Document Detail

Cytotoxicity of cortivazol in childhood acute lymphoblastic leukemia.
MedLine Citation:
PMID:  16158972     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Glucocorticoids are the most important group of drugs used in the treatment of childhood acute lymphoblastic leukemia (ALL), however, resistance to this group remains the main obstacle in curing the disease. One of the possibilities to circumvent glucocorticoid resistance is the use of new compounds, such as cortivazol (CVZ), which has two binding sites for the glucocorticoid receptor. AIM: Analysis of ex vivo sensitivity to cortivazol and other glucocorticoids in childhood acute lymphoblastic leukemia, as well as the relationship to anticancer therapy outcome. PATIENTS AND METHODS: Leukemic samples from 60 children with ALL were tested by the M7T assay for glucocorticoid resistance. Cell cycle before and after ex vivo glucocorticoid treatment was analyzed by flow cytometry. RESULTS: Although all tested glucocorticoids presented significant cross-resistance, CVZ showed high antileukemic activity. The equivalent activity of CVZ was 165-fold higher than prednisolone, 7.ZS5-fold higher than dexamethasone and 2.8-fold higher than betamethasone. CVZ showed relatively better cytotoxicity than other glucocorticoids in prednisolone-poor-responders. CVZ, like other glucocorticoids, caused cell cycle arrest in the GI-phase, and increased the percentage of apoptotic cells to a greater extent than other glucocorticoids. The results of antileukemic therapy were strongly related to the ex vivo resistance to all tested glucocorticoids. CONCLUSION: Cortivazol has potent antileukemic activity in childhood ALL. Its activity is related to cell cycle arrest and induction of apoptosis.
Jan Styczynski; Andrzej Kurylak; Mariusz Wysocki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  25     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2005 May-Jun
Date Detail:
Created Date:  2005-09-14     Completed Date:  2005-11-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2253-8     Citation Subset:  IM    
Department of Pediatric Hematology and Oncology, Ludwik Rydygier's Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University of Torun, Poland.
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MeSH Terms
Cell Cycle / drug effects
Child, Preschool
Drug Resistance, Neoplasm
Glucocorticoids / pharmacology
Lymphocytes / drug effects,  pathology
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*,  pathology
Prednisolone / pharmacology
Pregnatrienes / pharmacology*
Reg. No./Substance:
0/Glucocorticoids; 0/Pregnatrienes; 1110-40-3/cortivazol; 50-24-8/Prednisolone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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