H. pylori-Induced Inflammation and gastric cancer

幽门螺杆菌引起的炎症和胃癌

• 批准号: 8821584
• 负责人: RICHARD M. PEEK
• 金额: $ 137.54万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821584
• 关键词: Academic Medical Centers; Address; Adverse effects; Animal Model; Attenuated; Award; Bacterial Infections; Bacterial Proteins; Basic Science; Bioinformatics; Biological; Biological Models; Cancer Biology; Cancer Etiology; Carcinogens; Cessation of life; Chronic; Clinical; Clinical Research; Clinical Sciences; Clinical and Translational Science Awards; Core Facility; Development; Diet; Dietary Factors; Disease; Environmental Risk Factor; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Esophageal Adenocarcinoma; Etiology; Evaluation; Event; Exposure to; Financial Support; Funding; Funding Mechanisms; Future; Gastric Adenocarcinoma; Gastroenterology; Genes; Genetic Variation; Genomics; Goals; Helicobacter pylori; High Prevalence; Histopathology; Housing; Human; Human Resources; Immune response; Individual; Infection; Infectious Agent; Inflammation; International; Investigation; Iron; Lead; Lesion; Letters; Link; Malignant Neoplasms; Microbiology; Molecular; Neoplasms; Oncogenic; Pathogenicity Island; Persons; Pharmacology; Phenotype; Physiology; Polyamines; Population; Premalignant; Prevention; Proteomics; Reagent; Receptor Activation; Recruitment Activity; Regulation; Research; Research Activity; Research Personnel; Resources; Risk; Risk Factors; Rodent Model; Role; Signal Pathway; Signal Transduction; Sodium Chloride; Stomach; System; Technology; Testing; Translating; Translational Research; Translations; Type IV Secretion System Pathway; Variant; Virulence; Work; World Health Organization; anticancer research; antimicrobial; cancer risk; carcinogenesis; cost; disorder risk; effective therapy; gastric cancer prevention; high risk; human DNA sequencing; human genome sequencing; improved; innovation; insight; iron deficiency; malignant stomach neoplasm; microbial; microbial host; molecular imaging; neoplastic; new therapeutic target; novel; novel strategies; pathogen; personalized medicine; polyamine oxidase; programs; response; square foot; therapeutic target

DESCRIPTION (provided by applicant): Gastric adenocarcinoma is the second leading cause of cancer-related death in the world. Helicobacter pylori is the strongest identified risk factor fr this malignancy, yet only a fraction of colonized persons ever develop neoplasia. One H. pylori determinant associated with increased gastric cancer risk is the cag pathogenicity island, and several cag genes encode components of a type IV secretion system which exports bacterial proteins such as CagA into host epithelial cells. Our group has now demonstrated that H. pylori cag+ strains selectively activate ¿-catenin, the EGF receptor (EGFR), and spermine oxidase (SMO), host effectors that influence carcinogenesis, in gastric epithelial cells. We have also demonstrated that environmental factors associated with gastric cancer, such as iron deficiency and salt, augment the ability of H. pylori cag+ strains to induce gastric cancer. Therefore, the overarching objective of this Application is delineation of the molecular signaling events initiate by H. pylori:epithelial cell contact that regulate phenotypes related to gastric carcinogenesis. This PPG will integrate studies of host-pathogen interactions initiated by biomedical researchers who have made a strong and clear commitment to research within the fields of gastroenterology, cancer biology, carcinogenesis, and microbiology, and will generate results that would not be attainable through independent investigation. The component Projects are driven by discrete hypotheses, yet are cohesive in that each focuses on H. pylori:epithelial interactions that induce cellular responses with carcinogenic potential. The individual projects include: Project 1. Role of iron and ¿ -catenin activation in gastric carcinogenesis (Pi-Richard Peek). Project 2. EGFR activation and polyamines in H. pylori-induced gastric cancer (Pi-Keith T. Wilson). Project 3. Regulation of H. pylori virulence by dietary factors that impact gastric cancer (Pi-Timothy Cover). The efforts of each Project will be further unified by dynamic interactions with Specific Core facilities, which include the Gastric Histopathology Core (Core A), the Proteomics Core (Core B), and an Administrative Core (Core C). By maintaining a grounded focus on fundamental interactions that occur at the H. pylori:epithelial interface, results from this proposal will not nly improve our understanding of gastric cancer, but will also identify potential therapeutic targets for prevention and more effective treatment of this disease.

描述（由适用提供）：胃腺癌是世界上与癌症相关死亡的第二大主要原因。幽门螺杆菌是这种恶性肿瘤的强烈识别危险因素，但只有一小部分殖民者发生了肿瘤。 CAG致病岛是一家与胃癌风险增加相关的幽门螺杆菌，而几个CAG基因编码了IV型分泌系统的成分，该系统将CAGA等细菌蛋白（例如CAGA）导出到宿主上皮细胞中。现在，我们的小组已经证明，幽门螺杆菌CAG+菌株有选择地激活� -Catenin，EGF受体（EGFR）和氧化物氧化物（SMO），宿主的宿主作用会影响胃皮细胞中的致癌作用。我们还证明，与胃癌相关的环境因素（例如铁缺乏症和盐）增强了幽门螺杆菌CAG+菌株诱导胃癌的能力。因此，该应用的总体目标是幽门螺杆菌启动的分子信号事件的描述：调节与胃癌相关的表型的上皮细胞接触。该PPG将整合由生物医学研究人员引发的宿主 - 病原体相互作用的研究，这些研究人员在胃肠病学，癌症生物学，致癌物和微生物学领域做出了坚定而清晰的研究，并将产生无法通过独立研究而无法获得的结果。组件项目是由离散假设驱动的，但具有凝聚力，因为每个假设都集中在幽门螺杆菌：上皮相互作用上，这些相互作用会影响具有致癌潜力的细胞反应。各个项目包括： 项目1。铁和» - 帕宁激活在胃癌发生（PI -Richard PEEK）中的作用。 项目2。幽门螺杆菌诱导的胃癌（Pi-Keith T. Wilson）中的EGFR激活和多胺。 项目3。通过影响胃癌（PI-Timothy覆盖）的饮食因素来调节幽门螺杆菌病毒。 每个项目的努力将通过与特定核心设施的动态相互作用进一步统一，其中包括胃组织病理学核心（核心A），蛋白质组学核心（核心B）和行政核心（Core C）。通过保持对幽门螺杆菌：上皮界面发生的基本相互作用的扎根，该提案的结果不会改善我们对胃癌的理解，但还将确定预防和对该疾病更有效治疗的潜在治疗靶标。