Fig. 5

Effects on patient cells: In vitro simulation of treatment with inhibitor. Net live cells expressed as fold of cell numbers for cultures with vehicle only. HI-TOPK-032 was included in cultures at various concentrations. There was a trend of dose dependent reduction with concentration in all cultures (2-Way Anova: p = 0.0031; A, n = 22; B, n = 18; C, n = 6; D, n = 3; E, n = 3. Bar: + SEM). At an inhibitor concentration of 3.5 μM decreases in cell numbers were significant in GIC cultures (c-d) but not in NSC cultures (a) thus presenting a narrow therapeutic window (indicated with red rectangles). Using individual T-tests to compare dose concentrations, normal NSCs (a), normal differentiated cells (b) and tumor differentiated cells (e) were not significantly reduced at 3.5 μM when compared to 0 μM). At an inhibitor concentration of 3.5 μM both groups of tumor stem cells experienced a significant reduction in net live cells. However, at an inhibitor concentration of 5 μM decreases in cell numbers were significant in differentiated GIC cultures (e) but not in differentiated NSC cultures (b) thus presenting a narrow therapeutic window (indicated with red rectangle)