Tong Kan

A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis

Interferon-γ (IFN-γ) is considered essential for the regulation of anti-tumor reactions as it sensitizes Fas-related apoptosis in HT29 cells, but the mechanism is unclear. In the current study, our data demonstrated that IFN-γ stimulation and Fas activation suppressed Dicer processing and let-7 microRNA biogenesis, while let-7 microRNA strongly inhibited Fas expression by directly targeting Fas mRNA. Accordingly, our results indicate that Fas and let-7 microRNAs form a double-negative feedback loop in IFN-γ and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. We also found that a let-7 microRNA inhibitor increased Fas expression and sensitized cells to Fas-related apoptosis, which may have future implications in colon carcinoma therapy.

Bevacizumab Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

Results of en bloc resection for hepatocellular carcinoma extending to adjacent organs

BACKGROUND To curatively resect hepatocellular carcinoma (HCC) with adjacent organ extension, the combined resection of these organs is inevitable. We analyzed the safety and effectiveness of en bloc resection for HCC extending to adjacent organs. METHODS From December 2002 to May 2006, we compared the surgical outcomes of patients with HCC extending to adjacent organs with those of closely matched, randomly selected patients with HCC without adjacent organ extension. RESULTS We included 42 patients whose HCC extended to adjacent organs and 126 patients whose HCC did not extend to adjacent organs. There was no significant difference in survival, operative morbidity or mortality between the groups. In patients with HCC extending to adjacent organs, histopathological examination of the specimen revealed true tumour invasion in 13 and adhesion in 29 patients. Those with tumour invasion were more likely to have a high incidence of capsule infiltration, microvascular invasion and early intrahepatic recurrence (≤ 1 yr after hepatectomy). The 5-year overall survival of patients with tumour invasion was 11.5%, whereas that of patients with tumour adhesion was 38.1% (p = 0.033). CONCLUSION En bloc resection is a safe and effective therapy for HCC extending to adjacent organs. Tumour invasion to adjacent organs exhibits a more aggressive clinical behaviour and is associated with worse survival than tumour adhesion.

Infrahepatic inferior vena cava clamping in hepatectomy for tumors involving hepatocaval confluence

BACKGROUND Massive hemorrhage and the need for blood transfusion carry a high rate of morbidity and mortality after hepatectomy. The aim of this study was to evaluate the safety and potential benefit of infrahepatic inferior vena cava (IVC) clamping in hepatectomy for tumors involving hepatocaval confluence. METHODS We conducted a retrospective analysis of 113 consecutive patients who underwent hepatectomy with infrahepatic IVC clamping (n = 60, Group A) and without infrahepatic IVC clamping (n = 53, Group B) as the initial treatment for tumors involving hepatocaval confluence. RESULTS In Group A, central venous pressure reduced from 7.6 ± 3.2 to 4.4 ± 2.7 cm H₂O (p < 0.001). Patients in Group A experienced less blood loss (477.3 ± 340.3 vs. 794.5 ± 602.7 mL, p = 0.001), fewer blood transfusion requirements (8.3% vs. 22.6%, p = 0.034), lower postoperative complications (40% vs. 60.4%, p = 0.031), and shorter hospital stay (10.7 ± 2.2 vs. 12.9 ± 4.8 days, p = 0.008) than those in Group B. CONCLUSION Infrahepatic IVC clamping is generally effective and safe in controlling bleeding during hepatectomy for tumors involving hepatocaval confluence.