Fig. 6.

Efficacy of adenovirus (Ad)-mediated gene therapy using Ad vector expressing human soluble FMS-like tyrosine kinase 3 ligand (AdFlt3L) in combination with an Ad vector expressing herpes simplex virus type 1–thymidine kinase (AdTK) plus ganciclovir (GCV) in a model of multifocal glioblastoma multiforme with two GBM tumors implanted simultaneously and treatment delivered into a single tumor mass. (A) Diagram of the experimental paradigm in which 5,000 CNS-1 rat glioma cells were simultaneously implanted into right and left striatum. Four days later, saline or AdFlt3L and AdTK were delivered into the right tumor mass. All animals were treated with GCV 24 h later, twice daily for 7 days (25 mg/kg). Animals were evaluated for survival or euthanized at different time points to evaluate tumor progression. (B) To ensure tumor growth and evaluate the neuropathology of tumors on the day of treatment, animals were euthanized on day 4 prior to treatment, and brains were evaluated by Nissl staining or by immunocytochemistry (ICC) for myelin basic protein (MBP) or tyrosine hydroxylase (TH). Scale bar = 1,000 μ m. (C) Survival curves of multifocal tumor-bearing rats treated with either saline (squares) or AdFlt3L and AdTK (triangles). Animals treated with saline (n = 7) all died by day 15. All animals treated with AdFlt3L and AdTK (n = 6) survived long term. *p < 0.05 versus saline (Mantel-Haenszel log rank test).