Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Angiogenesis
Published in: Angiogenesis 2/2012

Open Access 01-06-2012 | Original Paper

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Authors: Nicholas Papadopoulos, Joel Martin, Qin Ruan, Ashique Rafique, Michael P. Rosconi, Ergang Shi, Erica A. Pyles, George D. Yancopoulos, Neil Stahl, Stanley J. Wiegand

Published in: Angiogenesis | Issue 2/2012

Login to get access

Abstract

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.
Appendix
Available only for authorised users
Literature
1.
Grothey A, Galanis E (2009) Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 6:507–518PubMedCrossRef
2.
Bressler SB (2009) Introduction: understanding the role of angiogenesis and antiangiogenic agents in age-related macular degeneration. Ophthalmology 116:S1–S7PubMedCrossRef
3.
Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA 291:1900–1901PubMedCrossRef
4.
Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug 6:273–286CrossRef
5.
Baluk P, Hashizume H, McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15:102–111PubMedCrossRef
6.
7.
Crawford Y, Ferrara N (2009) VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res 335:261–269PubMedCrossRef
8.
Cao Y (2009) Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2:rel
9.
Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM (1999) Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol 237:97–132PubMedCrossRef
10.
Miller JW, Adamis AP, Aiello LP (1997) Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes Metab Rev 13:37–50PubMedCrossRef
11.
Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin M, Noel A, Stalmans I, Barra A, Blacher S, Vandendriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Charnock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575–583PubMedCrossRef
12.
Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, Nishihira J (2002) Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes Care 25:2352PubMedCrossRef
13.
Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, Nguyen L, Foidart JM, Noel A, Munaut C (2003) Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3186–3193PubMedCrossRef
14.
Schlingemann RO, Witmer AN (2009) Treatment of retinal diseases with VEGF antagonists. Prog Brain Res 175:253–267PubMedCrossRef
15.
Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 22:1–29PubMedCrossRef
16.
Van de Veire S, Stalmans I, Heindryckx F, Oura H, Tijeras-Raballand A, Schmidt T, Loges S, Albrecht I, Jonckx B, Vinckier S, Van Steenkiste C, Tugues S, Rolny C, De Mol M, Dettori D, Hainaud P, Coenegrachts L, Contreres JO, Van Bergen T, Cuervo H, Xiao WH, Le Henaff C, Buysschaert I, Kharabi Masouleh B, Geerts A, Schomber T, Bonnin P, Lambert V, Haustraete J, Zacchigna S, Rakic JM, Jimenez W, Noel A, Giacca M, Colle I, Foidart JM, Tobelem G, Morales-Ruiz M, Vilar J, Maxwell P, Vinores SA, Carmeliet G, Dewerchin M, Claesson-Welsh L, Dupuy E, Van Vlierberghe H, Christofori G, Mazzone M, Detmar M, Collen D, Carmeliet P (2010) Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell 141:178–190PubMedCrossRef
17.
18.
Takahashi H, Shibuya M (2005) The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 109:227–241CrossRef
19.
Alitalo K, Carmeliet P (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1:219–227PubMedCrossRef
20.
Dumont DJ, Jussila L, Taipale J, Lymboussaki A, Mustonen T, Pajusola K, Breitman M, Alitalo K (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282:946–949PubMedCrossRef
21.
Tammela T, Zarkada G, Wallgard E, Murtomäki A, Suchting S, Wirzenius M, Waltari M, Hellström M, Schomber T, Peltonen R, Freitas C, Duarte A, Isoniemi H, Laakkonen P, Christofori G, Ylä-Herttuala S, Shibuya M, Pytowski B, Eichmann A, Betsholtz C, Alitalo K (2008) Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature 454:656–660PubMedCrossRef
22.
Tammela T, Zarkada G, Nurmi H, Jakobsson L, Heinolainen K, Tvorogov D, Zheng W, Franco CA, Murtomäki A, Aranda E, Miura N, Ylä-Herttuala S, Fruttiger M, Mäkinen T, Eichmann A, Pollard JW, Gerhardt H, Alitalo K (2011) VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat Cell Biol 13:1202–1213PubMedCrossRef
