Purpose: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential). Experimental Design: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases. Results: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner. Conclusion: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis.
Abstract:Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.
BackgroundDistribution equity assessment of computed tomography (CT) and magnetic resonance imaging (MRI) scanners is an important dimension of access to health technology. However, limited studies on the subject have been done in China. This study aims to reveal the distribution status of CT and MRI scanners and assess their distribution equity of them in China.MethodsFive provinces with 66 cities from China were selected as the study sites. Descriptive analysis was used for the absolute number and number per million population of CT and MRI scanners in the study sites. Fixed effect model was used to examine the health service factors that were associated with the allocation of CT and MRI scanners. The Gini coefficient and concentration index was used to evaluate the distribution equity of CT and MRI scanners.ResultsThe absolute number and number per million population of CT and MRI scanners in five provinces were lower than those of Organization for Economic Co-operation and Development (OECD) countries, but annual growth rates were relatively higher from 2005 or 2006 to 2013. Population, GDP, number of hospitals, number of health professionals, number of hospital beds, number of outpatient visits, and number of inpatient visits all had a positive correlation with the allocation number of CT and MRI scanners. Moreover, the number of health professionals and the number of beds had a much closer correlation than other variables. All the Gini coefficients of CT and MRI had decreased overall. The concentration indices of CT and MRI were all positive and no more than 0.30.ConclusionsLarge gaps in the number of CT and MRI scanners per million population between China and OECD countries emerge, although the growth rate is higher in China. The distribution equity of CT and MRI scanners in China was relatively good from 2005 or 2006 to 2013. The overall distribution equity of CT and MRI scanners also improved during the period. However, consideration attention should be given to the area with large economic disparities.
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