Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models
Autor: | Tsuneo Kusama, Akiko Tohgo, Yasuaki Osada, Tsunehiko Soga, Eiji Kumazawa |
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Rok vydání: | 1992 |
Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty medicine.medical_treatment Immunology Lentinan Antineoplastic Agents Mice Inbred Strains Disaccharides Picibanil Lipid A Mice chemistry.chemical_compound Bone Marrow Tumor Cells Cultured Animals Immunology and Allergy Medicine Fibrosarcoma Cisplatin business.industry Mitomycin C Ascites Lewis lung carcinoma Neoplasms Experimental Immunotherapy medicine.disease Oncology chemistry Systemic administration Cancer research business medicine.drug |
Zdroj: | Cancer Immunology Immunotherapy. 35:307-314 |
ISSN: | 1432-0851 0340-7004 |
Popis: | The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46 mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and 38 resulted in significant reductions in the weight of all tumors except Colon 26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal to that of an Escherichia coli-type synthetic lipid A (compound 506), and also to those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil and cisplatin. Furthermore, DT-5461 was more effective than other immunotherapeutics, including picibanil (OK-432) and lentinan. However, its antitumor effects were inferior to those of Adriamycin or OK-432 against the malignant ascites caused by intraperitoneal inoculation with MethA or with MH134 cells; life span was not prolonged by either intraperitoneal or intravenous administration. In addition, although DT-5461 showed direct inhibitory effects on the in vitro growth of MethA or MH134, these were much weaker than those of Adriamycin. These findings clearly indicated that DT-5461 with systemic administration is a highly effective antitumor agent on solid tumors, and suggest that the antitumor effect of DT-5461 with potent necrotizing activity might derive from indirect mechanisms related to the activation of host immune systems and not to the weak direct cytotoxicity. |
Databáze: | OpenAIRE |
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