Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that the administration of concanavalin A (ConA) into mice induces immune-mediated liver injury, which can be largely abrogated by neutralizing tumor necrosis factor(TNF)alpha. Vesnarinone is an experimental drug which is known to inhibit TNF alpha release. Here we demonstrate that vesnarinone inhibits ConA-induced hepatic injury. In a dose-dependent manner, vesnarinone inhibits in several mouse strains the increase of serum aminotransferase concentrations. additional experiments show that vesnarinone inhibits ConA-mediated accumulation of DNA fragmentation in the liver. Furthermore, the drug significantly reduces the levels of circulating TNF alpha and interleukin-6 (IL-6). Vesnarinone does not modulate TNF alpha and IL-6 action on hepatic cells, as shown by its failure to reduce the cytokine specific-stimulation of acute phase plasma proteins in the rat hepatoma H-35 cell line. Neither vesnarinone nor anti-TNF alpha protect against direct liver injury induced by a sublethal dose of agonist anti-Fas (CD95) antibody. Taken together, these results suggest that vesnarinone blocks hepatic injury, in part by inhibiting the release of TNF alpha in vivo.
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PMID:Vesnarinone inhibits immune-mediated but not Fas (CD95) agonist-mediated hepatic injury. 922 79

Vesnarinone, a quinolinone derivative, induces apoptosis and differentiation in some tumor cell lines. We examined the antitumor effect of vesnarinone on three human hepatocellular carcinoma (HCC) cell lines. Vesnarinone suppressed the proliferation of all three HCC cell lines, but did not induce apoptosis and differentiation. Vesnarinone has also been reported to inhibit both nucleoside and nucleobase transport. Concomitant administration of vesnarinone and a de novo nucleotide synthesis inhibitor potentiated the growth-inhibitory effect of vesnarinone on HCC cells. Vesnarinone may be useful as a new biochemical modulator of anticancer agents.
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PMID:Antitumor effect of vesnarinone on human hepatocellular carcinoma cell lines. 986 7