BRAIN TUMORS CURRENT AND EMERGING THERAPEUTIC STRATEGIES doc

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BRAIN TUMORS - CURRENT AND EMERGING THERAPEUTIC STRATEGIES Edited by Ana Lucia Abujamra Brain Tumors - Current and Emerging Therapeutic Strategies Edited by Ana Lucia Abujamra Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Iva Simcic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright dusan964, 2010. Used under license from Shutterstock.com First published August, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Brain Tumors - Current and Emerging Therapeutic Strategies, Edited by Ana Lucia Abujamra p. cm. ISBN 978-953-307-588-4 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Tumor Models, Molecular Mechanisms and Diagnostics 1 Xenograft Model of Human Brain Tumor 3 Chapter 1 Chen Hua, Dong Jun and Huang Qiang Experimental Brain Tumors: Current Concepts 21 Chapter 2 Jesús Vaquero and Mercedes Zurita Molecular Diagnostics of Brain Tumours Chapter 3 by Measuring the 5-Methylcytosine Level in Their DNA 37 Anna-Maria Barciszewska, Stanisław Nowak, Iwona Gawrońska and Mirosława Barciszewska The Bevacizumab “Pseudoresponse” Chapter 4 in Glioma: Disappointment or Opportunity? 53 Piia Thomas, Daniel Spielman and Lawrence Recht The Molecular Mechanism for Chapter 5 Differentiation Therapy of Malignant Glioma 67 Wenbo Zhu and Guangmei Yan DNA Double-Strand Breaks Repair and Chapter 6 Signaling of Human Gliomas and Normal Brain Cells in Response to Radiation: Potential Impact of the ATM- and BRCA1- Dependent Pathways 89 Adeline Granzotto, Zuzana Bencokova, Guillaume Vogin, Clément Devic, Aurélie Joubert, Jacques Balosso and Nicolas Foray Glioma Proteomics: Chapter 7 Methods and Current Perspective 105 Kumaravel Somasundaram, Mamatha B Nijaguna and Durairaj Mohan Kumar VI Contents Evolvement of Molecular Biomarkers Chapter 8 in Targeted Therapy of Malignant Gliomas 117 Erica Hlavin Bell, Mersiha Hadziahmetovic and Arnab Chakravarti Part 2 Chemotherapy and Other Therapeutic Strategies 143 Glioblastoma: Current Chemotherapeutic Chapter 9 Status and Need for New Targets and Approaches 145 Aditi Jain, James CK Lai, Golam MI Chowdhury, Kevin Behar and Alok Bhushan Chemotherapy of Medulloblastoma in Children 177 Chapter 10 Dezső Schuler, Péter Hauser and Miklós Garami New Therapeutic Strategies Chapter 11 for the Treatment of Brain Tumor 191 Rintaro Hashizume Transcription Factor Targets Chapter 12 as Treatment for Medulloblastoma 209 Mehdi H. Shahi and Elva Díaz Novel Therapeutic Venues for Glioblastoma: Chapter 13 Novel Rising Preclinical Treatment Opportunities 225 Siegelin Markus David and Siegelin Yasemin The Molecular Basis of Resistance to the Chapter 14 Antiproliferative Effect of EGFR Inhibition in Human Glioblastoma Multiforme Cell Lines 245 Georg Karpel-Massler and Marc-Eric Halatsch Medical Management Chapter 15 of Brain Metastases from Lung Cancer 253 Ryuya Yamanaka Part 3 Gene Therapy and Immunotherapy 267 Fundamentals of Gene Chapter 16 and Viral Therapy for Malignant Gliomas 269 Farizan Ahmad and Jafri Malin Abdullah New Therapeutic Strategies in Gliomas Treatment 281 Chapter 17 Gerardo Caruso, Mariella Caffo, Giuseppe Raudino, Concetta Alafaci and Francesco Tomasello Cellular Immunotherapy Chapter 18 for Malignant Brain Tumors 307 Catherine Flores and Duane A. Mitchell Contents VII Immunotherapeutic Strategies for Brain Tumors 331 Chapter 19 Mitsugu Fujita and Hideho Okada Immunotherapy with Dendritic Cells and Chapter 20 Newcastle Disease Virus in Glioblastoma Multiforme 355 Thomas Neßelhut, Dagmar Marx, Jan Neßelhut and Fred Fändrich Targeted Therapy for Gliomas: Chapter 21 the Oncolytic Virus Applications 375 Zulkifli Mustafa, Hidayah Roslan and Jafri Malin Abdullah Development of a DNA-Based Chapter 22 Vaccine for Treatment of an Intracerebral Tumor 389 Terry Lichtor and Roberta P Glick Gene Therapy of Glioblastoma Multiforme - Chapter 23 Clinical Experience on the Use of Adenoviral Vectors 403 Thomas Wirth and Seppo Ylä-Herttuala Preface Tumors of the central nervous system are extensively complex, not only because of their location, but because of the intricate cellular and molecular mechanisms involved in their pathogenesis. Special emphasis must be given to diagnose these tumors cor- rectly, and to treat them as efficiently, albeit as conservatively as possible, in order to preserve the surrounding healthy tissue. Understanding the molecular mechanisms that give rise to this disease, and how this knowledge can be applied to diagnosis and treatment, has been a research focus for many years. With this in mind, the book is divided into three sections: The first section addresses the tumor models currently available to study brain tumors, new diagnostic methods and the molecular mechanisms that are frequently involved in the pathogenesis of brain tumors. Established and novel therapeutic strategies are described in section two, with a special focus of gene therapy and immunotherapy in section three. The main focus of this book is the gliomas, given their incidence and dismal prognosis, but other brain tumors, including medulloblastoma and brain metastases, are also dis- cussed. Written by experts in brain tumor research and in managing brain tumors, this book provides the most up-to-date information regarding tumor models, clinical diag- nostic methods and therapeutic strategies. The chapters here presented aim in contributing to the understanding of brain tumor pathogenesis, tumor behavior within the cellular niche, and of the new therapeutic methods for managing brain tumors. All topics possess translational potential in the hopes that the health care professional in the field can benefit not only by increasing knowledge, but increasing clinical applicability as well. Sincerely, Dr. Ana Lucia Abujamra Hospital de Clínicas de Porto Alegre Oncologia Pediátrica- Terceiro Leste R. Ramiro Barcelos, 2350 Bairro Rio Branco Porto Alegre, Rio Grande do Sul 90035-903 Brasil [...]