The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.
Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.
Saint Luke's Hospital, Dublin Institute of Technology, Ireland.
C
C
Mothersill
C B
CB
Seymour
A
A
Cusack
A
A
O'Brien
M
M
Butler
D016190:Carboplatin; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D046508:Culture Techniques; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007633:Keratins / Q000032:analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000187:drug effects* / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy
D009944:Organoplatinum Compounds; D007633:Keratins; D016190:Carboplatin; D002945:Cisplatin