The current data therefore suggest that upregulation of adenosine production abolished OSI-027 the suppressive effect of MTX on osteoclastic bone destruction. Involvement of the adenosine-A(2b)AR system may explain MTX resistance in
RA. Laboratory Investigation (2011) 91, 719-731; doi:10.1038/labinvest.2011.9; published online 21 February 2011″
“Imidazolium salts (IMSs) are precursors to N-heterocyclic carbenes (NHCs), which are routinely used as ligands or organo-catalysts in synthetic chemistry. We recently identified several IMSs as anti-fibrotic agents in liver fibrosis, which often has a consequence in the oncogenesis of hepatocellular carcinoma (HCC). Here, we investigate the potential anti-tumor property of three IMSs (named IBN-1, IBN-9, and DPIM) in HCC cell lines and in a xenograft mouse model. Our results showed that both IBN-1 and IBN-9 significantly inhibited the cell proliferation and arrested HCC cells in the G1-phase, whereas DPIM did not have any anti-tumor activity. When tested in a Huh7 HCC xenograft mouse model, IBN-1 reduced the tumor volume by 31% (P < 0.05), however accompanied by a 9% loss in body weight (P < 0.005), suggesting a general toxicity. In contrast, IBN-9 significantly reduced the tumor volume by 45% (P < 0.05) and 60% (P < 0.01) at doses of 0.6 and 1.5 g/l in drinking Panobinostat water, respectively, without any loss in body weight. Our in
vitro and in vivo data suggested that IBN-1 and IBN-9 inhibited the growth of HCC by suppressing the expression of Survivin and Cyclin-dependent kinases. The current study provides a proof of concept for using the metal-free IMSs to develop novel anti-cancer agents. Laboratory Investigation (2011) 91, 744-751; doi:10.1038/labinvest.2011.4; published online 21 February 2011″
“Hepatic fibrosis is the result of chronic liver injuries underlined by diverse etiologies. The massive accumulation of extracellular matrix (ECM) proteins during fibrogenesis
leads to structural distortion and functional disruption of the click here liver. There is currently no effective standard treatment for liver fibrosis. We previously identified a class of imidazolium salts (IMSs) with anti-fibrotic properties in a cell-based screen. In this report, we investigated the anti-fibrotic efficacy and mechanisms of a small IMS, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), in a hepatic fibrosis model induced by bile duct ligation (BDL) in mice. The orally available DPIM was administered to BDL mice via drinking water at three concentrations (0.5, 0.75, and 1 g/l) for 4 weeks. We observed a significant reduction in inflammation and collagen deposition in the liver, which could be mediated by a reduction in the expression of monocyte chemoattractant protein-1 (MCP-1) and by an enhancement in the matrix metalloproteinase-mediated ECM remodeling.