ROLE OF DIFFERENTIATION INDUCTION IN ACTION OF PURINE ANTIMETABOLITES

被引:12
作者
WEBER, G
HATA, Y
PRAJDA, N
机构
[1] Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, 46202 5200, IN
来源
PHARMACY WORLD & SCIENCE | 1994年 / 16卷 / 02期
关键词
DIFFERENTIATION; DRUG SYNERGISM; GEMCITABINE; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; IMP DEHYDROGENASE; LEUKEMIA; MYELOID; CHRONIC; ONCOGENES; RIBAVIRIN; TIAZOFURIN;
D O I
10.1007/BF01880659
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 of de 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 and c-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.
引用
收藏
页码:77 / 83
页数:7
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