A selective cyclooxygenase-2 inhibitor prevents inflammatio.pdf

A Selective Cyclooxygenase-2 Inhibitor Prevents Inflammation- related Squamous Cell Carcinogenesis of the Forestomach Via Duodenogastric Reflux in Rats Masaru Oba, MD, PhD1, Koichi Miwa, MD, PhD1, Takashi Fujimura, MD, PhD1, Shinichi Harada, PhD2, Shozo Sasaki, MD, PhD1, Katsunobu Oyama, MD, PhD1, Tetsuo Ohta, MD, PhD1, and Takanori Hattori, MD, PhD3 BACKGROUND: Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestom- ach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclo- oxygenase (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 ep- ithelium 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 eff