Jinushi K

Chemosensitivity tests in colorectal cancer patients

In order to assess the usefulness of chemosensitivity tests in the treatment of colorectal cancer, 71 tumor specimens were tested for chemosensitivity in the following assays: nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA). The agents examined were: mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-diamminedichloroplatinum (CDDP). The evaluability rates were 90.8, 93.9 and 92.3 per cent in NMIA, SRCA and ATPA, respectively, but only 42.9 per cent in HTCA. The tumor response rates were 50.8, 45.2, 16.7 and 33.3 per cent in NMIA, SRCA, HTCA and ATPA, respectively. Individual drug sensitivity rates differed among all 4 assays, ranging from 0 to 33.3 per cent. In the arbitrary judgment of the 4 assays, the most sensitive agent was CDDP, followed by CPM, ADM, 5-FU and MMC. In the prospective study, predictive accuracy rates of the clinical responses were 81.3 66.7, 100, 100 and 76.5 per cent in NMIA, SRCA, HTCA, ATPA and the arbitrary judgment, respectively. A significant correlation between the survival time and the results of SRCA was detected retrospectively. These results suggested that colorectal cancer might not be completely resistant to anticancer agents, and that chemosensitivity tests might be useful in the individual therapy of colorectal cancer patients.

The histological assessment and evaluation of a 4 day subrenal capsule assay by the percentage inhibition of DNA/protein

A four day subrenal capsule assay was investigated in order to determine its ability to clinically predict tumor chemosensitivity. To establish more objective and accurate evaluation criteria, a histological assessment and measurement of the DNA and protein content of excised tumor implants was conducted in ddY mice. The histological studies provided qualitative results concerning the percentage of cancer cells in the xenograft, the number of mitoses, the amount of necrosis, and the extent of lymphocytic infiltration. The DNA content was measured by a modified version of the Schmidt-Thannhauser-Schneider method and the protein content was estimated using the Bio-Rad protein assay. The percentage of cancer cells in the xenograft correlated poorly with the relative increase in tumor size, weight and the percentage inhibition of DNA/protein (per cent DNA/protein), however, the per cent DNA/protein correlated well with the clinical effects in 85.7 per cent of the tumors studied. Moreover, the histological assessment information was only consistent with those results obtained for per cent DNA/protein in the control group.

Prediction of the resistance of human tumors to adriamycin by chemosensitivity tests and DNA analysis of the multidrug resistance gene.

In order to predict natural resistance to Adriamycin (ADM), the amplification of multidrug resistance gene 1 (MDR1) was investigated in 50 human cancer specimens using Southern blot analysis. Genomic DNA was extracted from both human solid tumors and adjacent normal tissues for the analysis. MDR1 gene amplification was not observed in any of the patients tested, including 5 patients in whom ADM was not clinically effective. On the other hand, chemosensitivity tests performed on the tumor cells of these 5 patients indicated resistance to ADM. Our results therefore indicate that MDR1 gene amplification is rarely seen among clinical samples and that conventional chemosensitivity tests might be more useful for the prediction of ADM resistance in cancer patients than the analysis of MDR1 gene amplification.