Clonality, activated antigen‐specific CD8+ T cells, and development of autoimmune cholangitis in dnTGFβRII mice

Kazuhito Kawata, Guo‐Xiang Yang, Yugo Ando, Hajime Tanaka, Weici Zhang, Yoshimasa Kobayashi, Koichi Tsuneyama, Patrick S.C. Leung, Zhe‐Xiong Lian, William M. Ridgway, Aftab A. Ansari, Xiao‐Song He, M. Eric Gershwin – 26 March 2013 – There are several murine models described with features similar to human primary biliary cirrhosis (PBC). Among these models, the one which has the closest serologic features to PBC is a mouse with a T‐cell‐restricted expression of the dominant negative transforming growth factor β receptor type II (dnTGFβRII).

miR‐148a plays a pivotal role in the liver by promoting the hepatospecific phenotype and suppressing the invasiveness of transformed cells

Luc Gailhouste, Laura Gomez‐Santos, Keitaro Hagiwara, Izuho Hatada, Noriyuki Kitagawa, Kazushi Kawaharada, Muriel Thirion, Nobuyoshi Kosaka, Ryou‐u Takahashi, Tatsuhiro Shibata, Atsushi Miyajima, Takahiro Ochiya – 26 March 2013 – MicroRNAs (miRNAs) are evolutionary conserved small RNAs that post‐transcriptionally regulate the expression of target genes. To date, the role of miRNAs in liver development is not fully understood.

Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: A critical role for E‐selectin

Adeline Bertola, Ogyi Park, Bin Gao – 26 March 2013 – Chronic plus binge ethanol feeding acts synergistically to induce liver injury in mice, but the mechanisms underlying this phenomenon remain unclear. Here, we show that chronic plus binge ethanol feeding synergistically up‐regulated the hepatic expression of interleukin‐1β and tumor necrosis factor alpha and induced neutrophil accumulation in the liver, compared with chronic or binge feeding alone.

Expression of SLC22A1 variants may affect the response of hepatocellular carcinoma and cholangiocarcinoma to sorafenib

Elisa Herraez, Elisa Lozano, Rocio I.R. Macias, Javier Vaquero, Luis Bujanda, Jesus M. Banales, Jose J.G. Marin, Oscar Briz – 26 March 2013 – Reduced drug uptake is an important mechanism of chemoresistance. Down‐regulation of SLC22A1 encoding the organic cation transporter‐1 (OCT1) may affect the response of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CGC) to sorafenib, a cationic drug. Here we investigated whether SLC22A1 variants may contribute to sorafenib chemoresistance.

Sirtuin‐6–dependent genetic and epigenetic alterations are associated with poor clinical outcome in hepatocellular carcinoma patients

Jens U. Marquardt, Kerstin Fischer, Katharina Baus, Anubha Kashyap, Shengyun Ma, Markus Krupp, Matthias Linke, Andreas Teufel, Ulrich Zechner, Dennis Strand, Snorri S. Thorgeirsson, Peter R. Galle, Susanne Strand – 23 March 2013 – Sirtuin 6 (SIRT6) is a member of the sirtuin family of NAD+–dependent deacetylases. Genetic deletion of Sirt6 in mice results in a severe degenerative phenotype with impaired liver function and premature death. The role of SIRT6 in development and progression of hepatocellular carcinoma is currently unknown.

Proteome‐wide analyses of human hepatocytes during differentiation and dedifferentiation

Cliff Rowe, Dave T. Gerrard, Roz Jenkins, Andrew Berry, Kesta Durkin, Lars Sundstrom, Chris E. Goldring, B. Kevin Park, Neil R. Kitteringham, Karen Piper Hanley, Neil A. Hanley – 23 March 2013 – Failure to predict hepatotoxic drugs in preclinical testing makes it imperative to develop better liver models with a stable phenotype in culture. Stem cell‐derived models offer promise, with differentiated hepatocyte‐like cells currently considered to be “fetal‐like” in their maturity.

The degree of liver injury determines the role of p21 in liver regeneration and hepatocarcinogenesis in mice

Laura Elisa Buitrago‐Molina, Silke Marhenke, Thomas Longerich, Amar Deep Sharma, Aristeidis E. Boukouris, Robert Geffers, Bruno Guigas, Michael P. Manns, Arndt Vogel – 23 March 2013 – Hepatocellular carcinoma (HCC) frequently arises in the context of chronic injury that promotes DNA damage and chromosomal aberrations. The cyclin‐dependent kinase inhibitor p21 is an important transcriptional target of several tumor suppressors, which promotes cell cycle arrest in response to many stimuli.

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