[High clinical predictability of histoculture drug response assay (HDRA) for drug-sensitivity of cancer of the digestive organs].
Fresh surgical specimens from 250 patients with cancer were used for the histoculture drug response assay (HDRA) with MTT method. Scissor cut small pieces of the specimens were placed onto collagen-gel-matrix which was incubated in 24 well-plate dishes filled with medium containing mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU) or cisplatin (CDDP). The cutoff concentrations of the drugs used are 7.5 micrograms/ml for MMC, 15 micrograms/ml for ADM, 300 micrograms/ml for 5-FU and 20 micrograms/ml for CDDP. After 7 days incubation, the specimens were assessed the inability to reduce MTT. A 50% or greater inhibition of MTT reduction at the cutoff concentrations indicated in vitro sensitivity. The clinical effect of the drugs was evaluated according to the criteria of the Japanese Society for Cancer Therapy. Two hundred thirty two (93%) cases were evaluable, and in vitro and in vivo correlation was compared in 42 cases. Of the 33 patients whose tumors showed drug resistance in HDRA, 33 failed treatment with one or more of these agents. Of the nine patients whose tumors showed drug sensitivity in HDRA, six had chemo-responses (2 CRs and 4 PRs) for a total accuracy of 93% (34/42). The advantages of HDRA include, three-dimensional tumor cell growth in in vitro culture with cell to cell contact and maintenance of tissue architecture, 7 days to assess the effect of antitumor agents, ability to evaluate both growing and resting tumor cells, small amounts of specimen required for assay, and high evaluable and predictable rates for clinical use in designing optimal chemotherapy regimens for cancer patients.
Kubota
T
T
Dept. of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Furukawa
T
T
Kitajima
M
M
D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013778:Tetrazolium Salts; D013844:Thiazoles; D016685:Mitomycin; D004317:Doxorubicin; C022616:thiazolyl blue; D002945:Cisplatin; D005472:Fluorouracil