Human Brain and Spinal Cord Tumors: From Bench to Bedside. Volume 1 Neuroimmunology and Neurogenetics

Brain tumors comprise about 5–9% of all human neoplasms; and interestingly the central nervous system (CNS) neoplasms are ranked among the most prevalent neoplasms of childhood as well. Besides to the morphologic and histopathologic characteristics, and as each pathologic states first starts with molecular alterations, each tumor may have its own story in the matter of activating tumorigenesis pathways and having specific molecular characteristics. Importantly, the molecular classification of tumors has been highly considered in the past few decades for taking the most appropriate therapeutic approach. On the other hand, the tumors shall have tumor-scape mechanisms preventing the immunologic system to eliminate its invasion. The failure of innate and acquired immune system to defeat tumorigenesis mechanisms would consequently result in tumor development. Interestingly, the neuro-immunologic mechanism plays a role in development of psychiatric manifestations of brain tumors as well. Taking all these to account, the different arms of innate immunity, acquired immunity, and genetics have been approached to defeat development and/or progression of such tumors. Accordingly, the activation immunotherapeutic approaches focus on activating or strengthening the anti-tumor immunologic pathways in order to assist the weakened immune system to defeat the tumor (such as Dendritic cell vaccination, DNA vaccines, peptide vaccines, viral vector-based vaccines, monoclonal antibodies, and CAR T-cell therapy). In addition to immunologic components of brain and spinal cord tumors, numerous genes and genetic pathways have been recognized to take part in tumorigenesis. Taking these non-immune genetic pathways to account, some other therapeutic approaches such as stem cell therapy and gene therapy have been developed in the new era of cancer treatment. Moreover, and besides the biologic and medical aspects of these tumors, different physical/mathematical models have been proposed to either explain or predict tumor behavior. Such models would be advantageous in developing new therapeutic modalities in pre-clinical stages and enter new eras in cancer treatment. 

The first book of Human Brain and Spinal Cord Tumors, Neuro-immunology and Neuro-genetics, will mainly discuss the neuro-immunology and neurogenetic pathways associated with development of brain and spinal cord tumor. After a short introduction chapter, this book will focus on the role of innate and acquired immunity on development of these tumors and then the immunotherapeutic approaches to defeat these tumorigenesis mechanisms. This book will then focus on genetic aspects of brain and spinal cord tumors and bioinformatics models to describe the behavioral patterns of these tumors, as well as associated therapeutic approaches such as stem cell therapy and gene therapy. This volume of book could be useful for experts in basic sciences, mainly geneticists and immunologists, and also physicians of different specialties, mainly neurosurgeons, neurologists, neuropathologists and neuroradiologists.

Volume 1: Human Brain and Spinal Cord Tumors: Neuro-immunology and Neuro-genetics

Chaptre 1.      Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction

Arad Iranmehr, Mohamad Namvar, Nima Rezaei, Sara Hanaei

1.2.    Gliomas, Glioneuronal Tumors, and Neuronal Tumors

1.3.    Choroid Plexus Tumors

1.4.    Embryonal Tumors

1.5.    Pineal Tumors

1.6.    Meningiomas

1.7.    Hemangioblastomas

1.8.    Chondro-osseous Tumors

1.9.    Primary CNS Lymphomas (PCNSL)

1.10.   Germ-Cell Tumors (GCT)

1.11.   Sellar-Region Tumors

1.13.   The Spine and Spinal Cord Tumors

1.14.   CNS Tumors in Association with Other Diseases or Syndromes

1.15.   Conclusion

Chaptre 2.      Epidemiology of Brain and Spinal Cord Tumors

Parnian Shobeiri, Homa Seyedmirzaei, Amirali Kalantari, Esmaeil Mohammadi, Nima Rezaei, Sara Hanaei

2.1.    Introduction

2.2.    Descriptive Epidemiology

2.3.    Confirmed Risk Factors for CNS Tumors

2.4.    Potential Risk Factors for CNS Tumors

2.5.    The Epidemiology of Histological Variants of Primary Brain and Spinal Cord Tumors

2.6.    Anatomical Variants of Primary Brain and Spinal Cord Tumors

2.7.    Syndromes Associated with Central Nervous System Tumors

2.8.    Familial Associations of Brain Tumors

2.9.    Summary, Clinical Applications, and Directions for Future Research

Chaptre 3.      The Role of Neuro-inflammation and Innate Immunity in Pathophysiology of Brain and Spinal Cord Tumors

Giovanna Casili, Irene Paterniti, Michela Campolo, Emanuela Esposito and Salvatore Cuzzocrea

3.1.    Introduction

3.2.    General Characteristics of Brain and Spinal Cord Tumors

3.3.    Gliomas: Meeting Point Between Brain and Spinal Cord Tumors

3.4.    The Role of Neuroinflammation in Gliomas

3.5.    Innate Immunity System Cells and Gliomas: Friend or Foe?

3.7.    Conclusions

Chaptre 4.      The Role of Cellular Immunity and Adaptive Immunity in Pathophysiology of Brain and Spinal Cord Tumors

Angelique Sao Mai Sy Tay, Keith L. Black, John S. Yu

4.1.    Introduction

4.2.    Brief Review of Innate and Adaptive Immunity

4.3.    Immunity in Patients with Malignant Glioma

4.4.    Immunotherapy in Intracranial Gliomas

4.5.    Spinal Cord Tumors

4.6.    Conclusion

Chaptre 5.      Immunotherapy as a New Therapeutic Approach for Brain and Spinal Cord Tumors

