Vascular endothelial growth factor receptor-1 activation induces epithelial to mesenchmal transition in hepatocellular carcinoma cell line MHCC97-H / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the mechanism of increased invasion and migration of hepatocellular carcinoma (HCC) cells induced by vascular endothelial growth factor receptor-1 (VEGFR-1) activation.</p><p><b>METHODS</b>Vascular endothelial growth factor-B (VEGF-B) was used to induce and stimulate hepatocellular carcinoma cell line MHCC97-H. Morphologic changes of MHCC97-H were investigated. The expression of E-cadherin and alpha-catenin (two epithelial markers) and Vimentin and N-cadherin (two mesenchymal markers) was detected by reverse transcriptase polymerase chain reaction (RT- PCR), western blotting, and immunofluorescence staining. Cell invasion and migration test was performed.</p><p><b>RESULTS</b>Treatment of MHCC97-H cells with VEGF-B led to morphologic changes characteristic of epithelial to mesenchymal transition (EMT), including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Expression of the epithelial adhesion molecules, including E-cadherin and alpha-catenin, was decreased after VEGF-B treatment. Conversely, an increase in the expression of the mesenchymal cell markers, including N-cadherin and vimentin, was observed after VEGF-B treatment (P less than 0.05). VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state in which it was noted to be dispersed throughout the cytoplasm. Pretreatment with VEGFR-1 blocking antibody 18F1 inhibited the change in localization of E-cadherin induced by VEGF-B treatment. The ability of invasion and migration of MHCC97-H was enhanced by VEGF-B reatment (P less alpha 0.05).</p><p><b>CONCLUSION</b>Increased invasion and migration of HCC cells induced by VEGFR-1 activation was mediated by epithelial to mesenchymal transition.</p>

The expression and significance of vascular endothelial growth factor and its receptors in hepatocellular carcinoma cell lines with various metastatic potentialities / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To examine whether or not vascular endothelial growth factor (VEGF) and its receptors were expressed in hepatocellular carcinoma cell lines with various metastatic potentialities.</p><p><b>METHODS</b>Reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) and Western blot were employed to study the expressions of VEGFR-1, VEGFR-2, VEGF-A and VEGF-B in four hepatocellular carcinoma cell lines MHCC97-H, MHCC97-L, SMMC7721 and HepG-2 and one normal liver cell line L-02.</p><p><b>RESULTS</b>Three hepatocellular carcinoma cell lines (MHCC97-H, MHCC97-L, SMMC7721) expressed VEGFR-1 mRNA and their proteins. The expression level of VEGFR-1 in MHCC97-H was higher than that in MHCC97-L (P less than 0.05) and the expression level of VEGFR-1 in MHCC97-L was higher than that in SMMC7721 (P less than 0.05). No expression of VEGFR-1 was found in HepG-2 or L-02. All four hepatocellular carcinoma cell lines and the L-02 cell line expressed VEGFR-2 mRNA and the protein, as well as the VEGFR-1 ligands VEGF-A and VEGF-B. The expression level of VEGFR-2 in all tested hepatocellular carcinoma cell lines and normal liver cell line L-02 showed no significant differences (P more than 0.05).</p><p><b>CONCLUSION</b>VEGFR-1 was expressed in 4 hepatocellular carcinoma cell lines with various metastatic potentialities. The expression levels appeared to be positively correlated with the potentialities of metastasis of the hepatocellular carcinoma cell lines. VEGFR-1 may relate to the invasiveness and metastatic potential of the hepatocellular carcinoma.</p>

