The Crosstalk of miRNA and Oxidative Stress in the Liver: From Physiology to Pathology and Clinical Implications.

The liver is the central metabolic organ of mammals. In humans, most diseases of the liver are primarily caused by an unhealthy lifestyle-high fat diet, drug and alcohol consumption- or due to infections and exposure to toxic substances like aflatoxin or other environmental factors. All these noxae cause changes in the metabolism of functional cells in the liver.

The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression.

Post-translational modifications of chromatin components are significantly involved in the regulation of tumor suppressor gene and oncogene expression. Connective tissue growth factor (CTGF) is an epigenetically regulated growth factor with functions in angiogenesis and cell-matrix interactions and plays a pivotal role in hepatocellular carcinoma (HCC). The pharmacologic inhibition of histone and protein deacetylases represents a new approach to interfere with pathways of apoptosis and angiogenesis.

Combination of the deacetylase inhibitor panobinostat and the multi-kinase inhibitor sorafenib for the treatment of metastatic hepatocellular carcinoma - review of the underlying molecular mechanisms and first case report.

Advanced hepatocellular carcinoma still represents an unmet medical need that has only a limited overall survival despite the introduction of the multi-kinase inhibitor sorafenib. Recently, inhibitors of histone and other protein deacetylases have been established as novel therapeutic approaches to cancer diseases. We here review the molecular rationale for combining these two novel targeted therapies and report a patient with metastasized hepatocellular carcinoma who showed a partial remission of primary and metastatic lesions for five months after a combination therapy with sorafenib and the orally available pan-deacetylase inhibitor panobinostat.

Cannabinoid receptor type I modulates alcohol-induced liver fibrosis.

The cannabinoid system (CS) is implicated in the regulation of hepatic fibrosis, steatosis and inflammation, with cannabinoid receptors 1 and 2 (CB1 and CB2) being involved in regulation of pro- and antifibrogenic effects. Daily cannabis smoking is an independent risk factor for the progression of fibrosis in chronic hepatitis C and a mediator of experimental alcoholic steatosis. However, the role and function of CS in alcoholic liver fibrosis (ALF) is unknown so far.

Role of cannabinoid receptors and RAGE in inflammatory bowel disease.

Background: The endocannabinoid system is involved in many inflammatory diseases, such as Crohn's disease (CD) and ulcerative colitis (UC). The distribution and expression of cannabinoid receptors 1 (CNR1) and 2 (CNR2) in combination with inflammatory cytokines and RAGE (receptor of advanced glycation end products), which is also overactive in these diseases, in dependency of the extent of inflammation and alteration of the colon barrier is still unclear and needs to be elucidated.

Material And Methods: 10 specimens of CD patients who underwent colectomy and 14 colectomy specimens of patients suffering from UC were investigated histologically for inflammatory infiltrate, extent of fibrosis and for disturbance of the intestinal barrier.

The pan-deacetylase inhibitor panobinostat inhibits growth of hepatocellular carcinoma models by alternative pathways of apoptosis.

Inhibition of deacetylases represents a new treatment option for human cancer diseases. We applied the novel and potent pan-deacetylase inhibitor panobinostat (LBH589) to human hepatocellular carcinoma models and investigated by which pathways tumor cell survival is influenced. HepG2 (p53wt) and Hep3B (p53null) responded to panobinostat treatment with a reduction of cell proliferation and a significant increase in apoptotic cell death at low micromolar concentrations.

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo.

Tumor cells have the capability to trans- and to dedifferentiate, for example by reactivating embryonic development genes and stem cell characteristics. The aim of our study was to show the differential expression of stem- and progenitor cell markers in human hepatocellular carcinoma cell lines (HCC). Different human HCC cell lines (HUH7, HUH7 5-15, HUH7 pcDNA3.

The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice.

We investigated the effect of AEE788, a novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and Hep3B cells incubated with 0.1-100 microM AEE788 were quantified.