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Estramustine reversal of resistance to intravesical epirubicin chemotherapy.
Eur Urol. 1999 Apr; 35(4):327-35.EU

Abstract

OBJECTIVE

Failure of epirubicin treatment of superficial bladder cancer implies multidrug resistance (MDR) which is common. MDR is characterised by decreased cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to both epirubicin and mitomycin C were used to investigate augmented therapy by adding the MDR reversing agent estramustine to an in vitro model.

METHODS

Cells were cultured as monolayers. Fluorescence analysis was performed by flow cytometry and confocal microscopy. Cells were exposed to epirubicin 20 microg/ml for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under similar exposure conditions and MTT culture (dye reduction by live cells) allowed viable biomass to be read optically.

RESULTS

Resistant cells accumulated eight times less epirubicin than sensitive cells. Confocal microscopy confirmed this for nuclear uptake. Accumulation in resistant cells can be increased to near-sensitive cell levels using 40 microg/ml estramustine. Image analysis of confocal fluorescence showed a shift from cytoplasm to nucleus. This correlated with increased cytotoxicity.

CONCLUSION

Estramustine plus epirubicin chemotherapy can overcome MDR and may achieve more successful tumour killing in vivo. It may also prevent emergence of resistance. Primary TCC culture examination permits detection of sensitive and resistant cells and may predict outcome allowing a more logical treatment selection.

Authors+Show Affiliations

Department of Urology, Southampton University Hospitals NHS Trust, Southampton, UK. andrew.jennings@virgin.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10087397

Citation

Jennings, A M., et al. "Estramustine Reversal of Resistance to Intravesical Epirubicin Chemotherapy." European Urology, vol. 35, no. 4, 1999, pp. 327-35.
Jennings AM, Solomon LZ, Sharpe P, et al. Estramustine reversal of resistance to intravesical epirubicin chemotherapy. Eur Urol. 1999;35(4):327-35.
Jennings, A. M., Solomon, L. Z., Sharpe, P., Hayes, M. C., Cooper, A. J., & Birch, B. R. (1999). Estramustine reversal of resistance to intravesical epirubicin chemotherapy. European Urology, 35(4), 327-35.
Jennings AM, et al. Estramustine Reversal of Resistance to Intravesical Epirubicin Chemotherapy. Eur Urol. 1999;35(4):327-35. PubMed PMID: 10087397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estramustine reversal of resistance to intravesical epirubicin chemotherapy. AU - Jennings,A M, AU - Solomon,L Z, AU - Sharpe,P, AU - Hayes,M C, AU - Cooper,A J, AU - Birch,B R, PY - 1999/3/24/pubmed PY - 2000/8/16/medline PY - 1999/3/24/entrez SP - 327 EP - 35 JF - European urology JO - Eur Urol VL - 35 IS - 4 N2 - OBJECTIVE: Failure of epirubicin treatment of superficial bladder cancer implies multidrug resistance (MDR) which is common. MDR is characterised by decreased cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to both epirubicin and mitomycin C were used to investigate augmented therapy by adding the MDR reversing agent estramustine to an in vitro model. METHODS: Cells were cultured as monolayers. Fluorescence analysis was performed by flow cytometry and confocal microscopy. Cells were exposed to epirubicin 20 microg/ml for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under similar exposure conditions and MTT culture (dye reduction by live cells) allowed viable biomass to be read optically. RESULTS: Resistant cells accumulated eight times less epirubicin than sensitive cells. Confocal microscopy confirmed this for nuclear uptake. Accumulation in resistant cells can be increased to near-sensitive cell levels using 40 microg/ml estramustine. Image analysis of confocal fluorescence showed a shift from cytoplasm to nucleus. This correlated with increased cytotoxicity. CONCLUSION: Estramustine plus epirubicin chemotherapy can overcome MDR and may achieve more successful tumour killing in vivo. It may also prevent emergence of resistance. Primary TCC culture examination permits detection of sensitive and resistant cells and may predict outcome allowing a more logical treatment selection. SN - 0302-2838 UR - https://www.unboundmedicine.com/medline/citation/10087397/Estramustine_reversal_of_resistance_to_intravesical_epirubicin_chemotherapy_ L2 - https://medlineplus.gov/bladdercancer.html DB - PRIME DP - Unbound Medicine ER -