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. 2020 Aug 15;11(1):161–179. doi: 10.1016/j.jcmgh.2020.08.004

Figure 4.

Figure 4

ProAgio opens compressed tumor vessels and increases drug delivery. (A) Representative images of IHC staining of CD31 from GEM-KPC mice tumor sections treated with vehicle or 10 mg/kg ProAgio. Arrows indicate example vessels. (B and C) Quantification of CD31-positive vessel density (B), and mean vessel lumen area (C) in tumor sections of vehicle or ProAgio-treated GEM-KPC mice. (D) Intratumoral Gem levels measured in extracts of tumors of vehicle and ProAgio-treated (after 8 daily doses) GEM-KPC mice 2 hours after intravenous dose of Gem (n = 6). Gem levels were presented as nanogram of Gem per milligram of tumor tissue. (E) Representative images of IHC staining of CD31 in tumor sections of vehicle or ProAgio-treated OrKPC mice. Arrows indicate the tumor vessels. (F and G) Quantitative analyses of CD31 vessel stain density (F) and vessel lumen area (G) in tumor sections of vehicle or ProAgio-treated OrKPC mice. (H and I) Representative fluorescence images of Alexa Fluor 555–conjugated IgG, approximately 160 kilodalton (red) and Alexa Fluor 488–conjugated paclitaxel, approximately 1 kilodalton (green; left panel, 10×; right panel, 30×) (H) and quantification of fluorescence signals from paclitaxel and IgG (I) in tumor sections of vehicle or ProAgio-treated OrKPC mice using ImageJ. (J–L) Representative fluorescence images of Alexa Fluor 555–conjugated IgG, approximately 160 kilodalton (red) and Alexa Fluor 488–conjugated paclitaxel, approximately 1 kilodalton (green) (J) and quantification of fluorescence signals (K and L) in tumor sections of OrKPC mice treated with the indicated agents. Quantification is presented as fold change of the fluorescence integrated density (fold) by comparing it with the mean value of the vehicle treatment group as 1. Image analysis was performed by thresholding for positive staining and normalizing to total tissue area. (H and I) Fluorescence probe conjugated IgG and paclitaxel were injected intravenously after 8 daily doses of 10 mg/kg ProAgio treatment. (J–L) Fluorescence probe–conjugated IgG and paclitaxel were injected intravenously after 8 daily doses of ProAgio (ProAgio), 3 doses of Gem (Gem), or 8 doses of ProAgio plus 3 doses of Gem (ProAgio + Gem) treatments. Tumors were harvested and processed 40 minutes after the intravenous injection (analyses: n = 5 mice per treatment group, n = 7–8 images per mouse). Nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI) (blue), and yellow indicates colocalization. (D, I, K, and L) Error bars represent means ± SEM. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001. n.s., denotes not significant.