Antitumor Effect of DT-5461, a Lipid a Derivative, Against Human Tumor Xenografts Is Mediated by Intratumoral Production of Tumor Necrosis Factor and Affected by Host Immunosuppressive Factors in Nude Mice
| Autor: | Akiko Tohgo, Eiji Kumazawa, Noriko Joto, Takeshi Jimbo, Toshihiko Akimoto |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Cancer Research Ratón Fibrosarcoma Mice Nude Antineoplastic Agents Disaccharides Dinoprostone Lipid A Mice Immune system Adjuvants Immunologic Tumor Cells Cultured medicine Animals Humans Doxorubicin Cisplatin Mice Inbred BALB C Tumor Necrosis Factor-alpha business.industry General Medicine medicine.disease In vitro Neoplasm Proteins Oncology Immunology Macrophages Peritoneal Cancer research Tumor necrosis factor alpha Drug Screening Assays Antitumor business Neoplasm Transplantation medicine.drug |
| Zdroj: | Cancer Investigation. 15:522-530 |
| ISSN: | 1532-4192 0735-7907 |
| DOI: | 10.3109/07357909709047593 |
| Popis: | We previously reported that DT-5461, a synthetic low-toxic lipid A analog, inhibits growth of various murine tumors through activation of host immune systems. In the present study, DT-5461 also exhibited significant antitumor effects against 5 out of 6 human tumor xenografts in nude mice. The antitumor activity was similar to or greater than those of chemotherapeutics. Antitumor effects of DT-5461 significantly correlated with intratumoral levels of tumor necrosis factor (TNF) induced by the compound (r = 0.701, p < 0.05). In vitro TNF production by DT-5461-stimulated macrophages was augmented by tumor cells, and the augmentative effect correlated with TNF activity detected in these tumor tissues. Meanwhile, a weaker therapeutic efficacy of DT-5461 was observed against certain tumors that caused a significant increase in the level of immunosuppressive factors in host blood. These findings support the idea that intratumoral TNF plays a crucial role in the antitumor mechanisms of DT-5461 and suggest that its antitumor action is influenced by an augmentative effect of tumor cells on TNF production and by blood levels of immunosuppressive factors. |
| Databáze: | OpenAIRE |
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