Figure 6. YM155 exerts marked anti-MPNST effects in vivo.

A. SCID mice bearing STS26T xenografts (∼4-5mm in average larger dimension) were implanted with a subcutaneous micro-osmotic pump delivering YM155 (6mg/kg/d) or vehicle only in a continuous fashion for three consecutive days. Pumps were replaced once (on day 8; arrows denote days of pump implantation and bolded line days of treatment). YM155 markedly abrogated tumor growth (p<0.0001; upper graph). Moreover, treatment with YM155 significantly reduced tumor weight compared to control (p=0.005; lower graph). IHC analyses demonstrated decreased survivin and Ki67 and increased cleaved caspase 3 (CC3) expression in YM155 treated xenografts (scale bars are included); B. Experiment was repeated as per above for MPNST724 xenografts: YM155 treatment was found to delay tumor growth, a statistically significant decrease in tumor size (p<0.01; upper graph) and tumor weight (p<0.05; lower graph) was observed at study termination. IHC analyses results (right panel) aligned with the STS26T findings above (scale bars are included); D. STS26T lung metastases bearing mice were treated with YM155. A significant (p<0.001; right panel) difference in average lung weight between control and YM155 treated mice was found at study termination. Pulmonary metastases were macroscopically observed in all control mice but not in YM155 treated mice. H+E staining further demonstrated large lung tumor deposits in control mice lungs but no (n=6) or only small microscopic lesions (n=2) in the YM155 treated group (scale bars are included). [* denotes statistically significant effects (p<0.05)]