The influence of cold preservation on the microcirculation of intrahepatic bile duct after liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the influence of cold preservation on intrahepatic biliary microcirculation.</p><p><b>METHODS</b>Male Sprague Dawley (SD) rats were divided into 3 groups:cold preserve 1 h group (CP 1 h group), cold preserve 24 h group (CP 24 h group) and sham operation group (SO group). Five time points were determined as 0 h, 1 h, 6 h, 24 h and 72 h postoperation. Morphology was observed under light microscope. Dark microspheres were injected into hepatic artery and the number of microspheres in liver portal areas was measured under light microscope. The expressions of eNOS, ET-1 and ICAM-1 in microvascular endothelial cells of hepatic portal area were measured by immunofluorescence double staining technique and in situ hybridization histochemistry.</p><p><b>RESULTS</b>The histological changes of intrahepatic bile duct were more severe in CP 24 h group than in CP 1 h group. The number of microspheres in implanted liver portal areas was increased significantly in CP 24 h group than in CP 1 h group at the same time point. Compared with CP 1 h group, the expression of eNOS in CP 24 h group significantly reduced after liver transplantation, while the expressions of ET-1 and ICAM-1 in CP 24 h group were significantly increased after liver transplantation. The changes of their mRNA expressions were the approximately same as well as their proteins expressions.</p><p><b>CONCLUSIONS</b>Cold preservation brings obvious changes of intrahepatic biliary microcirculation and function of vascular endothelial cell after liver transplantation. The obstruction of microcirculation might play an important role in the reperfusion injury after cold preserve of intrahepatic biliary during liver transplantation.</p>

Liver transplantation for treating hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the role of orthotopic liver transplantation (OLT) in treating hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Data of 92 consecutive orthotopic liver transplantations (OLTs) performed during January 1999 and February 2005 at our institution were analyzed.</p><p><b>RESULTS</b>Of the 92 recipients, 8 HCC patients were stage I, 13 were stage II, 12 stage III and 59 stage IV (UICC TNM staging system). Overall 1-, 2-, 3-, 5-year patient survival rates were 65.3%, 27.0%, 20.0%, and 6.9%, respectively. When OLT indications were considered, best recipients survival was obtained in stage I patients (100.0%, 100.0%, 66.7%, and 50.0% at 1, 2, 3, and 5 years, respectively) and stage II patients (85.7%, 66.7%, and 66.7% at 1, 2 and 3 years, respectively). Whereas, 1, 2, 3 and 5-year recipients survival rates were 50.0%, 0, 0, 0 in stage III patients, and 58.1%, 20.0%, 13.0% and 5.0% in stage IV patients.</p><p><b>CONCLUSIONS</b>The prognosis of different stages of HCC patients who underwent OLT was significantly different. The OLT recipients with HCC should be strictly selected. Long-term recipient survival could be obtained in stage I and stage II patients.</p>

Primary duct closure versus T-tube drainage following laparoscopic choledochotomy / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of primary duct closure and T-tube drainage in laparoscopy choledochotomy to treat the common bile duct stones.</p><p><b>METHODS</b>The enrollment of the patients was in accordance with 6 criteria. 55 patients with cholecystolithiasis and secondary common bile duct stones from January 2000 to February 2003 were treated with laparoscopic choledochotomy. The patients were randomly divided into two groups: primary duct closure group and T-tube drainage group. Their all data were recorded and studied prospectively,and patients were followed up after discharge.</p><p><b>RESULTS</b>There were 27 patients and 28 patients in primary duct closure group and T-tube drainage group respectively. The operation time and the results of following up between the two groups had no significant difference. Compared with T-tube drainage group, primary duct closure group had less the total quantity of postoperative transfusion and hospital costs, shorter postoperative hospital stay. The incidence of postoperative complications in primary duct closure group was 11.1% (3/27), and all of them were biliary complications. The incidence of postoperative complications in T-tube drainage group was 28.6% (8/28), and seven of them were biliary complications. The incidence of severe complications that needed reoperations was 10.7% (93/28), and all of them were caused by T-tubes. There was no mortality in two groups.</p><p><b>CONCLUSIONS</b>The primary duct closure in laparoscopic choledochotomy can avoid the deficiency of T-tube drainage, and it is feasible and safe and lower complications in treating the common bile duct stones, so we advocate it in appropriate cases.</p>