Figure 3
Therapy of ME in PC14PE6-RFP tumor-bearing mice upon systemic injection of GLV-1h68. (A-B) PC14PE6-RFP tumor-bearing mice were either mock-infected or treated with 1 × 107 pfu GLV-1h68 (iv) 14 dpim (n = 6). (A) PC14PE6-RFP tumor growth was monitored by measuring the tumor volume revealing a continuous tumor growth in the mock-infected group and a significantly retarded growth rate in the GLV-1h68-treated group; all mice of the mock-infected group were euthanized due to tumor burden and ME formation 14 dpi; in the GLV-1h68-treated group two mice were euthanized due to ME formation (23, 42 dpi) before end of the study. Shown are the mean values +/− standard deviations. (B) same mice as shown in A were individually monitored for ME formation during the study; ME formation was evaluated by skin color of the tumor area (hematoma) and exudate accumulation in the groin; skin color index indicating increased hematoma: skin-coloured – light blue – middle blue – dark blue; red dot: palpable cyst in the groin (exudate accumulation), white square: area of tumor necrosis, cross: euthanization. (C) in vivo MR T2 maps of two mock- and two GLV-1h68-infected PC14PE6-RFP tumor-bearing mice 7 dpi. Tumor-associated effusions (arrow) with accumulation of solid/semi-solid cellular components (asterisk) are indicated in T2 images. The T2 maps are scaled from 0 to 200 ms. (D) the corresponding photographic images of the paraformaldehyde-fixed and decalcified mouse abdomen demonstrated the extended hematoma in the peritumoral area of mock-infected mice; in GLV-1h68-treated mice no peritumoral hematoma was detected. (E, F) H&E staining of the corresponding whole abdominal mouse sections revealed erythrocytes-containing blood lakes (black asterisks, E) in mock-treated and necrotic tumor areas (white asterisk, E) in GLV-1h68-treated mice. Different histopathology of the tumor margin of mock- and GLV-1h68-treated tumors (arrowheads, E) is shown with higher magnification in (F). All images are representative examples. Scale bars represent 2 mm (E) 20 μm (F).