diffusion, 35, 149, 157 Digestion, 149, 150, 158, 171, 188 Dihydrotestosterone, 158, 184 Direct, iii, 10, 26, 35, 43, 44, 45, 47, 50, 55, 133, 158, 180, 184, 188 Discrete, 43, 158 Discrimination, 158 Disease Vectors, 158, 168 Disease-Free Survival, 18, 35, 38, 158 Disposition, 5, 158 Dissociation, 146, 158, 169 Distal, 30, 158, 182 Dobutamine, 65, 66, 158 Dorsal, 158, 175, 180 Doxorubicin, 71, 82, 158 Drug Interactions, 158 Drug Resistance, 12, 41, 42, 51, 158 Drug Tolerance, 158, 190 Dysarthria, 114, 159 Dyspnea, 157, 159, 183 E Echocardiography, 65, 66, 159 Ectoderm, 159, 175 Edema, 157, 159, 190 Effector, 38, 45, 154, 159 Efficacy, 14, 17, 18, 35, 42, 47, 51, 159, 192 Elective, 67, 159 Electrolyte, 159, 161, 176 Electrons, 149, 159, 169, 170, 172, 183 Elementary Particles, 159, 172, 176, 182 Embryo, 152, 159, 168, 192 Emesis, 115, 159 Empirical, 50, 159 Enalapril, 82, 159 Enamel, 3, 120, 159 Endemic, 159, 188 Endocrine System, 159, 176 Endometrium, 159, 173 Endotoxic, 159, 171 Environmental Exposure, 22, 25, 159, 177 Environmental Health, 22, 57, 63, 68, 73, 80, 126, 128, 160 Environmental Pollutants, 24, 160 Enzymatic, 151, 154, 160 Enzyme, 27, 146, 151, 159, 160, 162, 173, 180, 184, 186, 193 Eosinophil, 160, 164

198

Childhood Cancer

Epidemic, 160, 188 Epidemiologic Studies, 14, 160 Epidemiological, 25, 62, 94, 160 Epithelial, 9, 145, 149, 160, 165 Erythrocyte Membrane, 160, 163 Erythrocytes, 150, 160 Erythroid Progenitor Cells, 160, 175 Estrogen, 23, 34, 160 Estrogen Replacement Therapy, 23, 160 Etoposide, 54, 100, 104, 160 Excitation, 160, 161, 176 Exogenous, 160, 162, 181 Expiration, 160, 185 External-beam radiation, 160, 170, 183, 194 Extracellular, 148, 155, 161, 169 Extracellular Matrix, 155, 161, 169 Extremity, 68, 150, 161, 178, 190 F Fallopian tube, 161, 185 Family Planning, 127, 161 Family Relations, 50, 161 Family Therapy, 106, 161 Fat, 7, 150, 155, 161, 171, 177, 187 Fathers, 50, 57, 161 Fatigue, 48, 85, 161, 164 Fetus, 161, 167, 179, 192 Fibrosis, 27, 161, 183 Flow Cytometry, 42, 45, 52, 55, 161 Fluid Therapy, 161, 176 Fluorescence, 161 Fluorescent Dyes, 161 Focus Groups, 22, 161 Follow-Up Studies, 33, 162 Forearm, 150, 162 Fossa, 112, 113, 114, 162 G Gallbladder, 145, 162 Gamma Rays, 162, 183 Ganglia, 162, 175, 189 Ganglion, 162, 175 Ganglioside, 14, 162 Gas, 151, 157, 162, 166, 176, 183 Gastrin, 162, 166 Gene Expression, 9, 21, 23, 28, 30, 44, 162, 166 Gene Expression Profiling, 30, 162 Gene Targeting, 20, 37, 162 Gene Therapy, 11, 38, 40, 45, 162 Gene-modified, 45, 162 Genetic Engineering, 149, 153, 162 Genetic Markers, 53, 163

