H. Pylori-Induced Inflammation and Gastric Cancer

幽门螺杆菌引起的炎症和胃癌

• 批准号: 8212343
• 负责人: RICHARD M. PEEK
• 金额: $ 135.36万
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212343
• 关键词: H.; Pylori; Induced; Inflammation; Gastric

DESCRIPTION (provided by applicant): Gastric adenocarcinoma is the second leading cause of cancer-related death in the world, and Helicobacter pylori is the strongest identified risk factor for this malignancy, yet only a fraction of colonized persons ever develop neoplasia. One H. pylori determinant associated with gastric cancer 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 and the EGF receptor (EGFR), host effectors that influence carcinogenesis, in gastric epithelial cells. We have also demonstrated that an environmental factor associated with gastric cancer, salt, augments the ability of H. pylori cag+ strains to induce aberrant epithelial responses. Therefore, the overarching objective of this Application is delineation of the molecular signaling events initiated 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. Mechanisms that regulate Helicobacter pylori-induced ?-catenin activation (PI-Richard Peek). Project 2. EGFR activation in H. pylori-induced gastric cancer (PI-Brent Polk). Project 3. Helicobacter pylori cag pathogenicity island and gastric carcinogenesis (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 only improve our understanding of gastric cancer, but will also facilitate identification of potential therapeutic targets for prevention and more effective treatment of this disease.

描述（由申请人提供）：胃腺癌是世界上与癌症相关死亡的第二大主要原因，而幽门螺杆菌是这种恶性肿瘤的最强识别危险因素，但只有一小部分殖民者会发展为新肿瘤。一种与胃癌相关的幽门螺杆菌决定因素是CAG致病岛，几个CAG基因编码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和EGF受体（EGFR），宿主效应子在胃皮细胞中影响癌变的宿主效应子。我们还证明，与胃癌相关的环境因素增强了幽门螺杆菌CAG+菌株诱导异常上皮反应的能力。因此，该应用的总体目标是描述幽门螺杆菌发起的分子信号事件：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，这些相互作用诱导了具有致癌潜力的细胞反应。各个项目包括： 项目1。调节幽门螺杆菌诱导的？ - 蛋白质激活（Pi-Richard Peek）的机制。 Project 2。幽门螺杆菌诱导的胃癌（Pi-Brent Polk）中的EGFR激活。 项目3。幽门螺杆菌cag致病岛和胃癌发生（Pi-Timothy覆盖率）。 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，该提案的结果不仅将改善我们对胃癌的理解，而且还将促进对预防和更有效治疗这种疾病的潜在治疗靶标的鉴定。