Orphan receptor small heterodimer partner suppresses tumorigenesis by modulating cyclin D1 expression and cellular proliferation

Yuxia Zhang, Ping Xu, Kyungtae Park, Yunhee Choi, David D. Moore, Li Wang – 20 June 2008 – The small heterodimer partner (SHP; NROB2), a member of the nuclear receptor superfamily, contributes to the biological regulation of several major functions of the liver. However, the role of SHP in cellular proliferation and tumorigenesis has not been investigated before. Here we report that SHP negatively regulates tumorigenesis both in vivo and in vitro.

R1626 plus peginterferon Alfa‐2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin

Paul J. Pockros, David Nelson, Eliot Godofsky, Maribel Rodriguez‐Torres, Gregory T. Everson, Michael W. Fried, Reem Ghalib, Stephen Harrison, Lisa Nyberg, Mitchell L. Shiffman, Isabel Najera, Anna Chan, George Hill – 20 June 2008 – R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time‐dependent and dose‐dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa‐2a ± ribavirin in HCV genotype 1‐infected treatment‐naive patients.

Hepatitis C virus–infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells

Takashi Ebihara, Masashi Shingai, Misako Matsumoto, Takaji Wakita, Tsukasa Seya – 20 June 2008 – Dendritic cell maturation critically modulates antiviral immune responses, and facilitates viral clearance. Hepatitis C virus (HCV) is characterized by its high predisposition to persistent infection. Here, we examined the immune response of human monocyte‐derived dendritic cells (MoDCs) to the JFH1 strain of HCV, which can efficiently replicate in cell culture. However, neither HCV RNA replication nor antigen production was detected in MoDCs inoculated with JFH1.

CD40ligand‐expressing dendritic cells induce regression of hepatocellular carcinoma by activating innate and acquired immunity in vivo

Maria A. Gonzalez‐Carmona, Veronika Lukacs‐Kornek, Anne Timmerman, Sara Shabani, Miroslaw Kornek, Annabelle Vogt, Yildiz Yildiz, Elisabeth Sievers, Ingo G.H. Schmidt‐Wolf, Wolfgang H. Caselmann, Tilman Sauerbruch, Volker Schmitz – 20 June 2008 – Dendritic cells (DCs) are professional antigen‐presenting cells able to prime T‐cells against tumor‐associated antigens (TAA), but their potential to induce hepatocellular carcinoma (HCC) regression is still limited. CD40/CD40L interaction is essential for DC activation and induction of antigen‐specific T‐cells.

Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy

Ahmed El‐Shamy, Motoko Nagano‐Fujii, Noriko Sasase, Susumu Imoto, Soo‐Ryang Kim, Hak Hotta – 20 June 2008 – A substantial proportion of hepatitis C virus (HCV)‐1b–infected patients still do not respond to interferon‐based therapy. This study aims to explore a predictive marker for the ultimate virological response of HCV‐1b–infected patients treated with pegylated interferon/ribavirin (PEG‐IFN/RBV) combination therapy. Nonstructural protein 5A (NS5A) sequences of HCV in the pretreated sera of 45 patients infected with HCV‐1b were analyzed.

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