Glutathione S-transferases and iododeoxyuridine labelling index during chemotherapy of gastric cancer.
BACKGROUND
Resistance to chemotherapeutic agents is a major problem in the treatment of patients with gastric cancer. Many factors may play a role in the resistance to cytotoxic drugs. The purpose of this study was to investigate the significance of glutathione (GSH), glutathione S-transferases (GSTs) and cell proliferation as parameters for response and resistance to chemotherapy in patients with gastric cancer.


METHODS
In endoscopic biopsies of normal and malignant gastric tissue from 15 patients with gastric cancer treated by chemotherapy, the GSH content, GST activity and levels of GST Alpha, Mu and Pi isoenzymes were determined before the start of chemotherapy and after 2 and 6 cycles. Furthermore, cell proliferation was determined in these biopsies after in vivo Iododeoxyuridine (IdU) labelling.


RESULTS
None of the above mentioned parameters were predictive for response to chemotherapy. After 2 courses of chemotherapy there was an increase of median GSH content (367%) in three patients with partial response (PR), whereas there was a decrease (43%) in five patients with progressive disease (PD) (p < 0.05). Median GST activity increased (257%) in patients with PR and declined (31%) in patients with PD (p < 0.05). GST Pi showed a median increase of 326% in responding patients and a 59% decrease in progressive patients (p < 0.05). There were no significant changes in GST Alpha and Mu. In seven patients with stable disease (SD) there were no significant changes in GSH/GST parameters.


CONCLUSIONS
GSH/GST parameters and IdU labelling index determined before the start of chemotherapy were not predictive for response to that chemotherapy. However, the differences of GSH and GST parameters between responding and progressive patients suggests a role for the GSH/GST system in the susceptibility of gastric tumor cells to chemotherapy.
Department of Medical Oncology, University Hospital Nijmegen, The Netherlands.
D L
DL
Schipper
M J
MJ
Wagenmans
W H
WH
Peters
J A
JA
Wils
D J
DJ
Wagener
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D001706:Biopsy; D002455:Cell Division; D019008:Drug Resistance, Neoplasm; D004724:Endoscopy; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000145:classification / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology
D018528:ATP-Binding Cassette Transporters; D005978:Glutathione; D005982:Glutathione Transferase; D006023:Glycoproteins; D007065:Idoxuridine; D007527:Isoenzymes; D027425:ATP-Binding Cassette, Sub-Family C Proteins