Knockdown of ezrin causes intrahepatic cholestasis by the dysregulation of bile fluidity in the bile duct epithelium in mice

Ryo Hatano, Kaori Akiyama, Atsushi Tamura, Shigekuni Hosogi, Yoshinori Marunaka, Michael J. Caplan, Yoshiyuki Ueno, Sachiko Tsukita, Shinji Asano – 13 October 2014 – Cholangiopathies share common features, including bile duct proliferation, periportal fibrosis, and intrahepatic cholestasis. Damage of biliary epithelium by autoimunne disorder, virus infection, toxic compounds, and developmental abnormalities causes severe progressive hepatic disorders responsible for high mortality.

Differential effects of targeting Notch receptors in a mouse model of liver cancer

Erik G. Huntzicker, Kathy Hötzel, Lisa Choy, Li Che, Jed Ross, Gregoire Pau, Neeraj Sharma, Christian W. Siebel, Xin Chen, Dorothy M. French – 13 October 2014 – Primary liver cancer encompasses both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). The Notch signaling pathway, known to be important for the proper development of liver architecture, is also a potential driver of primary liver cancer. However, with four known Notch receptors and several Notch ligands, it is not clear which Notch pathway members play the predominant role in liver cancer.

Performance of modified‐release tacrolimus after conversion in liver transplant patients indicates potentially favorable outcomes in selected cohorts

Aisling Considine, J. Michael Tredger, Michael Heneghan, Kosh Agarwal, Marianne Samyn, Nigel D. Heaton, John G. O'Grady, Varuna R. Aluvihare – 13 October 2014 – Clinical outcomes, dose changes, and dose‐equalized tacrolimus concentrations were examined sequentially in 129 liver transplantation (LT) recipients after successful conversion to once daily modified‐release tacrolimus either early (within 1 month) or late (>1 month) after LT. The data were compared with data for a group of 60 patients maintained on twice daily conventional‐release tacrolimus.

βII‐Spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling by regulation of Wnt inhibitor kallistatin

Xiuling Zhi, Ling Lin, Shaoxian Yang, Krithika Bhuvaneshwar, Hongkun Wang, Yuriy Gusev, Mi‐Hye Lee, Bhaskar Kallakury, Narayan Shivapurkar, Katherine Cahn, Xuefei Tian, John L. Marshall, Stephen W. Byers, Aiwu R. He – 12 October 2014 – βII‐Spectrin (SPTBN1) is an adapter protein for Smad3/Smad4 complex formation during transforming growth factor beta (TGF‐β) signal transduction. Forty percent of SPTBN1+/− mice spontaneously develop hepatocellular carcinoma (HCC), and most cases of human HCC have significant reductions in SPTBN1 expression.

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