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

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