Role of H. Pylori Infection in Esophageal Adenocarcinoma

描述（由申请人提供）：幽门螺杆菌在发达国家人群中的定殖率一直在下降。cagA+幽门螺杆菌患病率的下降可能与工业化国家食管腺癌发病率的上升有关。cagA+菌株的定植已被证明与反流性食管炎和巴雷特食管呈负相关。在胃食管反流病（GERD）患者中观察到cagA+幽门螺杆菌的患病率较低，这是由酸暴露于食管引起的。幽门螺杆菌定殖与胃食管反流之间负相关的一种解释是幽门螺杆菌对胃酸产生的影响。根除幽门螺杆菌导致一部分接受治疗的患者出现反流胃食管反流。这些临床证据表明幽门螺杆菌可能在反流性食管炎，尤其是反流性食管炎的发生中起保护作用。以下具体目的的实验将验证幽门螺杆菌，特别是cagA+菌株可能对GERD、Barrett食管和食管腺癌有保护作用的假设。

DESCRIPTION (provided by applicant): The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining. The decreasing prevalence of cagA+ Helicobacter pylori may be associated with the rising incidence of esophageal adenocarinomas in industrialized countries. Colonization with cagA+ strains has been shown to be inversely associated with reflux esophagitis and Barrett's esophagus. A lower prevalence of cagA+ Helicobacter pylori has been observed in patient with gastroesophageal reflux disease (GERD) which results from acid exposure to the esophagus. One explanation for the negative association between colonization with Helicobacter pylori and GERD is the effect of Helicobacter pylori on acid production. Eradication of Helicobacter pylori has led to the development of GERD in a proportion of treated patients. These clinical evidence has led to the hypothesis that Helicobacter pylori could play a protective role in the development of GERD, especially reflux esophagitis. Experiments proposed in the following specific aims will test the hypothesis that Helicobacter pylori, especially the cagA+ strains, may protect against GERD, Barrett's esophagus and esophageal adenocarcinoma. The specific aims are as follows: 1. To study the effects of gastric colonization of cagA+ and cagA- strains of Helicobacter pylori on host inflammatory responses in rats and mice. 2. To determine the effects of Helicobacter pylori infection in reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in rats. 3. To determine the effects of Helicobacter pylori infection in esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in wild-type and p53 knockout mice. The proposed studies aim to ascertain the role of Helicobacter pylori colonization in the development of reflux esophagitis, Barrett's esophagus and its associated adenocarcinoma in rodent models. This proposal utilizes the innovative surgical models of GERD, BE and EAC for studying the protective role of Helicobacter pylori against reflux complications.