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Effect of OK-432 on the lymphnode metastasis of MCA-sarcoma cell lines: a new therapeutic approach
Abstract:
The two unique highly metastatic MCA-sarcoma cell lines have been established by the present authors. The inoculation of 1153Ln, one of the cell lines, either into footpad or subcutaneously on the back of syngeneic mice resulted in the development of metastasis exclusively in almost all lymphnodes of the body. We evaluated the therapeutic effect of a streptococcal preparation, OK-432, on the lymphnode metastasis. Two KE per mouse of OK-432 were injected intratumorally (it) at 4, 7 or 10 days after the footpad inoculation of 1153Ln. OK-432 injected it at 7 days after tumor inoculation showed an inhibition of the lymphnode metastasis. Histological findings indicated that the proliferation of lymphoid cells in the drainage node was most prominent in mice treated with OK-432 at 7 days after the tumor inoculation. A combined treatment of it and intraperitoneal (ip) injections of OK-432 significantly reduced lymphnode metastasis as compared with that of ip injection alone. This can be attributed to the fact that the activated lymphocytes induced by it-injected OK-432 exhibited a potent antimetastatic activity together with general administration (ip) of OK-432 given after surgical removal of the tumor. Low dose of total-body irradiation (TBI), known to augment the antitumor potential of tumor-bearing animals together with general application of OK-432, showed synergistic action in inhibiting tumor growth. Overall results suggest that the better antitumor effect of OK-432 can be anticipated by combination of the agent itself and with other means.
Insights
The streptococcal preparation OK-432 effectively inhibited lymphnode metastasis in mice when administered intratumorally seven days post-tumor inoculation. Combined treatments enhanced its antitumor effects, suggesting synergistic potential with other therapies.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Metastasis
Background:
- Highly metastatic MCA-sarcoma cell lines were established for research.
- 1153Ln cell line inoculation led to exclusive lymphnode metastasis in syngeneic mice.
Purpose of the Study:
- To evaluate the therapeutic effect of OK-432 on lymphnode metastasis.
- To investigate combination therapies for enhanced antitumor activity.
Main Methods:
- Intratumoral injection of OK-432 at varying days post-inoculation.
- Combined intratumoral and intraperitoneal OK-432 administration.
- Evaluation of lymphnode metastasis and lymphoid cell proliferation.
- Combination therapy with low-dose total-body irradiation (TBI).
Main Results:
- Intratumoral OK-432 at 7 days post-inoculation inhibited lymphnode metastasis.
- Lymphoid cell proliferation was most prominent with 7-day intratumoral OK-432 treatment.
- Combined intratumoral and intraperitoneal OK-432 significantly reduced metastasis.
- TBI combined with OK-432 showed synergistic inhibition of tumor growth.
Conclusions:
- OK-432 demonstrates therapeutic potential against lymphnode metastasis.
- Combination strategies, including TBI, can augment OK-432's antitumor efficacy.
- Optimizing OK-432 administration timing and combining it with other treatments can improve outcomes.