Expression of COX-2 and VEGF-C in cholangiocarcinomas at different clinical and pathological stages.

The aim of this study was to investigate the expression and clinical significance of cyclooxygenase 2 (COX-2) and vascular en-dothelial growth factor C (VEGF-C) in cholangiocarcinomas at differ-ent clinical and pathological stages. Eighty cholangiocarcinoma sam-ples of patients treated with surgery between January 2012 and January 2014 were collected. Immunohistochemistry was used to detect COX-2 and VEGF-C expression at different clinical and pathological stages. ELISA, real-time PCR, invasive chambers, and MTT assay were ap-plied in cultured cholangiocarcinoma cells treated with a COX-2 inhib-itor. Expression of COX-2 and VEGF-C correlated positively with the clinical TNM stage but did not correlate with the differentiation status. Inhibition of COX-2 activity reduced VEGF-C mRNA expression and secretion in cholangiocarcinoma cells and decreased their migration but not proliferation. Because of its ability to inhibit invasion, COX-2 could be a new target for treatment of cholangiocarcinoma.

Efficacy of percutaneous radiofrequency ablation for the treatment of hepatocellular carcinoma.

In this study, we sought to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA; experimental group) versus RFA treatment (control group) in patients receiving palliative treatment for hepatocellular carcinoma. To summarize the available evidence, we used the Review Manager 5.1 software to perform a meta-analysis of English-language articles published in public databases prior to 2014. Based on 6 studies that met the inclusion criteria, a total of 531 (experimental group, 272; control group, 259) patients with hepatocellular carcinoma were included in the meta-analysis. The meta-analysis demonstrated that the experimental group had a higher 3-year survival rate [risk ratios (RRs) = 1.41; 95% confidence interval (CI) = 1.03-1.94; P < 0.05] and a higher 2-year survival rate (RR = 1.11; 95%CI = 1.01-1.23; P < 0.05) than the control group. In the overall meta-analysis, the overall RRs were 2.02 (95%CI = 1.40-2.91; P < 0.05) and 1.63 (95%CI = 1.06-2.51; P < 0.05) for 3- and 5-year recurrence-free survival, respectively. Furthermore, the overall meta-analysis showed an overall RR of 0.75 (95%CI = 0.60-0.93; P < 0.05) for the incidence of tumor progression and an overall RR of 1.19 (95%CI = 0.33-4.33; P > 0.05) for the major complication rate. In a sensitivity analysis, the above mentioned meta-analytic estimates were unchanged by the removal of 1 study at a time. The meta-analysis suggested that the experimental group had a higher survival rate, a higher recurrence-free survival rate, and a lower incidence of tumor progression than the corresponding control group.

Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds.

The repair of critical-sized defects (CSDs) is a significant challenge in bone tissue engineering. Combining the use of progenitor cells with gene therapy represents a promising approach for bone regeneration. MicroRNAs play important roles in most gene regulatory networks, regulate the endogenous expression of multiple growth factors and simultaneously modulate stem cell differentiation. Our previous study showed that knocking down miR-31 promotes the osteogenesis of bone marrow stromal stem cells (BMSCs). To investigate the therapeutic potential of cells engineered to express anti-miR-31 for CSD repair, lentiviral vectors encoding negative control, miR-31 precursor and anti-sense sequences were constructed and transduced into osteo-inductive BMSCs. The expression of osteogenic-specific genes, alkaline phosphatase activity and Alizarin Red S staining were investigated to evaluate the effects of miR-31 on the cell fate of BMSCs over a 3-week period. In addition, miR-31-modified BMSCs seeded on poly(glycerol sebacate) (PGS) scaffolds were used to repair 8 mm critical-sized calvarial defects in rats. The results showed that miR-31 suppression significantly increased the expression of osteogenic-specific genes in vitro at the mRNA and protein levels, and that robust new bone formation with high local bone mineral density was observed in the anti-miR groups in vivo. Moreover, the PGS scaffolds carrying anti-miR-31-expressing BMSCs exhibited good biocompatibility and a high regeneration rate (~60%) within in vivo bone defects. Our results suggest that miR-31 gene delivery affects the potential of BMSCs for osteogenic differentiation and bone regeneration and that PGS is a potential substrate for genetically modified, tissue-engineered bone in the repair of large bone defects.