Genetic Techniques, 17, 163 Genetics, 22, 42, 44, 55, 73, 85, 86, 90, 156, 163 Genital, 163, 193 Genotype, 53, 163, 179 Germline mutation, 4, 163, 165 Gestation, 163, 178, 179 Gland, 156, 163, 171, 175, 177, 181, 190 Glioma, 29, 163 Glucocorticoid, 34, 157, 163 Glucose, 8, 163, 169 Glucose tolerance, 8, 163 Glucose Tolerance Test, 8, 163 Glycophorin, 53, 163 Glycoprotein, 5, 163, 164 Gonad, 163 Gonadal, 23, 74, 80, 163 Governing Board, 163, 180 Grade, 11, 29, 151, 163 Graft, 17, 33, 164, 167 Graft Rejection, 164, 167 Grafting, 164, 168 Graft-versus-host disease, 17, 33, 164 Granulocyte, 100, 164 Granulocyte-Macrophage ColonyStimulating Factor, 100, 164 Grasses, 164, 165 Growth factors, 75, 164 H Haematemesis, 159, 164 Haptens, 146, 164 Health Behavior, 25, 26, 46, 86, 164 Health Promotion, 26, 164 Health Resources, iv, 4, 164, 172 Health Status, 46, 164 Heart attack, 152, 164 Heart failure, 164, 183 Heart Valves, 120, 164 Hematology, 16, 31, 40, 58, 59, 60, 64, 77, 79, 89, 94, 96, 100, 104, 164 Hematopoiesis, 11, 13, 44, 53, 165 Hematopoietic growth factors, 14, 165 Hematopoietic Stem Cell Transplantation, 12, 33, 45, 165 Hematopoietic Stem Cells, 9, 45, 165, 175 Hematuria, 115, 165 Hemoglobinopathies, 162, 165 Hemostasis, 165, 169 Hepatic, 27, 163, 165 Hepatitis, 27, 67, 77, 117, 165 Hepatocellular, 27, 77, 165 Hepatocellular carcinoma, 27, 77, 165

199

Hepatocytes, 165 Hepatoma, 27, 165 Hepatotoxic, 27, 165 Herbicides, 48, 165 Hereditary, 30, 77, 163, 165 Hereditary mutation, 163, 165 Heredity, 162, 163, 165 Heterodimers, 165, 169 Heterogeneity, 4, 30, 46, 146, 165 Heterogenic, 165 Heterogenous, 10, 165 Histones, 153, 165 Homeobox, 23, 166 Homeodomain Proteins, 37, 166 Homeotic, 23, 166 Homogeneous, 155, 166 Homologous, 37, 146, 156, 162, 166, 185, 189 Hormonal, 160, 166, 172 Hormonal therapy, 166, 172 Hormone, 23, 34, 100, 156, 160, 162, 166, 169, 186, 190 Hormone Replacement Therapy, 34, 166 Hybrid, 47, 166 Hybridization, 30, 166 Hydrogen, 149, 151, 166, 174, 176, 178, 182 Hydrolysis, 153, 166, 179, 180 Hypercalcemia, 94, 166 Hypersensitivity, 51, 157, 160, 166 Hypertension, 152, 159, 166 Hypoplasia, 4, 166 Hypothalamic, 8, 80, 166 Hypothalamus, 8, 166, 190 Hypoxia, 51, 166 I Ifosfamide, 34, 54, 167 Immune response, 45, 145, 148, 156, 164, 167, 189, 192, 193 Immune system, 38, 148, 149, 167, 172, 192, 193 Immune Tolerance, 45, 167 Immunity, 38, 167 Immunization, 146, 167 Immunogenic, 167, 171 Immunoglobulins, 167 Immunologic, 45, 146, 167, 183 Immunology, 15, 44, 45, 54, 55, 145, 146, 161, 167 Immunosuppressant, 146, 167, 173 Immunosuppression, 27, 167, 171 Immunosuppressive, 27, 156, 163, 167 Immunosuppressive Agents, 167

