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

Five distinctly different types of naphthyl acetate esterase in rat liver were examined for study of liver enzymes during hepatocarcinogenesis. Three types of esterase in normal adult liver were separated by column chromatography. Main esterase in adult hepatocytes, which was demonstrated near the origin in cellulose acetate electrophoresis, was very sensitive to diisopropyl phosphorofluoridate (DFP). The other two esterases showed different electrophoretic mobility, while their Km values did not differ and both were considerably resistant to DFP. An anodic minor component in normal adult liver, which had a characteristic esterase pattern of infant liver, increased in the liver of rats fed 3'-methyl-4-(dimethylamino) azobenzene. This esterase was obtained by electrophoresis on Cellogel block. It was partially inhibited by DFP and p-chloromercuribenzoate, activated by cysteine, and showed a different Km value from the above esterases. Another minor component situated at the most cathodic side, which had characteristic esterase patterns of fetal liver and hepatoma, was very sensitive to DFP and eserine, and showed a characteristic of nonspecific cholinesterase as proved by staining.
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PMID:Some properties and electrophoretic patterns of rat liver esterases in relation to hepatocarcinogenesis by 3'-methyl-4-(dimethylamino) azobenzene. 18 20

Plasma membranes were purified from rat liver, muscle and sarcoma tissues and from human liver and hepatoma tissues. The plasma membranes all contained DFP-sensitive, neutral proteolytic activity. Plasma membranes from all normal tissues contained a single DFP-binding protein of apparent molecular weight 68,000. Only the plasma membranes from tumour tissue contained a plasminogen activator; the DFP-binding proteins from these membranes were more diverse than those from the normal samples. The rat liver plasma membrane proteinase was purified. It was a labile enzyme sensitive to inhibition by DFP and by calcium ions, and with a broad substrate specificity. A similar protein was the sole DFP-binding protein in rat liver microsomes. This and the properties of the enzyme suggested a possible role in the processing and secretion of newly-synthesized protein.
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PMID:Membrane proteinases from normal and neoplastic tissues in man and the rat. 609 93

The therapeutic effect of iron (Fe) chelators on the potentially toxic plasma pool of nontransferrin-bound iron (NTBI), often present in Fe overload diseases and in some cancer patients during chemotherapy, is of considerable interest. In the present investigation, several multidentate pyridinones were synthesized and compared with their bidentate analogue, deferiprone (DFP; L1, orally active) and desferrioxamine (DFO; hexadentate; orally inactive) for their effect on the metabolism of NTBI in the rat hepatocyte and a hepatoma cell line (McArdle 7777, Q7). Hepatoma cells took up much less NTBI than the hepatocytes (< 10%). All the chelators inhibited NTBI uptake (80-98%) much more than they increased mobilization of Fe from cells prelabelled with NTBI (5-20%). The hexadentate pyridinone, N,N,N-tris(3-hydroxy-1-methyl-2(1H)-pyridinone-4-carboxaminoethyl)amine showed comparable activity to DFO and DFP. There was no apparent correlation between Fe status, Fe uptake and chelator activity in hepatocytes, suggesting that NTBI transport is not regulated by cellular Fe levels. The intracellular distribution of iron taken up as NTBI changed in the presence of chelators suggesting that the chelators may act intracellularly as well as at the cell membrane. In conclusion (a) rat hepatocytes have a much greater capacity to take up NTBI than the rat hepatoma cell line (Q7), (b) all chelators bind NTBI much more effectively during the uptake phase than in the mobilization of Fe which has been stored from NTBI and (c) while DFP is the most active chelator, other multidentate pyridinones have potential in the treatment of Fe overload, particularly at lower, more readily clinically available concentrations, and during cancer chemotherapy, by removing plasma NTBI.
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PMID:Multidentate pyridinones inhibit the metabolism of nontransferrin-bound iron by hepatocytes and hepatoma cells. 1269 82