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. 2021 Oct 17;24(5):694–707. doi: 10.1093/neuonc/noab244

Fig. 4.

Fig. 4

Verteporfin decreases infiltrative tumor burden in aggressive PDX tumors. (A) Experimental setup and representative histological sections of infiltrative G-16302 PDX tumors at 4-week post-transplantation (wk pt) treated with vehicle or Verteporfin (100 mg/kg IP, days 21-30). Tumors are stained with human nuclear antigen (HNA). “Core” is defined as tumor area near the injection site with highest tumor density (>100 HNA+/HNA− cells) and “infiltrative edge” (IE) is defined as adjacent tumor area of lower tumor density (~50-100 HNA+/HNA− cells) and confluent tumor spread, marked by yellow lines. Scale bar = 1 mm. (B) Quantification of PDX tumor burden area within the tumor “core” and “infiltrative edge” in 8 serial histological sections per mouse, 4-wk pt and VEH/VP treatment and 3-wk pt with no treatment (NT) (*P = .0161; n = 11 mice (dots) per condition from 2 combined experiments, normalized to average VEH tumor burden area; similar results observed in 3 independent experiments). (C, D) Representative histological images (C) and quantifications (D) of Ki67 tumor core intensity normalized to HNA (10 mg/kg IP VP administration days 1-28; *P = .027; n = 6 (VP) and n = 4 (VEH)-treated G-16302 PDX mice (dots)). Scale bars = 100 µm. (E, F) Representative immunofluorescence images (E) and quantification (F) of CDH2 expression in VP/VEH-treated PDX tumors (10 mg/kg IP days 1-28 and 100 mg/kg IP days 21-30; *P = .0136; n = 4 G-16302 PDX mice (dots) per condition). Scale bars = 30 µm. (G, H) Representative images (G) and quantifications (H) of single migratory HNA+ tumor cells (annotated in yellow) away from the core and infiltrative edge in PDX mice with early Verteporfin treatment regimen (10 mg/kg IP days 1-28) (*P = .04; n = 6 G-16302 PDX mice (dots) per condition, section with largest tumor burden annotated for each). Scale bars = 1 mm. See also Supplementary Figure 5F. For parts B, D, F, and H, lines in box-and-whisker plots represent mean and bars represent min/max; P-values determined by Student t test. Abbreviations: IP, intraperitoneally; PDX, patient-derived orthotopic xenograft; VEH, vehicle; VP, Verteporfin.