GASTRITIS AND GASTRIC CANCER – NEW INSIGHTS IN GASTROPROTECTION, DIAGNOSIS AND TREATMENTS Edited by Paola Tonino Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments Edited by Paola Tonino Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Martina Blecic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Sebastian Kaulitzki, 2010. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments, Edited by Paola Tonino p. cm. ISBN 978-953-307-375-0 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathophysiology of Gastric Mucosal Defense System and Gastritis 1 Chapter 1 Protective Effects of Gastric Mucus 3 Takafumi Ichikawa and Kazuhiko Ishihara Chapter 2 Approach to Role of Capsaicin - Sensitive Afferent Nerves in the Development and Healing in Patients with Chronic Gastritis 25 Gyula Mozsik, Imre L. Szabo and Andras Dömötör Chapter 3 Oxidative Stress Pathway Driven by Inflammation in Gastric Mucosa 47 Dovhanj Jasna and Švagelj Dražen Chapter 4 Oxidative Stress Involved Autophagy and Apoptosis in Helicobacter pylori Related Gastritis 63 Jyh-Chin Yang and Chiang-Ting Chien Part 2 Molecular Pathogenesis and Treatment of Chronic Gastritis 73 Chapter 5 Chronic Gastritis 75 Wojciech Kozlowski, Cezary Jochymski and Tomasz Markiewicz Chapter 6 The Role of Morphometry in Diagnostic of Chronic Gastritis 93 Tomasz Markiewicz, Wojciech Kozlowski and Cezary Jochymski Chapter 7 Molecular Pathology of Gastritis 115 Alejandro H. Corvalán, Gonzalo Carrasco and Wilda Olivares Chapter 8 Role of Natural Antioxidants in Gastritis 127 Mohamed M. Elseweidy VI Contents Chapter 9 New Approaches in Gastritis Treatment 153 Guillermo Marcial, Cecilia Rodríguez, Marta Medici and Graciela Font de Valdez Part 3 Helicobacter Pylori Infection in Gastritis and Gastric Cancer 177 Chapter 10 Gastric Cancer Risk Diagnosis and Prevention in Subjects with Helicobacter pylori-related Chronic Gastritis 179 Shotaro Enomoto, Mika Watanabe, Chizu Mukoubayashi, Hiroshi Ohata, Hirohito Magari, Izumi Inoue, Takao Maekita, Mikitaka Iguchi, Kimihiko Yanaoka, Hideyuki Tamai, Jun Kato, Masashi Oka and Masao Ichinose Chapter 11 Role of Genetic and Environmental Risk Factors in Gastric Carcinogenesis Pathway 197 Bárbara Peleteiro and Nuno Lunet Chapter 12 Effects of Helicobacter pylori Infection on the Histology, Cellular Phenotype, K-ras Mutations, and Cell Kinetics in Gastric Intestinal Metaplasia in Patients with Chronic Gastritis and Gastric Cancer 217 Jiro Watari, Hiroki Tanabe, Kentaro Moriichi, Mikihiro Fujiya, Peter S. Amenta, Hiroto Miwa, Yutaka Kohgo and Kiron M. Das Chapter 13 Helicobacter pylori Lipopolysaccharide as a Possible Pathogenic Factor for Gastric Carcinogenesis 243 Shin-ichi Yokota, Ken-ichi Amano and Nobuhiro Fujii Chapter 14 Virulence Factors of Helicobacter pylori and Their Relationship with the Development of Early and Advanced Distal Intestinal Type Gastric Adenocarcinoma 259 Bruna Maria Roesler, Sandra Cecília Botelho Costa and José Murilo Robilotta Zeitune Chapter 15 Role of Gastrokine 1 in Gastric Cancer 281 Emilia Rippa, Paolo Mallardo and Paolo Arcari Preface In the last two decades, the research on gastritis, gastroduodenal ulcers and gastric carcinoma focused on the Helicobacter pylori infection process, but the mechanisms leading to these diseases are not completely understood. Gastritis is an inflammatory disease of the gastric mucosa in response to several intrinsic and extrinsic factors. Diet antigens, extracellular pollutants and pathogenic infections trigger the inflammatory process in the gastrointestinal tract. Thus, the disruption of the intestinal barrier results in intestinal inflammation by pro-inflammatory reactions of immune cells. The inflammatory progression into the gastric lining depends on environmental factors, host state and H. pylori-specific virulence factors. Albeit the stomach is frequently ex- posed to hazardous agents, several gastroprotective mechanisms exist to response to this harsh environment. Furthermore, a better understanding of the mechanisms of gastric mucosal defense system might provide new insights into potential therapeutic targets. The modification of functional capsaicin-sensitive afferent nerves also offers new opportunities in gastroprotective therapy. The severity of gastric inflammation has also been related to high concentration of free