23.
Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351:2805–2816PubMedCrossRef
24.
Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5:123–132PubMedCrossRef
25.
Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400PubMedCrossRef
26.
Ferrara N, Damico L, Shams N, Lowman H, Kim R (2006) Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 26:859–870PubMedCrossRef
27.
Campochiaro PA (2007) Targeted pharmacotherapy of retinal diseases with ranibizumab. Drugs Today (Barc) 43:529–537CrossRef
28.
Chen Y, Wiesmann C, Fuh G, Li B, Christinger HW, McKay P, de Vos AM, Lowman HB (1999) Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J Mol Biol 293:865–881PubMedCrossRef
29.
Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431PubMedCrossRef
30.
Monés J (2010) A review of ranibizumab clinical trial data in exudative age-related macular degeneration and how to translate it into daily practice. Ophthalmologica 225:112–119PubMedCrossRef
31.
Ziemssen F, Grisanti S, Bartz-Schmidt KU, Spitzer MS (2009) Off-label use of bevacizumab for the treatment of age-related macular degeneration: what is the evidence? Drugs Aging 26:295–320PubMedCrossRef
32.
The CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ (2011) Ranibizumab and bevacizumab for neovascular age-realted macular degeneration. N Engl J Med 364:1897–1908PubMedCrossRef
33.
Economides AN, Carpenter LR, Rudge JR, Wong V, Koehler-Stec EM, Hartnett C, Pyles EA, Xu X, Daly TJ, Young MR, Fandl JP, Lee F, Carver S, McNay J, Bailey K, Ramakanth S, Hutabarat R, Huang TT, Radziejewski C, Yancopoulos GD, Stahl N (2003) Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med 9:47–52PubMedCrossRef
34.
Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 99:11393–11398PubMedCrossRef
35.
Rudge JS, Holash J, Hylton D, Russell M, Jiang S, Leidich R, Papadopoulos N, Pyles EA, Torri A, Wiegand SJ, Thurston G, Stahl N, Yancopoulos GD (2007) VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc Natl Acad Sci USA 104:18363–18370PubMedCrossRef
36.
Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMed
37.
Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M (2007) Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res 85:425–430PubMedCrossRef
38.
Carneiro A, Falcao M, Pirraco A, Milheiro-Oliveira P, Falcao-Reis F, Soares R (2009) Comparative effects of bevacizumab, ranibizumab and pegaptanib at intravitreal dose range on endothelial cells. Exp Eye Res 88:522–527PubMedCrossRef
39.
Klettner A, Roider J (2008) Comparison of bevacizumab, ranibizumab, and pegaptanib in vitro: efficiency and possible additional pathways. Invest Ophthalmol Vis Sci 49:4523–4527PubMedCrossRef
40.
Yu L, Liang XH, Ferrara N (2011) Comparing protein VEGF inhibitors: in vitro biological studies. Biochem Biophys Res Commun 408:276–281PubMedCrossRef
41.
Drake AW, Myszka DG, Klakamp SL (2004) Characterizing high-affinity antigen/antibody complexes by kinetic- and equilibrium-based methods. Anal Biochem 328:35–43PubMedCrossRef
42.
43.
Darling RJ, Brault PA (2004) Kinetic exclusion assay technology: characterization of molecular interactions. Assay Drug Dev Technol 2:647–657PubMedCrossRef
44.
Quinn TP, Peters KG, De Vries C, Ferrara N, Williams LT (1993) Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 90:7533–7537PubMedCrossRef
45.
Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH (1994) Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 269:26988–26995PubMed
46.
Fuh G, Wu P, Liang WC, Ultsch M, Lee CV, Moffat B, Wiesmann C (2006) Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab. J Biol Chem 10;281:6625–6631CrossRef
47.
Yu L, Wu X, Cheng Z, Lee CV, LeCouter J, Campa C, Fuh G, Lowman H, Ferrara N (2008) Interaction between bevacizumab and murine VEGF-A: a reassessment. Invest Ophthalmol Vis Sci 49:522–527PubMedCrossRef
48.
Lu F, Adelman RA (2009) Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization? Graefes Arch Clin Exp Ophthalmol 247:171–177PubMedCrossRef
49.
