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  • Introduction. Glucocorticoids, particularly prednisone/ prednisolone and dexamethasone, play a prominent role in the treatment of pediatric patients with acute lymphoblastic leukemia due to their ability to induce apoptosis in susceptible cells. Current therapeutic protocols use prednisone for both the prophase and the induction phase of the therapy because the greater antileukemic activity of dexamethasone is compromised by its high frequency of serious adverse reactions. Aim. To compare, for the first time, the in vitro antileukemic activity of prednisolone alone to that of a combination of prednisolone and dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50 w/w). Methods. Lymphoblasts were isolated from bone marrow and/or blood samples from children with newly diagnosed acute lymphoblastic leukemia. The cytotoxic activity of prednisolone, dexamethasone and the prednisolone/dexamethasone combination against isolated leukemia cells was analyzed using the MTT cytotoxicity assay. Results. We observed differences in the in vitro antileukemic activity of prednisolone and dexamethasone in 21% of the tested patients. 3% of the children were prednisolone sensitive but dexamethasone resistant, while 18% were prednisolone resistant and dexamethasone sensitive. 32% were sensitive to both glucocorticoids and 18% were resistant to both. Cells from patients with good in vivo responses to prednisone monotherapy were more responsive to prednisolone in vitro than were cells from patients with poor prednisone responses (P{0.07). Importantly, we demonstrated that the use of even a minimal dose (1/50 w/w) of dexamethasone with prednisolone dramatically increases the in vitro anti-leukemic activity of prednisolone (P{0.0006). Conclusion. The high inter-individual variability of acute lymphoblastic leukemia responses to glucocorticoids suggest that either patients should...
  • Introduction. Glucocorticoids, particularly prednisone/ prednisolone and dexamethasone, play a prominent role in the treatment of pediatric patients with acute lymphoblastic leukemia due to their ability to induce apoptosis in susceptible cells. Current therapeutic protocols use prednisone for both the prophase and the induction phase of the therapy because the greater antileukemic activity of dexamethasone is compromised by its high frequency of serious adverse reactions. Aim. To compare, for the first time, the in vitro antileukemic activity of prednisolone alone to that of a combination of prednisolone and dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50 w/w). Methods. Lymphoblasts were isolated from bone marrow and/or blood samples from children with newly diagnosed acute lymphoblastic leukemia. The cytotoxic activity of prednisolone, dexamethasone and the prednisolone/dexamethasone combination against isolated leukemia cells was analyzed using the MTT cytotoxicity assay. Results. We observed differences in the in vitro antileukemic activity of prednisolone and dexamethasone in 21% of the tested patients. 3% of the children were prednisolone sensitive but dexamethasone resistant, while 18% were prednisolone resistant and dexamethasone sensitive. 32% were sensitive to both glucocorticoids and 18% were resistant to both. Cells from patients with good in vivo responses to prednisone monotherapy were more responsive to prednisolone in vitro than were cells from patients with poor prednisone responses (P{0.07). Importantly, we demonstrated that the use of even a minimal dose (1/50 w/w) of dexamethasone with prednisolone dramatically increases the in vitro anti-leukemic activity of prednisolone (P{0.0006). Conclusion. The high inter-individual variability of acute lymphoblastic leukemia responses to glucocorticoids suggest that either patients should... (en)
Title
  • Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistence in acute childhood lymphoblastic leukemia
  • Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistence in acute childhood lymphoblastic leukemia (en)
skos:prefLabel
  • Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistence in acute childhood lymphoblastic leukemia
  • Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistence in acute childhood lymphoblastic leukemia (en)
skos:notation
  • RIV/61989592:15110/14:33140501!RIV15-MSM-15110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED0030/01/01), S
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 7795
http://linked.open...ai/riv/idVysledku
  • RIV/61989592:15110/14:33140501
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • MTT assay; drug resistance; dexamethasone; prednisolone; prednisone; glucocorticoids; acute lymphoblastic leukemia (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [8E47C417A38B]
http://linked.open...i/riv/nazevZdroje
  • Biomedical Papers-Olomouc
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 158
http://linked.open...iv/tvurceVysledku
  • Džubák, Petr
  • Hajdúch, Marián
  • Konečný, Petr
  • Mihál, Vladimír
  • Pospíšilová, Dagmar
  • Radová, Lenka
  • Starý, Jan
  • Novák, Zbyněk
  • Blažek, Bohumír
  • Hak, Jiří
  • Srovnal, Josef
  • Votava, Tomáš
  • Timr, Pavel
  • Špenerová, Michaela
  • Bubanská, Eva
  • Buriánová, Renata
  • Kaiserová, Emília
  • Šálková, Soňa
issn
  • 1213-8118
number of pages
http://bibframe.org/vocab/doi
  • 10.5507/bp.2012.059
http://localhost/t...ganizacniJednotka
  • 15110
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