Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistance in acute childhood lymphoblastic leukemia
| Autor: | Josef Srovnal, Bohumir Blazek, Tomas Votava, Marian Hajduch, Emilia Kaiserova, Michaela Spenerova, Jan Stary, Sona Salkova, Petr Konecny, Zbynek Novak, Vladimír Mihál, Lenka Radová, Jiri Hak, Renata Burianova, Eva Bubanska, Petr Dzubak, Pavel Timr, Dagmar Pospisilova |
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| Rok vydání: | 2014 |
| Předmět: |
Prednisolone
In Vitro Techniques Pharmacology Dexamethasone General Biochemistry Genetics and Molecular Biology In vivo Prednisone hemic and lymphatic diseases medicine Humans Child Glucocorticoids Childhood Acute Lymphoblastic Leukemia business.industry Lymphoblast Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Leukemia medicine.anatomical_structure Drug Resistance Neoplasm Drug Therapy Combination Bone marrow business medicine.drug |
| Zdroj: | Biomedical Papers. 158:422-427 |
| ISSN: | 1804-7521 1213-8118 |
| DOI: | 10.5507/bp.2012.059 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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