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

Cell surface alteration was studied in a subline of murine lymphocytic leukaemia resistant to the broad-spectrum anticancer agent adriamycin (P388/ADR) employing concanavalin A(Con A)-induced agglutination and rearrangement of lectin receptors. Con A induced more agglutination of P388/ADR when compared to the drug-sensitive parental cell line (P388/S). Studies on the redistribution of Con A and Ricinus communis agglutinin-I revealed a high percentage of P388/ADR showing internalized fluorescence, while a majority of P388/S displayed a uniform distribution of fluorescence on the cell surface.
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PMID:Cell surface alterations in murine leukaemia P388 adriamycin-resistant cells: studies on lectin-induced agglutination and rearrangement of lectin receptors. 403 47

The calcium antagonists verapamil and nifedipine promote responsiveness to anthracyclines in certain drug-resistant cell lines. Their mode of action involves inhibition of anthracycline exodus, leading to promotion of intracellular drug retention. We examined the relationship between calcium fluxes and anthracycline responsiveness in the P388 murine leukemia, and in a drug-resistant sub-line, P388/ADR. Verapamil and nifedipine promoted daunorubicin accumulation by P388/ADR cells, but this occurred regardless of extracellular calcium concentration and did not involve perturbation of calcium transport. We conclude that these agents promote drug retention via mechanisms not related to calcium ion fluxes.
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PMID:Interactions between calcium antagonists, calcium fluxes and anthracycline transport. 609 54

Effects of ruthenium red on accumulation and cytotoxicity of m-AMSA, vinblastine and daunorubicin were examined in the P388 murine leukemia cell line and in an adriamycin-resistant subline, P388/ADR, which is cross-resistant to all three agents. Ruthenium red increased m-AMSA accumulation by both P388 and P388/ADR cells; the extent of this effect was a function of the concentration of both agents. Uptake enhancement occurred within 5 min of exposure of cells to ruthenium red and was readily reversed when cells were suspended in fresh medium. A 24-hr exposure to ruthenium red was needed to affect vinblastine or daunorubicin accumulation, and the effect was substantially less than that observed with m-AMSA. Ruthenium red protected P388 cells from m-AMSA toxicity. These data, together with reports indicating a protective effect of ruthenium red against vinblastine and anthracycline toxicity, suggest that the dye promotes tight binding of m-AMSA and other agents to cellular loci on which toxic effects are not exerted.
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PMID:Effects of ruthenium red on accumulation and cytotoxicity of m-AMSA, vinblastine and daunorubicin in leukemia cells. 620 58

We have studied the structural order of the lipid phase of plasma membranes from P388 murine leukemia cells and from a Doxorubicin-resistant subline, P388/ADR, using electron spin resonance spectroscopy and fluorescence depolarization measurements. Measurements of the order parameter, S, following incubation of cells from both lines with the N-oxyl-4'-4'-dimethyloxazolidine derivative of 5-ketostearic acid show higher values for the resistant cells at all temperatures where S was measured (4-37 degrees). Fluorescence depolarization measurements following incubation of the cells, or cell fractions, with 1,6-diphenylhexatriene indicate more restricted motion of the probe in resistant cells. These measurements also show increased amounts of cytoplasmic lipid in the resistant cells. The higher degree of structural order in the lipid phase of the plasma membranes of P388/ADR cells and their larger intracellular lipid content may account for the decreased rate of intracellular accumulation of anthracycline drugs (and other compounds) seen in these cells and, in part, for their relative resistance to the cytotoxic effects of these drugs.
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PMID:Plasma membrane lipid structural order in doxorubicin-sensitive and -resistant P388 cells. 631 8

The effects of the triparanol analogues chlorotrianisene, clomiphene, tamoxifen, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (MDL 10393), MDL 8917v, nafoxidine, 2-[p-(6-methoxy-2-phenylinden-3-yl)phenoxy]triethylamine (U-11555A), 2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]triethylamine (U-10520A), and nitromifene, as well as triparanol itself, were studied in the P388 murine leukemia cell line and in a doxorubicin-resistant subline (P388/ADR). At noninhibitory concentrations, all the analogues increased the sensitivity of P388/ADR cells to doxorubicin but did not have such an effect on the doxorubicin-sensitive cells. Diethylstilbestrol, deacetylated cyclofenil (F6060), hexestrol, and 17 beta-estradiol did not have such an activity. The effects of tamoxifen on doxorubicin sensitivity of P388/ADR cells could not be reversed by 17 beta-estradiol. Estrogen receptors could not be demonstrated in either cell line. It is therefore suggested that the reversal of the doxorubicin-acquired resistance by the triparanol analogues is unrelated to their estrogenic or antiestrogenic activities. The possible clinical implications of these findings are discussed.
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PMID:Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by tamoxifen and other triparanol analogues. 646

The antitumor action of L-alanosine (NSC 153553) was investigated in murine leukemia P388 (P388/S), P388 resistant to adriamycin (P388/ADR), P388 resistant to vincristine (P388/VCR) and leukemia L5178Y sensitive to L-asparaginase (L5178Y/S). L-alanosine demonstrated good antineoplastic activity against P388/S and P388/ADR, whereas it showed better anticancer activity against P388/VCR and L5178Y/S at the various dose levels employed.
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PMID:Antitumor effect of L-alanosine (NSC 153553) on sensitive and resistant sublines of murine leukemias. 647 81

