Wyniki wyszukiwania - Biblioteka Nauki

1

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.

100%

Styczyński J. , Wysocki M. , Dębski R. , Kurylak A. , Balwierz W. , Rokicka-Milewska R. , Matysiak M. , Balcerska A. , Kowalczyk J. , Wachowiak J. , Sońta-Jakimczyk D. , Chybicka A.

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tom 49

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nr 1

99-107

EN

Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.

2

Targeting drug-efflux pumps - a pharmacoinformatic approach

86%

Pleban K. , Kaiser D. , Kopp S. , Peer M. , Chiba P. , Ecker G. F.

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nr 3

EN

In line with our studies on propafenone-type inhibitors of P-glycoprotein (P-gp), we applied several methods to approach virtual screening tools for identification of new P-gp inhibitors on one hand and the molecular basis of ligand-protein interaction on the other hand. For virtual screening, a combination of autocorrelation vectors and selforganising artificial neural networks proved extremely valuable in identifying P-gp inhibitors with structurally new scaffolds. For a closer view on the binding region for propafenone-type ligands we applied a combination of pharmacophore-driven photoaffinity labeling and protein homology modeling. On LmrA, a bacterial homologue of P-gp, we were able to identify distinct regions on transmembrane helices 3, 5 and 6 which show significant changes in the labeling pattern during different steps of the catalytic cycle.

3

Cytosolic superoxide dismutase activity after photodynamic therapy, intracellular distribution of Photofrin II and hypericin, and P-glycoprotein localization in human colon adenocarcinoma

86%

Saczko J. , Kulbacka J. , Chwilkowska A. , Pola A. , Lugowski M. , Marcinkowska A. , Malarska A. , Banas T.

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tom 45

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nr 2

4

Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine

72%

Jaszewska E. , Kosmider A. , Kiss A. K. , Naruszewicz M.

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tom 61

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nr 5

5

Relative profiling of L-tryptophan derivatives from selected edible mushrooms as psychoactive nutraceuticals to inhibit P-glycoprotein: a paradigm to contest blood-brain barrier

72%

Margret A. A. , Mareeswari R. , Kumar K. A. , Jerley A. A.

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nr 1

6

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats

58%

Toklu H. Z. , Kabasakal L. , Imeryuz N. , Kan B. , Celikel C. , Cetinel S. , Orun O. , Yuksel M. , Dulger G. A.

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tom 64

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nr 4

7

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia

58%

Styczynski J. , Wysocki M. , Debski R. , Kurylak A. , Balwierz W. , Rokicka-Milewska R. , Matysiak M. , Balcerska A. , Kowalczyk J. , Wachowiak J. , Sonta-Jakimczyk D. , Chybicka A.

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nr 1

EN

Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.