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Priming with G-CSF effectively enhances low-dose Ara-C-induced in vivo apoptosis in myeloid leukemia cells

Priming with G-CSF effectively enhances low-dose Ara-C-induced in vivo apoptosis in myeloid leukemia cells,10.1016/S0301-472X(98)00041-1,Experimental

Priming with G-CSF effectively enhances low-dose Ara-C-induced in vivo apoptosis in myeloid leukemia cells   (Citations: 17)
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We investigated the role of apoptosis in chemotherapy for hematologic malignancies. Twelve consecutive patients with acute myelogenous leukemia (AML) or refractory anemia with excess of blasts in transformation (RAEB-t) who were not tolerable for standard-dose chemotherapy were treated with CAG regimen (low-dose cytosine arabinoside [Ara-C] plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor [G-CSF]). Bone marrow mononuclear cells obtained before the commencement of the chemotherapy were cultured with various concentrations (0ā€“10āˆ’5 M) of Ara-C in the presence or absence of 10 ng/mL of G-CSF, and the resultant cell proliferation/cytotoxicity was assayed. In all but one patient, half killing concentration (LC50) of Ara-C was significantly reduced in the presence of G-CSF (by 400- and 1.45-fold, median: 21-fold). Furthermore, LC50 values in responders assayed in the presence of 10 ng/mL of G-CSF were significantly lower than those in nonresponders (p = 0.02). In vitro killing tests using a G-CSF-dependent leukemic cell line suggested that addition of G-CSF potentiates Ara-C-induced cytotoxicity through the mechanism of apoptosis. We thus assayed apoptosis in peripheral blood leukemic cells during CAG chemotherapy by flow cytometry using 7-amino-actinomycin D. Peak percentages of apoptosis in responders were significantly higher than those in nonresponders (p = 0.02). These results collectively suggest that apoptosis plays an important role for eradicating leukemic cells by CAG chemo-therapy.
Journal: Experimental Hematology - EXP HEMATOL , vol. 27, no. 2, pp. 259-265, 1999
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    • ...The drug also improved the transport of chemotherapeutic agent like cytosine arabinoside into the leukaemic cell and is used for this purpose in certain chemotherapeutic combination for treatment of AML (FLAG-Ida) [15]...

    Kanjaksha GhoshKinjalka Ghoshet al. Advances in Haematological Pharmacotherapy in 21st Century

    • ...In vitro studies have proved that granulocyte colony-stimulating factor (G-CSF) can increase the cytotoxic effects of cytosine arabinoside (Ara-C) and anthracyclines on the leukemia cells [18]...
    • ...Investigators found that the half-killing concentration (LC50) of Ara-C was significantly reduced in the presence of G-CSF (between 1.45 and 400 times; median, 21 times) [18]...

    J. M. Liet al. Aclarubicin and Low-Dose Cytosine Arabinoside in Combination with Gran...

    • ... This has been accomplished by the introduction of refined schedules of combination chemotherapy (...

    P. Kaaijket al. Cell proliferation is related to in vitro drug resistance in childhood...

    • ...Some studies show that either coadministration of or pretreatment with G-CSF enhances chemotherapeutic effects on the acute myeloid leukemia (AML) blast by recruiting quiescent cells to the S-phase of the cell cycle and by increasing apoptosis [5-7]...
    • ...It has been reported that G-CSF enhances the chemotherapeutic effect in AML [5,6] and refractory anemia with excess blasts in transformation [7] through recruitment of leukemic cells in cell kinetic quiescence [6] and increase of apoptosis [7]...
    • ...It has been reported that G-CSF enhances the chemotherapeutic effect in AML [5,6] and refractory anemia with excess blasts in transformation [7] through recruitment of leukemic cells in cell kinetic quiescence [6] and increase of apoptosis [7]...
    • ...The report by Bai et al [7] showed heterogeneous responses to G-CSF, implying that these discrepancies may be due to the different characteristics of leukemic cell lines...

    Kwang Eun Chaet al. Effect of Granulocyte Colony-Stimulating Factor on Chemotherapeutic Ac...

    • ...One report showed that G-CSF attenuates the cytotoxic effect of etoposide on myeloid cells in vivo (55), but another claimed that G-CSF enhanced Ara-Cā€ induced apoptosis of myeloid leukemia cells (56)...

    Andreas Villungeret al. Fas Ligand, Bcl2, Granulocyte Colony-Stimulating Factor, and p38 Mitog...

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