Document Detail

Determination and reversal of resistance to epirubicin intravesical chemotherapy. A confocal imaging study.
MedLine Citation:
PMID:  8705215     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To evaluate the use of confocal microscopy in the study of resistance to epirubicin and to determine the effect of temperature, viability and a resistance-reversing agent on the intracellular distribution of this drug in sensitive and resistant derivatives of a superficial bladder cancer cell line. MATERIALS AND METHODS: Viable and non-viable adherent cells were incubated in epirubicin solutions under various conditions. After incubation, the distribution of intracellular epirubicin fluorescence was visualized using confocal microscopy and a x50 water-immersion lens. RESULTS: There was a striking and consistent difference between resistant and sensitive cells in the intracellular distribution of the drug. In addition to having greater overall levels of epirubicin fluorescence, sensitive cells accumulated epirubicin predominantly in the nucleus. Epirubicin fluorescence in resistant cells was cytoplasmic and granular in appearance. When incubated at 0 degrees C, both cell lines showed no nuclear uptake and thus resembled resistant cells at 37 degrees C. However, dead cells rapidly acquired brightly fluorescent nuclei. The resistance-reversing agent verapamil appeared to cause reversion of the resistant to the sensitive phenotype. CONCLUSION: Confocal microscopy allows epirubicin-sensitive and resistant cultured tumour cells to be differentiated reliably and provides information about the mechanisms of action of, and resistance to, epirubicin. Applying this technique to clinical specimens should enable patients who have the resistant phenotype to be detected and the efficacy of intravesical resistance-reversing agents to be evaluated in such cases.
P M Duffy; M C Hayes; S K Gatrell; A Cooper; C J Smart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of urology     Volume:  77     ISSN:  0007-1331     ISO Abbreviation:  Br J Urol     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-09-11     Completed Date:  1996-09-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  15740090R     Medline TA:  Br J Urol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  824-9     Citation Subset:  IM    
Department of Urology, Southampton University Hospitals NHS Trust, UK.
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MeSH Terms
Administration, Intravesical
Antibiotics, Antineoplastic / administration & dosage,  metabolism*,  therapeutic use
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Epirubicin / administration & dosage,  metabolism*,  therapeutic use
Microscopy, Confocal
Sensitivity and Specificity
Tumor Cells, Cultured
Urinary Bladder Neoplasms / drug therapy,  metabolism*
Verapamil / pharmacology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 52-53-9/Verapamil; 56420-45-2/Epirubicin

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