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In addition to tumor studies using anti-DLL4 as a single agent, additive anti-tumor activity was observed in combination with anti-VEGF therapy in a majority of tested tumor models. Since angiogenic sprouting after DLL4 blockade remains a VEGF-dependent process , DLL4 inhibition may increase the dependency of the tumor microvasculature on a VEGF-mediated survival signal. In anti-Dll4 treated neonatal mouse retinas, there was a defect in arteriogenesis with a complete absence of pericyte coverage of the retinal vessels . Soluble DLL4 was also able to reduce the recruitment of pericytes in a murine xenograft tumor model. |
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