Immunosuppressive therapy, 167 Immunotherapy, 45, 146, 149, 157, 167 Immunotoxins, 14, 167, 183 Impairment, 112, 113, 114, 168, 173, 182 Implant radiation, 168, 169, 170, 183, 194 Implantation, 70, 155, 168 In vitro, 12, 21, 30, 45, 79, 162, 168, 190 In vivo, 12, 21, 30, 45, 162, 168, 171 Incision, 168, 169 Induction, 35, 38, 45, 47, 168, 183 Induction therapy, 35, 168 Infancy, 7, 168 Infant, Newborn, 146, 168 Infection, 27, 77, 91, 149, 156, 164, 168, 171, 187, 189, 192, 193 Infertility, 67, 118, 168 Inflammation, 145, 148, 161, 164, 165, 168, 180, 183, 188 Influenza, 163, 168 Informed Consent, 28, 32, 39, 41, 168 Infusion, 168, 191 Ingestion, 163, 168 Initiation, 19, 30, 168, 191 Inorganic, 153, 168 Insecticides, 48, 168, 178 Insulin, 8, 163, 169 Insulin-dependent diabetes mellitus, 169 Integrins, 52, 169 Interferon, 67, 169, 171 Interferon-alpha, 169 Internal Medicine, 18, 45, 54, 164, 169 Internal radiation, 169, 170, 183, 194 Interstitial, 150, 169, 170, 194 Intestinal, 163, 169 Intestines, 145, 169, 185 Intracellular, 19, 29, 163, 168, 169, 186, 193 Intrinsic, 146, 169 Introns, 169, 182 Invasive, 35, 50, 167, 169, 172 Ionization, 169, 170 Ionizing, 58, 147, 160, 170, 183 Ions, 149, 158, 159, 166, 169, 170 Irinotecan, 51, 170 Irradiation, 7, 8, 33, 45, 58, 94, 170, 194 Ischemia, 162, 170, 190 K Kb, 126, 170 Kinetic, 170 L Language Disorders, 112, 113, 114, 115, 170 Laryngeal, 115, 170

200

Childhood Cancer

Larynx, 170, 191 Latent, 170, 181 Lethal, 5, 170 Leucocyte, 160, 170, 171 Leukaemia, 88, 100, 105, 115, 170 Leukoencephalopathy, 47, 170 Levo, 170, 173 Ligaments, 155, 170 Ligands, 169, 171 Linkage, 22, 63, 163, 171 Lipid, 7, 169, 171 Lipid A, 7, 171 Lipopolysaccharides, 171 Liver, 27, 37, 145, 149, 153, 156, 162, 163, 164, 165, 171 Localized, 20, 55, 168, 171, 179 Longitudinal study, 23, 27, 59, 81, 171 Lymph, 153, 171, 175 Lymph node, 153, 171, 175 Lymphatic, 17, 168, 171, 173, 187, 188, 190 Lymphatic system, 171, 187, 188, 190 Lymphoblastic, 15, 48, 88, 115, 171 Lymphoblasts, 52, 145, 171 Lymphocyte Depletion, 167, 171 Lymphocytes, 148, 157, 167, 170, 171, 188, 190, 193 Lymphocytic, 171 Lymphoid, 33, 54, 147, 156, 170, 171, 175 Lymphoma, 3, 12, 18, 40, 45, 54, 55, 132, 171 M Macrophage, 164, 171 Magnetic Resonance Imaging, 33, 172 Magnetic Resonance Spectroscopy, 35, 88, 106, 172 Malformation, 19, 172 Malignancy, 16, 27, 38, 53, 72, 172 Malignant tumor, 115, 172, 185 Mammogram, 151, 172, 174 Mania, 48, 172 Manic, 172, 182 Manic-depressive psychosis, 172, 182 Marital Status, 68, 172 Maximum Tolerated Dose, 39, 158, 172 Meat, 62, 172 Medial, 172, 177, 190 Mediate, 9, 19, 43, 172 Medical oncologist, 34, 172 Medical Records, 36, 172 Medically Underserved Area, 50, 172 MEDLINE, 127, 172 Medulloblastoma, 29, 172