The results obtained using a rapid assay for in vitro chemosensitivity detection of leukemias are presented. The assay, performed according to the technique already described, involves in vitro incubation of a tumor cell suspension with various concentrations of antitumor drugs for 1 h and evaluation of drug-induced cell damage by addition to the cultured cells of 125I-deoxyuridine 48 h after pharmacological treatment. Results are expressed as percent inhibition of the isotope incorporation with respect to untreated controls. Preliminary results demonstrated that this assay is able to evidence differential chemosensitivity exhibited in vivo by murine leukemias. The present study reports the results obtained using comparatively P388 and P388/ADR, a subline of P388 murine leukemia with acquired resistance to Adriamycin in vivo. We found that P388/ADR exhibited resistance to ADR and DNR at all the concentrations tested, whereas P388 was highly sensitive. Cross-resistance of P388/ADR was also found to some structurally dissimilar agents, i.e. VCR and Act-D. These in vitro results correlate well with much data in the literature concerning the characteristics of resistance and cross-resistance exhibited in vivo by P388/ADR. These results suggest the possibility of using a similar in vitro assay for predicting the in vivo drug resistance of human leukemias.
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PMID:[In vitro evaluation of the chemosensitivity of an experimental murine leukemia rendered resistant in vivo to adriamycin]. 647 49

The effects of certain compounds on the in vitro growth rate and the sensitivity to doxorubicin of P388 murine leukaemia cell line and of a doxorubicin-resistant subline (P388/ADR) were studied. The calcium channel blocking activity of these compounds was evaluated by measuring their effects on the sodium-dependent and membrane potential-dependent calcium uptake in synaptic plasma membrane vesicles. At non-inhibitory concentrations, verapamil, dipyridamole, meclizine and nicardipine were highly active in restoring the sensitivity to doxorubicin of P388/ADR cells. Moderately active were propranolol, N-(beta-diethylaminoethyl)-N-(beta-hydroxy-beta-phenylethyl)-2,5-dich loranaline (MDL-6792), thioridazine and chlorocyclizine, while nifedipine, guanethidine, phentolamine, chloroquine and papaverine had zero or only minimal synergistic activity to doxorubicin in this cell line. Doxorubicin synergistic activity could not be demonstrated in the parent drug-sensitive cell line. No sodium-dependent or membrane potential-dependent calcium uptake could be demonstrated in vesicles prepared from plasma membranes of either cell line. There is no correlation between the ability of these compounds to inhibit calcium uptake in synaptic vesicles and their potency in restoring the sensitivity of P388/ADR cells to doxorubicin.
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PMID:Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells. 648 16

Antitumor activity of doxorubicin made in the USSR was studied on mice in respect to three transplantable tumors (lymphadenosis NK/LI, sarcoma 37 and Ehrlich's carcinoma) and hemocytoblastosis La. Doxorubicin injected intravenously 4 times was shown to be highly active against the above ascites tumors. The highest inhibitory effect of doxorubicin was observed in respect to the development of Ehrlich's carcinoma. By the selectivity of the therapeutic effect on this tumor it was superior to rubomycin and carminomycin. A high antileukemic activity of doxorubicin in respect to hemocytoblastosis La was shown. In experiments with this leukemia, intravenous injection of doxorubicin provided a higher efficacy than intraperitoneal injection. When used intravenously in the doses equivalent by their toxicity doxorubicin was inferior to rubomycin in terms of the therapeutic effect on leukemia La. However, on intraperitoneal injection of the drugs rubomycin showed no such advantage. Doxorubicin made in the USSR did not differ by its antitumor activity from the analogous foreign drug.
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PMID:[Antitumor activity of doxorubicin in the treatment of hemocytoblastosis La and various ascites tumors in mice]. 652 89

The 4-(N-methylcarboxamido)-5-methyl derivative of amsacrine (NSC 249 992) has been synthesized as part of a program aimed at optimizing solid tumor activity in this series. Physicochemical studies of this analogue (N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide; NSC 343 499) indicate a slightly increased lipophilicity (estimated log p = 1.10), a decreased acridine base strength (pKa 6.40), and a 16-fold-higher association constant for double-stranded calf thymus DNA (Ka 2.1 X 10(6) M-1 at 0.01 ionic strength). Like amsacrine, the drug binds to DNA by intercalation. Inhibition of cell growth has been monitored by continuous drug exposure assays with a variety of rodent and human cell lines. The concentration for 50% inhibition varied from 6.7 nM (T-47D, a human breast carcinoma line) to 800 nM (P388/ADR, a murine cell line resistant to Adriamycin). N-5-Dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide was cytotoxic at growth-inhibitory concentrations and also induced cell cycle arrest in the G2 phase. It was active against P388 leukemia following administration by p.o., i.v., or i.p. routes, and it was superior to amsacrine, daunorubicin, and Adriamycin. It was curative towards i.v.-injected Lewis lung tumor in a proportion of animals when treatment was started on Day 1 or Day 5 after tumor inoculation. It also produced highly significant life extensions against advanced tumors (treatment starting Day 9 after i.v. inoculation or on Day 8 after s.c. inoculation) and was comparable to cyclophosphamide in its effectiveness. It is a candidate drug for clinical trial.
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PMID:Synthesis, antitumor activity, and DNA binding properties of a new derivative of amsacrine, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide. 654 35


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