**Meet the editor**

Dr. Anirban Ghosh completed his M.Sc in Zoology from University of Calcutta in 2000 and started his research in the Institute of Post Graduate Medical Education and Research (IPGMER) on brain tumor and glioma immunology. He achieved Junior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India after qualifying the National Eligibility Test

(NET) and completed his Ph.D as Senior Research Fellow in 2007 under the guidance of Prof. Swapna Chaudhuri now at School of Tropical Medicine, Kolkata, India. From 2006 onwards, he is engaged in teaching in Zoology at Panihati Mahavidyalaya and acts as invited faculty in M.Sc and M.Phil courses on Immunology in Calcutta University and West Bengal State University. He is presently involved in research on developmental immunology in brain and acts as reviewer of different journal articles.

Contents

**Preface IX** 

Chapter 1 **Epidemiology of Glioma 3**  Jimmy T. Efird

Chapter 2 **Molecular Etiology of Glioblastomas: Implication of Genomic Profiling** 

> Kimberly Ng, Santosh Kesari, Bob Carter and Clark C. Chen

Chapter 3 **Biological Markers of Recurrence** 

Kerrie L. McDonald

**Part 2 Gliomagenesis 77** 

**From the Cancer Genome Atlas Project 25** 

**and Survival of High-Grade Gliomas: The Role of Hepatocyte Growth Factor 37**  Roberto García-Navarrete, Esperanza García Mendoza,

Alfonso Marhx-Bracho and Julio Sotelo

**Application for Patients Diagnosed with Glioma 49** 

Chapter 4 **Biomarker Discovery, Validation and Clinical** 

Chapter 5 **Genomic Abnormalities in Gliomas 79** 

Chapter 6 **Genetic Diversity of Glioblastoma** 

Aline Custódio and Cacilda Casartelli

Franz-Josef Klinz, Sergej Telentschak, Roland Goldbrunner and Klaus Addicks

Giovanny Pinto, France Yoshioka, Fábio Motta, Renata Canalle, Rommel Burbano, Juan Rey,

**Multiforme: Impact on Future Therapies 103** 

**Part 1 Introduction 1** 

### Contents

#### **Preface XIII**

#### **Part 1 Introduction 1**

	- **Part 2 Gliomagenesis 77**

X Contents


Contents VII

**Part 5 Glioma Model and Culture Systems 343**

**in Glioma Research - Focus on Spheroids 373**  Stine Skov Jensen, Charlotte Aaberg-Jessen, Ida Pind Jakobsen, Simon Kjær Hermansen, Søren Kabell Nissen and Bjarne Winther Kristensen

Susana Bulnes, Harkaitz Bengoetxea, Naiara Ortuzar, Enrike G. Argandoña and José Vicente Lafuente

Bárbara Meléndez, Ainoha García-Claver, Yolanda Ruano, Yolanda Campos-Martín, Ángel Rodríguez de Lope, Elisa Pérez-Magán, Pilar Mur, Sofía Torres, Mar Lorente,

**Drugs by the Action on Neuroepithelial Tumors 465**

Chapter 19 **Copy Number Alterations in Glioma Cell Lines 429** 

Guillermo Velasco and Manuela Mollejo

**Glutamate Release in Glioma 451** Robert Ungard and Gurmit Singh

Chapter 21 **Improving the Efficiency of Chemotherapeutic**

and Vladimir N. Kalunov

Vladimir A. Kulchitsky, Michael V. Talabaev, Alexander N. Chernov, Dmitry G. Grigoriev, Yuri E. Demidchik, Dmitry G. Shcharbin, Nicholas M. Chekan, Vladimir V.Kazbanov, Tatiana A. Gurinovich, Anatoly I. Gordienko Elena K. Sergeeva, Vladimir I. Potkin

