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)

Daunomycin was coupled via its amino group to omega-carboxypentyl agarose (CH-Sepharose 4B). Nonhistone proteins from rat leukemia cells (DBLA-6) were fractionated on a column of the adsorbent. The adsorption of nonhistone proteins to the column was increased by high salt concentration (4 M NaCl) and was reversed by 20% glycerol (v/v), indicating a hydrophobic interaction. Complexity of the chromatographic patterns may reflect the occurrence of several species of binding protein in the tumor cells used. Thus the hydrophobic chromatography in the presence of a high concentration of salt was a useful method for fractionation of nonhistone proteins under non-rigorous conditions.
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PMID:Fractionation of nonhistone proeins on a column of daunomycin-CH-Sepharose 4B. 62 48

The uptake of Adriamycin (AM) and Daunomycin (DM) in L1210 leukemia cells was found to be dependent on drug dose, time, and temperature. DM was taken up to a greater extent in human leukemia cells in vitro and in L1210 leukemic cells both in vitro and in vivo. Intracellular retention of DM was less than that of AM. Drug transport appears to be a factor in developing resistance to DM in L1210 cells, but the data for AM were inconclusive in this regard. The importance of cellular uptake and retension operative in determining differences in the overall therapeutic efficacy in vivo remains to be elucidated.
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PMID:Uptake of adriamycin and daunomycin in L1210 and human leukemia cells: a comparative study. 106 79

The human leukemia cell line K562 expresses constitutively high levels of c-myc mRNA and can be induced to differentiate along the erythroid lineage. Treatment of K562 cells with the antineoplastic drugs 1-beta-D-arabinofuranosylcytosine and daunomycin causes differentiation into hemoglobin-producing cells. The differentiation process is associated with an early block of cellular proliferation occurring during the first 24 h of treatment. RNA synthesis is progressively reduced to 20 to 30% of the control levels after 3 days of exposure to the drugs. Dot and Northern blot analyses were performed to evaluate the levels of c-myc or globin mRNA during the differentiation of K562. Daunomycin and 1-beta-D-arabinofuranosylcytosine, despite their distinct chemical nature, induced similar modulation of mRNA levels. Globin mRNA did not change during the first 24 h of culture and began to increase after 48 h of treatment with drugs, reflecting the kinetic of appearance of hemoglobin-producing cells. In contrast, a transient decrease of c-myc mRNA was observed after the first 24 h of drug treatment, followed by a return to normal levels of c-myc mRNA after 48 h of treatment. Thus, the expression of c-myc mRNA in K562 did not reflect their proliferative activity nor their stage of differentiation. We speculate that the transient down-regulation of c-myc mRNA may be an initial event in the erythroid differentiation of K562.
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PMID:Erythroid differentiation and modulation of c-myc expression induced by antineoplastic drugs in the human leukemic cell line K562. 347 95

The aim is to examine experimentally whether injections of LPS in combination with Daunomycin are effective on a rat myelomonocytic leukemia. Effects of Lipopolysaccharide (LPS), one of the major differentiation-inducing agents in the mouse myeloid leukemia cell line M1, were investigated on the cells of a rat myelomonocytic leukemia cell line c-WRT-7 in vitro and in vivo. It was shown that sensitive cells of c-WRT-7 cells changed remarkably into macrophage-like cells, which lost the growth potential by LPS-treatment, whereas such change and growth inhibition in insensitive cells of c-WRT-7 were not so remarkable by LPS-treatment. Although the sensitive cells were extremely malignant in vivo, the sensitive cells treated with LPS in vitro lost the transplantability into the syngeneic rats. The sensitive cells by injections of LPS developed morphologically into macrophage-like cells in diffusion chamber i.p. in syngeneic rat. Injections of LPS inhibited the progression of leukemia in 60% of the rats which had been inoculated with the sensitive cells, whereas the leukemia-development was inhibited in only 20% of the rats which had been inoculated with the insensitive cells and i.p. treated with LPS. Daunomycin, Aclacinomycin A and Vincristine induced phagocytic activities in c-WRT-7 cells, whereas Actinomycin D and Cycloheximide showed no such effects. Daunomycin in combination with LPS increased the number of phagocytic cells, whereas cycloheximide inhibited the LPS induced phagocytosis. Injections of LPS in combination with Daunomycin inhibited doubtlessly the leukemia-development in rats which had been i.p. inoculated with the sensitive cells, compared to the injections of LPS or Daunomycin alone. In conclusion, it is suggested that the effects of LPS and Daunomycin on the inhibition of the leukemia-development could be associated in part with their differentiation-inducing activities.
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PMID:[Experimental studies on the therapy of rat myelomonocytic leukemia with lipopolysaccharide (LPS) and daunomycin (DM)]. 386 74

