Expression of MDR1, GST-pi and topoisomerase II as an indicator of clinical response to adriamycin.
The usefulness of MDR1, GST-pi or topoisomerase II mRNA expression detected by dot blot analysis as an indicator of intrinsic resistance to adriamycin was investigated in 15 fresh human tumor specimens. MDR1 and GST-pi expression, which is known to be a marker for adriamycin resistance, was detected in six (66.7%) and seven (77.8%) of the nine clinically resistant tumors, respectively. However, in four of the six adriamycin responsive tumors, MDR1 and/or GST-pi expression were detected. Thus these two markers were not indicators of clinical response to adriamycin. In contrast, topoisomerase II mRNA expression was significantly correlated with clinical response (p less than 0.01, chi 2 test). The expression of topoisomerase II mRNA was detected at a high level in five (83.3%) of the 6 clinically responsive tumors, and the other nine tumors resistant to adriamycin treatment exhibited undetectable or low levels of topoisomerase II mRNA. We therefore suggest that the level of topoisomerase II mRNA expression is a useful marker of the clinical response to adriamycin.
Kim
R
R
Department of Surgery, Hiroshima University, Japan.
Hirabayashi
N
N
Nishiyama
M
M
Saeki
S
S
Toge
T
T
Okada
K
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*
D007527:Isoenzymes; D012333:RNA, Messenger; D004317:Doxorubicin; D003520:Cyclophosphamide; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II; D005472:Fluorouracil