Supplementary Figure Legends from Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-EGFR Antibodies Converge on MEK/ERK Pathway Activation and Can Be Overcome by Combined MEK/EGFR Inhibition

PDF file - 116KB</p

Supplementary Figures 1 - 3, Tables 1 - 3 from Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-EGFR Antibodies Converge on MEK/ERK Pathway Activation and Can Be Overcome by Combined MEK/EGFR Inhibition

PDF file - 1325KB, Caption Supplementary Figure 1 A and 1B. The combined treatment of cetuximab and the selective MEK1/2 inhibitor BAY 86-9766 induce a synergistic growth inhibitory effects in CRC cell lines with primary and acquired resistance to cetuximab and an antagonistic effects in cetuximab-sensitive CRC cell lines. Caption Supplementary Figure 2. The BAY 86-9766 treatment, in CRC cancer cell lines with primary and acquired resistance to cetuximab, induce a dose dependent reduction of MAPK and MEK phosphorylation. Caption Supplementary Figure 3. The combined treatment of cetuximab and the selective MEK1/2 inhibitor BAY 86-9766 was well tolerated by mice, with no weight loss or other signs of acute or delayed toxicity. Caption Supplementary Table 1A and 1B. The panel of CRC cell lines have been treated with several concentrations of cetuximab and selective MEK1/2 inhibitors (BAY 86-9766, Selumetinib and Pimasertib), showing differential sensitivity to the drugs. Caption Supplementary Table 2. We have performed the experiments on a panel of eight human CRC cell lines having different mutation profiles in KRAS, NRAS, BRAF, PIK3CA and EGFR genes. Caption Supplementary Table 3. In the CRC cell lines with acquired and primary resistance to cetuximab, the treatment with the selective MEK1/2 inhibitor BAY 86-9766 determined synergistic growth inhibitory effects in combination with cetuximab.</p

Supplementary Figure 1 Legend from Synergistic Effects of Metformin Treatment in Combination with Gefitinib, a Selective EGFR Tyrosine Kinase Inhibitor, in LKB1 Wild-type NSCLC Cell Lines

Supplementary Figure 1 Legend - PDF file 52K, Effects on CALU-3, CALU-3 GEF-R, H1299, H1975 and GLC82 cell growth of the combination of metformin and gefitinib. Cell viability was determined using a 3-(4,5 methylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay. Treatment combinations and sequences are described in Materials and Methods. CI values were calculated according to the Chou and Talalay mathematical model for drug interactions using the Calcusyn software for different fractions affected (fa). CI is a quantitative measure of the degree of interaction between different drugs. If CI = 1, it denotes additivity; if CI > 1, it denotes antagonism; if 1 0.7, it denotes slight synergism; if CI = 0.7-0.3, it denotes synergism; if CI < 0.3, it denotes strong synergism. Results are the median of three independent experiments, each done in eight replicate wells for experimental point</p

supplementary figure 3 from Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab

supplementary figure 3. Pro-apoptotic effects of cetuximab in combination with regorafenib in SW620 CRC cell line with primary resistance to anti-EGFR inhibitor.</p

Supplementary Figure 2 Legend from Synergistic Effects of Metformin Treatment in Combination with Gefitinib, a Selective EGFR Tyrosine Kinase Inhibitor, in LKB1 Wild-type NSCLC Cell Lines

Supplementary Figure 2 Legend - PDF file 58K, Supplementary Figure 2 legend: Effects on the downstream pathways by metformin treatment in A549 and H460. Western blotting analysis of AMPK, ACC, MAPK, AKT, p70S6K, S6, 4EBP1, activation following treatment with the indicated concentration of metformin. beta-actin was included as a loading control</p

Supplementary Figure 2 from Synergistic Effects of Metformin Treatment in Combination with Gefitinib, a Selective EGFR Tyrosine Kinase Inhibitor, in LKB1 Wild-type NSCLC Cell Lines

Supplementary Figure 2 - PDF file 194K, Supplementary Figure 2. Effects on the downstream pathways by metformin treatment in A549 and H460</p

supplementary figure 1 from Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab

supplementary figure 1. Effects of cetuximab in combination with regorafenib in a panel of CRC cell lines with primary and acquired resistance to anti-EGFR inhibitor in vitro.</p

supplementary figure 4 from Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab

supplementary figure 4. Effects of cetuximab in combination with regorafenib on mice body weight.</p

supplementary figure legend from Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab

supplementary figure legend</p

Supplementary Figure 1 from Synergistic Effects of Metformin Treatment in Combination with Gefitinib, a Selective EGFR Tyrosine Kinase Inhibitor, in LKB1 Wild-type NSCLC Cell Lines

Supplementary Figure 1 - PDF file 81K, Effects on CALU-3, CALU-3 GEF-R, H1299, H1975 and GLC82 cell growth of the combination of metformin and gefitinib</p