Ethidium bromide, compared on a molar basis, was a more effective inhibitor of the DNA polymerases of the Rauscher and Moloney murine leukemia viruses than either 4-N-demethylrifampicin or 4-N-benzyldemethylrifampicin. Daunomycin inhibited the polymerases weakly, and chromomycin A(3) inhibited almost not at all. 4-N-Benzyldemethylrifampicin was a more active inhibitor than the 4-N-demethyl congener.
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PMID:Inhibitors of DNA polymerases of murine leukemia viruses: activity of ethidium bromide. 432 20

Twenty-three patients with acute myelocytic leukemia (aml) were treated with daunomycin and the results contrasted to those obtained in a subsequent group of 18 patients treated with cytosine arabinoside (ara-c) and 6-thioguanine (tg). The complete remission (cr) rate with daunomycin was 17 percent (mean duration 10.6 months) and the partial remission (pr) rate 26 percent (mean duration 44 days). Corresponding figures in the ara-c and tg group were: cr rate 44 percent (mean duration 5.8 months) and pr rate 17 percent (mean duration 48 days). There were 12 deaths resulting from daunomycin-induced pancytopenia and in ten of the patients who died persistent leukemia infiltrate was found in antemortem marrow specimens or at autopsy. This contrasts with death of six patients from ara-c and tg-induced pancytopenia, in four of whom residual leukemic infiltrate was not evident. Daunomycin alone is deemed not suitable for induction of remission in aml. The results obtained with ara-c and tg are encouraging and may be improved if the number of infectious deaths associated with drug-induced pancytopenia can be reduced.
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PMID:Therapy of acute myelocytic leukemia. Daunomycin contrasted with a combination of cytosine arabinoside and 6-thioguanine. 450 67

Daunoblastin in free and liposome-encapsulated form was tested in the L1210 murine leukemia and the intramuscularly transplanted 276A sarcoma. Both therapeutic (% ILS, tumor volume inhibition) and toxicologic (leukocytes, body weight difference) parameters were evaluated. The liposome preparations showed similar therapeutic effects as the free substance but caused a lower toxicity with a lower mortality rate, higher leukocyte values and smaller body weight reduction. Longer sonication time with the output of more smaller unilamellar vesicles had no influence on the parameters in the solid model, but resulted in shorter ILS values in the L1210 model. Administration of empty liposomes immediately before liposomal Daunoblastin did not result in better antineoplastic activity but yielded higher leukocyte values.
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PMID:Therapeutic evaluation of liposome-encapsulated Daunoblastin in murine tumor models. 725 32

Ubenimex (Bestatin, Ubx) has been shown to have anti-tumor activity and immuno-modulating activities. Ubx has been used in immuno-therapy in combination with remission maintenance chemotherapy after induction of complete remission for adult acute non-lymphocytic leukemia (ANLL, AML). Daunomycin (DNR), arabinosylcytosine (Ara-C) and 6-mercaptopurine (6-MP) are used for the standard chemotherapy for ANLL. It is, however, believed that emergence of resistant cells to chemotherapy cause minimal residual leukemia resulting in poor prognosis. Ubx has been administered in combination with these chemotherapeutic agents. We examined the combinatorial effect of Ubx with DNR, Ara-C, 6-MP and etoposide on K562 leukemic cell line and the chemotherapeutic agent resistant cells derived from K562 cell line. Ubx showed growth inhibitory effects on these cell lines. A synergistic effect was observed on growth inhibition and with colony formation of parent k562 cell line when DNR and Ubx were used in combination. A combination of Ubx with Ara-C or etoposide showed additional effects on parent cells and other resistant cell lines. The combined growth inhibitory effect of 6-MP and Ubx was stronger than the effect of 6-MP alone. These results show that Ubx has a direct growth inhibitory effect on leukemic cells and additional or synergistic effects are obtained on K562 leukemic cell line and on chemotherapeutic agent resistant cells derived from the K562 cell line when Ubx is used combination with the above chemotherapeutic agents.
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PMID:[Growth inhibitory effects of ubenimex on leukemic cell lines resistant to chemotherapeutic agents]. 903 97

