4 research outputs found

    Chemical structure of 1R-Chl, imatinib, dasatinib, and their effects on BCR-ABL unmutated and mutated genes transduced into murine BM cells.

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    <p>(A) 1R-Chl (left) targets the DNA sequences 5′-WGGWGW-3′. Bold, imidazole rings. imatinib (middle) targets Bcr-Abl kinase, and dasatinib (right) targets 14 out of 15 Bcr-Abl mutants. (B) Murine BM cells transduced with unmutated BCR-ABL and single point mutation Y253H, E255K, and T315I genes were tested for the effectiveness of 1R-Chl (125 nM to 1000 nM), 1S-Chl (500 nM and 1000 nM), imatinib (500 nM and 5000 nM; IC<sub>50</sub> = 260 nM for the native BCR-ABL transduced cells) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003593#pone.0003593-OHare1" target="_blank">[6]</a>, and dasatinib (10 nM and 100 nM; IC<sub>50</sub> = 0.8 nM for the native BCR-ABL transduced cells) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003593#pone.0003593-OHare1" target="_blank">[6]</a>. Triplicate experiments were done, and the numbers of colonies were quantified 7 days after initial plating.</p

    Cytotoxicity (MTS) assays on resting murine BM cells and human MNCs.

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    <p>(A) Ficoll-Hypaque-separated murine BM cells were plated in triplicate with 1R-Chl (10, 100, 500, and 1000 nM) without any growth factors or mitogens. After 72 and 96 hours, 20 µL of Celltiter 96 Aqueous One solution (Promega, WI) was added. The absorbances of the MTS metabolites were read corresponding to the numbers of metabolically active cells. (B) Ficoll-Hypaque-separated human MNCs were treated as above, and the viabilities of the cells were assessed after 72 and 96 hours.</p

    Additive effects of 1R-Chl and imatinib treatments.

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    <p>(A) Murine BM cells transduced with unmutated BCR-ABL were treated with 500 nM imatinib, 500 nM 1R-Chl, and 500 nM 1S-Chl individually, or in combination of either 500 nM 1R-Chl or 500 nM 1S-Chl with 500 nM imatinib. (B) Same treatment routines were used on CML patient MNCs. The CML patient MNCs were treated 500 nM imatinib, 500 nM 1R-Chl, and 500 nM 1S-Chl individually, or 500 nM 1R(S)-Chl in combination with 500 nM imatinib. (C) Same experiments were done on normal blood donor MNCs.</p

    Effects of 1R-Chl on colony formation of CML patient MNCs and normal human MNCs.

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    <p>(A) MNCs from CML patients were cultured with rh stem cell factor, rh IL-3, rh GM-CSF with or without erythropoietin which lead to CFU-GM or BFU-E cell lineages. The experiments were done in duplicate with 1R-Chl ranging from 125 to 1000 nM, 1S-Chl at 500 and 1000 nM, and imatinib at 500 and 5000 nM. The colonies were counted and results were calculated as the percentage of the control plates (without treatment) after 2 weeks. (B) MNCs from normal donors were cultured and plated under the same condition as CML patient cells. The cells were exposed to 500 and 1000 nM 1R-Chl, 500 and 1000 nM 1S-Chl, and 500 and 5000 nM imatinib. The colonies were counted and percent growth inhibition was calculated after 2 weeks.</p
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