Ex vivo modulation of response to prednisolone in childhood acute lymphoblastic leukaemia.
We hypothesised that the intensity of mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukaemia might be decreased by concurrent ex vivo use of compounds with specific blocking or activating properties at different steps of the glucocorticoid intracellular pathway. The following modifiers were used: ciclosporin A, rifampicin, doxycycline, meta-iodobenzylguanidine, buthionine sulfoximine, ethacrinic acid, pentoxifylline, indomethacin, rotenone, forskolin, olomoucin, 5-aza-2'-deoxycytidine, 3-aminobenzamide, O(6)-benzylguanidine and nitroprusside sodium. All modulators sensitised lymphoblasts and potentiated prednisolone cytotoxicity in most cases indicating that various compounds, which can influence the antileukaemic effect of prednisolone during anticancer therapy, might modulate some mechanisms of glucocorticoid resistance.
Styczynski
Jan
J
Department of Paediatric Haematology and Oncology, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland. jstyczynski@cm.umk.pl
Wysocki
Mariusz
M
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011239:Prednisolone / Q000494:pharmacology*; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D011239:Prednisolone