Molecular mechanisms of acid exposure in Barrett's esophagus.
Esophageal adenocarcinoma is one of the most deadly gastrointestinal tumors. Gastroesophageal reflux has been established as a major risk factor for esophageal adenocarcinoma and Barrett's esophagus, the condition in which the normal squamous cells of the esophagus are replaced by metaplastic, specialized intestinal cells that are predisposed to malignancy. Data from ex vivo and in vitro model systems suggests that acid exposure has pro-proliferative and anti-apoptotic effects which may facilitate neoplastic progression of Barrett's esophagus. Such data have led some authorities to propose complete elimination of gastric acid production as a chemopreventive strategy for Barrett's patients. However, it is not clear whether the effects of acid exposure on proliferation and apoptosis are a direct result of the acid exposure itself, or whether they result indirectly from the effects of acid on inducing esophageal inflammation. Such distinction may help in optimizing the level of gastric acid suppression for the prevention of cancer in Barrett's esophagus. This report describes the molecular mechanisms whereby acid exposure directly and indirectly, through inducing inflammation, may contribute to the neoplastic progression of Barrett's esophagus and the potential role for acid suppression as a chemopreventive strategy in patients with Barrett's esophagus.
Dallas VA Medical Center, University of Texas-Southwestern Medical School, Harold C. Simmons Comprehensive Cancer Center, 4500 South Lancaster Road, Dallas, TX 75216, USA. rhonda.souza@UTSouthwestern.edu
R F
RF
Souza
D000143:Acids / Q000009:adverse effects; D001471:Barrett Esophagus / Q000150:complications*; D016207:Cytokines / Q000502:physiology; D004938:Esophageal Neoplasms / Q000209:etiology*; D004941:Esophagitis / Q000150:complications; D005764:Gastroesophageal Reflux / Q000150:complications*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000143:Acids; D016207:Cytokines; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species