610 Development of novel targeting therapy for pro-angiogenesis factor in cutaneous angiosarcomas

PAI-1 is classically known as a pro-angiogenic factor that promote the proliferation of endothelial cells in cancer microenvironment. Cutaneous angiosarcoma (CAS) vascular tumor histologically characterized by detachment cell-derived cells. Since CAS expresses multiple angiogenic growth factors and has increased expressions receptor tyrosine kinase transcripts including VEGFR1/2/3, pro-angiogenesis are potential drug targets CAS. In this study, at first, expression was examined 31 cases CAS, next, immunomodulatory effects on human cell line, ISO-HAS-B, were evaluated. intensely expressed 64.5% cases, overall survival (OS) significantly longer merely expressing group (1380 days: n=11) than (413 n=20) compared log-rank test (p=0.0258). A multivariate Cox proportional hazards model revealed well serum LDH levels correlate with OS Next,in vitroanalysis mRNA IL-23p19, VEGF-C CXCL5 ISO-HAS-B. IL-23p19 production from ISO-HAS-B validated Western blot. Moreover, stimulated culture supernatant promoted favorable tube networks, suggesting these tumor-derived effect development. These results suggested could angiogenesis to induce progression blockade might enhance anti-tumor standard therapy Accordingly, we set up phase 2 study for treatment taxane-resistant using paclitaxel combination inhibitors (TM5614). presentation, describe protocol which contribute development novel