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Updated: Aug 18, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Mouse subrenal capsule assay chemosensitivity and DNA flow cytometry parameters of human melanoma metastases
T Muhonen1, S Pyrhönen, A Laasonen
1Department of Radiotherapy and Oncology, Helsinki University Central Hospital, Finland.
Abstract:
Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry. The most effective combination was dacarbazine, vincristine, and carmustine (DOB), followed by cisplatin plus etoposide (Plat-VP16). By the original criteria of the assay, 35% of tumors were sensitive to DOB treatment while 15% responded to Plat-VP16. Chemosensitivity of DNA diploid and aneuploid tumors showed no significant difference; 35% of the aneuploid tumors were sensitive to DOB and 19% to Plat-VP16, whereas 41% and 13% respectively of the diploid tumors were sensitive. An association between DNA index and chemosensitivity was observed. Growth of the implant was observed in 44% of tumors with a DNA index above 1.5 receiving DOB treatment, whereas only 12% of tumors with an aneuploid DNA index < or = 1.5 grew. No significant difference was observed in the SPF of chemotherapy sensitive and insensitive tumors, though a tendency to lower SPF was observed in sensitive tumors.
Insights
Chemotherapy effectiveness in human melanoma metastases was assessed using the mouse subrenal capsule assay (SRCA). Dacarbazine, vincristine, and carmustine (DOB) showed higher sensitivity rates compared to cisplatin plus etoposide (Plat-VP16).
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Melanoma metastasis presents significant treatment challenges.
- Predicting chemosensitivity in melanoma is crucial for effective therapy selection.
Purpose of the Study:
- To evaluate the chemosensitivity of human melanoma metastases using the mouse subrenal capsule assay (SRCA).
- To compare the efficacy of dacarbazine, vincristine, and carmustine (DOB) versus cisplatin plus etoposide (Plat-VP16).
- To investigate the association between DNA content (ploidy and DNA index) and chemosensitivity.
Main Methods:
- Mouse subrenal capsule assay (SRCA) for chemosensitivity testing.
- DNA flow cytometry analysis for ploidy and DNA index determination.
- Analysis of 103 human melanoma metastases, with 79 undergoing both SRCA and DNA flow cytometry.
Main Results:
- Dacarbazine, vincristine, and carmustine (DOB) demonstrated higher tumor sensitivity (35%) compared to cisplatin plus etoposide (Plat-VP16) (15%).
- No significant difference in chemosensitivity was observed between DNA diploid and aneuploid tumors.
- An association between a higher DNA index (>1.5) and increased tumor growth with DOB treatment was noted, while tumors with a DNA index <=1.5 showed less growth.
Conclusions:
- The DOB combination appears more effective than Plat-VP16 for chemosensitivity in melanoma metastases.
- DNA ploidy status alone did not significantly predict chemosensitivity.
- DNA index may offer insights into treatment response, warranting further investigation in melanoma chemosensitivity.
