Discovery of novel src homology region 2 domain‐containing phosphatase 1 agonists from sorafenib for the treatment of hepatocellular carcinoma

Wei‐Tien Tai, Chung‐Wai Shiau, Pei‐Jer Chen, Pei‐Yi Chu, Hsiang‐Po Huang, Chun‐Yu Liu, Jui‐Wen Huang, Kuen‐Feng Chen – 2 August 2013 – Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma (HCC). Here, we report that Src homology region 2 (SH2) domain‐containing phosphatase 1 (SHP‐1) is a major target of sorafenib and generates a series of sorafenib derivatives to search for potent SHP‐1 agonists that may act as better anti‐HCC agents than sorafenib.

Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease

Cynthia A. Moylan, Herbert Pang, Andrew Dellinger, Ayako Suzuki, Melanie E. Garrett, Cynthia D. Guy, Susan K. Murphy, Allison E. Ashley‐Koch, Steve S. Choi, Gregory A. Michelotti, Daniel D. Hampton, Yuping Chen, Hans L. Tillmann, Michael A. Hauser, Manal F. Abdelmalek, Anna Mae Diehl – 2 August 2013 – Clinicians rely upon the severity of liver fibrosis to segregate patients with well‐compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high‐ versus low‐risk for eventual liver‐related morbidity and mortality.

Changing donor characteristics in liver transplantation over the last 10 years in canada

Nathalie Sela, Kris P. Croome, Natasha Chandok, Paul Marotta, William Wall, Roberto Hernandez‐Alejandro – 2 August 2013 – Liver donor characteristics have a significant impact on graft quality and, in turn, recipient outcomes. In this study, we examined deceased liver donor characteristics and donor risk index (DRI) trends in Canada over the past decade. Data were extracted from the Canadian Organ Replacement Register and Transplant Québec for the decade (2000‐2010).

The role of macrophage migration inhibitory factor in autoimmune liver disease

David N. Assis, Lin Leng, Xin Du, Clarence K. Zhang, Gerrit Grieb, Melanie Merk, Alvaro Baeza Garcia, Catherine McCrann, Julius Chapiro, Andreas Meinhardt, Yuka Mizue, David J. Nikolic‐Paterson, Jürgen Bernhagen, Marshall M. Kaplan, Hongyu Zhao, James L. Boyer, Richard Bucala – 2 August 2013 – The role of the cytokine, macrophage migration inhibitory factor (MIF), and its receptor, CD74, was assessed in autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC).

MicroRNA‐494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer

Lionel Lim, Asha Balakrishnan, Noelle Huskey, Kirk D. Jones, Mona Jodari, Raymond Ng, Guisheng Song, Jesse Riordan, Brittany Anderton, Siu‐Tim Cheung, Holger Willenbring, Adam Dupuy, Xin Chen, David Brown, Aaron N. Chang, Andrei Goga – 2 August 2013 – Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC.

Highly efficient infectious cell culture of three hepatitis C virus genotype 2b strains and sensitivity to lead protease, nonstructural protein 5A, and polymerase inhibitors

Santseharay Ramirez, Yi‐Ping Li, Sanne B. Jensen, Jannie Pedersen, Judith M. Gottwein, Jens Bukh – 2 August 2013 – Hepatitis C virus (HCV) is a genetically diverse virus with multiple genotypes exhibiting remarkable differences, particularly in drug susceptibility. Drug and vaccine development will benefit from high‐titer HCV cultures mimicking the complete viral life cycle, but such systems only exist for genotypes 1a and 2a. We developed efficient culture systems for the epidemiologically important genotype 2b.

The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection

Jason Grebely, Kimberly Page, Rachel Sacks‐Davis, Maarten Schim Loeff, Thomas M. Rice, Julie Bruneau, Meghan D. Morris, Behzad Hajarizadeh, Janaki Amin, Andrea L. Cox, Arthur Y. Kim, Barbara H. McGovern, Janke Schinkel, Jacob George, Naglaa H. Shoukry, Georg M. Lauer, Lisa Maher, Andrew R. Lloyd, Margaret Hellard, Gregory J. Dore, Maria Prins, the InC3 Study Group – 2 August 2013 – Although 20%‐40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood.

Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation

Szun S. Tay, Bo Lu, Fred Sierro, Volker Benseler, Claire M. McGuffog, G. Alex Bishop, Peter J. Cowan, Geoffrey W. McCaughan, Karen M. Dwyer, David G. Bowen, Patrick Bertolino – 2 August 2013 – Donor passenger leukocytes (PLs) from transplanted livers migrate to recipient lymphoid tissues, where they are thought to induce the deletion of donor‐specific T cells and tolerance.

Subscribe to