PT=peritumoral, T=tumoral. (TIF) Click here selleck chemicals Enzastaurin for additional data file.(9.2M, tif) Figure S6 LT�� expression in cell lines stably expressing individual HCV proteins. Huh7 cells were transduced with retroviral vectors coding for myc-tagged HCV1b proteins NS3, NS4A, core and NS5A, as indicated. Viral proteins expression was revealed by immunoblotting with an anti-myc monoclonal antibody. (TIF) Click here for additional data file.(7.6M, tif) Figure S7 p65 and LT�� are efficiently silenced by their cognate shRNA. NS5B-expressing and parental Huh7 cells were transduced with retroviral vectors encoding shRNA for p65 (A) or LT�� (B) and protein expression was assayed by immunoblotting. GAPDH served as a loading control. (TIF) Click here for additional data file.(7.
0M, tif) Acknowledgments We are grateful to Eric Jouffre and the animal facility at IGMM for animal care and the RHEMM histology platform for help with immunohistochemistry. We thank Daniel Olive, Ivan Hirsch and Eric Assenat for stimulating discussions and Thierry Gostan for statistical analysis. Funding Statement This work was supported by CNRS, INSERM, Agence Nationale pour le SIDA et les h��patites virales (ANRS : www.anrs.fr) 2011-1494 (to UH) and a post-doctoral fellowship to DG, Association pour la Recherche contre le Cancer (ARC : www.arc-cancer.net) pre-doctoral fellowship to LA and Ligue Nationale contre le Cancer (comit�� Pyr��n��es Orientales) for JP and NIH grants CA155120 and AI043477 to MK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Hepatocellular carcinoma (HCC) is the third most common cancer, the incidence of which is reportedly increasing worldwide [1]. Moreover, cases of advanced HCC, which is characterized by an extremely poor prognosis, are increasing in number. Recently, sorafenib, an oral multikinase inhibitor, was reported to improve the median overall survival rate in advanced HCC patients [2], [3]. However, it did not improve overall survival and prognosis in advanced HCC patients with portal vein tumor thrombosis (PVTT) [4]. Although interferon-alpha (IFN-��)/5-fluorouracil (5-FU) combination therapy showed favorable effects in advanced HCC patients [5], especially compared to those with PVTT [6], [7], [8], its maximum efficacy was only 25%�C50% in some countries including Japan and USA, suggesting that chemoresistance limits the therapeutic potential of IFN-�� and 5-FU.
To achieve more favorable outcomes in advanced HCC patients, advances in IFN-��/5-FU therapy are urgently required. However, Brefeldin_A limited information is currently available on the genes involved in enhancing chemosensitivity to this therapy. Several screening strategies using DNA microarray and RNA interference technologies are developed to identify genes with unrecognized functions.