A Genomics and Mathematical Modeling Approach for the Study of Helicobacter Pylori Associated Gastritis and Gastric Cancer PDF Download
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Author: Shruti Marwaha
Publisher:
ISBN:
Category :
Languages : en
Pages : 134
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Book Description
Gastric cancer is the fifth most common malignancy in the world and third the leading cause of cancer-related mortality worldwide, with five-year survival rate of only 20-29%. In order to develop better drugs, diagnostics and preventive measures for gastric cancer, it is critical to understand the underlying molecular biology of the disease and factors that increase the risk for the disease. Helicobacter pylori-induced chronic gastritis is a major risk factor associated with gastric cancer development. We analyzed publically available gene expression data from patients with gastric cancer and patients with H. pylori mediated gastritis, to identify genes and pathways that play an important role in the two diseases. We further integrated the identified disease signature with Broad Institute's Connectivity Map to identify and prioritize drugs that can potentially reverse the molecular signature of gastric cancer cells and that of gastric tumors resistant to Cisplatin-Flurouracil (CF) chemotherapy. Our analysis identified vorinostat, trichostatin A and thiostrepton as potential therapeutic compounds for gastric cancer treatment. We identified genes and pathways that are differentially expressed (57 up-regulated and 86 down-regulated) in both gastric cancer and H. pylori mediated atrophic gastritis. The topmost pathways enriched for these genes include - cell-cell adhesion/communication, tight junctions, leukocyte transendothelial migration, gastric acid secretion, potassium ion transport and creatine pathways. Analysis of CF resistant and sensitive tumors suggests the role of metabolic and statin pathways towards resistance to the chemotherapy. We also developed a mathematical model of a sub-network comprising of sonic hedgehog (SHH), pro-inflammatory cytokines and anti-inflammatory cytokines, which play a critical role in H. pylori mediated gastritis. We integrated qPCR results, mathematical modeling technique and microarray data from H. pylori infected mice to explore the temporal behavior of the cytokine-SHH sub-network. Our mathematical model suggests that NF?B, SHH and the cytokines engage in a feedback loop which can result in damped oscillations. The model helps to bring out emergent properties of the network and generate testable hypotheses. Future experiments capturing cytokines and SHH profile over time can reveal more insights about the relationship between the different genes, their regulation and improve our current understanding of the dynamics and sequence of the events in the system.
Author: Shruti Marwaha
Publisher:
ISBN:
Category :
Languages : en
Pages : 134
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Book Description
Gastric cancer is the fifth most common malignancy in the world and third the leading cause of cancer-related mortality worldwide, with five-year survival rate of only 20-29%. In order to develop better drugs, diagnostics and preventive measures for gastric cancer, it is critical to understand the underlying molecular biology of the disease and factors that increase the risk for the disease. Helicobacter pylori-induced chronic gastritis is a major risk factor associated with gastric cancer development. We analyzed publically available gene expression data from patients with gastric cancer and patients with H. pylori mediated gastritis, to identify genes and pathways that play an important role in the two diseases. We further integrated the identified disease signature with Broad Institute's Connectivity Map to identify and prioritize drugs that can potentially reverse the molecular signature of gastric cancer cells and that of gastric tumors resistant to Cisplatin-Flurouracil (CF) chemotherapy. Our analysis identified vorinostat, trichostatin A and thiostrepton as potential therapeutic compounds for gastric cancer treatment. We identified genes and pathways that are differentially expressed (57 up-regulated and 86 down-regulated) in both gastric cancer and H. pylori mediated atrophic gastritis. The topmost pathways enriched for these genes include - cell-cell adhesion/communication, tight junctions, leukocyte transendothelial migration, gastric acid secretion, potassium ion transport and creatine pathways. Analysis of CF resistant and sensitive tumors suggests the role of metabolic and statin pathways towards resistance to the chemotherapy. We also developed a mathematical model of a sub-network comprising of sonic hedgehog (SHH), pro-inflammatory cytokines and anti-inflammatory cytokines, which play a critical role in H. pylori mediated gastritis. We integrated qPCR results, mathematical modeling technique and microarray data from H. pylori infected mice to explore the temporal behavior of the cytokine-SHH sub-network. Our mathematical model suggests that NF?B, SHH and the cytokines engage in a feedback loop which can result in damped oscillations. The model helps to bring out emergent properties of the network and generate testable hypotheses. Future experiments capturing cytokines and SHH profile over time can reveal more insights about the relationship between the different genes, their regulation and improve our current understanding of the dynamics and sequence of the events in the system.
