Correlation of drug response in human tumors histocultured in vitro with an image-analysis MTT end point and in vivo xenografted in nude mice.
We have in this study used the 3-(4,5-dimethyl-2- thiazoyl) -2,5-diphenyl 2-H-tetrazolium bromide (MTT) end point in our histoculture drug-response assay. We have previously demonstrated that the formazan crystals formed by MTT reduction by mitochondrial succinate dehydrogenase reflect polarized light and can be measured by pixel analysis in intact tissue. The results described here indicate a total specificity of 93.8% and a total accuracy of 74.6% of the MTT end point for drug response in histoculture correlating with nine different human xenograft tumors grown in nude mice with respect to the in vivo drug response data. This in vitro system allows prediction of positive and negative responses to drugs, with a rate of 70% and 71.8%, respectively. The system described here has potential for clinical use because of the possibility of simultaneous description of the MTT values and heterogeneous response to drugs within individual tumors.
Colangelo
D
D
AntiCancer Inc., San Diego, California 92110.
Guo
H Y
HY
Connors
K M
KM
Kubota
T
T
Silvestro
L
L
Hoffman
R M
RM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004396:Coloring Agents; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008937:Mitomycins / Q000494:pharmacology / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004396:Coloring Agents; D008937:Mitomycins; D013778:Tetrazolium Salts; D013844:Thiazoles; D004317:Doxorubicin; C022616:thiazolyl blue; D002945:Cisplatin; D008558:Melphalan; D005472:Fluorouracil