Corpus ID: 16971149

Biochemically directed therapy of leukemia with tiazofurin, a selective blocker of inosine 5'-phosphate dehydrogenase activity.

@article{Tricot1989BiochemicallyDT,
  title={Biochemically directed therapy of leukemia with tiazofurin, a selective blocker of inosine 5'-phosphate dehydrogenase activity.},
  author={Guido Tricot and Hiremagalur N. Jayaram and Erzs{\'e}bet Lapis and Yutaka Natsumeda and Craig R. Nichols and Patricia Kneebone and Nyla A. Heerema and George Weber and Richard Hoffman},
  journal={Cancer research},
  year={1989},
  volume={49 13},
  pages={
          3696-701
        }
}
Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193), a selective inhibitor of the activity of IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, provided in end stage leukemic patients a rapid decrease of IMP dehydrogenase activity and GTP concentration in the blast cells and a subsequent decline in blast cell count. Sixteen consecutive patients with end stage acute nonlymphocytic leukemia or myeloid blast crisis of chronic granulocytic… 
Tiazofurin: biological effects and clinical uses.
TLDR
Better patient selection, limitation of treatment duration and earlier recognition and treatment of complications have now made it possible to administer tiazofurin without undue toxicity, and a good correlation between biochemical parameters and clinical response was demonstrated in leukemic patients.
Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity in extracts of ovarian carcinomas.
TLDR
Results indicate that IMP DH activity is elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be inhibited by exposure to tiazofurin (TAD), which may merit serious consideration for a Phase II trial for patients with recurrent/refractory epithelial ovarian carcinoma.
Synergistic action of tiazofurin with hypoxanthine and allopurinol in human neuroectodermal tumor cell lines.
TLDR
Tiazofurin and hypoxanthine synergistically inhibited tumor cell growth, and the addition of allopurinol strengthened these effects, suggesting this drug combination, inhibiting guanylate de novo and salvage pathways, may prove useful in the treatment of human neuroectodermal tumors.
Effects of the IMP-dehydrogenase inhibitor, Tiazofurin, in bcr-abl positive acute myelogenous leukemia. Part II. In vitro studies.
TLDR
Findings indicate that the efficacy of standard chemotherapy in bcr-abl positive leukemias might be enhanced if combined sequentially with Tiazofurin.
Inhibition of IMP Dehydrogenase by Mycophenolic Acid in Molt F4 Human Malignant Lymphoblasts
TLDR
It is concluded that depletion of guanine nucleotides, induced by treatment with MPA, induces a severe and rapid cytotoxicity in Molt F4 cells.
Schedule-dependent synergistic action of tiazofurin and dipyridamole on hepatoma 3924A cells
TLDR
The studies indicate the importance of the order of the addition of drugs to obtain a synergistic response in combination chemotherapy and suggest the need for a careful selection of drug modulation in clinical trials of tiazofurin and dipyridamole.
Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin.
TLDR
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 and the possible relevance to clinical treatment that tiazofurin might also act through down-regulation of ras oncogene.
A novel series of non-nucleoside inhibitors of inosine 5'-monophosphate dehydrogenase with immunosuppressive activity.
TLDR
The novel pyridazines described in this report represent the first non-nucleoside uncompetitive inhibitors of IMPDH with immunosuppressive activity since the discovery of the inhibitory activity of mycophenolic acid and its derivatives thirty years ago.
Tiazofurin action in leukemia: evidence for down-regulation of oncogenes and synergism with retinoic acid.
TLDR
Because both tiazofurin and retinoic acid are licensed drugs, their potential use in combination chemotherapy may have clinical relevance in the treatment of end-stage leukemia where earlier studies have demonstrated the usefulness of tiaz ofurin.
Determination of thiazole-4-carboxamide adenine dinucleotide (TAD) levels in mononuclear cells of leukemic patients treated with tiazofurin.
TLDR
A highly sensitive method for the determination of TAD in biological samples, in addition to TAD, thirteen other biologically relevant adenine, guanine, cytosine and uridine nucleotides can be separated and quantitated accurately.
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References

SHOWING 1-10 OF 33 REFERENCES
Enzyme-pattern-targeted chemotherapy with tiazofurin and allopurinol in human leukemia.
TLDR
Bone marrow aspirates and peripheral blood samples showed that with tiazofurin treatment there was an induced differentiation of the myelocytes, and the hypothesis was tested that the increased IMP dehydrogenase activity in human myelocytic leukemic cells, and along with it guanylate biosynthesis, might be a sensitive target to chemotherapy by tiaz ofurin.
Modulation of IMP dehydrogenase activity and guanylate metabolism by tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide).
TLDR
This is the first report showing that a marked therapeutic response was achieved against rapidly growing hepatoma 3924A by treatment with a single anti-metabolite, and tiazofurin treatment resulted in significant anti-tumor activity in rats inoculated with hepatoma3924A.
Selective sensitivity to tiazofurin of human leukemic cells.
TLDR
The procedure reported in this work may be suitable as a rapid predictive test for the sensitivity of leukemic leukocytes to tiazofurin in the Phase II trials now being developed and should be helpful in identifying neoplastic cells sensitive to t DiazofurIn.
Alterations in glycoprotein synthesis and guanosine triphosphate levels associated with the differentiation of HL-60 leukemia cells produced by inhibitors of inosine 5'-phosphate dehydrogenase.
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.
Hematological and biochemical action of tiazofurin (NSC 286193) in a case of refractory acute myeloid leukemia.
TLDR
Tiazofurin appears to be a promising agent in the treatment of leukemia because of its selective action on leukemic cells and the availability of a rapid in vitro method capable of predicting sensitivity of leukeMic cells to the agent and monitoring its activity during treatment by measuring thiazole-4-carboxamide adenine dinucleotide and GTP concentrations.
Inosine monophosphate dehydrogenase and myeloid cell maturation.
TLDR
Findings are consistent with the concept that the regulation of myeloid cell maturation may be influenced by intracellular concentrations of guanine ribonucleotides because IMP dehydrogenase activity is known to be rate limiting for the production of these nucleotides.
Initial studies on the mechanism of action of a new oncolytic thiazole nucleoside, 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193).
TLDR
The drug was producing a state of guanine deprivation was provided by high performance liquid chromatography analysis of acid-soluble extracts: a time-dependent fall in the concentrations of GMP and GTP ensued upon exposure to the drug; on the other hand, IMP concentrations increased by ∼15-fold.
Inosine monophosphate dehydrogenase activity in acute leukaemia.
TLDR
IMPD levels are higher in B than T lymphocytes and in acute leukaemia blasts compared to more differentiated mixed bone marrow cells, and the results do not suggest that IMPD assay will be of value in differentiation of the various subtypes of acuteLeukaemia or of malignant haemopoietic cells from the equivalent normal cell at the same level of differentiation.
Arabinosyl cytosine: a useful agent in the treatment of acute leukemia in adults.
TLDR
The recommended schedule of treatment for ara-C based on data is, therefore, daily infusions of 100 or 50 mg./m.2 in one hour for approximately 3 to 6 weeks followed by maintenance therapy of once weekly subcutaneous injection of 30 mg./ m.2 of aRA-C.
Pediatric phase I trial and pharmacokinetic study of tiazofurin (NSC 286193).
TLDR
Neurotoxicity, including headache, drowsiness, and irritability, was common and was the principal dose-limiting toxicity at the higher doses, and severe myalgias were also dose limiting in one patient.
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