Abstract

A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response rates of these two groups to chemotherapy differ markedly, with patients who have relapsed following initial chemotherapy showing a reduction in response rates to subsequent chemotherapy. Analysis of these data show no statistically significant differences between the glutathione S-transferase activity or isoenzyme distribution in these two groups of patients. Significant differences were observed in the glutathione-S-transferase activities (GST) between tumours and normal ovaries. GST activities in pre-chemotherapy tumours (n = 33, P = 0.01) and post-chemotherapy tumours (n = 20, P = 0.001) where significantly higher than the GST activity in normal ovaries (n = 15). One feature was the expression of the basic isoenzyme which is expressed more in normal ovaries than in tumours. No differences in these parameters were observed in normal peritoneal tissue taken from patients before or after chemotherapy. These data do not support the hypothesis that changes in glutathione S-transferase enzyme activity or isoenzyme expression are major determinants of response to chemotherapy in ovarian tumours.

Highlights

  • Analysis of these' data reveals a significant difference in glutathione S-transferase isoenzyme expression between normal ovaries (n = 15), and tumours (n = 55) (Table II)

  • This change, is highly significant (P

  • No differences in glutathioneS-transferase activities (GST) activity or isoenzyme expression were seen in peritoneal tissue from the same groups of patients (n = 39)

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Summary

Methods

Ovarian tumour specimens were provided by gynaecological surgeons throughout the North West of England. Samples were frozen in liquid nitrogen within minutes of excision and stored at - 80°C until processing. Tumour histology was confirmed with the referring hospital and the presence of malignant tissue in the biopsy samples confirmed by one of the authors at the time of assay by routine histology. Samples of normal ovary were collected from patients undergoing routine prophylactic oophorectomy at the time of pelvic surgery for benign gynaecological disease (Median age = 46, range 39-54 years). Identical experimental procedures were performed on both these and the tumour samples. Wherever possible a sample of healthy peritoneal tissue was taken to compare with tumour and normal ovary

Results
Discussion
Conclusion

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