Article Figures & Data
Figures
- Figure 1.
Treatment of s.c. U87 gliomas. A, 2 wks after s.c. U87 tumor cell implantation, when tumors had achieved volumes of 80 to 120 mm3, biweekly tumor measurements began. Two and 5 d after measurements began (treatment days 2 and 5; X axis), treatment with 5 × 106 pfu G207, G47Δ, or saline intratumorally occurred. Fold growth of s.c. U87 tumors over time. Initially, the two viruses exhibited comparable efficacy, with 13-fold growth in G207-treated tumors and 6-fold growth in G47Δ-treated tumors after 21 d, both significant reductions compared with the 42-fold growth seen in saline-treated tumors at this time (P = 0.0003). However, after 27 d, G47Δ treatment was more effective than G207, resulting in 15-fold growth, compared with 60-fold growth with G207 (P = 0.0002) and 80-fold growth with saline-treated tumors. There were five mice per treatment group. Bars, SD. B, vessel density of residual s.c. U87 tumors after treatment day 27. The microvessel density of G207-treated tumors was significantly higher than that of saline- or G47Δ-treated tumors (P = 0.00007). Columns, upper panel, vessel density in residual tumor; bars, SD; lower panel, representative immunofluorescence anti-V WF–stained microvessels (red).
- Figure 2.
Assessing the effect of oncolytic HSV infection on the transcripts for TSP-1, TSP-2, VEGF, and MMP-9. mRNA was isolated from cultured U87 cells 6 h after infection with G47Δ or G207 at MOI of 3, and transcript levels were determined by real-time RT-PCR using 18S rRNA as a control. There was no significant change in the mRNA levels of the assessed transcripts (P > 0.5). Similar results were obtained 24 h after infection (data not shown).
- Figure 3.
Assessing the effect of oncolytic HSV infection on protein levels of TSP-1, TSP-2, VEGF, and MMP-9. Western blots revealed protein expression of TSP-1, TSP-2, VEGF, and MMP-9 (with actin as a control) 6 and 24 h after infecting cultured U87 (top five rows) and U373 (bottom five rows) cells with G207 (left) and G47Δ (right) at MOI of 3. Expression of both TSP-1 and TSP-2 was reduced after G207 infection of both cell lines to undetectable levels, whereas VEGF and MMP-9 levels were unchanged in either cell line with either virus. G47Δ caused only a slight reduction of TSP-1 levels at the 24-h time point in U87 but otherwise did not affect the levels of the assessed factors in either cell line.
- Figure 4.
TSP-1–derived peptide 3TSR in combination with G207 synergistically inhibits tumor growth and decreases vessel density. A, s.c. U87 tumors were treated with 5 × 106 pfu G207, G47Δ, or saline intratumorally on treatment days 2 and 5, along with 3 mg/kg/d 3TSR or saline i.p. on treatment days 1 to 27. 3TSR alone did not inhibit tumor growth (P = 0.1 compared with saline-treated tumors) and in combination with G47Δ was no better than G47Δ alone (P = 0.4). Combining 3TSR with G207 was significantly more effective than G207 alone (P = 0.04). B, microvessel density of residual s.c. U87 tumors after 27 d of treatment with saline, G47Δ, G207, G47Δ + 3TSR, and G207 + 3TSR was determined by staining tumor sections with anti-vWF antibodies. Addition of 3TSR did not alter the microvessel density of G47Δ-treated tumors (11 vessels/mm2) but did lower that of G207-treated tumors to 10 vessels/mm2 (P = 0.0006).
Volume 67, Issue 2
