1. Anti‐EGFL7 treatment for the treatment of glioma in vivo
Anti‐EGFL7 treatment for the treatment of glioma in vivo Glioma‐bearing mice were injected with anti‐EGFL7 or anti‐VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease, and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. A, BCD31 staining revealed that blocking of EGFL7, VEGF, or a combination of both leads to decreased tumor vessel density (n = 3; one‐way ANOVA).C–HStaining for (C, D) PDGFRβ (n = 3; one‐way ANOVA), (E, F) SMA (n = 3; one‐way ANOVA), or (G, H) Col IV (n = 3; one‐way ANOVA) revealed decreased amounts of blood vessel‐associated pericytes, smooth muscle cells and Col IV in the basement membrane of blood vessels upon treatment with anti‐EGFL7, anti‐VEGF, and most significantly, a combination of both antibodies.IThis resulted in an increased intratumoral vessel permeability as measured by T1‐weighted MRI analyses of extravasating Gadovist (n = 6; one‐way ANOVA).JTreatment with anti‐EGFL7 (47 days), anti‐VEGF (51 days), or a combination of both antibodies increased the median survival time of glioma‐bearing Rag1−/− mice (58 days) as compared to isotype‐treated controls (37 days; n = 6; log‐rank test).KTreatment of glioma‐bearing NOD SCID mice with temozolomide (TMD) as a chemotherapeutic agent and a combination of anti‐EGFL7 and anti‐VEGF antibody increased the median survival time (Combo; 87 days; n = 5; log‐rank test) as compared to anti‐VEGF alone (80 days; n = 5; log‐rank test) or isotype‐treated controls (69 days; n = 5; log‐rank test).Data information: Data presented as mean ± SEM; AU, arbitrary units. Scale bars represent 60 μm.
Nevenka Dudvarski Stanković et al. EMBO Mol Med. 2018;10:e8420
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