Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin

George Weber, Yasafumi Yamaji, E. Oláh, Yutaka Natsumeda, Hiremagalur N. Jayaram, Elizabeth Lapis, Weining Zhen, Noemi Prajda, Ronald Hoffman, Guido J. Tricot

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Abstract

The impact of tiazofurin on inhibition of IMP dehydrogenase was discussed at the clinical and molecular levels. 1. 1. Evidence was provided for the role of IMP dehydrogenase and guanylates in the expression of the neoplastic program in cancer cells with particular relevance to human leukemic cells. 2. 2. The argument for expecting an impact of tiazofurin in human myelocytic cells was provided. 3. 3. Similarity of the kinetics of human leukemic cell IMP dehydrogenase to the rat hepatoma enzyme was documented. 4. 4. New evidence was provided for the role of salvage in chemotherapy and the function of hypoxanthine in inhibiting guanine salvage. 5. 5. The action of tiazofurin and retinoic acid was reported in HL-60 leukemic cells. 6. 6. The effect of tiazofurin and retinoic acid on proliferation and cytotoxicity was outlined for hepatoma 3924A cells. 7. 7. The effect of guanine on induced differentiation by tiazofurin and retinoic acid was examined. 8. 8. Biochemical basis was provided for the lack of development of resistance in patients treated with tiazofurin. 9. 9. Presumptive evidence was provided that tiazofurin treatment induced differentiation of leukemic cells in the patients. 10. 10. The molecular biology of tiazofurin-induced differentiation in K-562 cells was reviewed with the possible relevance to clinical treatment that tiazofurin might also act through down-regulation of ras oncogene.

Original languageEnglish
Pages (from-to)335-356
Number of pages22
JournalAdvances in Enzyme Regulation
Volume28
Issue numberC
DOIs
Publication statusPublished - 1989

Fingerprint

tiazofurin
IMP Dehydrogenase
Tretinoin
Salvaging
Cells
Guanine
Hepatocellular Carcinoma
Molecular biology
Hypoxanthine
Chemotherapy
ras Genes
HL-60 Cells
Cytotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin. / Weber, George; Yamaji, Yasafumi; Oláh, E.; Natsumeda, Yutaka; Jayaram, Hiremagalur N.; Lapis, Elizabeth; Zhen, Weining; Prajda, Noemi; Hoffman, Ronald; Tricot, Guido J.

In: Advances in Enzyme Regulation, Vol. 28, No. C, 1989, p. 335-356.

Research output: Contribution to journalArticle

Weber, G, Yamaji, Y, Oláh, E, Natsumeda, Y, Jayaram, HN, Lapis, E, Zhen, W, Prajda, N, Hoffman, R & Tricot, GJ 1989, 'Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin', Advances in Enzyme Regulation, vol. 28, no. C, pp. 335-356. https://doi.org/10.1016/0065-2571(89)90080-0
Weber, George ; Yamaji, Yasafumi ; Oláh, E. ; Natsumeda, Yutaka ; Jayaram, Hiremagalur N. ; Lapis, Elizabeth ; Zhen, Weining ; Prajda, Noemi ; Hoffman, Ronald ; Tricot, Guido J. / Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin. In: Advances in Enzyme Regulation. 1989 ; Vol. 28, No. C. pp. 335-356.
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