radicals. Chronic inflammation of the gastric mucosa may predispose susceptible cells to neoplastic transformation. The reactive oxygen species (ROS, e.g. nitric oxide and superoxide) are key regulatory factors in molecular pathways linked to carcinogenesis. H. pylori infection increases the oxidative DNA damage by ROS in epithelial cells as a causal factor in malignant transformation. Two distinct molecular pathways for gastric carcinogenesis by H. pylori infection has been proposed; the direct action of the bacterial proteins such as Cag A on gastric epithelial cells, and the accumulation of genetic and epigenetic changes in tumor-related genes of the gastric epithelial cells caused by prolonged bacterial infection and chronic inflammation. Then the identification of novel genes regulated by H. pylori (cagA, cagT, vacA and dupA) in early stages of gastric cancer might help to understand the differential susceptibility to this pathogen. Recent studies have demonstrated the phenotypic and genotypic diversity of H pylori isolates that may engender differential host inflammatory responses with influence in the clinical outcome. New strategies for control of H. pylori infection involve the disruption of the interaction between the bacteria and target cells via downregulation of apoptosis and upregulation of autophagy. Besides, the integral analysis of immunohistopathology and overexpression of specific tumor suppressor genes (e.g. p53 and p73) or a protein secreted by antrum mucosa X Preface (gastrokine 1), might be important to the identification of possible biomarkers for the gastric carcinogenesis. DNA methylated genes have been detected not only in gastric mucosa but also in the plasma of gastric cancer patients (e.g. Reprimo, RPRM) as a cell-free DNA, which can be considered a diagnostic tool for non-invasive detection of premalignant gastritis and gastric cancer. It is also worth to mention that proper chronic gastritis classification considering both, clinical and histopathological aspects is fundamental for the diagnosis and successful therapy. Current classification of gastritis is the 1994 Houston-updated Sydney System. It has been suggested that digital morphometric evaluation of the inflammatory and epithelial cells of the gastric mucosa, and the density of neuroendocrine cells in association with chronic gastritis type, and clinicopathological factors may also be valuable in diagnosis. The treatment of gastritis depends on the specific cause. In the present, not only several drugs are in use, but also phytotherapy compounds including tannins and flavonoids (phenolic compounds) have been associated with healing properties attributed to the inhibition of cytokine-mediated inflammatory mechanism, suppression of inducible nitric oxide synthase and antioxidants activities. In addition, probiotic lactic acid bacteria and probiotic foods might promote beneficial effects on the gastric mucosa. Untreated chronic gastritis and other host factors could progress to gastric carcinogenesis. The model postulated by Correa and Houghton (2007) shows the combination of H. pylori factors, environmental insults, and the host immune response involved in the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer. It is known that H. pylori eradication changes the cellular phenotype of gastric intestinal metaplasia, which may be an important factor in the reduction of cancer incidence. Recently, H. pylori lipopolysaccharide (LPS) was associated with the enhancement of the inflammatory reaction and upregulation of the growth rate of epithelial cells via activation of the MEK1/2-ERK1/2 MAP kinase cascade. All these aspects are considered in this book, as a comprehensive overview of invited contributions about gastroprotection, gastritis and gastric carcinogenesis and new approaches in diagnosis and treatments. 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 importance of capsaicin-sensitive afferent nerves and the oxidative stress pathway involved in inflammation, apoptosis and autophagy in Helicobacter pylori related gastritis. The next chapters deal with molecular pathogenesis and treatments, 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 several factors such as, 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 [...]