Article Figures & Data
Figures
- Fig. 1.
Reciprocal changes in VEGF and sVEGFR-2 during treatment with SU11248 and during the 2-wk rest period. Plasma levels of VEGF and sVEGFR-2 were measured at the beginning of each cycle and at the end of each treatment period over four cycles (n = 53). Data shown is for patients receiving the 4/2 schedule and is presented as ratio to baseline levels. A, plasma VEGF increased during the 4-wk treatment period to a mean of 2.5 times the baseline level, and then decreased to 1.37 times of the baseline at the end of the 2-wk rest period. B, sVEGFR-2 levels decreased during 4 wks of treatment to a mean level of 65% of baseline, then rebounded during the 2-wk rest period. C, the decrease in sVEGFR-2 at cycle 1, day 14 (both 2/2 and 4/2 groups combined) showed a modest inverse correlation with trough plasma drug levels of SU11248 and its major metabolite SU12662 (R2 = 0.33).
- Fig. 2.
Screening PBMCs for VEGF binding and receptor expression. Histograms indicated fluorescent staining on X-axis and relative frequency on Y-axis. VEGF binds primarily to CD14+ cells (A). CD14+ PBMCs express VEGFR-1 (B) but not VEGFR-2 (C). VEGFR-1 staining is present in a minority of CD14− PBMC (D); isotype controls (gray). VEGFR-1 and VEGFR-2 staining on CECs (E).
- Fig. 3.
Changes in monocyte counts after 2 wks of treatment and 2 wks of rest. A, WBC and differential blood count were assessed at baseline and after 2 wks of treatment (cycle 1) of treatment with SU11248. Monocyte counts decreased by 53.7% (P < 0.001). The lymphocyte population did not significantly change. B, monocyte counts decreased during treatment, then rebounded after 2 wks of rest and continued this pattern of change during subsequent cycles (4/2 group). C, monocyte counts in the PD group decreased by 60.4% after the first 2 wks of treatment, whereas the counts in the CB group decreased only by 47.4% (P = 0.007). *, P = 0.005; **, P = 0.002; ***, P < 0.001.
- Fig. 4.
Detection of CECs using four-color flow cytometry. PBMCs were stained with CD45, CD31, CD146, and CD133 with human umbilical vein endothelial cells added as a positive control. A, forward and side scatter plot with gate for viable PBMCs. B, viable cells assessed for CD45-PerCp and CD31-FITC staining. C, CD45−/CD31+ cells, which were then assessed for P1H12-PE and CD133-APC staining (black rectangle). Mature CECs defined as CD45−/CD31+/P1H12+/CD133− (purple rectangle).
- Fig. 5.
Baseline levels of CECs in patients with GIST. A, CECs were quantified by four-color flow cytometry. Higher levels of mature CECs were observed in patients with GIST at baseline, with a median level of 1.09 (0.67-3.54) cells/μL compared with 0.54 (0.37-0.69) cells/μL for normal controls (P = 0.01). Interquartile range (
) and the range of the data (•). - Fig. 6.
Changes in CECs during treatment with SU11248. A, change in CECs in patients with CB versus PD. All seven patients with CB had an increase in their CEC numbers between baseline and a second sample taken 6 to 20 d after the initiation of SU11248 to a median value of 3.97 (3.80-52.46) CEC/μL and only three out of nine patients with PD had an increase in their CEC numbers to a median value of 0.45 (0.02-12.57) CEC/μL. Bottom, circled data on a different scale. The rate of change per day in CECs was significantly different between patients with CB and PD: 0.52 (0.30-8.10) versus −−0.01 (−−0.1 to 0.3) cells/μL/d (P = 0.03). B, changes in CECs over time. Pattern of change in CECs in two representative patients with CB treated with SU11248. After an initial increase during the first cycle of treatment, CEC levels returned to near-baseline levels.
Volume 13, Issue 9
