Such studies may obviously only be performed on animal models that generate granulom

Utilising the CalcuSyn program, CI values were estimated and these have already been described in Figures 2c and 2d. The CI values for 267/Dt combinations were, generally, below 0. 9 for both LCC6 and LCC6Her2 treated Celecoxib cells, indicating weak to strong synergistic relationships. Significantly, the CI values were constantly below one over a broad range of effective doses as determine from the fraction affected value. The mixture of Dt and 267 was also evaluated in many other breast cancer cell lines. CI values were calculated from cell stability dose response curves. These data are summarized in Figure 2e, which shows the CI values determined at the ED50. The show the observed synergistic relationships are achieved in at the very least five of the six cell lines examined. For KPL 4 cells the determined CI values were indicative of somewhat hostile relationships. If drug combinations communicate in a manner that result in synergy, then the dose of each drug found in the combination to achieve a certain measurable effect level will be substantially reduced when weighed against the dose required to Eumycetoma achieve the same effect level when the drugs get alone. This parameter can be determined and is described by the DRI. The DRI can be used to estimate the doses of 267 and Dt needed when used in combination to achieve a defined effect level which can then be weighed against the single agent dose required to achieve this effect. Based on these analyses, it was estimated that the concentration of 267 in the mix required to achieve an ED50 might be reduced by around 3. 6 fold within the LCC6 cell line. 267 dose reductions were less remarkable in the other cell lines evaluated, starting from no change to some 30% reduction. The same analysis was completed for Dt and it was estimated that the focus of Dt in the mix required to achieve an ED50 might be paid down BAY 11-7082 in every cell lines by 2 to 25 fold when compared with Dt alone. For example in SKBR3 cells the ED50 of Dt presented alone is 5 nM while in mixture with 267 the ED50 of Dt decreases to less than 1 nM. 267 and 267/Dt combination treatments cause dosedependent decrease in P AKT levels projected by western blot analysis Western blot analysis was used to examine P AKT levels in LCC6 and LCC6Her2 cells treated with increasing levels of 267 alone, Dt alone, or 267 in combination with Dt. In these reports P AKT was measured eight hours after addition of 267, a time point selected because no significant changes in cell viability were noted yet significant reductions in P AKT were noticeable as noted in the representative western blots shown in Figure 4. P AKT levels were paid down in a dose-dependent manner over the range of 267 levels examined in both LCC6Her2 cells and LCC6. Dt treatment alone was shown to have little if any measurable influence on P AKT levels.