Determination and reversal of resistance to epirubicin intravesical chemotherapy. A confocal imaging study
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1996 |
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| Erschienen: |
1996 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
British journal of urology - 77(1996), 6 vom: 03. Juni, Seite 824-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Duffy, P M [VerfasserIn] |
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| Themen: |
3Z8479ZZ5X |
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| Anmerkungen: |
Date Completed 11.09.1996 Date Revised 19.07.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM086774174 |
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| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM086774174 | ||
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| 007 | tu | ||
| 008 | 231222s1996 xx ||||| 00| ||eng c | ||
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| 041 | |a eng | ||
| 100 | 1 | |a Duffy, P M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Determination and reversal of resistance to epirubicin intravesical chemotherapy. A confocal imaging study |
| 264 | 1 | |c 1996 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 11.09.1996 | ||
| 500 | |a Date Revised 19.07.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibiotics, Antineoplastic |2 NLM | |
| 650 | 7 | |a Epirubicin |2 NLM | |
| 650 | 7 | |a 3Z8479ZZ5X |2 NLM | |
| 650 | 7 | |a Verapamil |2 NLM | |
| 650 | 7 | |a CJ0O37KU29 |2 NLM | |
| 700 | 1 | |a Hayes, M C |e verfasserin |4 aut | |
| 700 | 1 | |a Gatrell, S K |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, A |e verfasserin |4 aut | |
| 700 | 1 | |a Smart, C J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of urology |d 1945 |g 77(1996), 6 vom: 03. Juni, Seite 824-9 |w (DE-627)NLM000001449 |x 0007-1331 |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:1996 |g number:6 |g day:03 |g month:06 |g pages:824-9 |
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| 952 | |d 77 |j 1996 |e 6 |b 03 |c 06 |h 824-9 | ||