Accelerated liver regeneration and hepatocarcinogenesis in mice overexpressing serine‐45 mutant β‐catenin

Kari N. Nejak‐Bowen, Michael D. Thompson, Sucha Singh, William C. Bowen, Mohd Jamal Dar, Jaspal Khillan, Chunsun Dai, Satdarshan P.S. Monga – 22 April 2010 – The Wnt/β‐catenin pathway is implicated in the pathogenesis of hepatocellular cancer (HCC). We developed a transgenic mouse (TG) in the FVB strain that overexpresses Ser45‐mutated‐β‐catenin in hepatocytes to study the effects on liver regeneration and cancer. In the two independent TG lines adult mice show elevated β‐catenin at hepatocyte membrane with no increase in the Wnt pathway targets cyclin‐D1 or glutamine synthetase.

Down‐regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Li Fu, Sui‐Sui Dong, Yi‐Wu Xie, Lai‐Shan Tai, Leilei Chen, Kar Lok Kong, Kwan Man, Dan Xie, Yan Li, Yingduan Cheng, Qian Tao, Xin‐Yuan Guan – 22 April 2010 – Loss of 16q is one of the most frequent alterations in many malignancies including hepatocellular carcinomas (HCC), suggesting the existence of a tumor suppressor gene (TSG) within the frequently deleted region. In this report we describe the identification and characterization of one candidate TSG, tyrosine aminotransferase gene (TAT), at 16q22.1.

Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus

Josephine Simonetti, Lisa Bulkow, Brian J. McMahon, Chriss Homan, Mary Snowball, Susan Negus, James Williams, Stephen E. Livingston – 22 April 2010 – Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated.

Hepatic glycosphingolipid deficiency and liver function in mice

Richard Jennemann, Ulrike Rothermel, Shijun Wang, Roger Sandhoff, Sylvia Kaden, Ruud Out, Theo J. van Berkel, Johannes M. Aerts, Karen Ghauharali, Carsten Sticht, Hermann‐Josef Gröne – 22 April 2010 – Recent studies have reported that glycosphingolipids (GSLs) might be involved in obesity‐induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin resistance accompanied by improved glycemic control and decreased liver steatosis in obese mice. In addition, pharmacologic GSL depletion altered hepatic secretory function.

Generation of endoderm‐derived human induced pluripotent stem cells from primary hepatocytes

Hua Liu, Zhaohui Ye, Yonghak Kim, Saul Sharkis, Yoon‐Young Jang – 22 April 2010 – Recent advances in induced pluripotent stem (iPS) cell research have significantly changed our perspective on regenerative medicine. Patient‐specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to human embryonic stem (hES) cells or are safer than hES cells.

Dissociation between liver inflammation and hepatocellular damage induced by carbon tetrachloride in myeloid cell–specific signal transducer and activator of transcription 3 gene knockout mice

Norio Horiguchi, Fouad Lafdil, Andrew M. Miller, Ogyi Park, Hua Wang, Mohanraj Rajesh, Partha Mukhopadhyay, Xin Yuan Fu, Pal Pacher, Bin Gao – 22 April 2010 – Liver injury is associated with inflammation, which is generally believed to accelerate the progression of liver diseases; however, clinical data show that inflammation does not always correlate with hepatocelluar damage in some patients.

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