Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synergistic cytotoxic activity exhibited by bifunctional alkylating agents in the presence of methylxanthines has been associated with methylxanthine-induced reversal of alkylator-induced DNA replicon initiation inhibition. This has also been seen with methylxanthines and ionizing irradiation. Methylxanthines do not appear exacerbate drug or ionizing radiation-induced damage. We report here a situation in which methylxanthine-induced reversal of DNA replicon initiation inhibition is not associated with increased cytotoxicity of the alkylator. Murine L1210 leukemia cells were assayed for cytotoxicity following treatment with either L-PAM or cis-DDP in the presence or absence of theophylline. Theophylline increased the cytotoxicity seen after L-PAM treatment but failed to increase the cis-DDP induced cytotoxicity. Analysis of pulse-labeled DNA on alkaline sucrose gradients revealed the expected decrease in DNA replicon initiation in L1210 cells treated with either L-PAM or cis-DDP. Theophylline had no effect on replicon initiation in untreated cells. Theophylline reversed the replicon initiation inhibition in cells treated with either L-PAM or cis-DDP. The reason for the apparent lack of added toxicity of the replicon initiation inhibition reversal in L1210 cells treated with theophylline and DDP is unknown.
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PMID:Theophylline reversal of alkylator-induced replicon initiation inhibition: no correlation with DDP-induced cytotoxicity. 654 56

LP-BM5 murine leukemia virus induces immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dsyregulation. Theophylline induces apoptosis of leukemia cells in humans. Therefore the effects of theophylline on immune dysfunction in a murine model of leukemia were investigated. C57BL/6 mice consumed drinking water containing 0.3% theophylline beginning 2 weeks after murine retrovirus infection for 4 months. Theophylline largely prevented the retrovirus induced splenomagaly, lymphodenopathy, reduction in B and T cell proliferation, and suppression of Thl cytokines (IL-2) secretion. It also suppressed Th2 cytokine (IL-4, TNF-alpha, and IL-10) production, which was otherwise stimulated by retrovirus infection. These data suggest that immune dysfunction, induced by murine retrovirus infection, was largely prevented by theophylline treatment.
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PMID:Anti-inflammatory effects of theophylline: modulation of immune functions during murine leukemia virus infection. 1169 23

Idarubicin (IDA) is a member of an important class of anticancer agents, the anthracycline antibiotics. Although the clinical efficacy of anthracyclines is limited by a high incidence of severe cardiac toxicity, our understanding of IDA transport into the heart is still limited. In a previous study, we demonstrated that IDA is transported into the heart by a saturable mechanism. Based on in vitro data suggesting an enhancement by methylxanthines of IDA influx in leukemia cells, this study was designed to test the hypothesis that a commonly used methylxanthine, caffeine, might influence the myocardial uptake of IDA. In the Langendorff rat heart, after infusion of 0.5 mg IDA during 10 min, the presence of caffeine (1 microM) in perfusate enhanced the residual amount of IDA in the heart by 30% due to a 2.7-fold increase in the maximal uptake rate V(max). Theophylline (3 micro M), in contrast, did not influence the uptake process but caused a slight decrease of fractional myocardial sequestration rate (19% reduction). Caffeine reversed the cardiodepressive action of IDA (49% decrease in left ventricular developed pressure at the end of infusion) to a positive inotropic effect (18% increase of basal level). Theophylline significantly attenuated the negative inotropic effect of IDA (only 21% decrease) and led to positive inotropism in the washout phase (21% increase at the end of experiment). We speculate that co-administration of caffeine may enhance the chronic cardiotoxicity of IDA by increasing its accumulation in the heart.
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PMID:Caffeine enhances myocardial uptake of idarubicin but reverses its negative inotropic effect. 1259 56