Fig. 2.

Lack of radiosensitization of orthotopic GIC-driven GB by ATRi. a Development of the orthotopic GIC-driven adult COMI GB in NOD SCID mice. Bottom. Coronal section of mouse brain with the orthotopic tumor developed for 52 days. H/E staining. A dimensional bar of 850 μm is shown for reference. Left. Detail of tumor specimen subjected to IHC with antibody specific for the stem cell marker nestin. A large tumor necrosis central region is encompassed by nestin-positive tissue. A dimensional bar of 250 μm is shown for reference. Top. Detail of tumor edge showing infiltration of normal brain parenchyma. A dimensional bar of 20 μm is shown for reference. H/E staining. b Kaplan-Meier survival curves of mice treated with ATRì+IR. At d22 of tumor development, TP53⁻ COMI tumor-bearing mice were i.p.- injected with 25 mg/Kg body weight of NVP-BEZ235 (red), AZD6738 (green) or vehicle (DMSO-black) followed by irradiation with 0.5 Gy four hours later. This treatment was repeated at d23 and d24. No significant difference in median survival was observed between the three animal groups. A trend towards accelerated dying was observed in NVP-BEZ235-treated animals. c Brains of mice treated with ATRi+IR as described under B were explanted and stained with H/E for histopathology analysis at d88. No significant variation of brain histology was observed in mice treated with NVP-BEZ235 + IR (center-red) or AZD6738 + IR (right-green) as compared to DMSO+IR treated mice (left-black)