Author: Steffen Backert
Publisher: Springer Nature
ISBN: 3031473310
Category : Medical
Languages : en
Pages : 328
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Book Description
This volume explores in detail the molecular biology, genetics and immunology of the bacterium Helicobacter pylori that causes serious gastric diseases such as gastric cancer. The book provides in-depth insights into the mechanisms of H. pylori-induced pathogenicity, gives an overview of how the bacterium colonizes the human gut, how it manages to persist in the body and which factors play a role in the development of H. pylori-induced gastric cancer. Furthermore, the interaction between the Gram-negative bacterium and the human gut microbiome is explored, and clinical management and treatment strategies to combat gastric cancer are discussed. Helicobacter pylori is an extremely successful pathogen that persistently colonizes the gut of about 50% of the world’s population. H. pylori and its human host share a long co-evolutionary relationship that dates back for at least last 100,000 years and possibly longer. Infection by this bacterium is a high-risk factor for the development of gastric diseases, including gastric cancer. Gastric cancer is associated with high morbidity and mortality and represents the 5th most common malignant tumour and the 4th leading cause of cancer-related death worldwide. H. pylori is the first bacterium that has been classified as a type-I carcinogen by the International Agency for Research on Cancer (IARC). Recent research progress identified crucial bacterial, host and environmental factors which control H. pylori-induced gastric malignancy. New studies also suggest that specific human germline mutations and other genetic aberrations have an important impact on H. pylori-induced pathology. In this volume, all these recently discovered mechanisms are reviewed in the light of gastric cancer development, and H. pylori epidemiology, virulence factors, immune evasion, pathophysiology, cancer signalling and novel therapeutic protocols are presented. This volume is aimed at researchers in the fields of immunology, genetics, microbiology and medicine who are interested in the detailed mechanisms of the pathogenicity of this carcinogenic stomach bacterium.
Author: Mohamed Tarek Badr
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Abstract: Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa and can lead to gastric inflammation, ulcers, and stomach cancer. Due to the increase in H. pylori antimicrobial resistance new methods to identify the molecular mechanisms of H. pylori-induced pathology are urgently needed. Here we utilized a computational biology approach, harnessing genome-wide association and gene expression studies to identify genes and pathways determining disease development. We mined gene expression data related to H. pylori-infection and its complications from publicly available databases to identify four human datasets as discovery datasets and used two different multi-cohort analysis pipelines to define a H. pylori-induced gene signature. An initial Helicobacter-signature was curated using the MetaIntegrator pipeline and validated in cell line model datasets. With this approach we identified cell line models that best match gene regulation in human pathology. A second analysis pipeline through NetworkAnalyst was used to refine our initial signature. This approach defined a 55-gene signature that is stably deregulated in disease conditions. The 55-gene signature was validated in datasets from human gastric adenocarcinomas and could separate tumor from normal tissue. As only a small number of H. pylori patients develop cancer, this gene-signature must interact with other host and environmental factors to initiate tumorigenesis. We tested for possible interactions between our curated gene signature and host genomic background mutations and polymorphisms by integrating genome-wide association studies (GWAS) and known oncogenes. We analyzed public databases to identify genes harboring single nucleotide polymorphisms (SNPs) associated with gastric pathologies and driver genes in gastric cancers. Using this approach, we identified 37 genes from GWA studies and 61 oncogenes, which were used with our 55-gene signature to map gene-gene interaction networks. In conclusion, our analysis defines a unique gene signature driven by H. pylori-infection at early phases and that remains relevant through different stages of pathology up to gastric cancer, a stage where H. pylori itself is rarely detectable. Furthermore, this signature elucidates many factors of host gene and pathway regulation in infection and can be used as a target for drug repurposing and testing of infection models suitability to investigate human infection
Author: Timothy Wang
Publisher: Springer Science & Business Media
ISBN: 0387691820
Category : Medical
Languages : en
Pages : 654
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Book Description
As someone who has spent nearly half his life wondering about the relationship between Helicobacter and gastric cancer, I find this textbook on the subject exciting and timely. In fact, I am not aware of any other volume that has been able to distil so much new knowledge into such a comprehensive account of a poorly understood field. Taking my own view, as a scientist placed in the middle of the spectrum between basic science and clinical medicine, I can see that the editors, Jim Fox, Andy Giraud, and Timothy Wang, provide a broad mix of expertise, which ensures that the subject is treated with the right balance. From clinicopathologic observations in humans, to epidemiology, through animal models, to molecular and cell biology, this team has hit the mark for most readers. Fox is a well-known leader in animal models with broad expertise. He pioneered the field with observations on Helicobacter species in animals, from the time when only one spiral gastric bac- rium was known, “Campylobacter pyloridis. ” Fox partners with Wang, whose team recently announced a dramatic advance in the field of carcinogenesis—the obser- tion that bone marrow–derived stem cells participate in the changes that become cancer. To this nice mix has been added Andy Giraud from my own country, who brings to the table some remarkable genetic models of gastric cancer based on alterations in the gp130/stat3-signaling pathway.
