Assessment of the classical MDR phenotype in epithelial ovarian carcinoma using primary cultures: a feasibility study.
This in vitro feasibility study has assessed a number of techniques and their applicability when looking at the role of multidrug resistance (MDR) in solid tumours. Fresh tumour material was obtained from 34 patients, (11 previously treated, 23 untreated) with ovarian adenocarcinoma. Doxorubicin sensitivity was measured using the MTT assay +/- the cyclosporins, Pgp expression was assessed by immunocytochemistry with the MRK-16 MoAb and flow cytometry was used to assess intracellular drug accumulation +/- PSC 833. 85% of samples showed some evidence of modest chemosensitisation by the cyclosporins (median 1.74-fold). We saw a marked variation in the number of Pgp positive cells between patients (1-87%, median 31%). 63% of samples tested showed an enhancement of DNR accumulation in the presence of PSC 833, with a median increase of 7% (sample range 0-29%). The present study highlights some of the technical difficulties encountered when working with fresh tumour material ex vivo. We conclude that screening of patients for their suitability to enter clinical trials incorporating MDR modulating agents is technically demanding, but feasible.
Coley
Helen M
HM
Haematology Research, Pembury Hospital, Kent, UK.
Sargent
Jean M
JM
Williamson
Christine J
CJ
Titley
Jenny
J
Scheper
Rik J
RJ
Gregson
Sarah E
SE
Elgie
Alena W
AW
Lewandowicz
Grazyna M
GM
Taylor
Colin G
CG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000502:physiology*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010641:Phenotype
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003524:Cyclosporins; D004317:Doxorubicin; C070272:valspodar