**Links Between Glioma Stem Cells and Angiogenesis 405**

Chapter 16 **Animal Models of Glioma 345** 

Chapter 17 **Three-Dimensional In Vitro Models**

Chapter 18 **Endogenous Experimental Glioma Model,**

Lijun Sun

**Part 6 Miscellaneous 449** 

Chapter 20 **Oxidative Stress and** 

#### **Part 5 Glioma Model and Culture Systems 343**

Chapter 16 **Animal Models of Glioma 345**  Lijun Sun

VI Contents

Chapter 7 **Role of the Centrosomal** 

Chapter 8 **New Insight on the Role of Transient** 

Chapter 10 **Bone Marrow-Derived Cells Support** 

**Part 3 Glioma Progression 223** 

and Maribel Vazquez

Chapter 13 **The Role of Chemoattractant** 

**Part 4 Glioma Immunology 303** 

Chapter 14 **Immune Connection in**

Anirban Ghosh

Chapter 15 **Direct Antitumor Activity of** 

and Elena Chernykh

Chapter 12 **Extracellular Matrix** 

**Receptor Potential (TRP) Channels in Driven Gliomagenesis Pathways 163** Giorgio Santoni, Maria Beatrice Morelli,

**MARK4 Protein in Gliomagenesis 131**  Ivana Magnani, Chiara Novielli and Lidia Larizza

Chapter 9 **The Role of Stem Cells in the Glioma Growth 189**  Sergio Garcia, Vinicius Kannen and Luciano Neder

Jeffrey P. Greenfield, William S. Cobb,

Chapter 11 **Migration and Invasion of Brain Tumors 225**  Richard A. Able, Jr., Veronica Dudu

Keqiang Chen, Wanghua Gong,

Consuelo Amantini, Matteo Santoni and Massimo Nabissi

**Malignant Transformation of Low-Grade Glioma 201**

Caitlin E. Hoffman, Xueying Chen, Prajwal Rajappa, Chioma Ihunnah, Yujie Huang and David Lyden

**Microenvironment in Glioma Progression 257** Marzenna Wiranowska and Mumtaz V. Rojiani

**Receptors in the Progression of Glioma 285** Xiao-hong Yao,Ying Liu, Jian Huang, Ye Zhou,

Mingyong Liu, Xiu-wu Bian and Ji Ming Wang

**Glioma: Fiction, Fact and Option 305** 

**Interferon-Induced Dendritic Cells of Healthy** 

Olga Leplina, Tamara Tyrinova, Marina Tikhonova, Ekaterina Shevela, Vyacheslav Stupak, Sergey Mishinov, Ivan Pendyurin, Mikhail Sadovoy, Alexander Ostanin

**Donors and Patients with Primary Brain Tumors 325** 


#### **Part 6 Miscellaneous 449**


Preface

pertinent as the problem is still unmanageable.

glioma is a much needed obligation.

'Glioma' is the term that hits the human psyche with absolute despair. All our efforts to cease glioma limits it to an average of maximum 18 – 21 months of life after diagnosis and notably, this life expectancy altered marginally despite constant research of last two decades. When I was working for my Ph.D thesis and allied projects, I had to encounter a number of glioma patients and patient parties. Many of them I found first diagnosed, started treatment with surgery, radiation and chemotherapy in various combinations and after few months they disappeared. Some of them reappeared within a year with recurrence and others never turned. Rarely, a trivial number of patients were traced after 3 or 5 years. Many of those gloomy faces, their eager questions, earnest appeals, anxiety are pertinent globally and the fate varies negligibly with economic or developmental status of the society. Such an issue always provoked me to know and contribute something which is larger than my focused thesis work. As a considerable section of my work was at the interface of medical practitioners and basic scientists, I was lucky enough to observe the pattern of proceedings and attitude of both the fields at least partially. Strangely, I also sensed a fissure between these two interdependent fields. Along with, the common question of common mass that "What is medical science exactly doing against it?" is always

To face these questions and find their suitable answers, at least on the basis of current knowledge, a multitude of information from different facets of glioma research is needed to be analyzed. The fundamental biological nature of the problem, extent of its graveness as a disease, diagnostic efforts and shortcomings, level of efficiency and inefficiency of present medical interventions and therapeutics, current trends of medical research to combat glioma etc has to be scrutinized with extreme sincerity. This mammoth gathering of facts is possible if only the experts of different areas can share their expertise at the same platform. I also feel that, sometimes the gaps among medical scientists and doctors are due to the inability to build up an overview of this vast expanse as well as shortfall of awareness about this rapidly developing arena by either side. Therefore, a podium to cater the diverse problems and achievements in

In this situation, I got the offer to be involved in the effort of the book project "Glioma" by the present publisher. That was a simple but superb coincidence of my

