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

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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.


Author(s): Nima Rezaei, Sara Hanaei
Series: Advances in Experimental Medicine and Biology, 1394
Publisher: Springer
Year: 2023

Language: English
Pages: 243
City: Cham

Foreword to the Book
Preface to the Book
Contents
Contributors
1 Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction
Abstract
1.1 Introduction
1.2 Gliomas, Glioneuronal Tumors, and Neuronal Tumors
1.2.1 Adult-Type Diffuse Gliomas
1.2.1.1 Diffuse Astrocytoma
1.2.1.2 Oligodendroglioma
1.2.1.3 Glioblastoma
1.2.2 Pediatric-Type Diffuse Low-Grade Gliomas
1.2.3 Pediatric-Type Diffuse High-Grade Gliomas
1.2.4 Circumscribed Astrocytic Gliomas
1.2.4.1 Pilocytic Astrocytoma (PA)
1.2.4.2 Pleomorphic Xanthoastrocytoma (PXA)
1.2.4.3 Subependymal Giant Cell Astrocytoma (SEGA)
1.2.4.4 Chordoid Glioma (CG)
1.2.4.5 Astroblastoma
1.2.5 Glioneuronal and Neuronal Tumors
1.2.5.1 Ganglioglioma
1.2.5.2 Desmoplastic Infantile Astrocytoma (DIA) and Desmoplastic Infantile Ganglioglioma (DIG)
1.2.5.3 Gangliocytoma
1.2.5.4 Central Neurocytoma
1.2.6 Ependymal Tumors
1.3 Choroid Plexus Tumors
1.4 Embryonal Tumors
1.4.1 Medulloblastoma
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
1.11.1 Craniopharyngioma
1.11.2 Pituitary Adenoma
1.12 Metastases to the CNS
1.13 The Spine and Spinal Cord Tumors
1.13.1 Benign Primary Bony Tumors of the Spine
1.13.1.1 Osteochondroma
1.13.1.2 Osteoid Osteoma and Osteoblastoma
1.13.1.3 Giant Cell Tumor
1.13.1.4 Aneurysmal Bone Cyst
1.13.1.5 Hemangioma
1.13.1.6 Eosinophilic Granuloma
1.13.2 Malignant Bony Tumors of the Spine
1.13.2.1 Multiple Myeloma
1.13.2.2 Chordoma
1.13.2.3 Chondrosarcoma
1.13.2.4 Osteosarcoma and Ewing Sarcoma
1.13.2.5 Metastatic Disease
1.13.3 Tumors of the Spinal Cord
1.13.3.1 Extradural Tumors
1.13.3.2 Intradural-Extramedullary Lesions
1.13.3.3 Intradural-Intramedullary Tumors
1.14 CNS Tumors in Association with Other Diseases or Syndromes
1.15 Conclusion
References
2 The Epidemiology of Brain and Spinal Cord Tumors
Abstract
2.1 Introduction
2.2 Descriptive Epidemiology
2.2.1 Incidence
2.2.2 Survival, Morbidity, and Mortality
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
2.5.1 Glioma
2.5.2 Meningioma
2.5.3 Medulloblastoma
2.5.4 Ganglioglioma
2.5.5 Schwannoma
2.6 Anatomical Variants of Primary Brain and Spinal Cord Tumors
2.6.1 Pituitary Adenoma/Craniopharyngioma
2.6.2 Metastatic Brain Disease (Mets)
2.6.3 Pineal Tumors
2.7 Syndromes Associated with Central Nervous System Tumors
2.7.1 Tuberous Sclerosis Complex (TSC)
2.7.2 Neurofibromatosis Type 1 (Von Recklinghausen Disease)
2.7.3 Neurofibromatosis Type 2 (Central Neurofibromatosis)
2.7.4 Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
2.7.5 Von Hippel-Lindau Disease
2.7.6 Turcot Syndrome
2.7.7 Li-Fraumeni Syndrome
2.8 Familial Associations of Brain Tumors
2.8.1 CNS Tumors Among Twins
2.8.2 CNS Tumors Among Siblings
2.9 Summary, Clinical Applications, and Directions for Future Research
2.10 Conclusion
References
3 The Role of Neuro-Inflammation and Innate Immunity in Pathophysiology of Brain and Spinal Cord Tumors
