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. 2011 Oct 27;105(12):1830–1838. doi: 10.1038/bjc.2011.456

Figure 1.

Figure 1

Effect of dulanermin-induced pharmacodynamic marker increases in a Colo205 xenograft model. (A) Average tumour size in Colo205 xenografts treated with dulanermin. Mice were injected subcutaneously with 7 × 105 Colo205 cells (n=10 per group). When tumours reached approximately 200 mm3, mice were treated with either phosphate-buffered saline (PBS) or dulanermin (10, 30, 60 and 90 mg kg−1 intraperitoneally on days 1–5). Tumour volumes were monitored over the treatment period and up to 12 days and are expressed as mean±SD. (B) Serum samples from Colo205 tumour-bearing mice (treated as described in A) were collected at the indicated times and analysed using the Promega Caspase Glo assay (n=7 per group). Data were initially plotted as mean±SD for each group and then converted to % of change over the vehicle group at each time point. Significant per cent increases in caspase 3/7 activity were seen at 24 h in the three higher dose groups as compared with vehicle control (30 mg kg−1, P=0.0089 vs vehicle; 60 mg kg−1, P=0.0112 vs vehicle; 90 mg kg−1, P=0.0129 vs vehicle). (C) Colo205 tumour-bearing mice (as described in A) were treated with either 60 mg kg−1 dulanermin or PBS daily for 2 days. Serial serum samples were collected at the indicated times and analysed using the M30 Apoptosense ELISA assay (day −3 (pretreatment)=18 per group; all other time points=6 per group). Data were initially plotted as mean±SD for each group and then converted to % of change over the vehicle group at each time point. M30 values were extrapolated by the plate reader through the standard curve. *P<0.0001 vs vehicle at each time point. (D) Mice were inoculated with either 3 × 105, 5 × 105 or 1 × 106 Colo205 cells and treated with one dose of 60 mg kg−1 dulanermin when tumours reached approximately 50, 125 or 225 mm3 (n=8 per group). Serum samples were collected before treatment and 24 h after treatment and analysed using the M30 Apoptosense ELISA assay. (E) Dulanermin-induced Colo205 tumour-specific caspase 3 activity correlates with circulating serum caspase 3 and M30 antigen levels. Histological sections from Colo205 tumours in mice receiving either vehicle or dulanermin (60 mg kg−1) were collected at 8, 24 or 72 h and stained with haematoxylin and eosin (H&E) or active caspase 3. Images are × 20 magnification.