### Preface

'Glioma' is the term that hits the human psyche with absolute despair. All our efforts to cease glioma limits it to an average of maximum 18 – 21 months of life after diagnosis and notably, this life expectancy altered marginally despite constant research of last two decades. When I was working for my Ph.D thesis and allied projects, I had to encounter a number of glioma patients and patient parties. Many of them I found first diagnosed, started treatment with surgery, radiation and chemotherapy in various combinations and after few months they disappeared. Some of them reappeared within a year with recurrence and others never turned. Rarely, a trivial number of patients were traced after 3 or 5 years. Many of those gloomy faces, their eager questions, earnest appeals, anxiety are pertinent globally and the fate varies negligibly with economic or developmental status of the society. Such an issue always provoked me to know and contribute something which is larger than my focused thesis work. As a considerable section of my work was at the interface of medical practitioners and basic scientists, I was lucky enough to observe the pattern of proceedings and attitude of both the fields at least partially. Strangely, I also sensed a fissure between these two interdependent fields. Along with, the common question of common mass that "What is medical science exactly doing against it?" is always pertinent as the problem is still unmanageable.

To face these questions and find their suitable answers, at least on the basis of current knowledge, a multitude of information from different facets of glioma research is needed to be analyzed. The fundamental biological nature of the problem, extent of its graveness as a disease, diagnostic efforts and shortcomings, level of efficiency and inefficiency of present medical interventions and therapeutics, current trends of medical research to combat glioma etc has to be scrutinized with extreme sincerity. This mammoth gathering of facts is possible if only the experts of different areas can share their expertise at the same platform. I also feel that, sometimes the gaps among medical scientists and doctors are due to the inability to build up an overview of this vast expanse as well as shortfall of awareness about this rapidly developing arena by either side. Therefore, a podium to cater the diverse problems and achievements in glioma is a much needed obligation.

In this situation, I got the offer to be involved in the effort of the book project "Glioma" by the present publisher. That was a simple but superb coincidence of my

#### X Preface

thoughts and their offer. As the subject editor of the project I had to evaluate near about 90 chapter proposals submitted from nearly every corners of the world. These worldwide contributions were then categorized and distributed into three volumes. The approach was initially to understand glioma and its biology with experimental approaches to explore the basics of the disease (vol. 1); next to share the knowledge about present diagnostic and prognostic approaches as well as current developments in modern therapeutics (vol. 2); and finally, to accustom the readers about the cutting edge basic to experimental developments and trends of biomedical research to restrict glioma (vol. 3). As the book editor I have chosen to edit the first volume, partially because of my personal background as a biomedical researcher from basic life-sciences and mostly the chapters arranged in this volume are aimed to find out the basic nature of the disease. Next two volumes are much oriented with facts that are directly relevant to medical practice to deal glioma.

Preface XI

**Dr. Anirban Ghosh** 

India

Assistant Professor and Head Department of Zoology

Panihati Mahavidyalaya (West Bengal State University), Kolkata,

Kolkata, India; Prof. Ingo Bechmann, Institut für Anatomie der Universität Leipzig, Germany; Prof. Helmut Kettenmann, Max-Delbrück-Center for Molecular Medicine, Germany; Prof. Serge Rivest, Laval University, Québec, Canada and many others who helped or inspired me anyways in my recent research and activities. I am appreciative to my graduate students Nabanita Mukherjee and Payel Ghosh with other colleagues and students of my institute who cooperate me in this journey. The continuous support of the Principle of my institute Dr. Sanjoy K Ghosh and the authority made this process easier for me. Finally and most importantly, without the unparallel motivation and bearing of my wife Malabika and little son Upamanyu this effort would have never been achieved. I am dedicating this endeavor to them and all who

are fighting to control glioma.

The name of the first volume "Glioma – Exploring Its Biology and Practical Relevance" is indicative of its content. This introducing first volume contains 21 chapters basically intended to explore glioma biology and discussing the experimental model systems for the purpose. Under the section "Introduction" first two chapters discuss general glioma epidemiology and etiology and the next two shows the relevance of biomarkers in glioma. Following six chapters under section "Gliomagenesis" deals with different genetic, molecular and cell biological aspects of origin and development of glioma. The next section "Glioma progression" contains three chapters which discusses about glioma invasiveness which is followed by the section "Glioma Immunology" that contains two chapters. A stretch of four chapters have been clustered next in the section "Glioma Model and Culture Systems" which are devoted to present different facets of experimental models and cell culture methods that are now utilized in glioma research. In the final section "Miscellaneous" the penultimate chapter deals with oxidative stress in glioma and the final chapter of this volume talks about a special experimental approach of glioma therapeutics. It is hoped that the present volume will provide supportive and relevant awareness and understanding on the fundamental advances of the subject to the professionals from any sphere interested about glioma and deliver the momentum to the audience for the following volumes of 'Glioma'.