Abstract
3.1 Introduction
3.2 Gliomas: Meeting Point Between Brain and Spinal Cord Tumors
3.2.1 Characteristics and Different Types of Gliomas
3.3 The Role of Neuroinflammation in Gliomas
3.3.1 Involvement of Inflammatory Cells in the Development of Glioma
3.4 Innate Immunity System Cells and Brain Tumors: Friend or Adversary?
3.5 Palmitoylethanolamide (PEA): the Next Line of Treatment for Glioma
3.6 Conclusions
References
4 The Role of Cellular Immunity and Adaptive Immunity in Pathophysiology of Brain and Spinal Cord Tumors
Abstract
4.1 Introduction
4.2 Brief Review of Innate and Adaptive Immunity
4.2.1 Innate Immunity in Tumor
4.2.1.1 The Complement System
4.2.1.2 Phagocytes and the M1 to M2 Transition
4.2.1.3 Natural Killer Cells
4.2.2 Adaptive Immunity in Tumor
4.2.2.1 Activation and Deactivation of Adaptive Immune System
4.2.2.2 Dendritic Cells Are the Most Potent Antigen Presenting Cells
4.2.2.3 Chimeric Antigen Receptor Engineered T Cells
4.2.3 Interactions Between Innate and Adaptive Immunity that Induce Anti-Tumor Immunity
4.3 Immunity in Patients with Malignant Glioma
4.3.1 Suppressive Effect on the Immune System of Malignant Gliomas
4.3.2 Inactivation of the Immune System by the Glioma Microenvironment
4.3.2.1 Glioma Stem Cells
4.3.2.2 Monocytes
4.3.2.3 Glial Cells
4.3.2.4 Regulatory T Cells
4.3.2.5 Other Cell Types
4.4 Immunotherapy in Intracranial Gliomas
4.4.1 Current Classification of Intracranial Gliomas
4.4.2 Current Therapy of Intracranial Gliomas
4.4.3 Current Immunotherapy—Checkpoint Inhibitors
4.4.3.1 Anti-CTLA-4
4.4.3.2 PD-1 Inhibitor
4.4.3.3 Anti-CD47
4.4.4 Current Immunotherapy—Vaccine-Mediated Immunizations
4.4.4.1 Passive Immunotherapy
4.4.4.2 Active and Adoptive Immunotherapy
4.4.4.3 Adoptive Immunotherapy
4.5 Spinal Cord Tumors
4.5.1 Typical Spinal Tumors
4.5.2 Primary Spinal Astrocytomas
4.5.3 Current Drug Treatment Modalities for Spinal Cord Astrocytoma
4.5.4 Metastatic Glioma in the Spine and Current Immunologic Treatments
4.6 Conclusion
References
5 Immunotherapy as a New Therapeutic Approach for Brain and Spinal Cord Tumors
Abstract
5.1 Introduction
5.2 Non-Specific Immunotherapy
5.3 Specific Active Immunotherapy: Cancer Vaccines
5.3.1 Antigen Non-Specific Vaccines
5.3.2 Antigen-Specific Vaccines
5.4 Specific Passive Immunotherapy
5.4.1 Monoclonal Antibodies: Immune Checkpoint Inhibitors
5.4.2 Oncolytic Virus Therapy
5.4.3 CAR T Cell Therapy
5.5 Conclusion
References
6 Cell of Origin of Brain and Spinal Cord Tumors
Abstract
6.1 Introduction
6.2 Diffuse Gliomas
6.2.1 Glioblastoma
6.2.1.1 Neural Stem Cells
Neural Stem Cells as Cells of Origin for Glioblastoma: Evidence from Mouse Models
Neural Stem Cells as Cells of Origin for Glioblastoma: Evidence from Human Studies
6.2.1.2 Committed Precursor Cells
6.2.1.3 Mature Cells
6.2.2 Oligodendroglioma
6.2.3 Glioma Harboring Histone Mutations
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
References
7 The Role of Bioinformatics and Imaging Models in Tumorigenesis and Treatment Response of Brain and Spinal Cord Neoplasm
Abstract
7.1 Introduction
7.2 Key-Related Research
