Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Gastroesophageal Reflux Disease , Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 2/9/2019 |
| Start Date: | November 2015 |
| End Date: | October 2019 |
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.
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.
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.
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.
Inclusion Criteria:
- U.S. Veteran
- Barrett's Esophagus
Exclusion Criteria:
- 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
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Dallas VA Medical Center VA North Texas Health Care System (VANTHCS) is a progressive health...
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