Ravi Medikonda, Ayush Pant, Michael Lim

5.1.    Introduction

5.2.    Non-Specific Immunotherapy

5.3.    Specific Active Immunotherapy: Cancer Vaccines

5.4.    Specific Passive Immunotherapy

5.5.    Conclusion

Chaptre 6.      Cell of Origin of Brain and Spinal Cord Tumors

Alice Laurenge, Emmanuelle Huillard, Franck Bielle, Ahmed Idbaih

6.1.    Introduction

6.2.    Diffuse Gliomas

6.3.    Meningioma

6.4.    Medulloblastoma

6.5.    Ependymoma

6.6.    Pilocytic astrocytoma

6.7.    Chordoid Glioma

6.8.    Atypical Teratoid/Rhabdoid Tumor (AT/RT)

6.9.    Germ Cell Tumors

6.10.   Primary Central Nervous System Lymphoma (PCNSL)

6.11.   Conclusion

Chaptre 7.      The Role of Bioinformatics and Imaging Models in Tumorigenesis and Treatment Response of Brain and Spinal Cord Neoplasms

Pooja Verma, Ravi Shanker, Vinal Patel, and Mahua Bhattacharya

7.1.    Introduction

7.2.    Key-related Research

7.3.    Background

7.4.    Analysis

7.5.    Methodology

7.6.    Experiment Design and Results

7.7.    Conclusion

Chaptre 8.      The Role of Epigenetics in Brain and Spinal Cord Tumors

Sung-Hye Park*

8.1.    Introduction

8.2.    What Is the Epigenome?

8.3.    Three Types of Genes in The Epigenetics of Cancer

8.4.    Histone Methylation in Brain Tumors

8.5.    Relevance to Cancer Stem Cells

8.6.    Alterations in Histone Modifications in Glioma

8.7.    CpG Islands Hypermethylation

8.8.    Epigenetic Features of Human Telomeres

8.9.    Methylation Profile of CNS Tumors

8.10.   Epigenetic Therapies for Glioma

8.12.   Conclusion

Chaptre 9.      Stem Cells and Targeted Gene Therapy in Brain and Spinal Cord Tumors

Ahmad Pour-Rashidi, Esmaeil Mohammadi, Nima Rezaei, Sara Hanaei

9.1.    Introduction

9.2.    Neurogenesis

9.3.    Mechanism

9.4.    Therapeutic Approaches

9.5.    Gene-editing Therapy

9.6.    Conclusion

Chaptre 10.     Nutrition and Diet: A Double-Edged Sword in Development and Treatment of Brain Tumors

Shaghayegh Sadeghmousavi, Nima Rezaei, Sara Hanaei

10.1.   Introduction

10.2.   Carcinogens

10.3.   Protective Nutrients 

10.4.   Conclusion

Chaptre 11.     The Role of Nanotechnology in Brain Tumors

Maria Caffo, Gerardo Caruso, Antonello Curcio, Roberta Laera, Concetta Crisafulli, Elena Fazzari, Marcello Passalacqua, Antonino Germanò

11.2.   Blood Brain Barrier

11.3.   Nanoparticles Drug Delivery

11.4.   Nanoparticles in Cerebral Gliomas

11.5.   Conclusion

Chaptre 12.     The Role of Nanotechnology in Spinal Cord Tumors

Maria Caffo, Gerardo Caruso, Roberta Laera, Antonello Curcio, Fabio Cacciola, Emanuela Esposito, Antonino Germanò

12.2.   Classification of Spinal Cord Tumors

12.3.   Nanomedicine

12.4.   Nanoparticles

12.5.   Nanoparticles

Prof. Nima Rezaei entered the TUMS School of Medicine in 1995. He received his M.D. degree in 2002 and further studied Molecular and Genetic Medicine, in the School of Medicine and Biomedical Sciences, The University of Sheffield, UK and further received his Ph.D. in Clinical Immunology and Human Genetics there. He received a short-term fellowship in Clinical Immunology and Bone Marrow Transplantation in Pediatric Immunology and Bone Marrow Transplant Unit for SCID and Related Disorders, Newcastle, UK, awarded by the ESID (European Society of Immunodeficiency).

Professor Rezaei is now the Full Professor of Immunology and Vice Dean of Research and Technologies, School of Medicine, Tehran University of Medical Sciences, and the co-founder and Head of the Research Center for Immunodeficiencies. He is also the Founding President of Universal Scientific Education and Research Network (USERN). Prof. Rezaei has already been the Director of more than 100 research projects and has designed and participated in several international collaborative projects. Prof. Rezaei is the editor, editorial assistant, or editorial board member of more than 40 international journals. He has edited more than 50 international books, has presented more than 500 lectures/posters in congresses/meetings, and has published more than 1,100 scientific papers in the international journals.

Dr. Sara Hanaei started medicine at TUMS in 2010 and started a master of public health (MPH) in 2014. She graduated with MD-MPH in 2018. She also received TUMS Research Diploma (TUMS-RD) in a 2-year study period from 2013-2015. She was a research assistant at Research Center for Immunodeficiencies (RCID) from 2018-2021 and further continued neurosurgery as a clinical specialty at TUMS in 2021. She has experience in teaching research skills to students.

Medical research was one of her greatest interests since the beginning of her academic education, especially in the fields of Neurosurgery and Immunology, therefore, she started research in those fields. Over the past decade, she contributed to different research projects, books, and other research activities including instructing research workshops in statistics, systematic reviews, and meta-analysis. She got involved in executive tasks and developed some executive skills through membership in the Universal Scientific Education and Research Network (USERN), where she experienced organizing scientific events, congresses, festivals, scoring, rankings, etc.