... clones, and implanted it into C57BL / 6 × DBA / 2 F2 fertilized eggs Of the 93 fertilized eggs injected with the recombined DNA, 14 of them had offspring Four of the neonatal had brain tumors, which appeared in the underside of the 10 Brain Tumors - Current and Emerging Therapeutic Strategies brain, the thalamus and the posterior fossa and compressed the brain stem Under the light microscope, the brain tumors. .. generations and the biological characteristics of tumors are relatively stable, which play active roles in understanding the tumor development and in preventing tumors However, animal models of brain tumors induced by oncogenic have different cycles and different pathological types Compared to human brain tumors, the induced brain tumors in animals were different in genetics, cell biology and histology... cerebral cortex, white matter, gray matter, ventricles and cerebellum 12 Brain Tumors - Current and Emerging Therapeutic Strategies Fig 3 NC glioma in nude mice, SCID mice transplanted subcutaneously, dexamethasone immunosuppressed Wistar rats and brain transplantation model in Balbc nude mice: the cells in subcutaneous space and in brain grow into large tumors due to unlimited proliferation Intracranial... results, which can be used for monitoring tumor and adjacent structures and 14 Brain Tumors - Current and Emerging Therapeutic Strategies calculating tumor volume But it will take a long imaging time and can not mimic the patient pictures Tumor vessel imaging is part of the tumor imaging Percutaneous transcatheter and intravascular injection of contrast agents, and digital subtraction angiography (DSA) are... the proliferation and migration of glioma cells related closely with host vascular system Considering from the reconstruction of tumor tissue, host's own tissues and cells also play an important role and provide nutrition for the growth of tumor Yang (Yang et al, 2004) and we had inoculated human glioma stem cells non-transfected and 16 Brain Tumors - Current and Emerging Therapeutic Strategies transfected... Nervous System (CNS) or Peripheral Nervous System (PNS), so that 22 Brain Tumors - Current and Emerging Therapeutic Strategies we can not rule out the possible viral etiology of certain types of brain tumors in humans However, at present, numerous studies failed to establish any etiological association between viruses and humans brain tumors (Minn et al, 2002) We now know different animal viruses that... mainly in 26 Brain Tumors - Current and Emerging Therapeutic Strategies the periventricular region, in the subcortical white matter of the cerebral hemispheres, and hippocampus The periventricular tumors usually develop around the lateral ventricles, including the caudate nucleus and corpus callosum Tumors rarely appear localized in the cerebellum In the spinal cord, are normally at cervical and lumbar... mouse brain tumor Although allogeneic grafting of animals’ spontaneous tumors succeeded before, this method had been abandoned because of its poor simulation such as the low incidence, the early stage occult and short survival period of tumor-bearing animals It has been replaced by the development of induced animal brain tumor model The most commonly used cancer- 4 Brain Tumors - Current and Emerging Therapeutic. .. have been used to induce brain tumors Among DNA viruses, both adenoviruses and papovaviruses have been shown to induce brain tumors in animals The RNA viruses causing experimental brain tumors have consistently belonged to the retrovirus group, and have been generally limited to the murine sarcoma virus, the avian sarcoma virus, and the murine sarcoma virus In these models, brain tumors are induced in... of ENU-induced tumors: 1) Gliomas of periventricular subependymal plate, they are divided in turn into ependymomas and ependymoma-oligoastrocytomas 2) Astrocytic and oligodendrocytic tumors 3) Neural tumors of the spinal cord and intracranial nerve ganglia 4) Neuronal-like tumors and 5) Meningeal tumors Gliomas of periventricular subependymal plate are the first tumors are the first tumors that develop, . BRAIN TUMORS - CURRENT AND EMERGING THERAPEUTIC STRATEGIES Edited by Ana Lucia Abujamra Brain Tumors - Current and Emerging Therapeutic Strategies Edited. the Brain Tumors - Current and Emerging Therapeutic Strategies 10 brain, the thalamus and the posterior fossa and compressed the brain stem. Under the light microscope, the brain tumors. Hadziahmetovic and Arnab Chakravarti Part 2 Chemotherapy and Other Therapeutic Strategies 143 Glioblastoma: Current Chemotherapeutic Chapter 9 Status and Need for New Targets and Approaches