Megakaryocytes, 150, 172 Melphalan, 29, 172 Membrane, 5, 14, 148, 154, 157, 161, 170, 173, 175, 179, 186, 191 Memory, 18, 69, 173 Menarche, 57, 173 Meningeal, 48, 173 Meninges, 152, 173, 188 Menopause, 46, 67, 118, 173, 180 Menstrual Cycle, 66, 173 Menstruation, 173 Mental, iv, 4, 79, 81, 126, 128, 153, 158, 161, 172, 173, 182 Mental Disorders, 173, 182 Mental Health, iv, 4, 79, 81, 126, 128, 173, 182 Mental Processes, 158, 173, 182 Mentors, 32, 39, 173 Mercury, 161, 173 Mesenchymal, 164, 173 Metabolite, 36, 173 Metastasis, 173 Metastatic, 17, 60, 173 Methotrexate, 5, 47, 106, 173 Methylphenidate, 34, 78, 173 Methyltransferase, 21, 173 Microbe, 174, 191 Microbiology, 45, 145, 174 Microcalcifications, 151, 174 Microorganism, 154, 174, 193 Milliliter, 150, 174 Mitochondrial Swelling, 174, 175 Mitosis, 148, 174 Mitotic, 160, 174 Modeling, 23, 39, 174 Modification, 53, 162, 174, 183 Molecular, 4, 9, 10, 11, 13, 15, 17, 18, 22, 28, 40, 41, 42, 44, 45, 52, 54, 127, 129, 149, 155, 156, 174, 191 Molecule, 148, 149, 154, 158, 159, 160, 165, 166, 174, 176, 179, 180, 183, 184, 186, 192 Monitor, 174, 176 Monoclonal, 14, 167, 170, 174, 183, 194 Monoclonal antibodies, 14, 167, 174 Monocytes, 174, 175 Morphogenesis, 166, 174 Morphology, 55, 164, 174 Mucosa, 168, 175, 188 Multidrug resistance, 5, 14, 175 Mutagenic, 146, 175 Myelodysplasia, 53, 175 Myelogenous, 175

201

Myeloid Cells, 52, 175 Myeloid Progenitor Cells, 53, 175 Myocardial infarction, 158, 175 N Narcolepsy, 157, 173, 175 Nausea, 148, 175 NCI, 1, 11, 16, 19, 28, 31, 54, 84, 125, 153, 175 Necrosis, 48, 148, 175 Neonatal, 85, 100, 175 Neoplasia, 29, 42, 49, 175 Neoplasm, 10, 175, 185, 192 Neoplastic Processes, 10, 175 Nephrectomy, 115, 175 Nervous System, 18, 84, 152, 159, 175, 176, 189 Neural, 16, 30, 47, 175 Neural Crest, 30, 175 Neuroblastoma, 6, 11, 14, 16, 27, 30, 38, 40, 175 Neuroendocrine, 75, 176 Neurologic, 83, 176 Neurology, 42, 54, 58, 176, 190 Neuropeptide, 9, 16, 176 Neurosurgery, 41, 42, 54, 176 Neurotoxicity, 47, 83, 176 Neurotransmitter, 176, 186, 189 Neutrons, 147, 170, 176, 183 Nitrogen, 146, 156, 172, 176 Nuclear, 68, 80, 151, 159, 161, 162, 175, 176, 180, 182, 183 Nuclear Family, 161, 176 Nuclei, 147, 159, 162, 163, 165, 169, 172, 174, 176, 182 Nucleic acid, 156, 166, 176, 193 Nucleic Acid Hybridization, 166, 176 Nucleus, 148, 149, 153, 156, 159, 162, 171, 174, 176, 182, 188 Nurse Practitioners, 34, 40, 176 Nutritional Support, 13, 176 O Occupational Exposure, 59, 177 Oncogene, 9, 37, 177 Oncogenic, 11, 19, 37, 169, 177 Oncogenic Viruses, 11, 177 Oncologist, 21, 33, 106, 172, 177 Oncology nurse, 6, 11, 36, 38, 77, 177 Operon, 177, 185 Optic Chiasm, 166, 177 Organ Culture, 177, 190 Osteoporosis, 9, 23, 26, 34, 160, 177 Outpatient, 55, 177

