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Evaluation of Madison 109 lung carcinoma as a model for screening antitumor drugs
Abstract:
The Madison 109 lung carcinoma (M109) was evaluated as a model for the screening of antitumor agents. Thirty-five drugs with established antitumor activity were assayed in mice implanted ip or sc with M109. Depending on the mode of tumor implantation, drugs representing those affecting nucleic acids (through binding, interacalating, or inducing single-strand breaks), various alkylating agents, mitotic inhibitors, antimetabolites, and immunomodulators were able either to inhibit the growth of sc M109 or to extend the lifespan of mice given M109 ip. The ip implanted tumor was, for example, markedly affected (median survival time of treated/control mice, x 100: greater than or equal to 200% with occasional cures) by doxorubicin, mitomycin C, 10-hydroxy camptothecin, and dihydroxyanthraquinone. The sc implanted tumor, however, was markedly affected (treated - control of greater than or equal to 12 days with regard to median time to grow 1-g tumors) by bleomycin and an analog, talisomycin, and by 6-thioguanine. The M109 was responsive to many different classes of clinically active agents and can serve as a useful tool in the screening of drugs with such potential. It may be particularly useful in screening analogs of camptothecins, nitrosoureas, bleomycins, and mitomycins as well as for evaluating anthraquinones, anthracyclines, mitotic inhibitors, antimetabolites, and immunomodulators.
Insights
The Madison 109 lung carcinoma (M109) model effectively screened various antitumor drugs. This model demonstrated responsiveness to diverse drug classes, proving useful for evaluating novel cancer therapeutics.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- The Madison 109 lung carcinoma (M109) is a murine model utilized in cancer research.
- Evaluating effective screening models is crucial for identifying novel antitumor agents.
Purpose of the Study:
- To assess the M109 lung carcinoma model's utility in screening a diverse range of antitumor drugs.
- To determine the M109 model's responsiveness to various classes of chemotherapeutic agents.
Main Methods:
- Thirty-five established antitumor drugs were tested in mice bearing either intraperitoneal (ip) or subcutaneous (sc) M109 tumors.
- Drug efficacy was evaluated based on tumor growth inhibition (sc) or lifespan extension (ip).
Main Results:
- The M109 model responded to drugs affecting nucleic acids, alkylating agents, antimetabolites, mitotic inhibitors, and immunomodulators.
- Intraperitoneal M109 tumors showed significant responses to doxorubicin, mitomycin C, 10-hydroxy camptothecin, and dihydroxyanthraquinone.
- Subcutaneous M109 tumors were notably affected by bleomycin, talisomycin, and 6-thioguanine.
Conclusions:
- The M109 lung carcinoma model is a versatile tool for screening antitumor agents.
- The model's responsiveness to multiple drug classes supports its use in evaluating novel therapeutic candidates, including analogs of camptothecins, nitrosoureas, bleomycins, and mitomycins.