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T Kusuyama

Publications and source records attributed to T Kusuyama.

22 records · Page 2Linked to original sources

[Subrenal capsule assay for chemosensitivity test (II)--Sequential changes in the implanted tumor tissue and histological findings].

We carried out fundamental subrenal capsule assay methodology, using tumor specimens of human cancer xenografts (breast cancer and colon cancer) serially transplanted into nude mice. With regard to sequential changes in the tumor grafts implanted under the renal space of immunocompetent mice, tumor size was largest macroscopically around day 6 after inoculation, and later involuted gradually. Histological findings showed that implanted tumor tissues were preserved to a moderate extent until day 4 after inoculation, but leukocyte infiltration by host reaction had begun by day 4, and tumor tissues were almost replaced by host reactive tissues on day 6. Labeling index scoring did not indicate growth of implanted tumor cells. We found that macroscopic tumor size was largest around day 6 because we measured tumor size with involved leukocyte infiltration, and the macroscopic tumor did not represent the true extent of the tumor tissue.

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[Fundamental evaluation of the subrenal capsule assay as an in vivo chemosensitivity test].

Histological analyses of the subrenal capsule assay (SRCA) carried out with modification of Bogden's original method revealed that the major portion of cancer tissue implanted were almost replaced by the host immune cells and reactive tissue by day 6. For the purpose to find a more improved condition, the following experiments were performed using human cancer lines xenografted in nude mice. No prominent differences in the host reaction to xenograft were found between 3 kinds of immunocompetent mice. Subrenal space of the athymic nude mice allowed cancer tissue to grow well until 15 days after inoculation, and then chemosensitivity test to judge the growth inhibition rates. The similar condition as in nude mice was achieved in CDF1 mice by daily injection of 60 mg/kg of cyclosporin A.

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[Subrenal capsule (SRC) assay as a chemosensitivity test (IV)--Evaluation of the SRC assay method as a system for growing implanted tumor-xenografts].

Using tumor specimens of human cancer serially transplanted in nude mice, we examined fundamentally the subrenal capsule assay method in order to improve the subrenal space as an area where implanted tumor-xenografts persistently grow. Host reaction in immunocompetent mice treated with cyclosporin A (CsA) (60 mg/kg subcutaneously, daily) was suppressed almost completely, and tumor-xenografts persistently grew similarly to those implanted under the renal capsule of BALB/c-nu/nu mice. CsA treatment, 30 mg/kg given subcutaneously; daily, or 60 mg/kg subcutaneously; every other day, could not suppress the host reaction. Bredinin treatment, 200 mg/kg subcutaneously; every other day, or 100 mg/kg subcutaneously; daily, could not suppress the host reaction also, and tumor-xenografts implanted under the renal capsule were rejected.

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[Application to chemosensitivity tests of the human tumor-nude mouse system and subrenal capsule assay system].

Since 1974, approximately 200 fresh cancer tissues obtained from various types of cancer patients were inoculated into athymic BALB/c nude mice, of which 30 percent were taken and grown in the subcutaneous space of mice. Among them 15 lines of gastrointestinal and breast cancer xenografts were selected for experimental single agent chemotherapy. The response rates of 14 drugs examined in this xenograft system were compared with the cumulative clinical response rate of each drug in the same type of cancer. Drugs which were clinically effective against one type of tumor were found to be also effective against the corresponding xenograft in nude mice. Thus the human cancer-nude mouse system was considered useful as a predictive secondary screening method for new drugs. This evidence suggested to us the feasibility of utilizing the system as a chemosensitivity test for determining the drugs effective for an individual human malignancy. In our present study, the responses to 15 experimental chemotherapies with single agent or drug combination of 11 lines of cancer xenografts in nude mice were directly compared with the clinical response in each donor patient to the corresponding chemotherapy. Good correlation was obtained between these respective results, the overall predictive accuracy of the experimental results being 93%. Therefore, if the rate of transplantability to nude mice were to be improved, this nude mouse system would become a promising tool for the individual chemosensitivity test. The subrenal capsule (SRC) assay recently introduced by Bogden and his colleagues has excited much attention among Japanese clinical oncologists. In our study, cancer tissues implanted under the renal capsule 6 days after inoculation, did not show marked proliferation and a high percentage of implants was almost replaced by host reactive tissue. It therefore seems necessary to solve some fundamental problems before we can apply this assay method to clinical chemosensitivity trial.

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