Ovaries, 177, 185, 186 Ovary, 163, 177, 188 Overall survival, 52, 177 Overexpress, 53, 177 Overweight, 25, 101, 177 Oxygen Consumption, 177, 185 P Palliative, 177, 190 Pancreas, 145, 149, 169, 177, 192 Paradoxical, 57, 178 Paralysis, 178, 190 Paresis, 178, 190 Paresthesia, 178, 190 Partial remission, 178, 185 Particle, 178, 191, 193 Pathologic, 148, 155, 166, 178, 180, 182, 192 Pathologic Processes, 148, 178 Pathologist, 178 Pathophysiology, 8, 9, 178 Pedigree, 36, 178 Penis, 178, 185 Peptide, 178, 180, 182, 184 Perfusion, 166, 178, 190 Perinatal, 24, 79, 178 Peripheral blood, 10, 11, 12, 53, 165, 169, 178 Peripheral stem cells, 164, 178 Pesticides, 22, 24, 43, 48, 165, 168, 178 PH, 78, 150, 178 Pharmacists, 11, 179 Pharmacodynamics, 42, 179 Pharmacokinetic, 5, 51, 179 Pharmacologic, 14, 147, 179, 190, 191 Phenotype, 9, 30, 53, 179 Phospholipases, 179, 186 Phospholipids, 161, 179 Phosphorus, 151, 179 Physiologic, 9, 146, 157, 173, 179, 184 Physiology, 22, 34, 37, 151, 164, 179 Pilot Projects, 22, 179 Pilot study, 8, 100, 104, 179 Placenta, 179, 192 Plants, 146, 151, 163, 165, 174, 179, 180, 191 Plaque, 4, 179 Plasma, 30, 147, 163, 165, 179, 190 Plasma cells, 147, 179 Plasmid, 38, 179, 192 Platelet Activation, 180, 186 Pneumonia, 155, 180 Podophyllotoxin, 160, 180 Point Mutation, 9, 180

202

Childhood Cancer

Polymerase, 180, 185 Polymorphism, 21, 48, 180 Polypeptide, 147, 166, 180 Pons, 151, 180 Posterior, 112, 113, 114, 147, 158, 177, 180 Postmenopausal, 160, 177, 180 Postnatal, 5, 180, 188 Postoperative, 100, 105, 114, 180 Postoperative Complications, 114, 180 Postsynaptic, 180, 186 Post-traumatic, 35, 180 Potentiation, 180, 186 Power Plants, 68, 180 Practicability, 180, 192 Practice Guidelines, 128, 180 Precancerous, 19, 153, 181 Preclinical, 13, 14, 38, 51, 92, 181 Precursor, 156, 159, 160, 181 Predisposition, 14, 30, 181 Premalignant, 181 Prevalence, 4, 27, 46, 49, 181 Primary endpoint, 52, 181 Primary tumor, 30, 181 Primitive neuroectodermal tumors, 172, 181 Prognostic factor, 181, 189 Progression, 19, 27, 53, 147, 181, 192 Progressive, 7, 152, 153, 158, 160, 175, 180, 181, 183, 192 Projection, 94, 157, 181 Promoter, 37, 181 Prophylaxis, 47, 96, 116, 181, 185, 192 Prospective study, 7, 171, 181 Prostate, 44, 45, 149, 181, 185, 192 Protein Binding, 181, 190 Protein S, 150, 181, 185 Proteins, 11, 37, 147, 148, 153, 154, 156, 165, 166, 174, 176, 178, 179, 181, 182, 186, 191, 193 Protocol, 11, 14, 33, 35, 39, 41, 42, 47, 53, 92, 182 Protons, 147, 166, 170, 172, 182, 183 Proximal, 158, 182 Pseudogenes, 85, 182 Psoriasis, 182, 185 Psychiatric, 118, 173, 182 Psychiatry, 57, 81, 182 Psychic, 173, 182, 186 Psychology, 11, 42, 56, 57, 61, 69, 70, 78, 81, 158, 182 Psychosexual, 46, 182 Psychosis, 48, 182

