ROLE OF BACTERIAL COLONIZATION IN DEVELOPMENT OF UPPER GI PATHOLOGY

细菌定植在上消化道病理发展中的作用

• 批准号: 7605742
• 负责人: FRITZ FRANCOIS
• 金额: $ 0.67万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605742
• 关键词: Acids; Address; Adenocarcinoma; Age-Years; Alleles; Atrophic Gastritis; Bacteria; Barrett Esophagus; Biopsy; Biopsy Specimen; Blood; Carcinoma; Cell Proliferation; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Dysplasia; Enrollment; Esophageal; Esophageal Adenocarcinoma; Esophageal Diseases; Esophagitis; Esophagogastric Junction; Esophagus; Evaluation; Evolution; Female; Funding; Gastroesophageal reflux disease; Gastrointestinal Endoscopy; Genes; Genetic; Genetic Polymorphism; Grant; Helicobacter pylori; Histologic; Hospitals; Hour; Immune response; Inflammation; Inflammatory Response; Institution; Metaplasia; Monitor; Outpatients; Pathology; Patients; Pepsinogens; Population; Prevalence; Production; Reflux; Research; Research Personnel; Resources; Risk; Role; Serological; Serum; Source; Stomach; United States National Institutes of Health; cell growth regulation; cyclooxygenase 2; cytokine; gastrointestinal; male; protein expression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigators hypothesize the following: 1) Normal bacterial flora exists in the esophagus and that they change during the evolution of gastroesophageal reflux disease (GERD) into Barrett's esophagus and esophageal adenocarcinoma. 2) Specific host and bacterial factors may determine the development of esophageal disease. 3) The IL-1b-31*T allele and the functionally related IL-1RN*2 allele decrease the risk of esophageal inflammation, metaplasia, and consequent development of adenocarcinoma by modulating the host inflammatory response to H. pylori and subsequent acid production and cellular proliferation. The specific aims are as follows: 1. To define the bacterial flora at a population level in the normal esophagus and the esophagus of patients with GERD-related diseases such as esophagitis and Barrett's esophagus 2. To define the bacterial flora at a species level in the normal esophagus and the esophagus of patients with GERD-related diseases. 3. To determine host humoral immune responses to the esophageal colonizing bacteria in patients with a normal esophagus or with GERD-related diseases. 4. To assess the presence of H. pylori and its strain characteristics in patients with and without reflux disease 5. To assess for the progression of atrophic gastritis by examination of serum pepsinogens in the patients with GERD or with normal esophagus 6. To determine the effect of Helicobacter pylori strain characteristics on gastric and esophageal mucosal IL-1b protein expression, and on the development of inflammation, metaplasia, and dysplasia. 7. To determine the prevalence of the IL-1b-31 and IL-1RN alleles in relation to esophageal acid exposure, also in relation to H. pylori colonization. In particular, we also will evaluate the effect of the IL-1b-31 and IL-1RN alleles on gastroesophageal junction (GEJ) cellular proliferation and cyclooxygenase-2 (COX-2) expression in patients with or without H. pylori colonization. 8. To evaluate the effect of H. pylori eradication on GEJ cellular proliferation, and on IL-1b and COX-2 expression in relation to the IL-1b-31 allele The study will be conducted in outpatients referred for endoscopic evaluation for clinically indicated reasons. Endoscopic evaluation will be performed to assess for gastrointestinal pathology, esophageal bacterial colonization, and H. pylori colonization. Biopsies will be subjected to histologic review as well as determination of COX-2 expression as a marker of abnormal cellular regulation, and pH monitoring will be performed to determine esophageal acid exposure over 24 hours. Blood collected will be used for evaluating for serologic evidence of H. pylori colonization as well as for evaluating polymorphisms in the cytokine IL-1b gene locus. A total of 300 male and female patients between 18 and 75 years of age undergoing upper gastrointestinal endoscopy at Bellevue hospital and at the VANYHHS for clinically indicated reasons will be enrolled in this study. This study is an "add-on" study to an ongoing attempt to look at the role of bacterial colonization on the likelihood of GEJ inflammation (SPID #1229). It will utilize the same biopsy specimens as the original study but will also address the role of host genetics on the risk for inflammation. This study will help clarify the progression from reflux to Barrett's disease and to carcinoma.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 研究人员假设：1）正常细菌植物群存在于食管中，并且它们在胃食管反流病（GERD）演变为巴雷特食管和食管腺癌期间发生变化。 2)特定的宿主和细菌因素可能决定食管疾病的发展。 3)IL-1b-31*T等位基因和功能相关的IL-1 RN *2等位基因通过调节宿主对H.幽门螺杆菌和随后的酸产生和细胞增殖。 具体目标如下： 1. 确定正常食管和GERD相关疾病（如食管炎和Barrett食管）患者食管中的群体水平细菌植物群 2. 在种属水平上确定正常食管和GERD相关疾病患者食管中的细菌植物群。 3. 目的探讨正常食管或GERD相关疾病患者对食管定植菌的体液免疫应答。 4. 评估H.有无反流病患者的幽门螺杆菌及其菌株特征 5. 胃食管反流病与正常食管患者血清胃蛋白酶原检测对萎缩性胃炎进展的评估 6. 确定幽门螺杆菌菌株特征对胃和食管粘膜IL-1b蛋白表达以及炎症、化生和异型增生发展的影响。 7. 确定IL-1b-31和IL-1 RN等位基因的患病率与食管酸暴露以及与H.幽门定植。 特别是，我们还将评估IL-1b-31和IL-1 RN等位基因对有或无H患者胃食管连接部（GEJ）细胞增殖和环氧合酶-2（考克斯-2）表达的影响。幽门定植。 8. 评价H.幽门螺杆菌根除对GEJ细胞增殖以及IL-1b和考克斯-2表达与IL-1b-31等位基因的关系 本研究将在因临床指征原因转诊接受内镜评价的门诊患者中进行。 将进行内镜评价，以评估胃肠道病理学、食管细菌定植和H。幽门定植。 将对活检进行组织学检查，并测定作为异常细胞调节标志物的考克斯-2表达，并进行pH监测以确定24小时内的食管酸暴露。 采集的血液将用于评估H. pylori定植以及评价细胞因子IL-1b基因座的多态性。 本研究将入组共计300例因临床指征原因在Bellevue医院和VANYHHS接受上消化道内镜检查的18 - 75岁男性和女性患者。 本研究是一项“附加”研究，旨在观察细菌定植对GEJ炎症可能性的作用（SPID #1229）。它将使用与原始研究相同的活检标本，但也将解决宿主遗传学对炎症风险的作用。 这项研究将有助于澄清从反流到巴雷特病和癌症的进展。