Clinical study of ursodeoxycholic acid in Barrett's esophagus patients

Bhaskar Banerjee, Nicholas J. Shaheen, Jessica A. Martinez, Chiu-Hsieh Hsu, Eugene A Trowers, Blake A. Gibson, Gary Della'Zanna, Ellen Richmond, Hsiao-Hui Chow

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)528-533
Number of pages6
JournalCancer Prevention Research
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Ursodeoxycholic Acid
Barrett Esophagus
Bile Acids and Salts
Gastric Acid
DNA Damage
Cell Proliferation
Apoptosis
Clinical Studies
Taurine
Liquid Chromatography
Caspase 3
Glycine
Mass Spectrometry
Stomach
Biomarkers
Biopsy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical study of ursodeoxycholic acid in Barrett's esophagus patients. / Banerjee, Bhaskar; Shaheen, Nicholas J.; Martinez, Jessica A.; Hsu, Chiu-Hsieh; Trowers, Eugene A; Gibson, Blake A.; Della'Zanna, Gary; Richmond, Ellen; Chow, Hsiao-Hui.

In: Cancer Prevention Research, Vol. 9, No. 7, 01.07.2016, p. 528-533.

Research output: Contribution to journalArticle

Banerjee, Bhaskar ; Shaheen, Nicholas J. ; Martinez, Jessica A. ; Hsu, Chiu-Hsieh ; Trowers, Eugene A ; Gibson, Blake A. ; Della'Zanna, Gary ; Richmond, Ellen ; Chow, Hsiao-Hui. / Clinical study of ursodeoxycholic acid in Barrett's esophagus patients. In: Cancer Prevention Research. 2016 ; Vol. 9, No. 7. pp. 528-533.
@article{f354614a283d477cb6b4857afef0e628,
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 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.",
author = "Bhaskar Banerjee and Shaheen, {Nicholas J.} and Martinez, {Jessica A.} and Chiu-Hsieh Hsu and Trowers, {Eugene A} and Gibson, {Blake A.} and Gary Della'Zanna and Ellen Richmond and Hsiao-Hui Chow",
year = "2016",
month = "7",
day = "1",
doi = "10.1158/1940-6207.CAPR-15-0276",
language = "English (US)",
volume = "9",
pages = "528--533",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

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 A

AU - Gibson, Blake A.

AU - Della'Zanna, Gary

AU - Richmond, Ellen

AU - Chow, Hsiao-Hui

PY - 2016/7/1

Y1 - 2016/7/1

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

VL - 9

SP - 528

EP - 533

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 7

ER -