Tranilast treatment prevents chronic radiation-induced colitis in rats by inhibiting mast cells infiltration.

INTRODUCTION: Mast cells are the principal cells leading to acute and chronic colitis due to irradiation, radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups: control group (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). The rats in RG and TG were irradiated in the pelvic area (1.5cm from anus) with a single dose of 20 Gray under general anesthesia. Tranilast (100 mg/kg) was intraperitonially injected to mice of the TG for 10 days starting from the day of pelvic irradiation. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were evaluated histologically for the total inflammation score (TIS) and mast cell count. Expression of MUC2, MUC5AC and matrix metalloproteinase 9 (MMP9) were also assessed immunohistochemically. RESULTS: Both TIS and some components of TIS, epithelial atypia, vascular sclerosis and colitis cystica profunda (CCP) were significantly higher in RG than in TG (P=0.02, 0.038, 0.025, 0.01, respectively). The number of infiltrating mast cells was significantly higher in the RG than in TG (20, 3-54 and 6, 3-25, respectively, P=0.034). Quantitatively, the number of MMP9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (P<0.05). TIS and MMP9 exhibited strong associations (correlation coefficient r=0.56, P<0.05) Immunohistochemically, mucin-lake of CCP showed no staining for MUC5AX but positivity for MUC2. CONCLUSION: Tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC in association with the reduction of mast cell infiltration and MMP9 expression.

A Case of Sporadic Multiple Colonic Polyps in a Young Woman.

Sporadic colorectal cancer arises from an adenoma. As mutations in the adenomatous polyposis coli (APC) tumor suppressor gene have been frequently detected in colorectal adenomas, the APC gene is considered a gatekeeper in colorectal carcinogenesis. Here, we report a case of sporadic multiple colonic adenomas that were accompanied by an APC-truncating mutation. A 25-year-old Korean woman presented with dozens of incidentally found colonic polyps. There was no family history of colorectal polyposis or colon cancer in her first or second-degree relatives. All the polyps were removed endoscopically at once, and their pathological examination revealed tubular adenoma. Mutational analysis showed a 2-bp deletion mutation at codon 443, which generates a premature stop codon at codon 461 of the APC gene, and Western blot analysis demonstrated both wild-type and truncated APC proteins in adenoma tissue. This study suggests that a single truncating mutation of the APC gene may initiate adenoma formation.