Psychotherapy, 161, 182 Public Health, 8, 22, 44, 48, 58, 62, 69, 78, 128, 182 Public Policy, 127, 182 Publishing, 55, 115, 182 Pulmonary, 49, 80, 88, 150, 164, 182, 183, 193 Pulmonary Artery, 150, 183, 193 Pulmonary Fibrosis, 80, 183 Q Quality of Life, 10, 13, 14, 17, 26, 33, 46, 56, 76, 81, 84, 93, 95, 183, 189 R Race, 36, 48, 173, 183 Racemic, 173, 183 Radiation oncologist, 39, 177, 183 Radiation therapy, 34, 35, 42, 89, 115, 160, 169, 170, 183, 194 Radioactive, 166, 167, 168, 169, 170, 174, 176, 177, 183, 194 Radioactivity, 156, 183 Radioimmunotherapy, 183 Radiolabeled, 170, 183, 194 Radiology, 3, 11, 35, 42, 45, 83, 183 Radiotherapy, 8, 17, 40, 73, 83, 85, 89, 91, 93, 111, 115, 150, 170, 183, 194 Radium, 183, 184 Radon, 62, 89, 118, 183 Random Allocation, 184 Randomization, 29, 184 Randomized, 15, 18, 23, 31, 34, 35, 42, 49, 50, 54, 159, 184 Randomized clinical trial, 42, 184 Ras gene, 53, 184 Reality Testing, 182, 184 Receptor, 51, 52, 145, 148, 184, 186 Recombinant, 45, 100, 184, 193 Recombination, 37, 162, 163, 184 Recurrence, 36, 100, 153, 172, 184 Reductase, 21, 173, 184 Reentry, 134, 184 Refer, 1, 151, 154, 176, 182, 183, 184, 191 Refraction, 184, 187 Regimen, 153, 159, 184 Registries, 63, 184 Regurgitation, 164, 184 Relapse, 20, 27, 38, 39, 52, 54, 184 Relative survival rate, 20, 185 Remission, 115, 172, 184, 185 Repressor, 37, 177, 185 Reproductive cells, 163, 165, 185 Reproductive system, 81, 185

203

Research Personnel, 40, 185 Residual disease, 17, 185 Respiration, 115, 151, 174, 185 Retinoids, 54, 185 Retrospective, 33, 85, 185 Retroviral vector, 162, 185 Rhabdomyosarcoma, 9, 16, 18, 41, 54, 185 Ribosome, 185, 191 Risk factor, 7, 8, 24, 27, 33, 43, 46, 49, 60, 71, 160, 181, 185 Rodenticides, 178, 185 Rural Population, 48, 185 S Sarcoma, 53, 54, 181, 185, 187 Screening, 14, 25, 36, 61, 94, 118, 153, 185 Second cancer, 49, 91, 185 Segmentation, 47, 185 Segregation, 184, 185 Seizures, 47, 58, 186 Selection Bias, 65, 186 Semantics, 114, 186 Semisynthetic, 151, 160, 167, 186 Senile, 177, 186 Sensibility, 147, 186 Serum, 80, 91, 146, 154, 167, 171, 186 Sex Characteristics, 145, 186, 190 Shock, 186, 191 Side effect, 83, 146, 149, 156, 186, 189, 191 Signal Transduction, 51, 186 Signs and Symptoms, 184, 185, 186 Skeletal, 19, 23, 34, 81, 186 Skeleton, 186, 187 Skull, 187, 190 Small intestine, 166, 169, 187 Smallpox, 187, 192 Smoking Cessation, 49, 187 Social Environment, 183, 187 Social Support, 35, 50, 187 Social Work, 11, 34, 76, 83, 89, 104, 187 Soft tissue, 3, 9, 12, 16, 54, 150, 186, 187 Soft tissue sarcoma, 9, 12, 16, 54, 187 Solid tumor, 14, 31, 38, 41, 42, 51, 54, 100, 104, 158, 187 Soma, 187 Somatic, 4, 19, 44, 145, 174, 187 Somatic mutations, 4, 44, 187 Specialist, 135, 187, 188 Species, 147, 152, 156, 165, 166, 174, 183, 187, 189, 192, 193 Specificity, 28, 146, 187, 190 Spectrum, 9, 24, 29, 30, 33, 35, 187 Speech Disorders, 112, 187

