Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascertain the involvement of three cancerrelated genes: K-ras, adenomatous polyposis coli (APC), and p53. Four groups of rats were used: reactivated 1,2-dimethylhydrazine [DMH; trinitrobenzene sulfonic acid (TNBS) was used to induce colitis followed by a weekly s.c. dose of DMH], prolonged reactivation (inflammation was induced with TNBS,
Erlotinib can decrease the development of colitis-associated dysplasia, suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.
Long‐standing colitis markedly increases the risk of developing colorectal cancer. Neurokinin‐1 receptors (NK‐1R) have been shown to be involved in chronic colonic inflammation but their role in the transition to dysplasia is unclear.AimTo investigate the role of NK‐1R in a novel model of colitis‐associated dysplasia.MethodsSprague Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol ic), followed six weeks later by reactivation with TNBS (5 mg/kg iv) for three days. To induce colitis‐associated dysplasia the rats then received TNBS (iv) twice a week for ten weeks. One group received the NK‐1R antagonist SR140333 (1 mg/kg ip) twice a week for ten weeks; the rest received vehicle. After sacrifice the colons were removed and analyzed for total macroscopic damage, histological analysis, and real‐time RT‐PCR.ResultsPathological analysis revealed a decreased incidence of dysplasia in animals treated with the NK‐1R antagonist compared with the vehicle treated group. Animals receiving SR140333 had significantly less macroscopic and microscopic damage, and a down‐regulation of mRNA levels for EGFR and NK‐1R, which correlated with the pathology.ConclusionOur results suggest that a selective NK‐1R antagonist can delay the development of damage and dysplasia in a novel model of colitis‐associated dysplasia, offering its potential therapeutic use. 1U56 CA126379‐01 & 1F31 GM078951.
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