MOLECULAR TARGETS OF CNS TUMORS Edited by Miklos Garami Molecular Targets of CNS Tumors Edited by Miklos Garami 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 Sebastian Kaulitzki, 2011. 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 Molecular Targets of CNS Tumors, Edited by Miklos Garami p. cm. ISBN 978-953-307-736-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface XI Part 1 CNS Tumors - Regulatory Components and Effector Pathways 1 Chapter 1 Genetic and Immunology of Brain Tumors 3 Sahika Liva Cengiz and Aynur Emine Cicekcibasi Chapter 2 Genetic Instability in Paediatric and Adult Brain Tumours 19 Marta Viana-Pereira, Chris Jones and Rui M. Reis Chapter 3 Brain Tumor Exosomes and Microvesicles: Pleiotropic Effects from Tiny Cellular Surrogates 43 Michael W Graner Chapter 4 Recurrent Malignant Primary Brain Tumor: the Pathophysiology and Management 79 Victor Tse and Harish Babu Part 2 Sox Transcription Factors - CNS Tumors 97 Chapter 5 The Role of Sox Transcription Factors in Brain Tumourigenesis 99 Maria Ferletta Part 3 Endoglin: Role of Angiogenesis - CNS Tumors 125 Chapter 6 Angiogenesis of Primary Brain Tumors: The Role of Endoglin (CD105) 127 Yasuo Sugita Part 4 AQPs Proteins- CNS Tumors 141 Chapter 7 The Role of Aquaporines in Brain Tumors 143 Tatsuo Sawada VI Contents Part 5 Gliomas - Regulatory Components and Effector Pathways 149 Chapter 8 Glioma Stem Cells 151 Kouichi Tabu, Tetsuya Taga and Shinya Tanaka Chapter 9 Molecular Hallmarks of Gliomas 177 Marta Pojo and Bruno Marques Costa Chapter 10 Integrated Network Analysis of Genetic and Epigenetic Factors in Glioblastoma Multiform 201 Hua Dong and MomiaoXiong Chapter 11 The Neural Extracellular Matrix, Cell Adhesion Molecules and Proteolysis in Glioma Invasion and Tumorigenicity 239 Chrissa A. Dwyer and Russell T. Matthews Chapter 12 Portrait of Transcriptional Expression Profiles Displayed by Different Glioblastoma Cell Lines 265 Paulo R. D. V. Godoy, Stephano S. Mello, Daniele A. Magalhães, Flavia S. Donaires, Ana P. Lima-Montaldi, Patricia Nicolucci, Eduardo A. Donadi, Geraldo A. S. Passos and Elza T. Sakamoto-Hojo Chapter 13 Genetics and Biology of Glioblastoma Multiforme 289 Anália Carmo, Inês Crespo and Maria Celeste Lopes Chapter 14 Chemokines in Glioma Progression 315 Marco Locatelli and Alberto Mantovani Chapter 15 Biomarkers of Glioma 325 Shufang Liang and Guobo Shen Chapter 16 MicroRNA (miRNA) Regulation in Glioma: Implications in Development, Progression, Grading, Prognosis and Therapy 343 Kumaravel Somasundaram, Soumya Alige Mahabala Rao and Zahid Nawaz Chapter 17 MicroRNA in Human Gliomas 363 Alfredo Conti, Lucia Merlo, Domenico La Torre and M’Hammed Aguennouz Part 6 WNT/β – Catenin / TCF Signaling Pathway - Gliomas 377 Chapter 18 Gliomas: Role of Wnt/ -Catenin/Tcf Signaling Pathway 379 Gangadhara Reddy Sareddy and Phanithi Prakash Babu Contents VII Part 7 IGFBP2 - Gliomas 393 Chapter 19 Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma 395 Tsuyoshi Fukushima and Hiroaki Kataoka Part 8 IDHs Mutations- Gliomas 411 Chapter 20 The Role of Isocitrate Dehydrogenase Mutations in Glioma Brain Tumors 413 Chi-Ming Chang, Kaiming Xu and Hui-Kuo G. Shu Part 9 BORIS as a Transcription Factor - Gliomas 437 Chapter 21 The Expression of BORIS Protein in a Newly Established Primary Glioma Cell Culture Line 439 Siti Zawani Mohd Ramli, Shaharum Shamsuddin, Nik Norliza Hassan, Azmi Alias, Mohd Saffari Mohd Haspani and Jafri Abdullah Part 10 miR-221/222 Cluster - Gliomas 459 Chapter 22 MiR-221/222 Promote the Growth of Malignant Glioma Cells by Regulating Its Target Genes 461 Zhang Chunzhi, Jiang Tao, Wang Jinhuan, Cheng Jinquan, Pu Peiyu and Kang Chunsheng Part 11 EGFR /EGFRvIII Amplification - Glioblastoma 483 Chapter 23 Primary Glioblastoma with Different Patterns of EGFR Amplification and the Relationship with Gene Expression Profile 485 Concha Lopez-Gines, Rosario Gil-Benso, Daniel Monleon, Jose Gonzalez-Darder and Miguel Cerda-Nicolas Chapter 24 Nuclear Signaling of EGFR and EGFRvIII in Glioblastoma 515 Anupama E. Gururaj, Oliver Bögler and Khatri Latha Part 12 AP-1 Transcription Factor - Glioblastoma 537 Chapter 25 Ap 1 in Glioblastomas 539 Densie Smith and Bruce Bejcek Part 13 Musashi1 RNA-Binding Protein - Glioblastoma 547 Chapter 26 The Musashi1 RNA-Binding Protein: A Critical Regulator in Glioblastoma 549 Dat T. Vo, Devraj Sandhu, Jonathan A. Gelfond and Luiz O. Penalva VIII Contents Part 14 GSK3b Acts Like Tumor Promoter - GBM 565 Chapter 27 The Pivotal Roles of GSK3 in Glioma Biology 567 Mitsutoshi Nakada, Toshinari Minamoto, Ilya V. Pyko, Yutaka Hayashi and Jun-ichiro Hamada Part 15 Astrocytomas - Regulatory Components and Effector Pathways 591 Chapter 28 The Role of Matrix Metalloproteinases a nd Tissue Inhibitors of Metalloproteinases in the Progression of Astrocytomas 593 Fábio Motta, Renata Canalle, France Yoshioka, Giovanny Pinto, Lúcia Harada, Carlotti Jurnior, Elvis Valera, Carlos Scrideli and Luiz Tone Part 16 Medulloblastoma - Regulatory Components and Effector Pathways 621 Chapter 29 Medulloblastoma – Genetic Alterations 623 Esther Manor and Lipa Bodner Part 17 HGF/cMET Signaling Pathway - MBL 639 Chapter 30 The Role of HGF/c-Met Pathway Signaling in Human Medulloblastoma 641 Claudia Faria, Christian Smith and James Rutka Part 18 The Importance of Redox Regulation of Malignant Cell Survival 661 Chapter 31 The Impact of Redox Balance in Brain Tumors 663 Pinar Atukeren [...]