Figure 5. Antitumor and antimetastatic effects of combined bio- and chemotherapy and side effects.
(A) Prophylactic setting. Ten days after the last of 3 vaccinations at 1-week intervals with empty vector, PBS, or pFap, BALB/c mice (n = 8, mean ± SEM) were challenged orthotopically with 3 × 105 D2F2 cells. After 5, 10, and 15 days, indicated mice were treated with doxorubicin (dox). (B) Therapeutic setting. Five days after i.v. injection of 105 D2F2 tumor cells, BALB/c mice (n = 8) were treated weekly with pFap or empty vector. One day after each immunization, mice were treated with doxorubicin i.v. as indicated (*statistically significant compared with vector group, P < 0.0001; **statistically significant compared with vector, vector/dox, and pFap groups, P < 0.0001). (C) Intratumoral doxorubicin concentration. Vaccinated BALB/c mice (n = 4) were challenged s.c. with 5 × 105 D2F2 cells, and after 16 days the doxorubicin concentration in pooled tumor lysates was determined by liquid chromatography and mass spectrometry (LC-MS) (representative of 2 experiments, mean + SD, †P < 0.001). (D) Circular wounds 3 mm in diameter were inflicted on the upper backs of vaccinated mice (n = 4), and the average time until complete wound closure was measured (mean + SD).