IMPROVEMENT OF IN-VITRO CHEMOSENSITIVITY ASSAY FOR HUMAN SOLID TUMORSBY APPLICATION OF A PRECULTURE USING COLLAGEN MATRIX

The use of [H-3]thymidine incorporation assay (TIA) to evaluate the dr ug response of tumor cells has been recognized as a useful chemosensit ivity assay for fresh human tumor specimens. However, its low evaluabi lity has been a disadvantage for clinical application, To overcome thi s drawback, we have applied a preculture stage prior to the TIA, This preculture requires plating the tumor cell suspension onto a collagen matrix for 24 h. In 29 fresh human tumor specimens, a significant incr ease in both cell viability (P <0.05) and [H-3]thymidine incorporation (P <0.001) of the cultured cells was observed with preculturing; the composition of cancer cells (epithelial membrane antigen positive) and stromal cells (vimentin positive) did not change, In comparisons betw een 66 specimens that were precultured and 705 specimens that were not , the evaluability rate increased significantly from 48.5% (342/705) t o 75.8% (50/66; P <0.0001) after preculturing. No significant change i n in vitro chemosensitivities was observed, When the clinical response s for cancer chemotherapy were retrospectively compared with the in vi tro sensitivities of the corresponding drugs on 16 patients who had me asurable lesions, the correlation between the two was satisfactorily s trong; the prediction accuracy for sensitivity was 83.3% (5/6), the pr ediction accuracy for resistance was 95.0% (19/20), and the overall co rrelation was 92.3% (24/26). These results indicate that TIA with prec ulturing yields increased rates of evaluability, preserving in vitro d rug responses of cultured tumor cells, and has an improved potential t o be used for determining clinical chemotherapy.