s-1743 and candesartan

Patients with dysplasia in Barrett's esophagus (BE) have a considerable risk of developing esophageal adenocarcinoma (EAC). The mucosal expression of the pro-inflammatory angiotensin II receptor type 1 (AT1R) is elevated in these patients, suggesting a role in carcinogenesis. The purpose of this study was to determine whether interference with the renin-angiotensin system (RAS) would influence downstream markers of carcinogenesis.. Endoscopic mucosal biopsies from BE patients with low-grade dysplasia (LGD) were sampled before and after a three-week period of RAS-interfering treatment. Thirty patients were randomly allocated to enalapril (ACE inhibitor, 5 mg od), candesartan (AT1R antagonist, 8 mg od), or no drug. The expression of 12 proteins known to be associated with RAS and carcinogenesis was assessed using western blot.. We found altered expression of several proteins after enalapril treatment (decreased: NFκB, p = .043; NLRP3, p = .050; AMACR, p = .017; and caspase 3, p = .025; increased: p53, p = .050). Candesartan treatment was associated with increased iNOS expression (p = .033). No significant changes were seen in the no-drug group.. Interference with angiotensin II formation was associated with altered expression of inflammation- and carcinogenesis-related proteins. The present results speak in favor of involvement of angiotensin II in BE dysplasia, but the role of AT1R should be investigated further.

Topics: Adenocarcinoma; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Barrett Esophagus; Benzimidazoles; Biomarkers, Tumor; Biphenyl Compounds; Enalapril; Endoscopy; Esomeprazole; Esophageal Neoplasms; Female; Humans; Hyperplasia; Male; Middle Aged; Neoplasm Proteins; Nitric Oxide Synthase Type II; Precancerous Conditions; Prospective Studies; Proton Pump Inhibitors; Renin-Angiotensin System; Risk Factors; Sweden; Tertiary Care Centers; Tetrazoles