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)

Studies were made on the effects of inosine, guanosine 5'-monophosphate (GMP), cytidine, uridine, thymidine, and their mixture (4:4:4:3:1, OG-VI) on DNA and RNA syntheses in primary monolayer cultures of normal hepatocytes and cultures of hepatoma cells, AH130, to use these compounds for total parenteral nutrition. Addition of an appropriate amount of inosine, GMP, uridine, or thymidine to primary cultures of hepatocytes enhanced both DNA and RNA syntheses by the salvage and de novo pathways. Cytidine appeared to have lower optimal concentration for enhancing these pathways. The OG-VI mixture also enhanced the syntheses of DNA and RNA, but the composition of the mixture was not optimal. Additions of inosine, GMP, uridine, and thymidine to cultured hepatoma cells also enhanced their DNA and RNA syntheses, but the cells consumed more of the added nucleic acid compounds than hepatocytes did. Addition of cytidine had no effect on proliferation of the cells. The OG-VI mixture at relatively higher concentration inhibited the syntheses of DNA and RNA by hepatoma cells. Addition of high concentrations of nucleic acid compounds was found to suppress the proliferation of both hepatocytes and hepatoma cells. These results suggest that addition of optimal amounts of nucleic acid compounds such as nucleosides and nucleotides would enhance growth of hepatocytes, particularly during liver regeneration, but that they may also enhance proliferation of tumor cells in the liver.
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PMID:Effects of nucleosides and a nucleotide on DNA and RNA syntheses by the salvage and de novo pathway in primary monolayer cultures of hepatocytes and hepatoma cells. 246 17

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FU) selectively in tumours through a cascade of three enzymes. The present study investigated tissue localisation of the three enzymes in humans, which was helpful for us to design the compound. Carboxylesterase was almost exclusively located in the liver and hepatoma, but not in other tumours and normal tissue adjacent to the tumours. Cytidine (Cyd) deaminase was located in high concentrations in the liver and various types of solid tumours. Finally, thymidine phosphorylase (dThdPase) was also more concentrated in various types of tumour tissues than in normal tissues. These unique tissue localisation patterns enabled us to design capecitabine. Oral capecitabine would pass intact through the intestinal tract, but would be converted first by carboxylesterase to 5'-deoxy-5-fluorocytidine (5'-dFCyd) in the liver, then by Cyd deaminase to 5'-deoxy-5-fluorouridine (5'-dFUrd) in the liver and tumour tissues and finally by dThdPase to 5-FU in tumours. In cultures of human cancer cell lines, the highest level of cytotoxicity was shown by 5-FU itself, followed by 5'-dFUrd. Capecitabine and 5'-dFCyd had weak cytotoxic activity only at high concentrations. The cytotoxicity of the intermediate metabolites 5'-dFCyd and 5'-dFCyd was suppressed by inhibitors of Cyd deaminase and dThdPase, respectively, indicating that these metabolites become effective only after their conversion to 5-FU. Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than 5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models.
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PMID:Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. 984 91

During hepatitis B virus (HBV)-induced hepatocarcinogenesis, chronic inflammation facilitates the evolution of hepatocellular carcinoma (HCC)-promoting HBV mutants. Cytidine deaminases, whose expression is stimulated by inflammatory cytokines and/or chemokines, play an important role in bridging inflammation and HCC. Through G-to-A hypermutation, cytidine deaminases inhibit HBV replication and facilitate the generation of HCC-promoting HBV mutants including C-terminal-truncated HBx. Cytidine deaminases also promote cancer-related somatic mutations including TP53 mutations. Their editing efficiency is counteracted by uracil-DNA glycosylase. Understanding the effects of cytidine deaminases in HBV-induced hepatocarcinogenesis and HCC progression will aid in developing efficient prophylactic and therapeutic strategies against HCC in HBV-infected population.
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PMID:Human cytidine deaminases facilitate hepatitis B virus evolution and link inflammation and hepatocellular carcinoma. 2412 Jul 59