TY - JOUR
T1 - Clinical study of ursodeoxycholic acid in Barrett's esophagus patients
AU - Banerjee, Bhaskar
AU - Shaheen, Nicholas J.
AU - Martinez, Jessica A.
AU - Hsu, Chiu Hsieh
AU - Trowers, Eugene
AU - Gibson, Blake A.
AU - Della'Zanna, Gary
AU - Richmond, Ellen
AU - Chow, H. H.Sherry
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/7
Y1 - 2016/7
N2 - 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 againstoxidative stress induced bycytotoxic bile acids.Weconducted 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 15mg/kg/day for 6months. 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 fluidweremeasured 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.
AB - 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 againstoxidative stress induced bycytotoxic bile acids.Weconducted 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 15mg/kg/day for 6months. 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 fluidweremeasured 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.
UR - http://www.scopus.com/inward/record.url?scp=84977110707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977110707&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-15-0276
DO - 10.1158/1940-6207.CAPR-15-0276
M3 - Article
C2 - 26908564
AN - SCOPUS:84977110707
SN - 1940-6207
VL - 9
SP - 528
EP - 533
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 7
ER -