Role of H. Pylori Infection in Esophageal Adenocarcinoma

描述(申请人提供)：幽门螺杆菌在发达国家人群中的定植流行率一直在下降。CagA+幽门螺杆菌感染率的下降可能与工业化国家食管腺癌发病率上升有关。CagA+菌株的定植已被证明与反流性食管炎和Barrett‘s食道呈负相关。胃食道反流病(GERD)患者中cagA+幽门螺杆菌的感染率较低，这种疾病是由食管酸暴露引起的。幽门螺杆菌定植与GERD之间负相关的一个解释是幽门螺杆菌对产酸的影响。根除幽门螺杆菌导致了一部分接受治疗的患者发生GERD。这些临床证据导致了幽门螺杆菌在GERD，特别是反流性食管炎的发生中可能起到保护作用的假设。在以下特定目的中提出的实验将检验幽门螺杆菌，特别是cagA+菌株，可能预防GERD，Barrett‘s食道癌和食管腺癌的假设。 具体目的如下：1.研究幽门螺杆菌cagA+和cagA-菌株在大鼠和小鼠胃内定植对宿主炎症反应的影响。2.探讨幽门螺杆菌感染在大鼠反流性食管炎、Barrett‘s食管炎和食管腺癌中的作用。3.在野生型和p53基因敲除小鼠的手术反流模型中，确定幽门螺杆菌感染在食管炎、Barrett‘s食管炎和食管腺癌中的作用。本研究旨在确定幽门螺杆菌定植在啮齿动物模型中反流性食管炎、Barrett‘s食道及其相关腺癌发生中的作用。这项建议利用创新的GERD、BE和EAC手术模型来研究幽门螺杆菌对反流并发症的保护作用。

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.