The mrp2 expression selleck kinase inhibitor of TAA was significantly higher than those of HCCwell, HCCmod, HPN and control (P < 0.01). The mrp2 expression of HPN tended to be higher than those of HCCwell and HCCmod. Conclusion:  It was suggested that the signal enhancement on Gd-EOB-DTPA-enhanced MRI would correlate with the transporter expression in various hepatocellular nodules during hepatocarcinogenesis. "
“Tumor cells are characterized by uncontrolled proliferation, often driven by activation of oncogenes,

and apoptosis resistance. The oncogenic kinase inhibitor sorafenib can significantly prolong median survival of patients with advanced hepatocellular click here carcinoma (HCC), although

the response is disease-stabilizing and cytostatic rather than one of tumor regression. Bcl-xL (B cell lymphoma extra large), an antiapoptotic member of the B cell lymphoma-2 (Bcl-2) family, is frequently overexpressed in HCC. Here, we present in vivo evidence that Bcl-xL overexpression is directly linked to the rapid growth of solid tumors. We also examined whether ABT-737, a small molecule that specifically inhibits Bcl-xL but not myeloid cell leukemia-1 (Mcl-1), could control HCC progression, especially when used with sorafenib. Administration of ABT-737, even at an in vivo effective dose, failed to suppress Huh7 xenograft tumors in mice. ABT-737 caused the levels of Mcl-1 expression to rapidly increase by protein stabilization. This appeared to be related to resistance to ABT-737, because decreasing Mcl-1 expression levels to the baseline by a small interfering RNA–mediated strategy made hepatoma cells sensitive to this agent. Importantly, administration of ABT-737 to Mcl-1 knockout mice 上海皓元 induced severe liver apoptosis, suggesting that tumor-specific inhibition

of Mcl-1 is required for therapeutic purposes. Sorafenib transcriptionally down-regulated Mcl-1 expression specifically in tumor cells and abolished Mcl-1 up-regulation induced by ABT-737. Sorafenib, not alone but in combination with ABT-737, efficiently induced apoptosis in hepatoma cells. This combination also led to stronger suppression of xenograft tumors than sorafenib alone. Conclusion: Bcl-xL inactivation by ABT-737 in combination with sorafenib was found to be safe and effective for anti-HCC therapy in preclinical models. Direct activation of the apoptosis machinery seems to unlock the antitumor potential of oncogenic kinase inhibitors and may produce durable clinical responses against HCC. (HEPATOLOGY 2010) The B cell lymphoma-2 (Bcl-2) family proteins regulate the mitochondrial pathway of apoptosis, a major form of cell death.