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)

Thymidine kinase, dTMP kinase, and DNA polymerase activities were determined in cell lines of AH hepatoma, L1210 leukemia, and Yoshida sarcoma that were sensitive and resistant to 5-fluorouracil (5-FU). It was found that the levels of these enzymes in tumor cells were not consistently related to the property of sensitivity to 5-FU. A marked difference was observed between sensitive and resistant cell lines of L1210 leukemia and Yoshida sarcoma in the uptake of labeled 5-FU into the acid-soluble, nucleotide, and RNA fractions, the rate of incorporation of 5-FU into these fractions being 3 to 5 times greater in sensitive tumor cells than in resistant tumor cells. The radioactivities in the acid-soluble fractions of AH44 (sensitive) and AH109A (resistant) were similar after incubation of these cells with labeled 5-FU in vitro. However, a smaller volume of ascites and lower cell number were observed in AH44 (sensitive)-bearing rats than in AH109A (resistant)-bearing rats. These in vivo results indicate that the 5-FU injected intraperitoneally was diluted by ascites more in AH109A (resistant)-bearing rats than in AH44 (sensitive)-bearing rats.
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PMID:Metabolism of 5-fluorouracil in sensitive and resistant tumor cells. 55 50

1-(1,3-Dihydroxy-2-propoxymethyl)-5,6-tetramethylene-uracil (DHPTU) is a newly synthesized acyclonucleoside which shows cytostatic properties. It was tested in Syrian hamster 6 days after heterotransplantation of Kirkman-Robbins hepatoma. A reduction of tumour weight by 61% was found 48 h after its intraperitoneal (i.p.) administration in doses of 20 mg per kg of body weight. Inhibition of tumour growth is accompanied by a reduction of dThd, dGuo and dTMP kinase activities in tumour cytosol (by 91% and 74% and 55%, respectively) and decrease in contents of dTTP, dGTP and dATP (by 92%, 77% and 67%, respectively) in dNTP pool. DHPTU is not phosphorylated by any tumour dN kinases, but undergoes cleavage with TU release in reaction catalyzed by the tumour cell enzyme, competitively inhibited by FA. After [14C]DHPTU or [14C]TU had been given i.p. to the animals with the tumour, 90% of the subcellular fraction labelling fell into the nuclear fraction. However, if [14C]DHPTU was administered with FA and DCF, 27% of radioisotope was found in the nuclear fractions and 68% in cytosol. Since DCF which prevented FA deamination to FB (which is not an inhibitor of the mentioned enzyme) reduces DHPTU-induced changes in activity of dN kinases and dTMP kinase in hepatoma cells, the cytostatic activity of DHPTU seems to be connected to an enzyme which releases TU from DHPTU.
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PMID:Growth inhibition of Kirkman-Robbins hepatoma by 1-(1,3-dihydroxy-2-propoxymethyl)-5,6-tetramethyleneuracil and possible mechanism of its biological activity. 256 Oct 52

Activites of the enzymes DNA polymerase, thymidine kinase, thymidylate kinase, thymidylate synthase, and deoxycytidylate deaminase have been measured in rat and human normal and neoplastic liver, in human fetal liver, and in cell lines derived from human hepatomas and rat transplantable hepatomas. The activities of these enzymes were increased in rat transplantable hepatomas, relative to rat normal or host liver, to a degree corresponding to the rapid growth rate of these tumors. With the exception of thymidine kinase, which did not change, the activities of these enzymes increased in human hepatomas relative to the corresponding host liver (apparently normal liver tissue from the same patient) and to human normal liver. The increases in enzyme activity observed in human hepatomas were small in comparison with those found in the rapidly growing rat hepatomas. The activities of deoxycytidylate deaminase in both human and rat liver tissues were 2 to 3 orders of magnitude higher than those of the other enzymes assayed. Activities of the enzymes of DNA synthesis in a slow-growing cell line derived from a human hepatoma were similar to those in human hepatoma tissues. In the case of rapidly growing cell lines derived from rat and human hepatomas, enzyme activities were higher than those in the corresponding tissues.
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PMID:Activities of some enzymes of pyrimidine and DNA synthesis in a rat transplantable hepatoma and human primary hepatomas, in cell lines derived from these tissues, and in human fetal liver. 624 89