Speech pathologist, 111, 113, 115, 188 Sperm, 153, 163, 165, 185, 187, 188 Spermatogenesis, 80, 188 Spermatozoa, 188 Spinal cord, 148, 149, 150, 151, 152, 162, 173, 175, 176, 188, 189 Spleen, 171, 188 Sporadic, 30, 36, 188 Standardize, 7, 134, 188 Stem Cells, 160, 165, 175, 178, 188 Sterility, 156, 168, 188 Steroids, 156, 163, 188 Stimulant, 157, 158, 173, 188 Stomach, 145, 162, 163, 166, 169, 175, 187, 188 Strand, 37, 180, 188 Stress, 35, 41, 50, 51, 59, 61, 65, 66, 70, 80, 88, 113, 114, 152, 175, 181, 188 Stroke, 126, 152, 188 Stroma, 52, 188 Stromal, 52, 150, 188 Stromal Cells, 52, 150, 188 Subacute, 168, 188 Subclavian, 188, 189, 190 Subclavian Artery, 188, 189, 190 Subclavian Vein, 189, 190 Subclinical, 7, 8, 168, 186, 189 Subcutaneous, 30, 159, 189 Subspecies, 187, 189, 192 Substance P, 173, 189 Support group, 115, 133, 134, 189 Supportive care, 13, 15, 189 Suppression, 37, 80, 189 Suppressive, 9, 189 Survival Analysis, 7, 189 Survival Rate, 23, 46, 177, 185, 189 Sympathetic Nervous System, 176, 189 Symptomatic, 7, 189 Synaptic, 176, 186, 189 Systemic, 45, 48, 51, 148, 150, 168, 170, 183, 189, 192, 194 T Tachycardia, 158, 189 Temporal, 35, 189 Teratogenic, 146, 190 Testosterone, 184, 190 Therapeutics, 15, 30, 40, 42, 44, 51, 55, 104, 190 Third Ventricle, 166, 190 Thoracic, 23, 150, 171, 188, 190, 193 Thoracic Outlet Syndrome, 23, 190 Thrombosis, 169, 175, 181, 188, 190

204

Childhood Cancer

Thymus, 8, 167, 171, 190 Thyroid, 56, 85, 91, 94, 190 Thyroid Gland, 190 Thyroid Neoplasms, 91, 190 Tissue Culture, 45, 190 Tissue Distribution, 5, 190 Tolerance, 38, 45, 145, 163, 190 Tomography, 150, 172, 190 Tone, 190, 191 Tonic, 58, 151, 191 Tooth Preparation, 145, 191 Topoisomerase inhibitors, 51, 170, 191 Topotecan, 51, 191 Toxic, iv, 25, 146, 156, 157, 160, 164, 165, 167, 173, 180, 191 Toxicity, 5, 11, 14, 17, 39, 41, 60, 151, 158, 172, 173, 191 Toxicokinetics, 22, 191 Toxicology, 72, 128, 191 Toxin, 159, 167, 190, 191 Trachea, 170, 190, 191 Transcription Factors, 9, 191 Transduction, 186, 191 Transfection, 149, 162, 191 Transfusion, 27, 191 Translation, 50, 182, 191 Translational, 11, 17, 19, 21, 32, 36, 39, 44, 191 Translocation, 9, 18, 28, 191 Trauma, 175, 191 Treatment Outcome, 52, 191 Tumor marker, 149, 192 Tumor model, 13, 192 Tumor suppressor gene, 30, 44, 192 Tumour, 88, 113, 162, 192 U Umbilical Arteries, 192 Umbilical Cord, 12, 192 Urethra, 178, 181, 192 Urine, 115, 150, 165, 192 Uterus, 153, 159, 173, 177, 185, 192

V Vaccination, 38, 192 Vaccine, 38, 45, 145, 182, 192 Vaccinia, 45, 192 Vaccinia Virus, 45, 192 Vagina, 153, 173, 185, 192, 193 Vaginal, 192, 193 Variola, 192 Vascular, 168, 179, 190, 192 Vasoconstriction, 158, 192 Vasomotor, 160, 192 Vector, 45, 55, 191, 192 Vein, 176, 188, 189, 192, 193 Venous, 157, 181, 193 Ventricle, 183, 190, 193 Ventricular, 7, 82, 193 Ventricular Dysfunction, 82, 193 Vertebrae, 23, 188, 193 Veterinary Medicine, 127, 193 Vinca Alkaloids, 193 Vincristine, 5, 51, 100, 104, 193 Viral, 17, 168, 177, 191, 193 Virulence, 191, 193 Virus, 44, 67, 77, 156, 162, 169, 179, 185, 187, 191, 192, 193 Virus Replication, 44, 193 Viscera, 187, 193 Vitro, 13, 21, 193 Vivo, 13, 52, 171, 193 Vulva, 24, 193 W White blood cell, 145, 147, 164, 171, 179, 193 Windpipe, 190, 193 Womb, 185, 192, 193 Wound Healing, 169, 193 X Xenograft, 29, 51, 147, 192, 193 X-ray, 66, 97, 98, 150, 161, 162, 170, 172, 176, 183, 194 X-ray therapy, 170, 194 Y Yeasts, 179, 194