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.

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.

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.

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.

Entecavir therapy for lamivudine‐refractory chronic hepatitis B: Improved virologic, biochemical, and serology outcomes through 96 weeks

Morris Sherman, Cihan Yurdaydin, Halis Simsek, Marcelo Silva, Yun‐Fan Liaw, Vinod K. Rustgi, Hoel Sette, Naoky Tsai, Daniel J. Tenney, James Vaughan, Bruce Kreter, Robert Hindes, AI463026 Benefits of Entecavir for Hepatitis B Liver Disease (BEHoLD) Study Group – 20 June 2008 – In hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization.

Physical chemistry of intestinal absorption of biliary cholesterol in mice

David Q.‐H. Wang, Sum P. Lee – 20 June 2008 – Although many putative sterol transporters influencing cholesterol absorption and physical–chemical factors affecting dietary cholesterol absorption have been extensively investigated, it is still unclear how biliary cholesterol contributes to the regulation of intestinal cholesterol absorption. We studied whether the gallbladder can modulate the microaggregates of cholesterol carriers, which may in turn influence the intestinal absorption of biliary cholesterol.

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