Determination and reversal of resistance to epirubicin intravesical chemotherapy. A confocal imaging study
| Autor: | C. J. Smart, P.M. Duffy, S.K.E. Gatrell, M.C. Hayes, Alan J. Cooper |
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| Rok vydání: | 1996 |
| Předmět: |
Pathology
medicine.medical_specialty Urology medicine.medical_treatment Sensitivity and Specificity Fluorescence law.invention Confocal microscopy law Tumor Cells Cultured polycyclic compounds medicine Humans Distribution (pharmacology) skin and connective tissue diseases Epirubicin Chemotherapy Antibiotics Antineoplastic Microscopy Confocal business.industry Molecular biology Drug Resistance Multiple carbohydrates (lipids) Multiple drug resistance Administration Intravesical Urinary Bladder Neoplasms Verapamil Drug Resistance Neoplasm Cytoplasm Cell culture business Intracellular medicine.drug |
| Zdroj: | BJU International. 77:824-829 |
| ISSN: | 1464-410X 1464-4096 |
| DOI: | 10.1046/j.1464-410x.1996.09539.x |
| Popis: | 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 ×50 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°C, both cell lines showed no nuclear uptake and thus resembled resistant cells at 37°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. |
| Databáze: | OpenAIRE |
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