Irinophore C™, liposomal vincristine and Caelyx
® treatments are associated with vascular normalization of the tumor vasculature in subcutaneous GBM tumors. a) The diameters of tumor blood vessels were reduced significantly by all three treatments compared to control tumors (■, left axis). The fraction of NG2-free CD31 pixels (■, right axis), collagen IV-free CD31 pixels (■, right axis) were reduced in Irinophore C™ treated tumors indicating that fewer immature vessels are present following treatments. The proportion of empty basement membranes (CD31 free-collagen IV staining; □, right axis) in the viable tissue was also reduced by all liposomal treatments. b and c) Representative and merged images of CD31, Collagen IV and NG2 staining for control tumors (b) and tumors from Irinophore C™ treated mice (c). A reduction in blood vessel diameter (CD31; green) and an increase in basement membrane coverage of blood vessels (collagen IV; yellow) following treatment can be seen. Following Irinophore C™ treatment, more pericytes are present (NG2; red) and more endothelial cells are associated with the pericytes (merged image, green and red). Treatment with Irinophore C™ also results in an increase in empty basement membrane sleeves (i.e. CD31 free-collagen IV; yellow). The entire image represents non-necrotic and viable tissue. Statistical significances are indicated (*p-value ≤ 0.05; **p-value ≤ 0.01; ***p-value ≤ 0.001; ****p-value ≤ 0.0001). Non-significant trends are indicated (&p-value = 0.121; &&p-value = 0.071; &&&p-value = 0.054).