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Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagus

Citation

Jacobson, GA and Narkowicz, CK and Lord, RJ and Howard, B-J and Chung, S, Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagus, Diseases of the Esophagus, 20, (3) pp. 265-268. ISSN 1120-8694 (2007) [Refereed Article]


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The definitive published version is available online at http://onlinelibrary.wiley.com/

Official URL: http://onlinelibrary.wiley.com/

DOI: doi:10.1111/j.1442-2050.2007.00684.x

Abstract

Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors could offer hope as chemoprevention therapy. The aim of the study was to investigate the in vivo effect of celecoxib on COX-2 expression in patients with Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28 days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence detection. COX-2 expression was found to decline 20% and 44% at two different biopsy sites compared to the baseline sample. Longer exposures revealed a number of previously unidentified proteins above and below the 67 kDa COX-2 protein including 38 kDa and 45 kDa proteins which were present only at study completion consistent with up-regulation after celecoxib therapy. Further investigations of the 38 kDa and 45 kDa proteins were undertaken using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF (matrix assisted laser desorption ionization time of flight) analysis but no matches were found and results were inconclusive. Unmatched masses from MALDI-TOF peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX-2b was found for a length of 19 amino acids. Based on immunodetection, molecular weight and equivical MALDI-TOF results, one of these up-regulated proteins may be COX-2b.

Item Details

Item Type:Refereed Article
Keywords:Barrett's esophagus;celecoxib;COX-2;cyclooxygenase-2
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmaceutical Sciences
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Jacobson, GA (Dr Glenn Jacobson)
Author:Narkowicz, CK (Dr Christian Narkowicz)
Author:Lord, RJ (Dr Roger Lord)
Author:Howard, B-J (Miss Bobbie-Jo Howard)
ID Code:44577
Year Published:2007
Web of Science® Times Cited:3
Deposited By:Pharmacy
Deposited On:2007-08-01
Last Modified:2011-05-02
Downloads:0

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