Author: Elvire Berthenet
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Nicole Tegtmeyer
Publisher: Springer
ISBN: 3319505203
Category : Medical
Languages : en
Pages : 364
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Book Description
This volume reviews the current state of research concerning bacterial virulence factors and the infection biology of Helicobacter pylori, which is the leading cause of peptic ulcers and gastric cancer worldwide. The chapters include cutting-edge findings on this fascinating microbe and discuss the general strategies of H. pylori infection and persistence, news on important H. pylori virulence factors, crosstalk with the microbiota, hot novel models and signaling mechanisms, risk factors of gastric disease and stomach cancer, and the impact of H. pylori infection on non-gastric diseases. Written by internationally respected scientists, this book will appeal to clinicians, researchers and advanced students alike.
Author: Paola Tonino
Publisher: BoD – Books on Demand
ISBN: 9533073756
Category : Medical
Languages : en
Pages : 312
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Book Description
This book is a comprehensive overview of invited contributions on Helicobacter pylori infection in gastritis and gastric carcinogenesis. The first part of the book covers topics related to the pathophysiology of gastric mucosal defense system and gastritis including the gastroprotective function of the mucus, the capsaicin-sensitive afferent nerves and the oxidative stress pathway involved in inflammation, apoptosis and autophagy in H. pylori related gastritis. The next chapters deal with molecular pathogenesis and treatment, which consider the role of neuroendocrine cells in gastric disease, DNA methylation in H. pylori infection, the role of antioxidants and phytotherapy in gastric disease. The final part presents the effects of cancer risk factors associated with H. pylori infection. These chapters discuss the serum pepsinogen test, K-ras mutations, cell kinetics, and H. pylori lipopolysaccharide, as well as the roles of several bacterial genes (cagA, cagT, vacA and dupA) as virulence factors in gastric cancer, and the gastrokine-1 protein in cancer progression.
Author: Yoshio Yamaoka
Publisher: Caister Academic Press Limited
ISBN: 9781904455318
Category : Science
Languages : en
Pages : 0
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Book Description
Helicobacter pylori is an important human pathogen that infects up to 50% of the human population. As the leading cause of peptic ulcers, gastritis, and gastric cancer worldwide, the organism has been the subject of intensive research to unravel the mysteries of its genetics and cellular biology. In fact, the number of publications in this field has risen dramatically in recent years making it extremely difficult for even the most diligent reader to stay abreast of progress. This book distills the most important cutting-edge findings in the field to produce a timely and comprehensive review. With contributions from leading international helicobacter researchers, topics include: lipopolysaccharides, outer membrane proteins, motility and chemotaxis, type IV secretions systems, metal metabolism, molecular mechanisms of host adaptation, genomotyping, and proteonomics. As a useful introduction to the subject for new researchers and as an invaluable reference for the experienced researcher, this book is essential reading for all researchers working with Helicobacter and related organisms.
Author: Wei Zhang
Publisher: Springer Science & Business Media
ISBN: 0306478250
Category : Science
Languages : en
Pages : 345
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Book Description
Computational and Statistical Genomics aims to help researchers deal with current genomic challenges. Topics covered include: overviews of the role of supercomputers in genomics research, the existing challenges and directions in image processing for microarray technology, and web-based tools for microarray data analysis; approaches to the global modeling and analysis of gene regulatory networks and transcriptional control, using methods, theories, and tools from signal processing, machine learning, information theory, and control theory; state-of-the-art tools in Boolean function theory, time-frequency analysis, pattern recognition, and unsupervised learning, applied to cancer classification, identification of biologically active sites, and visualization of gene expression data; crucial issues associated with statistical analysis of microarray data, statistics and stochastic analysis of gene expression levels in a single cell, statistically sound design of microarray studies and experiments; and biological and medical implications of genomics research.
Author: C. Stewart Goodwin
Publisher: CRC Press
ISBN: 1351090062
Category : Science
Languages : en
Pages : 575
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Book Description
Helicobacter pylori: Biology and Clinical Practice is the first book to fully describe H. pylori and the pathogenesis of H. pylori infections. It delineates the genome of H. pylori, discusses the molecular biology of the unique urease enzyme, and examines the clinical application of these discoveries. The book describes the epidemiology of H. pylori and its relevance to gastric cancer, and it offers clear guidance to clinicians for the diagnosis and treatment of peptic ulcer and non-ulcer dyspepsia in adults and children. Vaccine principles and possibilities are presented for the first time. Edited by the leader of the microbiology team that achieved the first culture of H. pylori, and named the Helicobacter genus, this book is essential for bacteriologists, gastroenterologists, microbiologists, infectious disease specialists, and other researchers interested in H. pylori.
