title: Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients.
abstract: Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512.
authors.affiliation: College of Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Banerjee
authors.affiliation: Division of Gastroenterology & Hepatology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona. Department of Nutritional Sciences, University of Arizona, Tucson, Arizona.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Martinez
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona.
authors.forename: Chiu-Hsieh
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: College of Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Eugene
authors.initials: E
authors.lastname: Trowers
authors.affiliation: College of Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Blake A
authors.initials: BA
authors.lastname: Gibson
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
authors.forename: Gary
authors.initials: G
authors.lastname: Della'Zanna
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
authors.forename: Ellen
authors.initials: E
authors.lastname: Richmond
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona. schow@azcc.arizona.edu.
authors.forename: H-H Sherry
authors.initials: HH
authors.lastname: Chow
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000473:pathology; D001647:Bile Acids and Salts; D049109:Cell Proliferation / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid