On day 70, the average tumor volume for control mice treated with saline was 6. 9 fold greater than that measured when treatment was initi ated. For mice treated with si Vav3, the tumor volumes were 5 fold greater and the size of tumors on day 70 were statistically selleck bio smaller than those of tumors from mice treated with the vehicle control. Docetaxel significantly inhibited tumor growth, and the tumor vol ume on day 70 was slightly larger than the average tumor volume determined when treatment was initiated. Tumors from mice treated with si Vav3 plus docetaxel were statistically smaller than those from mice treated with docetaxel alone, and the tumor volume on day 70 was 59% smaller than that when treatment was initiated.

It appears Inhibitors,Modulators,Libraries reasonable to suppose that a lower concentration of docetaxel can be used in combin ation therapy with si Vav3 because wide differences were not observed between these two groups despite the stat istical significance of the differences. In addition, during a 70 day observation period, we did not note any toxicity in mice treated with si Vav3 plus docetaxel, as evaluated by their body weights and physical appearance. These results in tumor xenografts support the data of the combined effect of si Vav3 with docetaxel on cancer cell growth in vitro. On day 70 after inoculation, tumor tissues were harvested from euthanized mice and subjected to immu noblot analysis of Vav3, H E staining and immunohisto chemical staining of Vav3, Ki 67, pAR, and a commercially Inhibitors,Modulators,Libraries available cell death marker, M30 CytoDeath.

Treatment with si Vav3 effectively downregulated Vav3 expression compared with its expression level in control and Inhibitors,Modulators,Libraries si Scr treated Inhibitors,Modulators,Libraries tumors, illustrating the effectiveness of intra tumoral injection. Histological evaluation revealed that docetaxel alone or si Vav3 plus docetaxel caused necrosis in some areas of xenograft tumors. Significant downregulation of Vav3 staining was observed in tumors from mice treated with si Vav3 alone or in combination with docetaxel but not in tumors from mice treated with docetaxel alone. Repre sentative immunohistochemical staining of Ki 67, pAR, and M30 CytoDeath is shown in Figure 5D, and the immu nohistochemical findings are summarized in Figure 5E. The mean percentage of Ki 67 positive tumor cells in si Vav3 or docetaxel treated tumors was significantly de creased compared with that in control tumors, and an even more significant reduction Inhibitors,Modulators,Libraries was observed in tumors treated with si Vav3 plus docetaxel.

A significant decrease in the number of pAR positive cells was observed in tumors treated with si Vav3 alone or in combination with docetaxel compared with the number of pAR positive cells in control tumors but not in tu mors treated with docetaxel alone. The average apoptotic index for the control tumors was Nilotinib Leukemia 0. 4 0.