Comparing survival curves using the Mantel Cox logrank analysis, we observed improved survival in the combination sorafenib plus rapamycin selleck Vismodegib treatment group compared with the rapamycin treatment group. We also com pared tumor volumes in these two groups. According to our protocol, we compared tumor volumes on treatment day 44 and Inhibitors,Modulators,Libraries found the average tumor volume of the rapamycin plus sorafenib treated group was smaller than the average tumor volume of the rapamycin treated group. this difference approaches statistical sig nificance. In this case, we also compared tumor volumes on day 43 when there were tumor measurements for all mice in both groups, the difference was statistically significant.

Atorvastatin as a single agent or in combination with rapamycin does not decrease tumor burden or increase survival in nude mice bearing Tsc2 tumors Inhibitors,Modulators,Libraries As shown in Figure 3 and Table Table 5, atorvastatin did not reduce tumor growth or improve survival as a single agent. Furthermore, adding atorvastatin Inhibitors,Modulators,Libraries to rapamycin did not reduce disease severity when compared with single agent rapamycin treatment. Data points for average tumor volume are included on days where at least four of the animals in a cohort had tumors measured. The day 26 average tumor volume was 544 110 mm3 for the rapamycin group and 390 186 mm3 for atorvastatin Inhibitors,Modulators,Libraries plus rapamycin. These were significantly lower than the day 26 average tumor volume for the untreated cohort. In contrast, the day 26 average tumor volume for single agent atorvastatin was not significantly different than the untreated group.

The day 26 average tumor volume for single agent atorvastatin was significantly higher than the rapamycin cohort, while the average tumor volume for atorvastatin plus rapamycin did not Inhibitors,Modulators,Libraries differ significantly from the average tumor volume for the single agent rapamycin cohort. At day 42, the average tumor volume for atorvastatin plus rapamycin group was not significantly lower than the single agent rapamycin cohort. Survival data from this experiment is shown in Fig ure 3b and Table 5. We observed a significant improve ment in median survival for both the rapamycin group and the atorvastatin plus rapamy cin group when compared to the untreated cohort. However, the median survival between the rapamycin treated group and the atorvastatin plus rapamycin treated group was not significantly differ ent. Although the median survival of atorvastatin treated animals was slightly longer than selleck chemicals in the untreated cohort, this difference was also not statistically significant. In summary, the survival data together with the tumor volume data demonstrate that we did not observe any benefit to adding atorvastatin to rapamycin treatment in this preclinical TSC tumor model.