In vitro chemosensitivity testing of human tumours by collagen gel droplet culture and image analysis.
It is necessary to develop an in vitro test to overcome the problems often associated with in vitro chemosensitivity tests on individual human tumours. We have developed a collagen gel droplet culture technique that allows for a three-dimensional in vitro growth and drug response assay for human solid tumour cells. Important features of chemosensitivity testing by the collagen gel droplet culture technique include the maintenance of high cloning efficiencies resulting in the need for fewer tumour cells, sufficient suppression of the in vitro proliferation of contaminating non-malignant cells by serum-free medium, and the application of the image analysis system which automatically discriminates between cancer cell colonies and fibroblasts. We described in vitro-in vivo correlations for drug response using 7 human lung cancer xenografts grown in the collagen gel droplet culture and as xenografts in nude mice. Results demonstrated significant correlations with the in vitro drug concentration at 1/10 of the peak plasma concentrations (1/10 Cmax) with the correlation coefficient 0.84 for all four drugs tested. We have cultured 206 tumours thus far obtaining 86% of evaluability for drug response. The drug response data of the fresh lung cancers were similar to not only to data for lung cancer lines but the reported clinical pattern. These results suggested that the collagen gel droplet culture at 1/10 Cmax may have potential in predicting clinical drug responses.
Tanigawa
N
N
Second Department of Surgery, Fukui Medical School, Japan.
Kitaoka
A
A
Yamakawa
M
M
Tanisaka
K
K
Kobayashi
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity; D003094:Collagen; D046508:Culture Techniques / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005047:Etoposide / Q000633:toxicity; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000633:toxicity
D000970:Antineoplastic Agents; D005047:Etoposide; D003094:Collagen; D002945:Cisplatin; D014751:Vindesine; D005472:Fluorouracil