Masao Sato

The usefulness of cyclophosphamide pretreatment for subrenal capsule assay against human esophageal cancer

In order to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pretreatment were compared to those obtained after cyclosporine A (CSA) treatment. CPM and CSA suppressed the host reaction until day 6 and day 12, respectively, however, the histological evaluation of the tumors on day 6 revealed no differences between the two groups. The cytotoxity of CPM in mouse serum against P388 cells was measured to evaluate the residual activity of CPM against the implanted tumor. No cytotoxicity was observed in the serum 36 hours after the CPM injection. In the histological analysis of clinical samples, inflammatory infiltration was observed in only 4 of 25 samples and tumor cell preservation recognized in 27 of 28 samples. A persistence of tumor cells was recognized in the samples rich in tumor cells. Adequate growth of the tumor in the control groups was obtained from 30 of 33 tumors (91 per cent), and the response rates of this assay were comparable to those of prior clinical experiences on each of these drugs. These results indicated the feasibility of SRCA with CPM pretreatment as a predictive test of chemotherapeutic agents for esophageal cancer.

Drug-sensitivity testing in patients with human oesophageal squamous cell carcinoma

To evaluate the response to chemotherapeutic agents against human oesophageal cancer, 19 samples were tested by the human tumour clonogenic assay (HTCA), 21 samples by subrenal capsule assay (SRCA) and 33 samples by SRCA with immunosuppressant (IS-SRCA). The evaluability rate of was 21% for HTCA, 95% for SRCA and 91% for IS-SRCA. No active agent was detected by HTCA, however, 29% of the drugs tested by SRCA and 22% by IS-SRCA were considered to be active. Histological analysis revealed substantial inflammatory infiltrates and poor tumour cell preservation with SRCA; however, infiltrates were minimal and there was a high degree of tumour cell preservation with IS-SRCA. The response rates of IS-SRCA were comparable with those of prior clinical tests for each drug. These results suggested that IS-SRCA is the most useful drug sensitivity test for human oesophageal cancer.