Download presentation
Presentation is loading. Please wait.
1
A. B. C. H1975 xenografts: long-term treatment
Vehicle CED 6 mg/kg Resistant Tumors B. P = 0.015 vehicle CED VAN P = 0.057 C. H1975 xenografts: short-term treatment A549 xenografts: long-term treatment Vehicle CED 6 mg/kg Resistant Tumors Cascone et al., Figure S1
2
A. C. B. Cascone et al., Figure S2 Common angiogenic human genes 42 43
VAN prog. vs. VAN sens. CED prog. CED sens. 42 43 14 56 57 VAN sens VAN prog Tumor genes VAN-resistant vs. sensitive tumors CED prog CED sens Tumor genes in CED-resistant vs. CED-sensitive tumors Significant human angiogenic genes in VAN-prog. vs. VAN-sens. H1975 tumors Significant human angiogenic genes in CED-prog. vs. CED-sens. tumors C. B. MARS TNFSF15 HIF3A RPS7 AGGF1 PTGS1 PGF PPIA IL6 SPTBN1 PSME2 PTN MOCS3 CASP1 Cascone et al., Figure S2
3
VAN vehicle progression sensitive p-MET Cascone et al., Figure S3
4
A. B. H1975 cells HCC827 cells vector HGF.20 HGF (pg/106 cells) vector
500 1000 1500 2000 2500 3000 3500 4000 vector HGF.20 HGF (pg/106 cells) A. HCC827 cells P < 2000 4000 6000 8000 10000 12000 14000 16000 18000 vector HGF.24 HGF (pg/106 cells) B. H1975 cells P < Cascone et al., Figure S4
5
A. B. H1975 xenograft tumors CAIX CAIX staining score
vehicle VAN sensitive progression CAIX A. sensitive progression vehicle VAN CAIX staining score B. P = 0.02 100 200 300 Cascone et al, Figure S5
6
Pazopanib in phase II trial of mRCC
PFS Probability 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Weeks 10 20 30 40 50 60 70 80 90 100 110 120 130 Plasma HGF < Median (E/N = 108/216) Median PFS 53 weeks Plasma HGF ≥ Median (E/N = 108/216) Median PFS 28 weeks P = 0.016 Cascone, Figure S6
7
Cascone, Supplementary Table S1&2
Table S1. Mouse angiogenic genes modulated in VAN-resistant (progression) vs. sensitive (14 days) H1975 xenografts Gene ID SYMBOL VAN prog (log2 value) VAN sens Fold Change P value ILMN_ Eng 2.79 0.025 ILMN_ Cxcl1 2.28 0.079 ILMN_ Rps7 2.11 0.037 ILMN_ Hgf 2.08 0.020 ILMN_ Nos3 1.70 0.073 ILMN_ Rpl37 -1.68 0.002 ILMN_ Npy -1.72 0.072 Table S2. Mouse angiogenic genes modulated in CED-resistant (progression) vs. sensitive (14 days) H1975 xenografts Gene ID SYMBOL CED sens (log2 value) CED prog CED sens (log2 value) Fold Change P value ILMN_ Eng 2.628 0.019 ILMN_ Cxcl1 2.227 0.058 ILMN_ Nos3 1.983 0.01 ILMN_ 1.725 0.042 ILMN_ Hgf 1.619 0.079 ILMN_ Npy -1.697 0.053 ILMN_ Rpl37 13.205 -1.795 0.0003 Cascone, Supplementary Table S1&2
8
Cascone, Supplementary Table 3
Table S3. Human angiogenic genes modulated in VAN-resistant (progression) vs. VAN-sensitive (14 days) H1975 xenografts Gene ID SYMBOL VAN prog (log2 value) VAN sens Fold Change P value ILMN_ HIF3A 11.237 0.0001 ILMN_ SPTBN1 5.7439 5.119 4.446 0.015 ILMN_ 5.3466 5.282 4.177 ILMN_ PPIA 5.0793 4.122 0.06 ILMN_ PGF 4.9316 3.919 0.0005 ILMN_ RPS7 5.142 5.3656 3.913 0.053 ILMN_ PTGS1 5.3512 5.2577 3.368 0.057 ILMN_ PSME2 5.2269 5.2968 2.974 0.054 ILMN_ IL6 5.4805 2.872 0.04 ILMN_ TNFSF15 5.2299 2.318 0.036 ILMN_ AGGF1 5.2961 1.907 0.045 ILMN_ MARS 5.2913 5.2604 1.903 0.033 ILMN_ 5.4138 1.729 0.002 ILMN_ PTN 5.6002 -2.143 0.062 ILMN_ CASP1 7.54 6.7092 -2.366 0.042 ILMN_ MOCS3 8.8423 6.2088 -3.246 0.018 Cascone, Supplementary Table 3
9
Cascone , Supplementary Table 4
Table S4. Human angiogenic genes modulated in CED-resistant (progression) vs. CED-sensitive (14 days) H1975 xenografts Gene ID SYMBOL CED prog (log2 value) CED sens Fold Change P value ILMN_ PPIA 5.2315 4.532 0.027 ILMN_ SPTBN1 9.1293 6.5697 4.249 0.009 ILMN_ HIF3A 5.1815 3.038 0.022 ILMN_ IL6 2.764 0.028 ILMN_ MOCS3 2.459 0.039 ILMN_ TNFSF15 5.2114 2.074 0.041 ILMN_ 1.54 0.026 ILMN_ MARS -1.77 0.034 ILMN_ PTN -2.124 ILMN_ AGGF1 -2.246 0.007 ILMN_ PGF -2.353 0.008 ILMN_ PSME2 8.6355 8.4577 -2.788 0.043 ILMN_ RPS7 8.0882 -3.179 0.066 ILMN_ CASP1 7.9338 -4.836 0.0003 ILMN_ PTGS1 -5.651 0.004 Cascone , Supplementary Table 4
10
Cascone, Supplementary Table 5&6
Table S5. Predictive plasma HGF at baseline adjusted by gender and smoking among VAN and CP arms in the NSCLC phase II study C/AF VAN arm Chemotherapy (CP) arm P for interaction* Median PFS (Days) HR Plasma Low HGF 121 (40, 202) 1.437 ( ) 140 (47, 194) 0.777 ( ) 0.0357 [HR 0.612 ( )] Plasma High HGF 80 (21,149) 167 (145, 228) Table S6. Predictive plasma HGF at baseline among VAN and E arms in the NSCLC phase III study Subgroup Randomized treatment N Number of events (%) Hazard Ratio 95% CI Positive Vandetanib 300 mg Erlotinib 150 mg 99 93 93 (93.9) 88 (94.6) 1.11 (0.82, 1.49) Negative 96 97 88 (91.7) 86 (88.7) 0.87 (0.63, 1.20) Unknown 428 427 371 (86.7) 371 (86.9) 0.95 (0.82, 1.10) Known 195 190 181 (92.8) 174 (91.6) 0.98 (0.79, 1.21) Cascone, Supplementary Table 5&6
Similar presentations
