Helicobacter pylori and Gastric Cancer (Current Topics in Microbiology and Immunology, 444)

Foreword
Contents
Abbreviations
Gastric Stem Cell Biology and Helicobacter pylori Infection
	1 Introduction
	2 Gastric Stem Cells
		2.1 Antrum Stem Cell Biology
		2.2 Corpus Stem Cell Biology
	3 H. pylori Infection
		3.1 Gland-Invading H. pylori Interact with Stem Cells
		3.2 H. pylori Induces Gastritis via Activation of NF-kB
		3.3 H. pylori Triggers Hyperplastic Gastritis in the Antrum
		3.4 H. pylori Triggers Atrophic Gastritis and Metaplasia in the Corpus
	4 Concluding Remarks
	References
Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development
	1 Introduction
	2 Epidemiology and Risk Factors for Gastric Cancer Development
		2.1 Helicobacter pylori
		2.2 H. pylori Virulence Factors
		2.3 Dietary Factors (Salt/Iron)
		2.4 Host Constituents
		2.5 Epstein-Barr Virus (EBV)
		2.6 Human Microbiome
		2.7 Yes-Associated Protein
	3 Mongolian Gerbils as a Model for Gastric Cancer Development
		3.1 Gastric Cancer Development in Mongolian Gerbils
		3.2 Host Constituents
		3.3 Crucial H. pylori Determinants in Mongolian Gerbils
		3.4 Dietary Factors in the Gerbil (Salt/Iron)
		3.5 Gerbil Microbiome
	4 Concluding Remarks
	References
Mitochondrial Function in Health and Disease: Responses to Helicobacter pylori Metabolism and Impact in Gastric Cancer Development
	1 Introduction
	2 Mitochondria, Essential Organelle in Cell Physiology
		2.1 Mitochondria Function with a Highly Dynamic Network
		2.2 Mitochondria, a Central Biosynthetic and Signaling Hub
		2.3 Mitochondria and Immune Response: Implication in Host Antimicrobial Defense
	3 H. pylori, Colonization of Gastric Glands, Metabolism, and Impact on Mitochondria
		3.1 H. pylori, the Conquest of the Gastric Glands, Adaptation, and Dialogue with Mucosal Gastric Cells
		3.2 Mitochondria, a Prime Target for the VacA Cytotoxin
		3.3 H. pylori-Derived Metabolites Have an Important Role in Mitochondrial Damage
		3.4 H. pylori-Induced Oxidative Stress and Inflammation
	4 H. pylori-Induced MtDNA Damage and Gastric Carcinogenesis
	5 Concluding Remarks
	References
Immune Biology and Persistence of Helicobacter pylori in Gastric Diseases
	1 Introduction
	2 Immune Response to H. pylori
		2.1 Innate Immune Response
		2.2 Adaptive Immune Responses
	3 Immune Evasion
		3.1 Avoidance of Recognition and Manipulation of PRR Signaling
		3.2 Resistance Against AMPs
		3.3 Inhibition and Survival of Phagocytosis
		3.4 Manipulation of DCs and Modulation of Adaptive Immune Responses
	4 Concluding Remarks
	References
Pathogenomics of Helicobacter pylori
	1 Introduction
	2 H. pylori Biogeography
		2.1 Population Structure of H. pylori
		2.2 H. pylori and Human Migrations
	3 Pathogenomics of H. pylori
		3.1 Genetics of H. pylori Virulence Factors and Pathogenicity
		3.2 GWAS to Identify Genes and/or SNPs Associated with Disease Outcome
		3.3 Cancer-Associated Mutations in H. pylori Serine Protease HtrA
	4 Genome Evolution: Mutation, Recombination, and Genome Shuffling
		4.1 Accumulation of H. pylori Mutations and Recombination During Infection
		4.2 Evolution and Shuffling of Virulence Factors
		4.3 Recombination Between Different H. pylori Populations and Origin of Local H. pylori Subpopulations
	5 Advances in NGS—From Multiple Contigs to Long Read-Based Complete Genomes
