title: Chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a COX-2 inhibitor.
abstract: Duodenogastric reflux (DGR) causes glandular stomach carcinogenesis in rats without carcinogens. We aimed to investigate how this carcinogenesis might be prevented by a selective COX-2 inhibitor, meloxicam. A series of 188 Fisher 344 rats underwent a surgical DGR procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other an experimental chow containing meloxicam [0.3 mg/kg bw/day] (meloxicam group). The animals were sequentially sacrificed at weeks 20, 30, 40, 50 and 60 after surgery. The stomachs were removed and examined for the presence of carcinoma, incidence of reflux-induced morphologic changes, COX-2 expression and its activity. Adenocarcinoma in the glandular stomach developed in 7 of 21 animals (33%) in the control group at week 60, but none of 20 (0%) in the meloxicam group (p < 0.01). Moreover, reflux-induced gastritis was definitely alleviated in the meloxicam group compared with the control group. COX-2 immunoreactivity was predominantly detected in stromal cells such as macrophages and fibroblasts. Compared with nonsurgical rats, RNA expression of COX-2 in the mucosa increased, reaching peak at an early phase of week 20 in both groups (p < 0.005). Expression of microsomal prostaglandin E synthase-1 was lower in the meloxicam group than in the control group. PGE(2) production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group (p < 0.01). Gastric carcinogenesis via duodenal reflux was mediated by the COX-2 pathway in rats. Administration of meloxicam prevented this carcinogenesis by suppressing the inflammatory process.
authors.affiliation: Gastroenterological Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Oba
authors.forename: Koichi
authors.initials: K
authors.lastname: Miwa
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.forename: Shozo
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000818:Animals; D001483:Base Sequence; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D004383:Duodenogastric Reflux / Q000150:complications*; D005753:Gastric Mucosa / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D000077239:Meloxicam; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D012333:RNA, Messenger; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000071876:Prostaglandin-E Synthases; C497818:Ptges protein, rat; D015232:Dinoprostone; D000077239:Meloxicam