Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiazofurin is an oncolytic nucleoside analog that has shown therapeutic activity in end-stage acute non-lymphocytic leukemia and in chronic granulocytic leukemia in blast crisis. Tiazofurin is anabolized to the active metabolite, TAD, which inhibits IMP dehydrogenase activity, leading to a reduction in guanylate pools and to the cessation of neoplastic cell proliferation. The drug exhibits potent cytostatic and cytotoxic activity against hepatoma 3924A cells in culture. In growth-inhibition and clonogenic assays, the 50% inhibitory concentration of tiazofurin was 3.8 and 4.2 microM, respectively. Dipyridamole, an inhibitor of nucleoside transport, curtails the salvage of nucleosides and bases for nucleotide biosynthesis. Dipyridamole exhibited cytotoxicity against hepatoma 3924A cells, with an LC50 of 24 microM and an IC50 of 29 microM being recorded. A combination of tiazofurin and dipyridamole provided synergistic cytotoxicity in hepatoma 3924A cells in culture. This synergistic activity was dependent on the order of addition of the drugs. Simultaneous addition of the two drugs produced antagonism, whereas preincubation of cells with tiazofurin or dipyridamole followed by addition of the second drug resulted in synergy. TAD concentrations were significantly higher (129% and 135%) in cells that had been pretreated with tiazofurin or dipyridamole before the addition of the second agent as compared with cells that had been treated simultaneously (113%). These 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.
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PMID:Schedule-dependent synergistic action of tiazofurin and dipyridamole on hepatoma 3924A cells. 145 Dec 38

Dipyridamole strongly inhibited spontaneous in vitro proliferation of peripheral blood mononuclear cells from patients with acute myelogenous leukaemia (n = 9), chronic myelogenous leukaemia in first chronic phase (n = 4) and blast phase (n = 1). Theophyllamine and verapamil also inhibited proliferation of leukaemia cells from all patients except the CML patient in blast phase where only minimal inhibition was seen. Only dipyridamole caused strong inhibition in concentrations corresponding to the therapeutic serum level, and this inhibition was not influenced by the presence of high levels of interleukin 2.
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PMID:Effect of dipyridamole, theophyllamine and verapamil on spontaneous in vitro proliferation of myelogenous leukaemia cells. 158 6

Dipyridamole inhibited the proliferation of functionally heterogeneous CD4+ TCR alpha beta+ T-cell clones prepared from CML-patients 4-6 weeks after allogeneic bone marrow transplantation. The effect was seen when testing concentrations corresponding to the therapeutic serum level. Dipyridamole caused a dose-dependent inhibition of PHA-stimulated proliferation both for clones dependent on exogenous IL2 and clones undergoing autocrine proliferation. The inhibition was seen when using different accessory cells (PBM or BCL), and also when dipyridamole was present during IL2- or IL4-dependent proliferation of activated T-cells. The effect of dipyridamole was also investigated for 76 T-cell clones (76 CD4+ and 7 CD8+ clones) prepared by different cloning procedures from three patients. Although these clones were heterogeneous with regard to cytotoxic function, lymphokine production or lymphokine responsiveness, dipyridamole inhibited IL2-dependent proliferation of all clones. In addition dipyridamole inhibited proliferation of CML cells.
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PMID:CD4+ TCR alpha beta+ T-cells developing after allogeneic bone marrow transplantation in patients with chronic myelogenous leukaemia. Dipyridamole inhibits functionally heterogeneous T-cell clones. 183 91