Influence of liver regeneration after partial hepatectomy on the development of liver metastasis of colon cancer in rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the stimulated effect of liver regeneration on colon cancer cells in remnant liver in rats.</p><p><b>METHODS</b>Rat models with liver metastases or retro-peritoneal metastases of colon cancer were established: animals underwent 37% or 70% liver resection and were compared with a sham laparotomy (15, 25, 15 cases, respectively). Metastases were performed two weeks before resection. Rats were killed 3 weeks after the resection. Total body weight, liver and tumor weights were recorded. The human colon adenocarcinoma cell line Lovo was cultured in the presence of portal serum withdrawn 24 hours and 14 days after partial hepatectomy (PH). DNA synthesis was assessed by flow cytometry analysis for 5-Bromodeoxyuridine (5-BrdU) incorporation.</p><p><b>RESULTS</b>The tumor growth was accelerated in the remnant liver in 70% PH group, but the tumors in 37% PH group and retro-peritoneal site were not influenced by PH. Compared with the control group, after cultured 72 hours with portal serum withdrawn 24 h after PH, a higher 5-BrdU incorporation was found in the Lovo cell lines (P < 0.05), and it reached the peak after 120 hours of culture (P < 0.05). No difference was found between the groups when cultured with the portal serum withdrawn 14 d after PH (P > 0.05).</p><p><b>CONCLUSIONS</b>PH may accelerate the growth of residual microscopic tumor in the liver which contributes to local recurrence. It has no systemic effect and effects on the cancer cell lines in extrahepatic sites. The excision extension is related to the stimulating effects on the cancer cell line, and subtotal hepatectomy is presumably a major determinant.</p>

The roles of caveolin-1 and endothelial nitric oxide synthase in the development of portal hypertension in rats with liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the relationship between the dynamic changes of caveolin-1 with the degrees of liver fibrosis and portal venous pressure (PVP) in the process of rat liver cirrhosis formation induced by dimethylnitrosamine (DMN); also to investigate the mechanisms of caveolin-1 in the regulation of endothelial nitric oxide synthase (eNOS).</p><p><b>METHODS</b>Liver cirrhosis was induced in rats by DMN. The degrees of liver fibrosis and PVP were measured. NOS activity was assessed by citrulline generation. Protein expressions of caveolin-1, eNOS and caveolin-1-eNOS interactions were examined by Western blot and immunoprecipitation, respectively.</p><p><b>RESULTS</b>Four weeks after DMN administration, liver fibrosis was at its peak and then decreased gradually. Immunoprecipitation and Western blot demonstrated that there was enhanced binding of caveolin-1 with eNOS in the process of rat liver cirrhosis. An increase in caveolin-1 expression was detected but the expression of eNOS was lower in cirrhotic tissues than in normal liver tissues. Caveolin-1 protein levels were positively correlated with the degrees of liver fibrosis and the levels of PVP (r=0.967, P < 0.01; r=0.922, P < 0.01, respectively), while NOS catalytic activity was negatively correlated with the degrees of liver fibrosis and levels of PVP (r= 0.973, P < 0.01; r=-0.947, P < 0.01) respectively.</p><p><b>CONCLUSIONS</b>Caveolin-1 upregulation is associated with the development of portal hypertension in liver cirrhosis. Over-expression of caveolin-1 in perisinusoidal cells may promote caveolin-1-eNOS binding and reduce the activity of eNOS.</p>