Liver international : official journal of the International Association for the Study of the Liver
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Comparative Study
Functional hepatocellular regeneration in elderly patients undergoing hepatectomy.
More than 50% of liver tumours occur in patients aged 65 years or more. Assessment of functional liver regeneration capacity is crucial to minimize postoperative liver failure. We aimed to study functional hepatocellular regeneration, through scintigraphic quantification of Mebrofenin hepatic extraction fraction (HEF), after partial hepatectomy, comparing elderly patients with younger ones. ⋯ Our results suggest that functional hepatocellular regeneration is early, fast and similar between elderly and younger patients. Thus, age alone, does not appear to represent an absolute contraindication to hepatectomy.
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The molecular cochaperone CDC37 regulates the activities of multiple protein kinases, and is an attractive broad-spectrum target in many types of cancers in which it is over-expressed. This study investigates the antitumour effects of inhibiting CDC37 in human hepatocellular carcinoma (HCC). ⋯ On the basis of the observed antitumour effects of inhibiting CDC37 expression, we propose that CDC37 is a promising therapeutic target in HCC. Its ability to regulate multiple pathways makes it potentially valuable in treating the heterogeneous subtypes of this malignancy.
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Serum concentrations of miR-122 were proposed as a marker for various inflammatory diseases, but the mechanisms driving alterations in miR-122 serum levels are unknown. ⋯ In mice and humans, miR-122 levels represent an independent and potent marker of ongoing liver injury and hepatic cell death regardless of the underlying disease.
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Cabozantinib, a small-molecule multitargeted tyrosine kinase inhibitor, has entered into a phase III clinical trial for the treatment of hepatocellular carcinoma (HCC). This study assessed the mechanistic effect of cabozantinib on the reversal of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). ⋯ Cabozantinib reverses P-gp-mediated MDR by directly inhibiting the efflux function of P-gp, indicating that cabozantinib may help to reverse P-gp-mediated MDR in HCC and other cancer chemotherapy.
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A critical role of the Toll-like receptor (TLR)-4 and its downstream mediators in the pathogenesis of small-for-size liver graft injury has been documented. Recently, the microRNA-146 (miR-146) was identified as a potent negative regulator of the TLR4 signalling pathway. In this study, the role of miR-146a and miR-146b in the attenuation of TLR-4 signalling and small-for-size liver graft injury was investigated. ⋯ miR-146a and miR-146b prevent liver injury in small-for-size liver graft injury via the inactivation of IRAK1 and TRAF6.