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Chemotherapy and human bladder carcinoma transplanted into NMRI nu/nu mice
Abstract:
Transitional and squamous-cell carcinomas of the bladder that were transplanted and successfully retransplanted in further passages to NMRI nu/nu mice were used to test the efficacy of chemotherapy. Mitomycin and bleomycin consistently retarded tumor growth; results with platinex and methotrexate were variable. Combination therapy was not much better than single-drug therapy. Substances that proved effective in the mouse model produced some response in the corresponding patients in a series of patients on specific chemotherapy. In a previous study we have shown that tumor growth of transplanted human bladder carcinoma accelerates, unlike transplanted renal cell carcinoma when successfully subpassaged, resulting in a uniformly fast growing rate similar in all transplanted tumors including those which initially started with slow growing rates. Most importantly, however, tests in a given tumor conducted on a slow-growing early passage and on a fast-growing late passage produced different results. We concluded that this finding might explain the clinical observation that tumor remission due to chemotherapy in patients with metastatic bladder carcinoma does not last very long and seldom prolongs survival. It is assumed--it is not proved--that substances that proved effective in fast growing passages are probably likely to yield greater prolongation of life than those effective in slow-growing passages.
Insights
Chemotherapy efficacy for bladder cancer varies with tumor growth rate in mice. Fast-growing tumors responded better to chemotherapy, potentially explaining short remission durations in patients.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Bladder cancer chemotherapy response can be variable.
- Transplanted human bladder carcinomas in mice show accelerated growth over passages.
- Tumor passage number influences chemotherapy efficacy.
Purpose of the Study:
- To evaluate chemotherapy efficacy in a mouse model of bladder cancer.
- To investigate the impact of tumor passage number on treatment response.
- To correlate mouse model findings with clinical observations in bladder cancer patients.
Main Methods:
- Transplantation of transitional and squamous-cell bladder carcinomas into NMRI nu/nu mice.
- Serial retransplantation to establish different tumor passages.
- Administration of single and combination chemotherapy agents (Mitomycin, Bleomycin, Platinex, Methotrexate).
- Monitoring tumor growth retardation and clinical response in patients.
Main Results:
- Mitomycin and Bleomycin consistently inhibited tumor growth.
- Platinex and Methotrexate showed variable efficacy.
- Combination therapy offered minimal advantage over single agents.
- Chemotherapy effective in fast-growing passages showed better patient response.
- Tumor passage number significantly altered treatment outcomes.
Conclusions:
- Tumor growth rate, influenced by passage number, is a critical factor in chemotherapy response.
- The mouse model suggests that fast-growing bladder tumors may benefit more from chemotherapy.
- Findings may explain limited long-term remission and survival benefits in metastatic bladder cancer patients.