The measurement of glucose consumption in histoculture to determine effects of doxorubicin and cisplatinum on human gastric carcinoma.
We have developed a chemosensitivity assay of human tumors growing on collagen-sponge-gel-supported histoculture. This assay is thus termed the Histoculture Drug Response Assay (HDRA). In the HDRA, the end points of [3H]thymidine incorporation measured by histological autoradiography and tetrazolium dye reduction were initially used and found to have good in vitro-in vivo correlations, including that determined in clinical trials. We have now developed glucose consumption as an endpoint in histoculture. We have monitored glucose consumption for 11 weeks with histocultured stomach cancer tissue that was obtained from a patient with stomach cancer metastatic to the lymph node. The histocultured lymph node specimens were treated with various concentrations of doxorubicin and cisplatinum. The glucose-consumption rate decreased with greater concentrations of both drugs. The results correlated with the thymidine labeling index. From these results, we conclude that the glucose-consumption-rate endpoint in histocultured cancer tissue is non-destructive, unlike the [3H]thymidine and tetrazolium dye end points, allowing serial determinations over extended periods in culture. Thus, the glucose consumption end point may enhance the development of optimal treatment doses and schedules. We also conclude that long-term histoculture drug response studies of metastatic stomach cancer are possible.
Chang
S G
SG
Department of Urology, School of Medicine, Kyung Hee University, Hoegidong Dongdaemun-ku, Seoul, Korea.
Chai
S E
SE
Kim
E S
ES
Yoon
C
C
Joo
H Z
HZ
Hoffman
R M
RM
D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism
D004317:Doxorubicin; D005947:Glucose; D002945:Cisplatin; D013936:Thymidine