Figures & data
Figure 1 Oral administration of HIF-PHI FG-4497 to normal FVB mice induces transient increases in kidney EPO mRNA and circulating EPO protein.
Notes: Mean time-course plots and individual data-points for each time-point (n=3) are shown as well as the 95% CI (gray area) for 24 h vehicle controls.
Abbreviations: CI, confidence interval; EPO, erythropoietin; HIF-PHI, hypoxia-inducible factor prolyl hydroxylase inhibitor; mRNA, messenger RNA; VEGF, vascular endothelial growth factor.
Figure 2 VEGF accelerates NeuYD tumor onset, growth, and metastasis.
Notes: Changes in body weight (A; n=19–20/group), tumor onset (B; n=19–20), tumor doubling times (C; n=10–11), number of pulmonary tumor emboli (D), plasma cytokines (E; n=17–19), and hematologic indicators of erythropoiesis (F; n=15–18) are shown for NeuYD (•, solid lines, open bars) and NeuYD;VEGF mice (▴, dashed lines, solid bars). Data indicate mean ± SE (A, E, F) or median plus data for individual biological replicates (C, D). ***p<0.001.
Abbreviations: EPO, erythropoietin; HCT, hematocrit; HGB, hemoglobin; No., number; RBC, red blood cell; SE, standard error; VEGF, vascular endothelial growth factor.
Figure 3 FG-4497 stimulates erythropoiesis without affecting NeuYD tumor onset, growth, or metastasis.
Notes: Changes in body weight (A; n=15–20), tumor onset (B; n=15–20), tumor doubling times (C), number of pulmonary tumor emboli (D; n=12–14), plasma cytokines (E; 24 h post-final dose, n=15–20), and hematologic indicators of erythropoiesis (F; n=10–15) are shown for NeuYD mice treated with vehicle (•, solid black lines, open bars), 20 mg/kg FG-4497 (▾, solid gray lines, light gray bars), and 40 mg/kg FG-4497 (▴, dashed lines, dark gray bars). Data indicate mean ± SE (A, E, F) or median plus data for individual biologic replicates (C, D). *p<0.05; **p<0.01.
Abbreviations: EPO, erythropoietin; HCT, hematocrit; HGB, hemoglobin; No., number; RBC, red blood cell; SE, standard error; VEGF, vascular endothelial growth factor.
Figure 4 Roxadustat stimulates circulating EPO production without affecting plasma VEGF or the growth or onset of NeuYD tumors.
Notes: Changes in body weight (A; n=20), tumor onset (B; n=20), tumor doubling times (C; n=11–14), and plasma cytokines (D; 6 h post-final dose, n=20) are shown for NeuYD mice treated with vehicle (•, solid black lines, open bars), 40 mg/kg roxadustat (▾, solid gray lines, light gray bars), and 80 mg/kg roxadustat (▴, dashed lines, dark gray bars). Final hematology was not available for this study. Data indicate mean ± SE (A, D) or median plus data for individual biologic replicates (C). *p<0.05; ***p<0.001.
Abbreviations: EPO, erythropoietin; SE, standard error; VEGF, vascular endothelial growth factor.
