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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F14%3A33140501%21RIV15-MSM-15110___
rdf:type
skos:Concept n18:Vysledek
dcterms:description
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...
dcterms: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
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
skos:notation
RIV/61989592:15110/14:33140501!RIV15-MSM-15110___
n4:aktivita
n12:S n12:P
n4:aktivity
P(ED0030/01/01), S
n4:cisloPeriodika
3
n4:dodaniDat
n9:2015
n4:domaciTvurceVysledku
n7:5489482 n7:1838318 n7:5281415 n7:8117284 n7:2999048 n7:1188852 n7:3978168 n7:7608543 n7:5660661 n7:2484994
n4:druhVysledku
n8:J
n4:duvernostUdaju
n5:S
n4:entitaPredkladatele
n19:predkladatel
n4:idSjednocenehoVysledku
7795
n4:idVysledku
RIV/61989592:15110/14:33140501
n4:jazykVysledku
n15:eng
n4:klicovaSlova
MTT assay; drug resistance; dexamethasone; prednisolone; prednisone; glucocorticoids; acute lymphoblastic leukemia
n4:klicoveSlovo
n6:drug%20resistance n6:MTT%20assay n6:prednisone n6:acute%20lymphoblastic%20leukemia n6:dexamethasone n6:prednisolone n6:glucocorticoids
n4:kodStatuVydavatele
CZ - Česká republika
n4:kontrolniKodProRIV
[8E47C417A38B]
n4:nazevZdroje
Biomedical Papers-Olomouc
n4:obor
n13:FD
n4:pocetDomacichTvurcuVysledku
10
n4:pocetTvurcuVysledku
18
n4:projekt
n17:ED0030%2F01%2F01
n4:rokUplatneniVysledku
n9:2014
n4:svazekPeriodika
158
n4:tvurceVysledku
Kaiserová, Emília Blažek, Bohumír Hak, Jiří Votava, Tomáš Hajdúch, Marián Novák, Zbyněk Timr, Pavel Buriánová, Renata Pospíšilová, Dagmar Mihál, Vladimír Špenerová, Michaela Radová, Lenka Bubanská, Eva Konečný, Petr Starý, Jan Džubák, Petr Šálková, Soňa Srovnal, Josef
s:issn
1213-8118
s:numberOfPages
6
n14:doi
10.5507/bp.2012.059
n16:organizacniJednotka
15110