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  • 00_preface_ Brain Tumors Current and Emerging Therapeutic Strategies

  • Tumor Models, Molecular Mechanisms and Diagnostics

  • 1_Xenograft Model of Human Brain Tumor

  • 2_Experimental Brain Tumors: Current Concepts

  • 3_Molecular Diagnostics of Brain Tumours by Measuring the 5-Methylcytosine Level in Their DNA

  • 4_The Bevacizumab “Pseudoresponse” in Glioma: Disappointment or Opportunity?

  • 5_The Molecular Mechanism for Differentiation Therapy of Malignant Glioma

  • 6_DNA Double-Strand Breaks Repair and Signaling of Human Gliomas and Normal Brain Cells in Response to Radiation: Potential Impact of the ATM- and BRCA1- Dependent Pathways

  • 7_Glioma Proteomics: Methods and Current Perspective

  • 8_Evolvement of Molecular Biomarkers in Targeted Therapy of Malignant Gliomas

  • Chemotherapy and Other Therapeutic Strategies

  • 9_Glioblastoma: Current Chemotherapeutic Status and Need for New Targets and Approaches

  • 10_Chemotherapy of Medulloblastoma in Children

  • 11_New Therapeutic Strategies for the Treatment of Brain Tumor

  • 12_Transcription Factor Targets as Treatment for Medulloblastoma

  • 13_Novel Therapeutic Venues for Glioblastoma: Novel Rising Preclinical Treatment Opportunities

  • 14_The Molecular Basis of Resistance to the Antiproliferative Effect of EGFR Inhibition in Human Glioblastoma Multiforme Cell Lines

  • 15_Medical Management of Brain Metastases from Lung Cancer

  • Gene Therapy and Immunotherapy

  • 16_Fundamentals of Gene and Viral Therapy for Malignant Gliomas

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