Multiple Drug Resistance Parameter Expression in Ovarian Cancer

doi:10.1006/gyno.1998.5085

Gynecologic Oncology

Volume 70, Issue 2, August 1998, Pages 176-182

https://doi.org/10.1006/gyno.1998.5085 Get rights and content

Abstract

Objective.Drug resistance represents a complex problem for the treatment of ovarian cancer. This study was undertaken to assess several putative resistance parameters (DRP) in parallel in cancer tissue from newly diagnosed patients with ovarian cancer in order to establish possible correlations to known clinical factors and prognosis.

Material and methods.Tumor and adjacent tumor free ovarian tissue samples from 39 consecutive, untreated female patients with ovarian cancer were obtained and as potential DRPs, the level of glutathione (GSH), the activities of glutathioneS-transferase (GST), glutathione-peroxidase (GPx),O⁶-alkylguanine-DNA alkyltransferase (Atase), and topoisomerase II (TOPO) were assessed biochemically, andP-glycoprotein (Pgp) was assessed by Western blotting.

Results.Interindividual variations were high and each patient exhibited an individual profile of resistance factor expression. Levels of GSH were increased with stage (linear trend:P< 0.002), and GST, GPx, and Atase showed a similar tendency. With few exceptions no correlation was found between the DRPs and other prognostic characteristics. All tested DRPs except Pgp showed significantly higher levels/activities in tumor tissues than in the surrounding tumor free tissues (P< 0.05). The tested DRPs were found not to influence response to treatment.

Conclusions.It is concluded that elevated DRPs reflect an intrinsic pattern of components of the detoxifying system in the tumor tissue. This pattern differs between patients and may partly explain the difficulty to assess the clinical importance of individual DRPs in order to translate them into recommendations for specific therapies.

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Objective. Clinical drug resistance is the major obstacle in the successful treatment of ovarian cancer. Besides elevated expression of adenosine triphosphate binding cassette (ABC) transporters, such as MDR1/P-gp or MRP2/cMOAT/ABCC2, alterations in the expression of DNA topoisomerase I (TOP1) are associated with drug-resistant phenotypes in various model systems.
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Results. Of the 59 primary ovarian tumors examined, 32 (54.2%) and 18 (30.5%) were positive for YB-1 and P-gp, respectively. Co-expression of these two proteins was observed in 20.3% (12/59) cases. Patients showing this co-expression had a worse 3-year survival than those without co-expression (40.0% vs. 73.1%, P = 0.0447). This co-expression significantly correlated with poor prognosis according to multivariate analysis (P = 0.0007).
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Regular ArticleMultiple Drug Resistance Parameter Expression in Ovarian Cancer

Abstract

Biochem Pharmacol

Cancer Treat Rev

Blood

Ann Biochem

J Biol Chem

Int J Radiat Oncol Biol Phys

Biochem Pharmacol

Gynecol Oncol

Cancer statistics

CA Cancer J Clin

Mechanisms and modulation of resistance to chemotherapy in ovarian cancer

Cancer

Glutathione S-transferase and anticancer drug resistance

Mechanisms of Drug Resistance in Neoplastic Cells

High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis

Proc Natl Acad Sci USA

Patterns of drug resistance parameters in adult leukemia

Leuk Lymph

Glutathione S-transferase expression in benign and malignant ovarian tumours

Br J Cancer

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Br J Cancer

Repair of DNA containing O6-alkylguanine

FASEB J

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Haematologica

Regular Article
Multiple Drug Resistance Parameter Expression in Ovarian Cancer