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Chemopreventive effects of a selective cyclooxygenase-2 inhibitor (etodolac) on chemically induced intraductal papillary carcinoma of the pancreas in hamsters.

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Title: Chemopreventive effects of a selective cyclooxygenase-2 inhibitor (etodolac) on chemically induced intraductal papillary carcinoma of the pancreas in hamsters.
Authors: Adachi, Tomohiko / Tajima, Yoshitsugu / Kuroki, Tamotsu / Mishima, Takehiro / Kitasato, Amane / Tsuneoka, Noritsugu / Kanematsu, Takashi
Issue Date: Apr-2008
Publisher: Oxford University Press.
Citation: Carcinogenesis, 29(4), pp.830-833; 2008
Abstract: The present study was designed to determine whether etodolac, a selective cyclooxygenase-2 inhibitor, prevents chemically induced intraductal papillary carcinoma (IPC) in the main pancreatic duct of hamsters. Hamsters were subjected to cholecystoduodenostomy with dissection of the distal end of the common duct. Four weeks after surgery, the surviving hamsters received subcutaneous injections of N-nitrosobis(2-oxopropyl)amine four times at a dose of 10 mg/kg body wt, every 2 weeks. The animals were divided into three groups according to the simultaneous oral intake of a standard pelleted diet containing etodolac at 0% (group CE, n = 30), 0.01% (group ET, n = 21) and 0.04% (group ET4, n = 25), respectively. Hamsters were killed for pathological examination at 36 weeks after the operation. The incidence of induced pancreatic carcinoma was 93, 81 and 72% in groups CE, ET and ET4, respectively. The pancreatic carcinomas were histologically classified into four types, i.e. tubular, papillary, cyst adenocarcinoma and IPC. The incidence of IPC and the number of IPCs per animal were significantly lower in groups ET4 (36% and 0.48) and ET (48% and 0.62) when compared with group CE (67% and 1.30). The proliferating cell nuclear antigen labeling indices in the non-cancerous epithelial cells of the main pancreatic duct were 2.8 and 6.8% in groups ET4 and ET, respectively, and were significantly lower than that in group CE (10.8%). In conclusion, etodolac inhibited N-nitrosobis(2-oxopropyl)amine-induced IPC in hamsters. Suppression of epithelial cell proliferation of the main pancreatic duct was considered as a possible mechanism of cancer prevention in this hamster model.
Keywords: intraductal papillary mucinous neoplasm / intraductal papillary mucinous neoplasm / cyclooxygenase-2 inhibitor / chemoprevention / hamster
URI: http://hdl.handle.net/10069/22959
ISSN: 01433334
DOI: 10.1093/carcin/bgn047
PubMed ID: 18296437
Rights: © The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org / This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis, 29(4), pp.830-833; 2008 is available online at: http://carcin.oxfordjournals.org/cgi/content/abstract/29/4/830.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22959

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