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Title:	A selective cyclooxygenase-2 inhibitor prevents inflammation-related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats
Authors:	Oba, Masaru Miwa, Koichi Fujimura, Takeshi Harada, Shin-ichi Sasaki, Shozo Oyama, Katsunobu Ohta, Tetsuo Hattori, Takanori 原田, 真市 太田, 哲生 ハラダ, シンイチ
Date of Issue:	Jan-2009
Publisher:	American Cancer Society / John Wiley & Sons
Journal:	Cancer
ISSN:	0008-543X
Volume:	115
Number:	2
Start page:	454
End page:	464
Keywords:	Chemoprevention COX-2 Duodenogastric reflux Forestomach Squamous carcinogenesis
Abstract:	Background: Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, in preventing this carcinogenesis. Methods: A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing meloxicam (0.3 mg/kg body weight/day) (meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux-related morphological changes, COX-2 expression, and its activity. Results: At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the meloxicam group (P <.05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the meloxicam group (P <.01). COX-2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX-2 in the epithelium was up-regulated, reaching peak at an early stage of Week 20 in both groups (P < .005). The expression of microsomal prostaglandin E synthase-1 was lower in the meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group (P < .005). Conclusions: Meloxicam was effective in preventing reflux-induced squamous cell carcinogenesis via an inflamed squamous epithelium. © 2009 American Cancer Society.
Description:	著者最終稿を登録可能.
DOI:	10.1002/cncr.23990
URI:	http://hdl.handle.net/2297/19401
Type:	Journal Article
Version:	author
Appears in Collections:	3-2.ファイル準備中(依頼済)

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