| Autor: |
Kumazawa, Eiji, Jimbo, Takeshi, Akimoto, Toshihiko, Joto, Noriko, Tohgo, Akiko |
| Zdroj: |
Cancer Investigation; 1997, Vol. 15 Issue: 6 p522-530, 9p |
| Abstrakt: |
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 immuosuppressive 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: |
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