vention of Colitis - Associated Carcinogenesis Pr R Infliximab

wnloaded emergence of infliximab was an epochal event in the treatment of inflammatory bowel disease . Because colitis-associated cancers arose in the setting of chronic inflammation, during which mmation-dysplasia-carcinoma sequence” prevails and anti-inflammatory agents can prevent carciesis, we hypothesized whether infliximab can prevent colitic cancer in animal models for which /6 mice were exposed to 15 cycles of dextran sulfate sodium (DSS), with each cycle consisting of DSS for 1 week followed by sterilized water for 10 days. Infliximab (4 mg/kg i.v.) was given on the d, and 7th weeks or 25th, 27th, and 31st weeks of cycle according to “step-up” versus “top-down” y. Molecular change about inflammation and carcinogenesis was compared between groups. Multilorectal tumors developed in 75% to 80% of control mice, whereas only 16.7% of mice treated with mab on the 1st, 3rd, and 7th weeks developed colon tumors. Significant decreases in tumor necrosis -α level, mast cell number, and the expression of inflammatory cytokines were observed in top-down y using infliximab. The expression and activity of matrix metalloproteinase-9 (MMP-9) andMMP-11 ignificantly decreased in mice treated with infliximab accompanied with attenuated numbers of enin–accumulated crypts.” In animal group where infliximab was administered at later stage of 27th, and 31st weeks, no reduction in tumorigenesis was noted. These biological effects of infliximab urther explored in in vitro experiment using Raw264.7 and Jurkat T cells. Conclusively, earlier and were f intensive therapy with infliximab should be considered for either mitigating clinical course or preventing ultimate development of colitic cancer in high-risk IBD patients. Cancer Prev Res; 3(10); 1314–33. ©2010 AACR.