(A) A schedule of chemotherapy in combination with disruption of GSC-derived pericytes in orthotopic GBM xenografts. GSCs transduced with luciferase and DesPro-HsvTK or DesPro-Vec were implanted into mouse brains. 5 days after GSC implantation, mice were treated with pulse administration of GCV (1mg/20g) for two consecutive days with a two-day interval. Etoposide (60µg/20g) was administered daily. Mice were monitored by bioluminescent imaging and maintained until manifestation of neurological signs.
(B) In vivo bioluminescent imaging of intracranial tumor growth in mice bearing GBM xenografts derived from T4121 GSCs transduced with DesPro-HsvTK or DesPro-Vec after treatment with GCV in combination with etoposide or DMSO control. Representative images on day 15 and day 25 post-transplantation of GSCs are shown.
(C) Kaplan-Meier survival curves of mice bearing GBMs derived from the GSCs transduced with DesPro-HsvTK or DesPro-Vec and treated with GCV in combination with etoposide or DMSO (n = 5 mice / group; p = 0.0278; two-tailed log-rank test).
(D) Immunofluorescent analysis of the apoptotic marker cleaved caspase-3 (red) and the pericyte marker Desmin (green) in xenografts derived from GSCs transduced with DesPro-Vec or DesPro-HsvTK after treatment with GCV plus etoposide or DMSO (scale bar, 80µm).
(E) Statistical quantification of (D) shows relative apoptosis in xenografts derived from the GSCs transduced with DesPro-Vec or DesPro-HsvTK after treatment with GCV plus etoposide or DMSO (n = 5 tumors / group; *, p < 0.05; **, p < 0.01; mean ± s.e.m.; Mann Whitney test).
See also Figures S5.