Role of differentiation induction in action of purine antimetabolites

@article{Weber2005RoleOD,
  title={Role of differentiation induction in action of purine antimetabolites},
  author={George Weber and Yukiko Hata and No{\'e}mi Prajda},
  journal={Pharmacy World and Science},
  year={2005},
  volume={16},
  pages={77-83}
}
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… Expand

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TLDR
Ganosine was effective in preventing the action of tiazofurin, thus providing evidence that the guanine nucleotides are critically involved in tiaz ofurin-initiated differentiation. Expand
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TLDR
The decrease in IMP DH activity, GTP concentration, and expression of c-Ki-ras oncogene were early markers of the successful chemotherapeutic impact of tiazofurin in a patient with chronic granulocytic leukemia in blast crisis. Expand
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Tiazofurin and DFDC are synergistically cytotoxic in hepatoma cells and additive in PANC-1 cells and should be helpful in treating leukemias and solid tumors in humans. Expand
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TLDR
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TLDR
The exposure of HL-60 leukemia cells to inhibitors of IMP dehydrogenase caused a marked reduction in the incorporation of [3H]mannose into both cellular glycoproteins and their lipid-linked oligosaccharide precursors; these effects are presumably due to the pronounced decrease in intracellular levels of guanosine triphosphate produced by blockage of IMP dehydration. Expand
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TLDR
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TLDR
Results suggested that the anabolite might be a dinucleotide with a phosphodiester linkage of the kind found in NAD, and attempts were made to synthesize such an analogue from the 5'-monophosphate of thiazole nucleoside and ATP-Mg2+, using a purified preparation of NAD pyrophosphorylase. Expand
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TLDR
The significance of GTP in cancer biochemistry and chemotherapy was highlighted by the discovery that IMP dehydrogenase activity increased in a transformation- and progression-linked fashion in rat hepatomas of different growth rates. Expand
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