Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

Figure 1 (PDF) Gene expression of sFlt1-3 in vitro. RT-PCR was performed with A₅₄₉ cells infected with AdsFlt1-3 or AdlacZ. Specific primer pairs for sFlt1-3 resulted in bands of about 250 bp (C₁ and C₂), whereas no bands were detectable in the negative control AdLacZ (A₁ and A₂). Expression of the house keeping gene b-actin (514 bp) was similar for AdLacZ (B₁ and B₂) and AdsFlt1-3 (D₁ and D₂).

Figure 2 (PDF) Tube formation assay in vitro. HUVE cells were incubated on Matrigel with CM from AdsFlt1-3- or AdLacZ-infected tumor cells. A: Exemplary light microscope image (40 magnifications) of HUVE cells incubated with CM of AdLacZ-infected cells and with CM of AdsFlt1-3-infected cells; B: So called tube-like formations were quantified per high power field. Data are shown as mean and SE (P = 0.10 compared to the control).

Figure 3 (PDF) Tumor treatment of pre-established CT-26 CRC. Vectors were administered systemically (5×10⁹ pfu, AdsFlt1-3, n = 10; AdLacZ, n = 11). Data are given as mean tumor volume and SE (P = 0.006 compared to the control).

Figure 4 No effect of AdLacZ and AdsFlt1-3 on the survival rate of tumor bearing mice. Tumor treatment of pre-established CT-26 CRC. (PDF) Vectors were administered systemically (5×10⁹ pfu, AdsFlt1-3, n = 10; AdLacZ, n = 11).

Figure 5 Time course of in vivo VEGF serum levels of tumor bearing mice that had been treated with AdLacZ or AdsFlt1-3 (mean±SE).

Figure 6 (PDF) Time course of ALT serum levels as marker of liver toxicity at d 3, 6, 9, 14, 19, 25, 32, and 42 after AdLacZ and AdsFlt1-3 treatment initiation (mean±SE).

Figure 7 (PDF) Effective inhibition of tumor angiogenesis in vivo by treatment with AdsFlt1-3. Pre-established CRC tumors were treated with AdLacZ or AdsFlt1-3. Animals were killed on d 9 after treatment and tumor tissue was removed. Microvessel density was determined by anti-von Willebrand factor staining. A and B: Representative photomicrographs show microvessel staining in tumors of AdLacZ- or AdsFlt1-3-treated mice; C: quantitative analysis of microvessel density was made by counting the positively stained cells per high-power fields (200× magnification). Data are given as mean of cell number/HPF and SE (P = 0.02 compared to the control).