Hypoxia‐inducible factor 1 alpha–activated angiopoietin‐like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule‐1/integrin β1 signaling in human hepatocellular carcinoma

Hong Li, Chao Ge, Fangyu Zhao, Mingxia Yan, Chen Hu, Deshui Jia, Hua Tian, Miaoxin Zhu, Taoyang Chen, Guoping Jiang, Haiyang Xie, Ying Cui, Jianren Gu, Hong Tu, Xianghuo He, Ming Yao, Yongzhong Liu, Jinjun Li – 14 June 2011 – Angiopoietin‐like protein 4 (ANGPTL4) plays complex and often contradictory roles in vascular biology and tumor metastasis, but little is known about its function in hepatocellular carcinoma (HCC) metastasis.

Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4‐associated cholangitis from cholangiocarcinoma

Abdul M. Oseini, Roongruedee Chaiteerakij, Abdirashid M. Shire, Amaar Ghazale, Joseph Kaiya, Catherine D. Moser, Ileana Aderca, Teresa A. Mettler, Terry M. Therneau, Lizhi Zhang, Naoki Takahashi, Suresh T. Chari, Lewis R. Roberts – 14 June 2011 – Elevated serum immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4‐associated cholangitis (IAC); a >2‐fold increase in sIgG4 is considered highly specific for these disorders.

Interleukin‐22 promotes human hepatocellular carcinoma by activation of STAT3

Runqiu Jiang, Zhongming Tan, Lei Deng, Yun Chen, Yongxiang Xia, Yun Gao, Xuehao Wang, Beicheng Sun – 14 June 2011 – Interleukin‐22 (IL‐22), one of the cytokines secreted by T helper 17 (Th17) cells, was recently reported to be a novel inflammation driver through STAT3 signaling activation. We aimed to investigate the role of IL‐22 expression in hepatocellular carcinoma (HCC). We demonstrated significant up‐regulation of IL‐22 in human HCC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes.

Prolonged hepatomegaly in mice that cannot inactivate bacterial endotoxin

Baomei Shao, Richard L. Kitchens, Robert S. Munford, Thomas E. Rogers, Don C. Rockey, Alan W. Varley – 14 June 2011 – Transient hepatomegaly often accompanies acute bacterial infections. Reversible, dose‐dependent hepatomegaly also occurs when animals are given intravenous infusions of bacterial lipopolysaccharide (LPS). We found that recovery from LPS‐induced hepatomegaly requires a host enzyme, acyloxyacyl hydrolase (AOAH), that inactivates LPS.

Role of ethnicity in overweight and obese patients with nonalcoholic steatohepatitis

Romina Lomonaco, Carolina Ortiz‐Lopez, Beverly Orsak, Joan Finch, Amy Webb, Fernando Bril, Christopher Louden, Fermin Tio, Kenneth Cusi – 14 June 2011 – The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy‐proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat.

The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug‐induced liver injury

Ayako Suzuki, Elizabeth M. Brunt, David E. Kleiner, Rosa Miquel, Thomas C. Smyrk, Raul J. Andrade, M. Isabel Lucena, Agustin Castiella, Keith Lindor, Einar Björnsson – 14 June 2011 – Distinguishing drug‐induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH versus DILI.

Tumor‐secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts

Antonio Mazzocca, Francesco Dituri, Luigi Lupo, Michele Quaranta, Salvatore Antonaci, Gianluigi Giannelli – 14 June 2011 – Hepatocellular carcinoma (HCC) occurs in fibrotic liver as a consequence of underlying cirrhosis. The goal of this study was to investigate how the interaction between HCC cells and stromal fibroblasts affects tumor progression. We isolated and characterized carcinoma‐associated fibroblasts (CAFs) and paired peritumoral tissue fibroblasts (PTFs) from 10 different patients with HCC and performed coculture experiments.

Efficient production of Fah‐null heterozygote pigs by chimeric adeno‐associated virus‐mediated gene knockout and somatic cell nuclear transfer

Raymond D. Hickey, Joseph B. Lillegard, James E. Fisher, Travis J. McKenzie, Sean E. Hofherr, Milton J. Finegold, Scott L. Nyberg, Markus Grompe – 14 June 2011 – Hereditary tyrosinemia type I (HT1) results in hepatic failure, cirrhosis, and hepatocellular carcinoma (HCC) early in childhood and is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH). In a novel approach we used the chimeric adeno‐associated virus DJ serotype (AAV‐DJ) and homologous recombination to target and disrupt the porcine Fah gene.

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