Clinical–Alimentary TractRofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus☆,☆☆
Section snippets
Patients and tissue collection
Over an 8-month period, 12 eligible patients with BE undergoing endoscopic surveillance at the Veterans Affairs Palo Alto Health Care System and Stanford University Hospital were selected for participation because they fulfilled the study inclusion and exclusion criteria and expressed interest in the study. Inclusion criteria were age >18 years, endoscopic and histologic evidence of BE on earlier endoscopy, and willingness to undergo repeat endoscopy and biopsies 10 days after rofecoxib
Clinical characteristics
The clinical characteristics of the patients studied are given in Table 1.Gender (M/F) 11/1 Age (mean ± SD) (yr) 67.5 ± 7.8 (47–79) Length of Barrett's esophagus (mean ± SD) (cm) 2.4 ± 1.6 (0.5–6) Hiatal hernia length (mean ± SD) (cm) 1.5 ± 1.7 (0–4) PPI therapy With omeprazole (mean ± SD) (mg/day) 32.5 ± 10 (n = 8) With lansoprazole (mean ± SD) (mg/day) 38.6 ± 14 (n = 4) Duration of PPI therapy (mean ± SD) (yr) 5.5 ± 3.1 (0.5–10) H. pylori status Negative (n = 12) Lower
Discussion
The results of our study suggest that, in contrast to normal esophagus or duodenum, the metaplastic BE epithelium is associated with enhanced proliferation, COX-2 expression, and PGE2 content that can be attenuated in vivo by rofecoxib therapy at the standard dose of 25 mg orally once daily. Therefore, our study is the first to suggest that, in conjunction with acid-suppressive therapy, selective COX inhibition may be useful as a chemopreventive strategy against Barrett's adenocarcinoma by
Acknowledgements
The authors thank the faculty, fellows, and staff of the Endoscopy Units of the Veterans Affairs Palo Alto Health Care System and Stanford University Hospital for their assistance in retrieval of mucosal specimens.
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Cited by (142)
Lifestyle and Cancer Prevention
2019, Abeloff’s Clinical OncologyCancer Prevention, Screening, and Early Detection
2013, Abeloff's Clinical Oncology: Fifth EditionAcid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux
2012, SurgeryCitation Excerpt :PCNA is an essential protein for cell proliferation. Like Ki-67, PCNA has been implicated in the transformation of normal squamous epithelial cells to esophageal adenocarcinoma,30,35 with progressively greater levels expressed when normal cells transform into Barrett’s esophagus and adenocarcinoma.35,36 Gillen et al37 found that PNCA expression in Barrett’s mucosa located adjacent to adenocarcinoma was greater than in normal Barrett’s mucosa.
COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention
2012, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :However, a recent clinical trial of selective COX-2 inhibition in combination with conventional therapy in advanced esophageal cancer patients was closed prematurely due to external safety concerns regarding celecoxib [199]. An increase in COX-2 expression has been reported in both esophageal squamous [200–202] and adenocarcinoma [88,203], and has generally been associated with a poor prognosis [89]. Daily use of a selective COX-2 inhibitor was associated with a significant reduction in the number and multiplicity of chemically induced esophageal tumors in a rat model [85].
Chemoprevention in Barrett's oesophagus
2011, Best Practice and Research: Clinical Gastroenterology
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Address requests for reprints to: George Triadafilopoulos, M.D., Chief, Gastroenterology Section (111-GI), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304. e-mail: [email protected]; fax: (650) 856-8024.
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Supported in part by the American College of Gastroenterology (to O.L.) and by Merck (to G.T.).