NAFLD may be a common underlying liver disease in patients with hepatocellular Carcinoma in the United States

Jorge A. Marrero, Robert J. Fontana, Grace L. Su, Hari S. Conjeevaram, Dawn M. Emick, Anna S. Lok – 7 March 2007 – The incidence of hepatocellular carcinoma (HCC) in the United States is increasing, but the clinical characteristics of American patients with HCC have not been well described. The aims of this study were to determine the etiology of liver disease and short‐term outcome among HCC patients presenting to a single center in the United States. One hundred five consecutive patients with HCC were studied; mean age was 59 years, 67% were men, and 76% were non‐Hispanic white.

Cerebral microdialysis in patients with fulminant hepatic failure

Flemming Tofteng, Linda Jorgensen, Bent Adel Hansen, Peter Ott, Jens Kondrup, Fin Stolze Larsen – 7 March 2007 – Fulminant hepatic failure (FHF) is often complicated by high intracranial pressure (ICP) and fatal brain damage. In this study, we determined if a rise in [glutamate] ec and [lactate] ec preceded surges of high ICP in patients with FHF (median age, 42; range, 20–55 years; 7 women; 3 men) by inserting a microdialysis catheter into the brain‐cortex together with an ICP catheter. The microdialysis catheter was perfused with artificial cerebrospinal‐fluid at a rate of 0.3 μL/min.

Outfoxing liver cancer with p19ARF tumor suppressor?

Snorri S. Thorgeirsson – 7 March 2007 – Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated deaths worldwide. Here, we provide evidence that the Forkhead Box (Fox) m1b (Foxm1b or Foxm1) transcription factor is essential for the development of HCC. Conditionally deleted Foxm1b mouse hepatocytes fail to proliferate and are highly resistant to developing HCC in response to a Diethylnitrosamine (DEN)/Phenobarbital (PB) liver tumor‐induction protocol.

STAT‐3 and the liver: A new station on our way to understand diabetes?

Marcin T. Kortylewski, Andreas Barthel – 7 March 2007 – The transcription factor, signal transducer and activator of transcription‐3 (STAT‐3) contributes to various physiological processes. Here we show that mice with liver‐specific deficiency in STAT‐3, achieved using the Cre‐loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. Restoration of hepatic STAT‐3 expression in these mice, using adenovirus‐mediated gene transfer, corrected the metabolic abnormalities and the alterations in hepatic expression of gluconeogenic genes.

TRAIL‐mediated apoptosis requires NF‐kB inhibition and the mitochondrial permeability transition in human hepatoma cells

Young‐Soo Kim, Robert F. Schwabe, Ting Qian, John J. Lemasters, David A. Brenner – 7 March 2007 – Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) induces apoptosis in a wide range of malignant cells. However, several cancers, including human hepatoma, are resistant to TRAIL. In this study, we analyzed TRAIL‐induced pro‐ and antiapoptotic signaling pathways in human hepatoma cells. Nuclear factor k B (NF‐kB) was found to be a critical TRAIL‐induced antiapoptotic factor in the PLC/PRF/5, HepG2, and Hep3B cell lines.

Endothelin‐1 and heme oxygenase‐1 as modulators of sinusoidal tone in the stress‐exposed rat liver

Hauke Rensing, Inge Bauer, Jian X. Zhang, Markus Paxian, Benedikt H. J. Pannen, Yukihiro Yokoyama, Mark G. Clemens, Michael Bauer – 7 March 2007 – Heme oxygenase (HO)‐1 is up‐regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO‐1 leads to an increased portal pressor response in the stress‐exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up‐regulation of the vasoconstrictor endothelin (ET)‐1.

Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Feng Hong, Svetlana Radaeva, Hong‐Na Pan, Zhigang Tian, Richard Veech, Bin Gao – 7 March 2007 – Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology indluding ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time. We therefore examined the effects of 10 days of interleukin 6 (IL‐6) injection in 3 murine models of fatty liver: leptin deficient ob/ob mice, ethanol‐fed mice, and mice fed a high‐fat diet.

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