A novel interaction of nucleophosmin with BCL2‐associated X protein regulating death evasion and drug sensitivity in human hepatoma cells

Shao‐Jung Lo, Li‐Ching Fan, Yow‐Fu Tsai, Kuo‐Yang Lin, Hsiao‐Ling Huang, Tong‐Hong Wang, Hsuan Liu, Tse‐Chin Chen, Shiu‐Fen Huang, Chee‐Jen Chang, Yu‐Jr Lin, Benjamin Yat‐Ming Yung, Sen‐Yung Hsieh – 19 December 2012 – Death evasion is crucial for both carcinogenesis and resistance to anticancer therapies. Recently, we identified nucleophosmin (NPM) as a key factor counteracting death stimuli in human hepatocellular carcinoma (HCC) cells. Here we report the identification of a novel NPM‐BCL2‐associated X protein (BAX) pathway orchestrating death evasion in human HCC cells.

Characterization of the regulation and function of zinc‐dependent histone deacetylases during rodent liver regeneration

Jiansheng Huang, Emily Barr, David A. Rudnick – 19 December 2012 – The studies reported here were undertaken to define the regulation and functional importance of zinc‐dependent histone deacetylase (Zn‐HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH.

Argonaute2 promotes tumor metastasis by way of up‐regulating focal adhesion kinase expression in hepatocellular carcinoma

Na Cheng, Yandong Li, Ze‐Guang Han – 19 December 2012 – Hepatocellular carcinoma (HCC) is one of the most common cancers and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. However, the mechanisms that contribute to tumor metastasis remain unclear. Here we evaluate the effect of Argonaute2 (Ago2), a member of the Ago gene family that plays a role in short interfering RNA‐mediated gene silencing, on HCC tumorigenesis, and metastasis. We found that Ago2 was frequently up‐regulated in HCC specimens compared to that in corresponding adjacent nontumor liver.

High lipophilicity and high daily dose of oral medications are associated with significant risk for drug‐induced liver injury

Minjun Chen, Jürgen Borlak, Weida Tong – 19 December 2012 – Drug‐induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals from the market. Although there is evidence that dosages of ≥100 mg/day are associated with increased risk for hepatotoxicity, many drugs are safe at such dosages. There is an unmet need to predict risk for DILI more reliably, and lipophilicity might be a contributing factor.

Association of γ‐glutamyl transferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV)

James E. Everhart, Elizabeth C. Wright – 19 December 2012 – Increased γ‐glutamyl transferase (GGT) activity is associated with liver injury and with mortality in the general population. Less is known about its association with chronic hepatitis C (HCV) outcomes. We examined GGT as a predictor of both virological response to treatment and long‐term clinical outcomes in the Hepatitis C Anti‐viral Treatment Against Cirrhosis Trial (HALT‐C).

Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents

Ina Rittelmeyer, Michael Rothe, Martijn H. Brugman, Marcus Iken, Axel Schambach, Michael P. Manns, Christopher Baum, Ute Modlich, Michael Ott – 19 December 2012 – Lentiviral (LV) vectors are promising tools for long‐term genetic correction of hereditary diseases. In hematopoietic stem cell gene therapies adverse events in patients due to vector integration‐associated genotoxicity have been observed. Only a few studies have explored the potential risks of LV gene therapy targeting the liver.

Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus–infected and ‐uninfected men who have sex with men

Yu‐Tzu Tseng, Sui‐Yuan Chang, Wen‐Chun Liu, Hsin‐Yun Sun, Cheng‐Hsin Wu, Pei‐Ying Wu, Ching‐Lan Lu, Chien‐Ching Hung, Shan‐Chwen Chang – 19 December 2012 – The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)‐infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV‐uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study.

Absence of receptor interacting protein kinase 3 prevents ethanol‐induced liver injury

Sanjoy Roychowdhury, Megan R. McMullen, Sorana G. Pisano, Xiuli Liu, Laura E. Nagy – 14 December 2012 – Hepatocyte cell death via apoptosis and necrosis are major hallmarks of ethanol‐induced liver injury. However, inhibition of apoptosis is not sufficient to prevent ethanol‐induced hepatocyte injury or inflammation. Because receptor‐interacting protein kinase (RIP) 3–mediated necroptosis, a nonapoptotic cell death pathway, is implicated in a variety of pathological conditions, we tested the hypothesis that ethanol‐induced liver injury is RIP3‐dependent and RIP1‐independent.

Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy

Gregory T. Everson, John C. Hoefs, Claus U. Niemann, Kim M. Olthoff, Robert Dupuis, Shannon Lauriski, Andrea Herman, Norah Milne, Brenda W. Gillespie, Nathan P. Goodrich, James E. Everhart – 13 December 2012 – We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation.

Liver transplantation after stage II palliation for hypoplastic left heart syndrome

Flavia H. Feier, Joao Seda Neto, Gilda Porta, Eduardo A. Fonseca, Rodrigo Vincenzi, Helry L. Cândido, Marcel Benavides, Bernardo Ketzer, Renata Pugliese, Irene K. Miura, Vera Baggio, Teresa Guimarães, Adriana Porta, Gustavo Foronda, Enis Donizete, Jose P. da Silva, Lucilia Faria, Mario Kondo, Paulo Chapchap – 13 December 2012 – The association of biliary atresia (BA) with congenital heart diseases has been extensively described, and there are a number of reports on the outcomes of patients in this group who undergo liver transplantation (LT).

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