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. 2014 Jul 1;22(9):1678–1687. doi: 10.1038/mt.2014.101

Figure 1.

Figure 1

Impact of CCN1 on GBM and OV propagation. (a) CCN1 mRNA expression data for 356 grade IV astrocytomas were obtained from TCGA project through Agilent (caintegrator.nci.nih.gov). Samples were divided into low (blue line: Cyr61<1.0E-5 (195 patients)), intermediate (red line: (79 patients)), and high (green line: Cyr61>0.62 (82 patients)) mRNA expression levels, and expression was correlated with respective patient survival data using Kaplan-Meier statistical analysis. (Data queried on 16 July 2013). (b,c) Quantification (b) and representative images (c) of virus encoded luciferase in tumor bearing mice treated with or without CCN1 blocking antibody. Briefly, athymic nude mice bearing subcutaneous tumors were randomized when their tumors reached an average volume of 200 mm3 (day 1). Mice were then treated intraperitoneally with either IgG or anti-CCN1 antibody (50 μg/mouse/day given daily for 5 days on days 1–5) and then treated with 1 × 106 pfu of rHSVQ-IE4/5-Luc by direct intratumoral injection on day 3 after start of antibody treatment. Bioluminescence imaging was performed on day 2 following OV therapy. Quantification of bioluminescence signal intensity of each region of interest (ROI) is shown in b, n = 5 mice/group. **P < 0.01 (d) Western blot analysis of CCN1 levels in blood plasma taken from mice treated with either IgG or anti-CCN1 antibodies. Samples were equally loaded with 10ug of protein as determined by standard BCA and verified by coomassie staining. (e,f) Representative images of OV treated tumor sections from mice treated with IgG or anti-CCN1 as described above on day 6, after initiation of antibody treatment, shown at 10× (top) and 20× (bottom) and immunostained for HSV-1 (e) and CD68 (f). (g) Representative images of OV treated tumor sections from mice treated with IgG or anti-CCN1 as described above on day 6, after initiation of antibody treatment, shown at 20x and immunofluorescence stained for NKp46 (NKp46+ NK cells (red), GFP+ oHSV-infected cells (green), and nuclei staining (blue)).