ISSN:
1573-739X
Keywords:
Differentiation
;
Drug synergism
;
Gemcitabine
;
Hypoxanthine-guanine phosphoribosyltransferase
;
IMP dehydrogenase
;
Leukemia, myeloid, chronic
;
Oncogenes
;
Ribavirin
;
Tiazofurin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract In cancer cells, particularly in leukaemic cells, guanylate biosynthesis is up-regulated as shown by the increased activities of IMP dehydrogenase, the rate-limiting enzyme ofde novo GTP biosynthesis, and of the salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). In enzyme pattern-targeted chemotherapy, tiazofurin inhibits IMP dehydrogenase activity in cancer cells and allopurinol-induced high serum hypoxanthine levels inhibit. HGPRT activity. A triad of responses was observed in the blast cells of patients treated with tiazofurin infusions: chemotherapy, induced differentiation, and down-regulation of c-Ki-ras andc-myc oncogenes. Tiazofurin was synergistic in cytotoxicity and in causing differentiation with ribavirin, retinoic acid, and difluorodeoxycytidine. Induced differentiation plays an important role in the overall impact of antipurine agents.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01880659
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