The acid labile derivative of Daunomycin cis-aconityl Daunomycin (cAD), was coupled to an amphoteric polypeptide, poly[Lys-(Glui-DL-Alam)] (EAK), which was selected for conjugation on the basis of its pharmacological and immunological properties. The systemic toxicity of covalently attached Daunomycin was studied by monitoring body weight, life-span, bone marrow and haematological parameters of BDF1 mice. More than 3-fold the lethal dose of free Daunomycin could be applied without serious toxic effect when the drug was attached to EAK. The dose- and time-dependent modulatory effect of free drug and [cAD]-EAK conjugate on the humoral and cellular immune response to sheep red blood cell antigens in mice was studied. The conjugation of Daunomycin to EAK carrier polypeptide compensated for the immunosuppression induced by free Daunomycin. [cAD]-EAK conjugate at Daunomycin doses of 2-10 mg/kg was very effective against L1210 leukaemia producing 66-100% long-term survivors (> 60 days), while Daunomycin in itself increased the mean survival only by 52%, with no long-term survivors. The mixture of free Daunomycin and EAK polypeptide had similar toxicity and antitumour activity as free Daunomycin, indicating the important role of covalent attachment in increased therapeutic efficacy.
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PMID:Low toxicity and high antitumour activity of daunomycin by conjugation to an immunopotential amphoteric branched polypeptide. 962 51

Basic and therapeutic trial results obtained in the spontaneous AK leukemia (lymphoma) model have been brought together for comparison with available information on the much used transplanted murine leukemia models and human leukemias and lymphomas. The etiologic agent for "spontaneous" AK lymphoma is an RNA virus present at birth in AKR mice. Lymphoma cells first appear in the thymuses of animals at 5-->12 months of age. The time lapse between the first appearance of viable lymphoma cells in the thymus and clinical diagnosis (eg, with about 10(9) widely disseminated viable plus nonviable lymphoma cells in the host) is about 1 month. Thus, the overall doubling time of lymphoma cells before diagnosis is about 1 day. This estimate is compatible with the doubling time of relatively small numbers of first-passage lymphoma cells, assay data on the rate of repopulation of viable lymphoma cells after therapeutic reduction, and the median intermitotic time of dividing lymphoma cells (ie, 0.6 day). In general, the cytokinetic parameters of advanced spontaneous AK lymphoma cell populations are more like those observed in advanced human leukemias than are those of early L1210 leukemia. This paper presents assay data on the reduction in viable spontaneous AK lymphoma cells after treatment with a variety of agents, and the rate of cell repopulation after cessation of treatment. Extensive therapeutic trial data indicate that cyclophosphamide is presently the most effective single agent against spontaneous AK lymphoma, with arabinosylcytosine or palmO-ara-C a close second. Daunomycin, 5-fluorouracil, the nitrosoureas, vincristine, methotrexate, and dexamethasone provided moderate increases in host survival time. The combination of vincristine plus prednisone was a good remission inducer but the median survival time after cessation of treatment was shorter than that observed for cyclophosphamide or palmO-araC. The best responses observed to date with two-drug combinations appear better on several scores than the best that have been observed with single drugs. The best overall responses observed to date with two-drug combinations were with palmO-ara-C plus methyl-CCNU, cyclophosphamide plus methyl-CCNU, and palmO-ara-C plus cyclophosphamide. Some three- and four-drug combinations have provided better therapeutic responses than have been observed with single agents but not significantly better than those obtained with two-drug combinations. Splenomegaly assays carried out immediately after cessation of treatment and 60 days and longer after cessation of treatment, suggest that eradication of all viable lymphoma cells is being achieved in some animals by combination chemotherapy; however, such animals eventually die of lymphoma, presumably as a result of the reinduction of a second lymphoma cell population. The requirements for permanent "cure" of spontaneous lymphoma in AKR mice include eradication of all viable lymphoma cells and prevention of reinduction. Two major differences between early L1210 leukemia and clinically diagnosed spontaneous AK lymphoma are the degree of disease advancement at the time therapy is usually started (and associated cytokinetic differences) and the reinduction problem in AKR mice. Spontaneous AK lymphoma is relatively more advanced at diagnosis than is acute leukemia in man (ie, with respect to nearness of the host to death), and it is presumed that the reinduction problem in AKR mice is more acute and more prevalent than in human neoplastic disease.
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PMID:Basic and therapeutic trial results obtained in the spontaneous AK leukemia (lymphoma) model-end of 1971. 1905 88


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