In this enormous task I got support from many of which only few names can be mentioned here. First and foremost, I extend my thanks to the 'InTech Open Access Publisher' for offering me the exciting opportunity to act as the subject editor of the 'Glioma' project, book editor of the present volume as well as chapter author. I enjoyed my involvement in a forum where participants are the biomedical researchers sharing their experiences and knowledge from every continents except Antarctica. To shape this gigantic effort Ms. Ana Panter and Ms. Petra Ninadic extended their continuous cooperation by building the liaison between editors, authors and the publisher. I express my heartiest thanks to them in spite of failing many 'deadline's set by them, and still getting their nonstop support to make this teamwork a success. I also express my gratitude to Prof. Swapna Chaudhuri, School of Tropical Medicine, Kolkata, India; Prof. Ingo Bechmann, Institut für Anatomie der Universität Leipzig, Germany; Prof. Helmut Kettenmann, Max-Delbrück-Center for Molecular Medicine, Germany; Prof. Serge Rivest, Laval University, Québec, Canada and many others who helped or inspired me anyways in my recent research and activities. I am appreciative to my graduate students Nabanita Mukherjee and Payel Ghosh with other colleagues and students of my institute who cooperate me in this journey. The continuous support of the Principle of my institute Dr. Sanjoy K Ghosh and the authority made this process easier for me. Finally and most importantly, without the unparallel motivation and bearing of my wife Malabika and little son Upamanyu this effort would have never been achieved. I am dedicating this endeavor to them and all who are fighting to control glioma.

X Preface

thoughts and their offer. As the subject editor of the project I had to evaluate near about 90 chapter proposals submitted from nearly every corners of the world. These worldwide contributions were then categorized and distributed into three volumes. The approach was initially to understand glioma and its biology with experimental approaches to explore the basics of the disease (vol. 1); next to share the knowledge about present diagnostic and prognostic approaches as well as current developments in modern therapeutics (vol. 2); and finally, to accustom the readers about the cutting edge basic to experimental developments and trends of biomedical research to restrict glioma (vol. 3). As the book editor I have chosen to edit the first volume, partially because of my personal background as a biomedical researcher from basic life-sciences and mostly the chapters arranged in this volume are aimed to find out the basic nature of the disease. Next two volumes are much oriented with facts that are directly

The name of the first volume "Glioma – Exploring Its Biology and Practical Relevance" is indicative of its content. This introducing first volume contains 21 chapters basically intended to explore glioma biology and discussing the experimental model systems for the purpose. Under the section "Introduction" first two chapters discuss general glioma epidemiology and etiology and the next two shows the relevance of biomarkers in glioma. Following six chapters under section "Gliomagenesis" deals with different genetic, molecular and cell biological aspects of origin and development of glioma. The next section "Glioma progression" contains three chapters which discusses about glioma invasiveness which is followed by the section "Glioma Immunology" that contains two chapters. A stretch of four chapters have been clustered next in the section "Glioma Model and Culture Systems" which are devoted to present different facets of experimental models and cell culture methods that are now utilized in glioma research. In the final section "Miscellaneous" the penultimate chapter deals with oxidative stress in glioma and the final chapter of this volume talks about a special experimental approach of glioma therapeutics. It is hoped that the present volume will provide supportive and relevant awareness and understanding on the fundamental advances of the subject to the professionals from any sphere interested about glioma and deliver the

In this enormous task I got support from many of which only few names can be mentioned here. First and foremost, I extend my thanks to the 'InTech Open Access Publisher' for offering me the exciting opportunity to act as the subject editor of the 'Glioma' project, book editor of the present volume as well as chapter author. I enjoyed my involvement in a forum where participants are the biomedical researchers sharing their experiences and knowledge from every continents except Antarctica. To shape this gigantic effort Ms. Ana Panter and Ms. Petra Ninadic extended their continuous cooperation by building the liaison between editors, authors and the publisher. I express my heartiest thanks to them in spite of failing many 'deadline's set by them, and still getting their nonstop support to make this teamwork a success. I also express my gratitude to Prof. Swapna Chaudhuri, School of Tropical Medicine,

momentum to the audience for the following volumes of 'Glioma'.

relevant to medical practice to deal glioma.

#### **Dr. Anirban Ghosh**

Assistant Professor and Head Department of Zoology Panihati Mahavidyalaya (West Bengal State University), Kolkata, India

**Part 1** 

**Introduction** 
