Fig. 3.

Continuous valGCV application eliminates the majority of TK+ tumor cells. (A) Hematoxylin and eosin stainings of recurrences (left panel: recurrence at the primary site in GCV treatment group; right panel: recurrence distant from the primary site in valGCV treatment group). (B) Immunohistochemistry with antibodies for HSV-TK show transduced cells in the recurrent tumor mass. (C) Double immunofluorescent staining using antibodies against human nestin (green) and GFP (red) for the TK.007-eGFP fusion protein. Representative images show TK.007-eGFP+ tumor cells that survived prodrug treatment. Scale bar: 50 μm. (D) Quantification of the remaining tumor cells expressing TK.007-eGFP: percentage of residual TK+ tumor cells in 3-month-long valGCV-treated group is lower compared with the short-term GCV-treatment group (P = 0.042). (E) Proliferative capacity of the remaining TK+ cells is significantly lower compared with TK− cells (P = 0.041) in the TK + GCV group.