... factors in gastric cancer, and the gastrokine-1 protein in cancer progression The topics presented in this book are suggested to all clinicians and researchers interested in gastroprotection, gastritis and gastrointestinal cancer diagnosis and treatments I would like to thank the In Tech Publishing team for this opportunity and especially to all the authors for their contribution to the better understanding... containing both a benzene ring and an amide structure, analogs A and B, but not C, stimulated mucin biosynthesis in a manner similar to that of roxatidine These three compounds contain a 14 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments Fig 11 Structures and pharmacological activities of lafutidine and its analogs Mucin biosynthetic activity was evaluated in. .. lumen in a solubilized 4 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments Fig 1 Composition of gastric mucus condition Mucus rapidly responds to pathological and physiological changes in the stomach Moreover, mucus present in the stomach exhibits various actions such as maintaining lubrication of the mucosal surface, covering ingested foods to mix them, helping... separating method for quantifying mucus glycoprotein localized in the different layer of rat gastric mucosa Gastroenterol Jpn Vol.27, No.4, pp.466-472, ISSN 04351339 Komuro, Y.; Ishihara, K.; Kojima, Y.; Saigenji, K & Hotta, K (1998) Distinct effects of tetragastrin in rat gastroduodenal mucosa on mucin content and mucosal 22 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments. .. features of roxatidine for the activation of mucin biosynthesis are the appropriate length of the flexible chain between the amide structure and the aromatic ring system bearing the methylpiperidinyl group at the meta position The thioether function can confer increased gastroprotective activity on lafutidine 16 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments 5.3... separately identify and determine the various mucins Through the establishment of the mucus determining method, which utilizes mAbs, the roles of the mucus with different origins as protecting factors would be made clearer 18 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments Second-generation H2-blockers offer the possibility of more effective prevention of gastritis. .. antibody against gastric mucin Previous studies have shown that different types of mucin, differing in their carbohydrates and core protein structure, are expressed in different regions of the gastrointestinal tract In the stomach, the corpus mucin differs from the antral mucin, and in each region the surfacetype mucins (surface mucus cell-type mucins) differ from the gland-type mucins, synthesized in deeper... oxyntic gland Fig 3 Polymeric structure of mucin molecules 5 6 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments properties Each glycoprotein subunit can be divided into two functional regions on the basis of the peptide core: (1) glycosylated regions in which carbohydrate chains form a closely packed sheath around the central peptide core, protecting it from... factors interact with each other, and damage to the mucosa occurs through an imbalance between the aggressive factors and protective factors (Fig 7) 10 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments Fig 7 Gastric protection: which is stronger, aggressive factor or protective factor? 4.2 Changes of gastric mucus The response of the gastric mucosa to acute injury... heteroaromatic rings Chem Pharm Bull (Tokyo) Vol.46, No.4, pp.616-622, ISSN 0009-2363 Ho, S.B.; Roberton, A.M.; Shekels, L.L.; Lyftogt, C.T.; Niehans, G.A & Toribara, N.W (1995a) Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression Gastroenterology Vol.109, No.3, 735-747, ISSN 0016-5085 20 Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments . GASTRITIS AND GASTRIC CANCER – NEW INSIGHTS IN GASTROPROTECTION, DIAGNOSIS AND TREATMENTS Edited by Paola Tonino Gastritis and Gastric Cancer – New Insights in. protein in cancer progression. The topics presented in this book are suggested to all clinicians and researchers interested in gastroprotection, gastritis and gastrointestinal cancer diagnosis and. structure of mucin molecules. Gastritis and Gastric Cancer – New Insights in Gastroprotection, Diagnosis and Treatments 6 properties. Each glycoprotein subunit can be divided into two functional