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A fluorescence-based assay for monitoring clinical drug resistance

A fluorescence-based assay for monitoring clinical drug resistance
A fluorescence-based assay for monitoring clinical drug resistance
BACKGROUND AND AIMS: Multidrug resistance (MDR) limits effectiveness in treating malignancy by modifying internalisation and/or externalisation of drugs through cancer cell membranes. In this study we describe an assay to monitor patients' responses to chemotherapy.

METHODS: The assay is based on the fluorescent properties of doxorubicin alone as well as in combination with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). The slide-based cell imaging technique was first optimised using a panel of breast and urothelial cancer cell lines and then extended to fine needle breast aspiration biopsy and urine cytology.

RESULTS: The drug fluorescence behaviour observed on smears of clinical specimens is identical to that obtained using fixed cultured cells. The fluorescence of sensitive cells to chemotherapy is mainly localised in the nucleus, whereas resistant cells show a weak fluorescence signal localised in the cytoplasm. The difference in terms of fluorescence intensity is also highlighted through fluorescence spectra.

CONCLUSIONS: The results suggest that the assay provides clinically valuable information in predicting responses to doxorubicin and/or MVAC therapy. Originally set up on a confocal microscope, the assay was also effective using a standard epifluorescence microscope; as such it is technically simple, reliable and inexpensive.
0021-9746
1003-1007
Deniset-Besseau, Ariane
aea3b7f3-c41d-4a18-a38a-0ba0edbff3a9
Miannay, François-Alexandre
337523c1-3aab-4a0f-8633-4af67a757867
Laplace-Builhe, Corinne
94a8be76-10cf-45db-9996-98ca520b13bf
Vielh, Philippe
44e69e25-f841-4693-b59d-f663de082079
Lecart, Sandrine
f1418e3a-7aef-449c-b643-30b8b224ee12
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Eschwege, Pascal
2a3b03e2-8b2a-4050-abb9-6a32b3e48e73
Fontaine-Aupart, Marie-Pierre
14f12265-4508-42b0-8c35-f29558224efa
Deniset-Besseau, Ariane
aea3b7f3-c41d-4a18-a38a-0ba0edbff3a9
Miannay, François-Alexandre
337523c1-3aab-4a0f-8633-4af67a757867
Laplace-Builhe, Corinne
94a8be76-10cf-45db-9996-98ca520b13bf
Vielh, Philippe
44e69e25-f841-4693-b59d-f663de082079
Lecart, Sandrine
f1418e3a-7aef-449c-b643-30b8b224ee12
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Eschwege, Pascal
2a3b03e2-8b2a-4050-abb9-6a32b3e48e73
Fontaine-Aupart, Marie-Pierre
14f12265-4508-42b0-8c35-f29558224efa

Deniset-Besseau, Ariane, Miannay, François-Alexandre, Laplace-Builhe, Corinne, Vielh, Philippe, Lecart, Sandrine, Lwaleed, Bashir A., Eschwege, Pascal and Fontaine-Aupart, Marie-Pierre (2012) A fluorescence-based assay for monitoring clinical drug resistance. Journal of Clinical Pathology, 65 (11), 1003-1007. (doi:10.1136/jclinpath-2012-200787). (PMID:22859393)

Record type: Article

Abstract

BACKGROUND AND AIMS: Multidrug resistance (MDR) limits effectiveness in treating malignancy by modifying internalisation and/or externalisation of drugs through cancer cell membranes. In this study we describe an assay to monitor patients' responses to chemotherapy.

METHODS: The assay is based on the fluorescent properties of doxorubicin alone as well as in combination with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). The slide-based cell imaging technique was first optimised using a panel of breast and urothelial cancer cell lines and then extended to fine needle breast aspiration biopsy and urine cytology.

RESULTS: The drug fluorescence behaviour observed on smears of clinical specimens is identical to that obtained using fixed cultured cells. The fluorescence of sensitive cells to chemotherapy is mainly localised in the nucleus, whereas resistant cells show a weak fluorescence signal localised in the cytoplasm. The difference in terms of fluorescence intensity is also highlighted through fluorescence spectra.

CONCLUSIONS: The results suggest that the assay provides clinically valuable information in predicting responses to doxorubicin and/or MVAC therapy. Originally set up on a confocal microscope, the assay was also effective using a standard epifluorescence microscope; as such it is technically simple, reliable and inexpensive.

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More information

e-pub ahead of print date: 2 August 2012
Published date: November 2012
Organisations: Faculty of Health Sciences

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Local EPrints ID: 347866
URI: http://eprints.soton.ac.uk/id/eprint/347866
ISSN: 0021-9746
PURE UUID: ef57672e-8441-4469-8566-fa2d19429ea9

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Date deposited: 31 Jan 2013 14:56
Last modified: 14 Mar 2024 12:53

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Contributors

Author: Ariane Deniset-Besseau
Author: François-Alexandre Miannay
Author: Corinne Laplace-Builhe
Author: Philippe Vielh
Author: Sandrine Lecart
Author: Pascal Eschwege
Author: Marie-Pierre Fontaine-Aupart

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