Hypoxia‐mediated sorafenib resistance can be overcome by EF24 through Von Hippel‐Lindau tumor suppressor‐dependent HIF‐1α inhibition in hepatocellular carcinoma

Yingjian Liang, Tongsen Zheng, Ruipeng Song, Jiabei Wang, Dalong Yin, Luoluo Wang, Haitao Liu, Lantian Tian, Xiang Fang, Xianzhi Meng, Hongchi Jiang, Jiaren Liu, Lianxin Liu – 8 January 2013 – The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low.

Cost‐effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma

Calogero Cammà, Giuseppe Cabibbo, Salvatore Petta, Marco Enea, Massimo Iavarone, Antonio Grieco, Antonio Gasbarrini, Erica Villa, Claudio Zavaglia, Raffaele Bruno, Massimo Colombo, Antonio Craxì, on behalf of the WEF and the SOFIA study groups – 8 January 2013 – The purpose was to assess the cost‐effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study.

Hepatic‐specific activation of peroxisome proliferator‐activated receptor γ coactivator‐1β protects against steatohepatitis

Elena Bellafante, Stefania Murzilli, Lorena Salvatore, Dominga Latorre, Gaetano Villani, Antonio Moschetta – 8 January 2013 – Development of hepatic steatosis and its progression to steatohepatitis may be the consequence of dysfunction of several metabolic pathways, such as triglyceride synthesis, very low‐density lipoprotein (VLDL) secretion, and fatty acid β‐oxidation. Peroxisome proliferator‐activated receptor γ coactivator‐1β (PGC‐1β) is a master regulator of mitochondrial biogenesis and oxidative metabolism, lipogenesis, and triglyceride (TG) secretion.

Reticulon 4B (Nogo‐B) facilitates hepatocyte proliferation and liver regeneration in mice

Lili Gao, Teruo Utsumi, Keitaro Tashiro, Bo Liu, Dahai Zhang, E. Scott Swenson, Yasuko Iwakiri – 8 January 2013 – Nogo‐B, also known as reticulon 4B, promotes liver fibrosis and cirrhosis by facilitating the transforming growth factor β (TGF‐β) signaling pathway in activated hepatic stellate cells. The aim of this study was to determine the role of Nogo‐B in hepatocyte proliferation and liver regeneration. Partial hepatectomy (PHx, 70% resection) was performed in male wild‐type (WT) and Nogo‐A/B knockout mice (referred to as Nogo‐B KO mice).

Ammonia detoxification via ureagenesis in rat hepatocytes involves mitochondrial aquaporin‐8 channels

Leandro R. Soria, Julieta Marrone, Giuseppe Calamita, Raúl A. Marinelli – 8 January 2013 – Hepatocyte mitochondrial ammonia detoxification via ureagenesis is critical for the prevention of hyperammonemia and hepatic encephalopathy. Aquaporin‐8 (AQP8) channels facilitate the membrane transport of ammonia. Because AQP8 is expressed in hepatocyte inner mitochondrial membranes (IMMs), we studied whether mitochondrial AQP8 (mtAQP8) plays a role in ureagenesis from ammonia.

Molecular subtype and response to dasatinib, an Src/Abl small molecule kinase inhibitor, in hepatocellular carcinoma cell lines in vitro

Richard S. Finn, Alexey Aleshin, Judy Dering, Peter Yang, Charles Ginther, Amrita Desai, Danyun Zhao, Erika von Euw, Ronald W. Busuttil, Dennis J. Slamon – 8 January 2013 – Hepatocellular carcinoma (HCC) is the fifth most common malignancy and is the third leading cause of cancer death worldwide. Recently, the multitargeted kinase inhibitor sorafenib was shown to be the first systemic agent to improve survival in advanced HCC.

Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease

Karima Begriche, Julie Massart, Marie‐Anne Robin, Fabrice Bonnet, Bernard Fromenty – 8 January 2013 – The worldwide epidemic of obesity and insulin resistance favors nonalcoholic fatty liver disease (NAFLD). Insulin resistance (IR) in the adipose tissue increases lipolysis and the entry of nonesterified fatty acids (NEFAs) in the liver, whereas IR‐associated hyperinsulinemia promotes hepatic de novo lipogenesis. However, several hormonal and metabolic adaptations are set up in order to restrain hepatic fat accumulation, such as increased mitochondrial fatty acid oxidation (mtFAO).

Toll‐like receptor 4 activity protects against hepatocellular tumorigenesis and progression by regulating expression of DNA repair protein Ku70 in mice

Ziyan Wang, Jun Yan, Heng Lin, Fang Hua, Xiaoxing Wang, Hanzhi Liu, Xiaoxi Lv, Jiaojiao Yu, Su Mi, Jiaping Wang, Zhuo‐Wei Hu – 8 January 2013 – Hepatocellular carcinoma (HCC) is a devastating consequence of chronic inflammatory liver diseases. The goal of this study was to investigate whether Toll‐like receptor 4 (TLR4) activity contributes to HCC initiation and progression in mice.

Retinol binding protein 4 stimulates hepatic sterol regulatory element‐binding protein 1 and increases lipogenesis through the peroxisome proliferator‐activated receptor‐γ coactivator 1β‐dependent pathway

Min Xia, Yan Liu, Honghui Guo, Duan Wang, Yun Wang, Wenhua Ling – 8 January 2013 – Recent studies have revealed the essential role of retinol binding protein 4 (RBP4) in insulin resistance. However, the impact of RBP4 on aberrant lipogenesis, the common hepatic manifestation in insulin resistance states, and the underlying mechanism remain elusive. The present study was designed to examine the effect of RBP4 on sterol regulatory element‐binding protein (SREBP‐1) and hepatic lipogenesis.

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