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  1. 1. Brain Tumors C O N T E M P O R A R Y C A N C E R R E S E A R C H Edited by Francis Ali-Osman, dsc Brain Tumors Edited by Francis Ali-Osman, dsc
  2. 2. Brain Tumors
  3. 3. Brain Tumors, edited by Francis Ali-Osman, 2005 Cancer Diagnostics: Current and Future Trends, edited by Robert N. Nakamura, Wayne W. Grody, James T. Wu, and Raymond B. Nagle, 2004 Cancer Gene Therapy, edited by David T. Curiel and Joanne T. Douglas, 2005 DNA Damage and Repair, Volume 3: Advances from Phage to Humans, edited by Jac A. Nickoloff and Merl F. Hoekstra, 2001 Prostate Cancer: Biology, Genetics, and the New Therapeutics, edited by Leland W. K. Chung, William B. Isaacs, and Jonathan W. Simons, 2001 Chemokines and Cancer, edited by Barrett J. Rollins, 1999 Breast Cancer: Moleuclar Genetics, Pathogens, and Therapeutics, edited by Anne M. Bowcock, 1999 DNA Damage and Repair, Volume 1: DNA Repair in Prokaryotes and Lower Eukaryotes, edited by Jac A. Nickoloff and Merl F. Hoekstra, 1998 DNA Damage and Repair, Volume 2: DNA Repair in Higher Eukaryotes, edited by Jac A. Nickoloff and Merl F. Hoekstra, 1998 Contemporary Cancer Research Jac A. Nickoloff, SERIES EDITOR
  4. 4. Brain Tumors Edited by Francis Ali-Osman, DSC Department of Surgery, Comprehensive Cancer Center, Duke University Medical Center, Durham, NC
  5. 5. 2005 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, since new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occur, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further, it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publishers, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication. This publication is printed on acid-free paper. ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Mark J. Breaugh. Cover design by Patricia F. Cleary. Cover illustration: MRI of a child with medulloblastoma. See Fig. 1 on p. 128. For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel: 973-256-1699; Fax: 973-256-8341; E-mail: humana@humanapr.com, or visit our Website: http://humanapress.com Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $25.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [1-58829-042-5/05 $25.00]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 e-ISBN: 1-59259-843-9 Library of Congress Cataloging in Publication Data Brain tumors / edited by Francis Ali-Osman. p. ; cm. -- (Contemporary cancer research) Includes bibliographical references and index. ISBN 1-58829-042-5 (alk. paper) 1. Brain--Tumors. [DNLM: 1. Brain Neoplasms. WL 358 B813465 2005] I. Ali-Osman, Francis. II. Series. RC280.B7B7232 2005 616.99'481--dc22 2004017417
  6. 6. v Preface Exciting new developments and discoveries of the last two decades are beginning to shed light on the complex biology of brain tumors and are advancing our understand- ing of the cellular and molecular processes involved in their initiation, progression, and clinical and biological behavior. The disease process in brain tumors is quite complex and the resulting tumors are characterized by a high degree of biological and clinical diversity. Thus, despite the advances of the last two decades, prognosis for patients with malignant brain tumors remains abysmal. Significant progress in the diagnosis, treatment and, ultimately, prevention of these tumors will require both the timely har- nessing of the advances in basic and clinical brain tumor research, and a continuing concerted effort at increasing our understanding of brain tumor biology, in particular, the molecular genetic changes and perturbations of cellular pathways involved in brain oncogenesis and which drive the biological and clinical behavior of the tumors. Brain tumor diagnosis and prognosis, which is still largely based on histopathology and other clinical criteria, will, in the future, acquire a significant molecular component, with the incorporation of knowledge of genes that are mutated, over-expressed, deleted, silenced, or functionally altered in the tumors. Treatment strategies for brain tumors, rather than being empirical, will be rationally developed based on an understanding of the cellular and molecular mechanisms and targets that have been activated, suppressed, or otherwise altered. The discovery of new therapeutics will employ novel paradigms of rational drug discovery that incorporate structural biology, genomics, proteomics, computational chemistry and high throughput approaches. Advances in genetic epide- miology and neuro-oncogenesis will lead to the definition of high risk genotypes and phenotypes and provide the basis for genetic counseling of individuals and populations at risk for brain tumors, and facilitate the development of brain tumor prevention strategies. The goal of Brain Tumors is to bring together the major scientific advances and developments in important areas of brain tumor research of the last two decades. The explosion of knowledge in the neurosciences and in neuro-oncology that has marked this period make this a timely and much needed undertaking. The chapters, organized into three main sections, emphasize recent research advances, rather than a review of established knowledge. The first section is devoted to the molecular biology, genetics, epidemiology, and pathology of brain tumors, and includes chapters on molecular pro- filing, molecular pathology and classification, in vitro and in vivo brain tumor models, brain metastasis and progenitor cell biology. The second section focuses on the cellular and genetic pathways involved in brain oncogenesis, malignant progression, and thera- peutic response. Individual chapters cover oncogenes and tumor suppressor genes, DNA damage and repair, invasion and migration, cell cycle, growth factors, signaling, apoptosis, and developmental biology. The final section covers areas relevant to brain tumor therapy, with chapters focusing on advances in pharmacological concepts, thera- peutic modalities, novel therapeutic targets, rational drug design, gene and viral therapy, drug delivery, and the bloodbrain barrier, immunotherapy, and brain imag-
  7. 7. ing. Brain Tumors provides for the established brain tumor scientist and clinician, as well as, for the new investigator, graduate, or undergraduate student, a comprehensive, up-to-date guide to the critical research topics in the rapidly evolving area of neuro- oncology. The contributors of the chapters in this volume are all leaders at the frontiers of basic and clinical neuro-oncology research and practice whose work over the years has helped define the field. To each of them, I express my deepest thanks for a schol- arly contribution that has resulted in a volume that is a major effort to better understand and ultimately eradicate, or at least minimize, human suffering from brain tumors. Francis Ali-Osman, DSC vi Preface
  8. 8. vii Contents Preface ................................................................................................................... v Contributors ........................................................................................................ix PART I: EPIDEMIOLOGY, BIOLOGY, GENETICS, AND PATHOLOGY 1 Epidemiology of Brain Tumors Randa El-Zein, Melissa Bondy, and Margaret Wrensch............................. 3 2 Molecular Genetics of Tumors of the Central Nervous System C. David James ..................................................................................................19 3 Molecular Pathology of Nervous System Tumors Catherine L. Nutt, Anat O. Stemmer-Rachamimov, J. Gregory Cairncross, and David N. Louis .............................................33 4 Genetic Modeling of Glioma Formation in Mice Martin Begemann, Vinagolu K. Rajasekhar, Gregory N. Fuller, and Eric C. Hollan