Anemia during treatment with peginterferon Alfa‐2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT‐2) trial

Mark S. Sulkowski, Fred Poordad, Michael P. Manns, Jean‐Pierre Bronowicki, K. Rajender Reddy, Stephen A. Harrison, Nezam H. Afdhal, Heather L. Sings, Lisa D. Pedicone, Kenneth J. Koury, Vilma Sniukiene, Margaret H. Burroughs, Janice K. Albrecht, Clifford A. Brass, Ira M. Jacobson, for the SPRINT‐2 Trial Investigators – 18 October 2012 – Boceprevir (BOC) added to peginterferon alfa‐2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1.

Inhibition of mammalian target of rapamycin aggravates the respiratory burst defect of neutrophils from decompensated patients with cirrhosis

Loïc Rolas, Nesrine Makhezer, Soumeya Hadjoudj, Jamel El‐Benna, Bahia Djerdjouri, Laure Elkrief, Richard Moreau, Axel Périanin – 18 October 2012 – Cirrhosis is commonly accompanied by impaired defense functions of polymorphonuclear leucocytes (PMNs), increased patient susceptibility to infections, and hepatocellular carcinoma (HCC). PMN antimicrobial activity is dependent on a massive production of reactive oxygen species (ROS) by nicotinamide adenine dinucleotide phosphate (NADPH) 2 (NADPH oxidase 2; NOX2), termed respiratory burst (RB).

Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll‐like receptor–induced TIMP‐1 gene transcription in hepatic stellate cells in mice

Maria J. Perugorria, Lindsay B. Murphy, Nicola Fullard, Jayashree B. Chakraborty, Dimitra Vyrla, Caroline L. Wilson, Fiona Oakley, Jelena Mann, Derek A. Mann – 18 October 2012 – Toll‐like receptors (TLRs) function as key regulators of liver fibrosis and are able to modulate the fibrogenic actions of nonparenchymal liver cells. The fibrogenic signaling events downstream of TLRs on Kupffer cells (KCs) and hepatic stellate cells (HSCs) are poorly defined.

Recruitment of a myeloid cell subset (CD11b/Gr1mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis*

Lei Zhao, Su Yin Lim, Alex N. Gordon‐Weeks, Thomas T. Tapmeier, Jae Hong Im, Yunhong Cao, John Beech, Danny Allen, Sean Smart, Ruth J. Muschel – 18 October 2012 – Liver metastasis from colorectal cancer is a leading cause of cancer mortality. Myeloid cells play pivotal roles in the metastatic process, but their prometastatic functions in liver metastasis remain incompletely understood. To investigate their role, we simulated liver metastasis in C57BL/6 mice through intrasplenic inoculation of MC38 colon carcinoma cells.

β‐catenin regulates innate and adaptive immunity in mouse liver ischemia‐reperfusion injury

Bibo Ke, Xiu‐Da Shen, Naoko Kamo, Haofeng Ji, Shi Yue, Feng Gao, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski – 18 October 2012 – Dendritic cells (DCs) are critical mediators of immune responses that integrate signals from the innate immune system to orchestrate adaptive host immunity. This study was designed to investigate the role and molecular mechanisms of STAT3‐induced β‐catenin in the regulation of DC function and inflammatory responses in vitro and in vivo.

The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination

Muhammad N. Zahid, Marine Turek, Fei Xiao, Viet Loan Dao Thi, Maryse Guérin, Isabel Fofana, Philippe Bachellier, John Thompson, Leen Delang, Johan Neyts, Dorothea Bankwitz, Thomas Pietschmann, Marlène Dreux, François‐Loïc Cosset, Fritz Grunert, Thomas F. Baumert, Mirjam B. Zeisel – 18 October 2012 – Scavenger receptor class B type I (SR‐BI) is a high‐density lipoprotein (HDL) receptor highly expressed in the liver and modulating HDL metabolism.

Contribution of mature hepatocytes to small hepatocyte‐like progenitor cells in retrorsine‐exposed rats with chimeric livers

Ya‐Hui Chen, Mei‐Hwei Chang, Chin‐Sung Chien, Shang‐Hsin Wu, Chun‐Hsien Yu, Hui‐Ling Chen – 18 October 2012 – The potential lineage relationship between hepatic oval cells, small hepatocyte‐like progenitor cells (SHPCs), and hepatocytes in liver regeneration is debated. To test whether mature hepatocytes can give rise to SHPCs, rats with dipeptidyl peptidase IV (DPPIV) chimeric livers, which harbored endogenous DPPIV‐deficient hepatocytes and transplanted DPPIV‐positive hepatocytes, were subjected to retrorsine treatment followed by partial hepatectomy (PH).

Osteopontin promoter polymorphisms at locus ‐443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma

Qiong‐Zhu Dong, Xiao‐Fei Zhang, Yue Zhao, Hu‐Liang Jia, Hai‐Jun Zhou, Chun Dai, Hai‐Jing Sun, Yi Qin, Wei‐De Zhang, Ning Ren, Qing‐Hai Ye, Lun‐Xiu Qin – 18 October 2012 – Osteopontin (OPN) plays a crucial role in hepatocellular carcinoma (HCC) metastasis. However, little is known about the impact of OPN polymorphisms on cancer progression. In this study, we first identified the single nucleotide polymorphisms (SNPs) in the OPN promoter region by direct sequencing in 30 HCCs, and then evaluated the prognostic values of the selected ones in two large cohorts of 826 HCC patients.

Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk

Roongruedee Chaiteerakij, Ju Dong Yang, William S. Harmsen, Seth W. Slettedahl, Teresa A. Mettler, Zachary S. Fredericksen, W. Ray Kim, Gregory J. Gores, Rosebud O. Roberts, Janet E. Olson, Terry M. Therneau, Lewis R. Roberts – 11 October 2012 – The associations between diabetes, smoking, obesity, and intrahepatic cholangiocarcinoma (ICC) risk remain inconclusive. Metformin is purportedly associated with a reduced risk for various cancers. This case‐control study evaluated risk factors for ICC and explored the effects of metformin on ICC risk in a clinic/hospital‐based cohort.

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