Tumor growth effects of rapamycin on human biliary tract cancer cells

<p>Abstract</p> <p>Background</p> <p>Liver transplantation is an important treatment option for patients with liver-originated tumors including biliary tract carcinomas <it>(</it>BTCs<it>).</it> Post-transplant tumor recurrence remains a limiting factor for long-term survival. The mammalian target of rapamycin-targeting immunosuppressive drug rapamycin could be helpful in lowering BTC recurrence rates. Therein, we investigated the antiproliferative effect of rapamycin on BTC cells and compared it with standard immunosuppressants.</p> <p>Methods</p> <p>We investigated two human BTC cell lines. We performed cell cycle and proliferation analyses after treatment with different doses of rapamycin and the standard immunosuppressants, cyclosporine A and tacrolimus.</p> <p>Results</p> <p>Rapamycin inhibited the growth of two BTC cell lines <it>in vitro</it>. By contrast, an increase in cell growth was observed among the cells treated with the standard immunosuppressants.</p> <p>Conclusions</p> <p>These results support the hypothesis that rapamycin inhibits BTC cell proliferation and thus might be the preferred immunosuppressant for patients after a liver transplantation because of BTC.</p

Inflammatory Cytokine Gene Expression in Mesenteric Adipose Tissue during Acute Experimental Colitis

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes