YM155 displayed potent antitumor activities in both CAL27 xenograft and transgenic HNSCC mice models by delaying tumor onset and suppressing tumor growth.

Furthermore, YM155 combined with docetaxel promoted HDAC inhibitor tumor regression better than either treatment alone without causing considerable body weight loss in the HNSCC xenograft models. Overall, targeting survivin by YM155 can benefit HNSCC therapy by increasing apoptotic and autophagic cell death, and suppressing prosurvival pathways.”
“Functional exhaustion of CD8(+) T cells due to increased expression of inhibitory molecule PD-1 (Programmed Death-1) causes reactivation of latent disease during later phases of chronic toxoplasmosis. Onset of disease recrudescence results in decreased parasite cyst burden concomitant with parasites undergoing stage conversion from a primarily encysted, quiescent bradyzoite to a fast-replicating, highly motile

tachyzoite. Thus, reduced cyst burden is one of the early hallmarks of disease recrudescence. This was further validated by depleting gamma interferon (IFN-gamma), a cytokine known to control latent toxoplasmosis, in chronically infected prerecrudescent mice. Since CD8(+) T cells (an important source of IFN-gamma) lose their functionality during the later phases HIF inhibitor of chronic toxoplasmosis, we next examined if adoptive transfer of functional CD8(+) T cells from acutely infected donors to the chronically infected prerecrudescent hosts could impede parasite de-encystation and rescue exhausted

CD8(+) T cells. While the transfer of immune CD8(+) T cells temporarily restricted the breakdown MLN8237 of cysts, the exhausted endogenous CD8(+) T cell population was not rescued. Over time, the donor population got deleted, resulting in parasite de-encystation and host mortality. Considering that donor CD8(+) T cells fail to become long-lived, one of the cardinal features of memory CD8(+) T cells, it bears the implication that memory CD8 differentiation is impaired during chronic toxoplasmosis. Moreover, our data strongly suggest that while adoptive immunotherapy can prevent parasite de-encystation transiently, reduced antigen burden in the chronic phase by itself is insufficient for rescue of exhausted CD8(+) T cells. The conclusions of this study have profound ramifications in designing immunotherapeutics against chronic toxoplasmosis.”
“Green tea catechins have been reported to have antitumor activity. The objective of this study was to examine the effect of catechins on the antitumor efficacy of doxorubicin (DOX) in a murine model for chemoresistant hepatocellular carcinoma (HCC). Epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) are the most abundant polyphenolic compounds in green tea.