Related Experiment Videos
[Subrenal capsule assay in normal mice immunosuppressed by cyclosporin A]
K Yamamoto1, M Yamauchi, H Takagi
1Department of Surgery II, Nagoya University School of Medicine, Japan.
Abstract:
The subrenal capsule assay in normal mice has more advantages to evaluate sensitivities of anticancer agents than other assays in vivo. However, this method has difficulties because mice reject human tumor grafts by their immune reaction. We examined three methods of immunosuppression in mice; radiation, administration of cyclophosphamide and that of cyclosporin A. The administration of cyclosporin A suppressed host reactions most effectively among the three, and the human tumor grafts in subrenal capsules grew well. We also investigated the intervals of administration and the doses of cyclosporin A in order to evaluate drug response. The minimal dose of cyclosporin A which inhibited host reactions was revealed to be 50mg/kg/day administered subcutaneously to mice. Then the adequate dosage of each anticancer drug for this assay system was investigated so that the body weights of mice do not decrease more than 20%, and the following doses were determined; Mitomycin C: 5mg/kg; Cisplatinum: 4mg/kg; Cyclophosphamide: 100mg/kg and 5FU: 90 mg/kg.
Insights
Cyclosporin A effectively suppresses mouse immune responses, enabling successful human tumor xenografts in vivo. This optimized subrenal capsule assay facilitates accurate anticancer drug sensitivity testing.
Area of Science:
- Pharmacology
- Immunology
- Oncology
Context:
- The subrenal capsule assay is a valuable in vivo method for evaluating anticancer agent sensitivity.
- Mouse immune responses pose a significant challenge, leading to rejection of human tumor xenografts.
Purpose:
- To investigate and compare three immunosuppression methods (radiation, cyclophosphamide, cyclosporin A) for enhancing human tumor xenograft success in mice.
- To determine the optimal dosage and administration of cyclosporin A for effective immunosuppression.
- To establish appropriate anticancer drug dosages for the assay, ensuring minimal host toxicity.
Summary:
- Cyclosporin A demonstrated superior immunosuppressive capabilities compared to radiation and cyclophosphamide, promoting robust growth of human tumor xenografts.
- The minimal effective dose of cyclosporin A was identified as 50mg/kg/day subcutaneously.
- Specific, non-toxic dosages for Mitomycin C, Cisplatinum, Cyclophosphamide, and 5-Fluorouracil (5FU) were determined for the assay.
Impact:
- This research optimizes the subrenal capsule assay, improving its reliability for preclinical anticancer drug efficacy studies.
- Establishes a refined methodology for in vivo drug sensitivity testing, crucial for personalized cancer treatment strategies.
- Provides critical data on immunosuppression and drug dosing, advancing the field of experimental cancer therapeutics.