Fig. 4.

Recurrent tumors after gene therapy are more invasive and less angiogenic compared with primary tumors. (A) Immunostaining with human nestin antibody showing extensive infiltration of glioma cells into corpus callosum in local and distant recurrent tumors, but not in the primary tumor. (B) Quantification of invasive tumor cells outside the solid tumor mass in control tumors and local recurrences (TK + GCV). (C) Hematoxylin and eosin stainings of primary and recurrent tumors showing necroses and microvascular proliferation only in the necrotic tumors. (D) Von Willebrand factor immunostaining reveals reduced angiogenesis in recurrent tumors compared with primary tumors. Scale bar: 50 μm. (E, F) Quantification of vessel area fraction among the groups. Overall recurrent tumors have significantly reduced vessel area compared with primary tumors (P = 0.001).