	6 Concluding Remarks
	References
Gastric Cancer: The Microbiome Beyond Helicobacter pylori
	1 Introduction
	2 The Microbiota of the Stomach
	3 The Microbiota of the Stomach and Gastric Cancer
		3.1 H. pylori Infection and Gastric Cancer
		3.2 The Gastric Bacterial Microbiota in Gastric Carcinogenesis
		3.3 The Microbiota in Animal Models of Gastric Cancer
		3.4 The Gastric Non-bacterial Microbiome in Gastric Cancer
	4 The Non-gastric Microbiome and Gastric Cancer
		4.1 The Oral Microbiome and Gastric Cancer
		4.2 The Gut Microbiome and Gastric Cancer
	5 Concluding Remarks
	References
Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development
	1 Introduction
	2 Genetic Predisposition of the Host, Induction of DNA Damage and Microbial Factors
		2.1 Host Genetic Factors and Mutations in Gastric Cancer
		2.2 Common SNPs in Gastric Cancer Development
		2.3 Role of Microsatellite Instability and EBV Infection
		2.4 Role of Bacteria-Triggered Oxidative Stress Responses
		2.5 Bacterial Induction of DNA Double-Strand Breaks
		2.6 DNA Damage Repair Reactions
		2.7 Therapeutic Options
	3 Concluding Remarks
	References
Gastric Epithelial Barrier Disruption, Inflammation and Oncogenic Signal Transduction by Helicobacter pylori
	1 Introduction
	2 H. pylori Factors, Model Systems and Oncogenic Signal Transduction
		2.1 Bacterial Virulence Factors, Adhesins and T4SS Function
		2.2 Cell Culture and Animal Model Systems to Study H. pylori Pathogenesis
		2.3 Epithelial Barrier Disruption by H. pylori
		2.4 Regulation of Oncogenic Signaling in Epithelial Cells
		2.5 Apoptotic Cell Death Signaling
		2.6 Impact of the Microenvironment on Gastric Carcinogenesis
	3 Concluding Remarks
	References
Impact of the Helicobacter pylori Oncoprotein CagA in Gastric Carcinogenesis
	1 Introduction
	2 The cag Pathogenicity Island and Type IV Secretion System (T4SS)
	3 T4SS-Mediated Delivery of CagA into Gastric Epithelial Cells
	4 Molecular Structure of the CagA Protein
	5 Direct Oncogenic Action of CagA (Tyrosine Phosphorylation-Dependent)
	6 Direct Oncogenic Action of CagA (Tyrosine Phosphorylation-Independent)
	7 Hit-and-Run Mechanism of CagA-Mediated Gastric Carcinogenesis
	8 CagA-Mediated Induction of BRCAness that Elicits Genomic Instability
	9 Induction of DSBs by H. pylori in a CagA-Independent Manner
	10 Cellular Status of p53, a Game Changer of CagA Action
	11 Role of BRCAness in the Development of Gastric Cancer
	12 Concluding Remarks
	References
Bacterial Proteases in Helicobacter pylori Infections and Gastric Disease
	1 Introduction
		1.1 The Gastric Epithelium
		1.2 Helicobacter pylori Disease Mechanisms
	2 H. pylori Proteases with Implications in Pathogenesis
		2.1 The Important Function of HtrA in Opening Lateral Junctions
	3 Concluding Remarks
	References
Clinical Management of Gastric Cancer Treatment Regimens
	1 Introduction
	2 Treatment of Localized Disease
		2.1 Endoscopic Resection of Early Gastric Cancer
		2.2 Surgery
		2.3 Adjuvant Treatments: Chemotherapy and Radiotherapy
	3 Treatment of Advanced and Metastatic Disease
		3.1 Cytotoxic Chemotherapies
		3.2 Targeted Therapies
		3.3 Immunotherapies
		3.4 Surgery for Metastatic GC
		3.5 Supportive Care
		3.6 Novel Targets and New Therapeutic Approaches
	4 Concluding Remarks
	References