miR-145 regulates chemoresistance in hepatocellular carcinoma via epithelial mesenchymal transition.

Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular carcinoma (HCC) therapy. MicroRNA—145 (miR—145) has been shown to be down—regulated in several cancers and may be involved in the process of carcinogenesis. The present study aimed to evaluate the effects of miR—145 in adriamycin (ADM)—resistant human HCC cells. We found that miR—145 was significantly reduced in HepG2/ADM and HuH7/ADM cells compared with the chemosensitive parental cells. Up—regulation of miR—145 increased the ADM cytotoxicity in chemoresistant tumor cells. In addition, Smad3 was identified as the target of miR—145 and miR—145 overexpression inhibited Smad3 expression both at the mRNA and protein levels. The luciferase reporter assay confirmed that Smad3 was a direct target of miR—145. Moreover, up—regulation of miR—145 suppressed Smad3 related EMT features as shown by increased expression of E—cadherin and reduced vimentin level in HepG2/ADM and HuH7/ADM cells. Our study demonstrated that miR—145 modulated both chemoresistance and EMT in HCC cells, and up—regulation of miR—145 might be a potential therapeutic strategy for treatment of chemoresistant HCC.

Suitable calcineurin inhibitor concentrations for liver transplant recipients in the Chinese population.

AIM: The aim was to deduce suitable calcineurin inhibitor concentrations for the Chinese liver transplantation population. METHODS: We retrospectively studied 97 liver transplant recipients who displayed stable liver and renal function. No grafts were obtained from prisoners, procurements were performed with donor consent conforming to international ethics regulations. At 3, 6, and 12 months, we increased the concentrations and doses of calcineurin inhibitors as well as the values of alanine transaminase and serum creatinine. RESULTS: Twenty-eight recipients received cyclosporine and 69 tacrolimus. The mean cyclosporine daily dosages were 203 ± 62 mg at 3, 188 ± 55 mg at 6, and 173 ± 52 mg at 12 months, the tacrolimus daily dosages were 3.08 ± 0.98, 2.82 ± 0.98, and 2.58 ± 0.93 mg, respectively. The corresponding mean cyclosporine peak concentrations (C(2)) were 806 ± 322 ng/mL, 681 ± 206 ng/mL, and 644 ± 190 ng/mL and the mean tacrolimus trought concentrations (C(0)) 6.61 ± 3.02 ng/mL, 5.85 ± 2.44 ng/mL, and 5.22 ± 2.33 ng/mL, respectively. In both groups, transaminases and serum creatinine were stable over time. CONCLUSIONS: An individualized immunosuppressive regimen for the local population is necessary. We delayed calcineurin inhibitors with subsequent low-dose mycophenolate mofetil plus minimized calcineurin inhibitors, which seemed to be nephroprotective and safe for Chinese liver transplantation patients.