... description of regulatory components and effector pathways of selected CNS tumors This book highlights some importance aspects of selected CNS tumors The editor would like to acknowledge the contribution of the authors and the team of the Publishing Process Management at InTech - Open Access Publisher Dr med habil Miklos Garami, MD., MSc PhD Associate Professor, Semmelweis University, Hungary Part 1 CNS Tumors. .. system (CNS) immune function, a highly adapted system of immune surveillance presents, and effective immune responses can occur in the 4 Molecular Targets of CNS Tumors CNS Function of both the complement system (Bernheimer et al., 1988) and the antigenantibody system, including functional B cells (Aloisi et al., 1999; Sandberg-Wollheim et al., 1986) have been found within the CNS In the case of CNS pathologies... approach for the treatment of malignant brain tumors 2 Genetic and immunology of brain tumors Brain tumors are one of the leading cause of cancer mortality and remain difficult to cure despite advances in surgery and adjuvant therapy Recent studies are focused on the molecular and cellular analysis of the bulk tumor mass Glioma is the most common and mortal type of brain tumors (Kleihues et al., 2002)... gliomas The estimated annual incidence rate of gliomas in the United States is 6.0 per 100,000 people Overall, the broad category of gliomas accounts for 36% of all CNS tumours and 81% of malignant lesions In young adults (20-34 years), gliomas represent 39% of all CNS tumours and 86% of malignant tumours; in adolescents (15-19 years), 45% of all CNS tumours and 81% of malignant; whereas in 21 Genetic Instability... healthy cells as well as brain tumors 8 4 5 6 7 Molecular Targets of CNS Tumors The new gene might also insert into the wrong location in the DNA, thus leading to harmful mutations of the DNA and triggering unwanted reaction by the immune system The transferred genes can also be overexpressed by producing a lot of missing proteins Finally, inflammation of the lining of the brain or infection can occur... the treatment of malignant brain pediatric and adult tumors These agents are generally well tolerated but have demonstrated only modest activity This book tries to cover the complexity of the rapidly developing area of targeted therapies in the field of Central Nervous System (CNS) tumors Brain tumors present a continuous challenge to the physicians regardless of the patients’ age The goal of this book... regulation of transcription (Nigg, 2005) During the last decade, the use of genome-scale profiling techniques to identify the key genetic alterations underlying different tumour types allowed fundamental findings about the drivers of oncogenesis, providing the rationale for specific targeted therapies in these malignancies The first studies 24 Molecular Targets of CNS Tumors using large-scale genome profiling... less developed regions (2.3 per 100,000 people) (Ferlay et al., 2008) The median age of diagnosis for all primary CNS tumours is 57 years, however the histology-specific median age ranges from 9 to 70 years ( Central Brain Tumor Registry of the United States [CBTRUS], 2010) 20 Molecular Targets of CNS Tumors In children, CNS tumours are the second most frequent malignancy after leukaemia and are therefore... Receptor Aggregation and Activation of Caspases Proceedings of the National Academy of Sciences of the United States of America, Vol.96, No.15, (July 1999), pp 8699-8704, ISSN 0027-8424 Bernheimer, H.; Lassmann, H & Suchanek, G (1988) Dynamics of IgG1, IgA1, and IgM1 Plasma Cells in the Central Nervous System of Guinea Pigs with Chronic Relapsing Genetic and Immunology of Brain Tumors 11 Experimental Allergic... Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage ColonyStimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor 12 Molecular Targets of CNS Tumors Immunity Proceedings of the National Academy of Sciences of the United States of America, Vol.90, No.8, (April 1993), pp 3539-3543, ISSN 0027-8424 Ekstrand, A.J.; James, C.D.; Cavenee, W.K.; Seliger, B.; Pettersson, R.F & Collins, . MOLECULAR TARGETS OF CNS TUMORS Edited by Miklos Garami Molecular Targets of CNS Tumors Edited by Miklos Garami Published. - CNS Tumors 97 Chapter 5 The Role of Sox Transcription Factors in Brain Tumourigenesis 99 Maria Ferletta Part 3 Endoglin: Role of Angiogenesis - CNS Tumors 125 Chapter 6 Angiogenesis of. complexity of the rapidly developing area of targeted therapies in the field of Central Nervous System (CNS) tumors. Brain tumors present a continuous challenge to the physicians regardless of the