7.3 Background
7.3.1 Brain Tumor
7.3.2 Magnetic Resonance Imaging (MRI)
7.3.3 Preprocessing and Skull Stripping
7.3.4 Chan-Vese Active Contour Segmentation
7.4 Analysis
7.4.1 Noise Filtering Technique
7.4.1.1 Adaptive Median Filter
7.4.1.2 Gaussian Filter
7.4.1.3 Alpha-Trimmed Mean Filter
7.4.1.4 Gabor Filter
7.4.1.5 High-Pass Filter
7.4.2 Performance Measure
7.4.2.1 Peak-Signal to Noise Ratio (PSNR)
7.4.2.2 Mean-Squared Error (MSE)
7.4.3 Chan-Vese Active Contour Model
7.5 Methodology
7.5.1 Proposed Skull Stripping Method
7.5.2 Feature Extraction
7.5.3 Proposed Chan-Vese Active Contour Segmentation
7.5.4 Percentage Tumor Area Calculation
7.6 Experiment Design and Results
7.6.1 Results of Proposed Skull Stripping Method
7.6.2 Results of Proposed C-V Method
7.7 Conclusion
References
8 The Role of Epigenetics in Brain and Spinal Cord Tumors
Abstract
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
8.7.1 DNA Hypomethylation and CpG Island Hypermethylation in Gliomas
8.7.2 MGMT Promoter Hypermethylation
8.7.3 Glioma CpG Island Methylator Phenotype (CIMP) and Ependymoma CIMP
8.7.4 P16 Methylation
8.8 Epigenetic Features of Human Telomeres
8.9 Methylation Profile of CNS Tumors
8.10 Epigenetic Therapies for Glioma
8.11 Future Perspectives
8.12 Conclusion
References
9 Stem Cells and Targeted Gene Therapy in Brain and Spinal Cord Tumors
Abstract
9.1 Introduction
9.2 Neurogenesis
9.3 Mechanism
9.4 Therapeutic Approaches
9.5 Gene-Editing Therapy
9.6 Conclusion
Referencess
10 Nutrition and Diet: A Double-Edged Sword in Development and Treatment of Brain Tumors
Abstract
10.1 Introduction
10.2 Carcinogens
10.2.1 N-nitroso Compounds
10.2.2 Alcohol Consumption
10.2.3 Caffeine
10.2.4 Dietary Fat
10.2.5 Cadmium
10.3 Protective Nutrients
10.3.1 Iron
10.3.2 Zinc
10.3.3 Calcium
10.3.4 Vitamins
10.3.4.1 Vitamins C and E
10.3.4.2 Vitamin A
10.3.4.3 Folic Acid
10.3.4.4 Vitamin D
10.3.5 The Ketogenic Diet
10.4 Conclusion
References
11 The Role of Nanotechnologies in Brain Tumors
Abstract
11.1 Introduction
11.2 Blood Brain Barrier
11.3 Nanoparticles Drug Delivery
11.4 Nanoparticles in Cerebral Gliomas
11.5 Conclusion
References
12 The Role of Nanotechnology in Spinal Cord Tumors
Abstract
12.1 Introduction
12.2 Classification of Spinal Cord Tumors
12.2.1 Intradural Extramedullary Tumors
12.2.1.1 Meningiomas
12.2.1.2 Schwannomas
12.2.2 Intradural Intramedullary Tumors
12.2.2.1 Astrocytomas
12.2.2.2 Ependymomas
12.2.2.3 Hemangioblastomas
12.3 Nanomedicine
12.3.1 Physiochemical Characteristics of NPs Influencing the Delivery
12.4 Nanoparticles
12.4.1 Polymer Nanoparticles
12.4.2 Liposomes
12.4.3 Metallic Nanoparticles
12.4.4 Carbon Nanotubes
12.4.5 Dendrimers
12.5 Nanoparticles Toxicity
12.6 Nanoparticles in Spinal Cord Tumors
12.7 Conclusion
References
13 The Economic Burden of Malignant Brain Tumors
Abstract
13.1 Introduction
13.2 Terminology
13.3 Primary Malignant Brain Tumors
13.3.1 Glioblastomas
13.4 Metastatic Brain Tumors
13.4.1 Lung Cancer
13.4.2 Breast Cancer
13.4.3 Melanoma
13.5 The Future of Malignant Brain Tumors
13.6 Policy Implications
13.7 Conclusion
Acknowledgements
References
Author Index
Subject Index