Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days
研究概览
简要总结
The purpose of this study is to elucidate mechanisms whereby oxidative stress induced by acute reflux esophagitis: 1) activates p38 to regulate proteins that control the G1/S cell cycle checkpoint, and 2) activates HIFs (hypoxia inducible factors) to cause autocrine VEGF (vascular endothelial growth factor) signaling that triggers the EMT (epithelial-mesenchymal-transition) program in Barrett's esophagus.
详细描述
Gastroesophageal reflux disease (GERD) and its complication, Barrett's esophagus (BE), are risk factors for esophageal adenocarcinoma. In BE, GERD causes inflammation with oxidative DNA damage and genomic instability that contributes to carcinogenesis. In BE, one response to oxidative stress is p38 pathway activation, which might protect against cancer development by initiating G1 arrest and enabling repair of DNA damage. Inflammation and oxidative stress also might induce epithelial-mesenchymal transition (EMT), the process in which epithelial cells acquire mesenchymal characteristics including the ability to migrate. This study will elucidate mechanisms whereby the oxidative stress of acute reflux esophagitis in BE activates p38 to regulate proteins controlling the G1/S cell cycle checkpoint, and activates HIFs to cause autocrine vascular endothelial growth factor (VEGF) signaling that triggers the EMT program.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •U.S. Veteran
- •Barrett's Esophagus
排除标准
- •Inability to provide informed consent
- •Pregnancy or breastfeeding
- •Esophageal varices
- •Warfarin use
- •Coagulopathy that precludes safe biopsy of the esophagus
- •Comorbidity that precludes safe participation in the study
结局指标
主要结局
Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days
时间窗: day 0, day 7, and day 14
Inflammation of the esophageal mucosa will be measured at baseline, 7 days, and at 14 days. Esophageal mucosal inflammation will be measured using esophageal mucosal biopsy specimens, and histopatholgical grading. Mucosal infiltration with inflammatory cells (neutrophils, eosinophils, and lymphocytes) will be measured.
次要结局
- Show oxidative DNA damage associated with p38 activation(day 0, day 7, and day 14)
- change in VEGF from baseline to 14 days(day 0, day 7, and day 14)
- change in p38 pathway from baseline to 14 days(day 0, day 7, and day 14)
- change in phosoho-p38 from baseline to 14 days(day 0, day 7, and day 14)
- change in APE-1 from baseline to 14 days(day 0, day 7, and day 14)
- change in NPM1 from baseline to 14 days(day 0, day 7, and day 14)
- change in phospho-NPM1 from baseline to 14 days(day 0, day 7, and day 14)
- change in miRNA expression from baseline to 14 days(day 0, day 7, and day 14)
- change in HIF expression from baseline to 14 days(day 0, day 7, and day 14)
研究者
Stuart Spechler
Professor of Medicine
Dallas VA Medical Center