Meyer RD, Singh A, Majnoun F, Latz C, Lashkari K, Rahimi N (2004) Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation. Oncogene 23:5523–5531PubMedCrossRef
50.
Dawson NS, Zawieja DC, Wu MH, Granger HJ (2006) Signaling pathways mediating VEGF165-induced calcium transients and membrane depolarization in human endothelial cells. FASEB J 20:991–993PubMedCrossRef
51.
Yoshida A, Anand-Apte B, Zetter BR (1996) Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor. Growth Factors 13:57–64PubMedCrossRef
52.
Hauser S, Weich HA (1993) A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 9:259–268PubMedCrossRef
53.
Meyer T, Robles-Carrillo L, Robson T, Langer F, Desai H, Davila M, Amaya M, Francis JL, Amirkhosravi A (2009) Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. J Thromb Haemost 7:171–181PubMedCrossRef
54.
Costa R, Carneiro A, Rocha A, Pirraco A, Falcao M, Vasques L, Soares R (2009) Bevacizumab and ranibizumab on microvascular endothelial cells: a comparative study. J Cell Biochem 108:1410–1417PubMedCrossRef
55.
Spitzer MS, Yoeruek E, Sierra A, Wallenfels-Thilo B, Schraermeyer U, Spitzer B, Bartz-Schmidt KU, Szurman P (2007) Comparative antiproliferative and cytotoxic profile of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on different ocular cells. Graefes Arc Clin Exp Ophthalmol 245:1837–1842CrossRef
56.
Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V (2005) Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci 46:726–733PubMedCrossRef
57.
Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444PubMedCrossRef
58.
Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N (2008) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 145:239–248PubMedCrossRef
59.
Schmidt-Erfurth U, Eldem B, Guymer R, Korobelnik JF, Schlingemann RO, Axer-Siegel R, Wiedemann P, Simader C, Gekkieva M, Weichselberger A (2011) Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration the EXCITE study. Ophthalmology 118:831–839PubMedCrossRef
60.
Holz FG, Amoaku W, Donate J, Guymer RH, Kellner U, Schlingemann RO, Weichselberger A, Staurenghi G (2011) Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study. Ophthalmology 118:663–671PubMedCrossRef
61.
62.
Stewart MW, Rosenfeld PJ (2008) Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol 92:667–668PubMedCrossRef
63.
Furfine E, Coppi A, Koehler-Stec E, Zimmer E, Tu W, Struble C. Pharmacokinetics and ocular tissue penetration of VEGF Trap after intravitreal injections in rabbits. Invest Opthalmol Vis Sci 47:E-abstract 1430
64.
Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ (2007) Pharmacokinetics of intravitreal ranibizumab (Lucentis). Ophthalmology 114:2179–2182PubMedCrossRef
65.
Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG (2009) A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology 116:1731–1739PubMedCrossRef
66.
Brown DM, Heier JS, Ciulla T, Benz M, Abraham P, Yancopoulos G, Stahl N, Ingerman A, Vitti R, Berliner AJ, Yang K, Nguyen QD, CLEAR-IT 2 Investigators (2011) Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118:1089–1097PubMedCrossRef
67.
Heier JS, Boyer D, Nguyen QD, Marcus D, Roth DB, Yancopoulos G, Stahl N, Ingerman A, Vitti R, Berliner AJ, Yang K, Brown DM, CLEAR-IT 2 Investigators (2011) The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118:1098–1106PubMedCrossRef
68.
Nguyen QD, Heier J, Brown D, Ho A, Kaiser P, Vitti R, VIEW 1 Study Group (2011) Randomized, double-masked, active-controlled phase 3 trial of the efficacy and safety of intravitreal VEGF Trap-eye in Wet AMD: one-year results of the view-1 study. Invest Ophthalmol Vis Sci 52:E-abstract 3073
69.
Schmidt-Erfurth U, Chong V, Kirchhof B, Korobelnik JF, Papp A, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Ogura Y (2011) Primary results of an international phase III study using intravitreal VEGF trap-eye compared to ranibizumab in patients with Wet AMD (VIEW2). Invest Ophthalmol Vis Sci 52:E-abstract 1650
70.
VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group, Chakravarthy U, Adamis AP, Cunningham ET Jr, Goldbaum M, Guyer DR, Katz B, Patel M (2006) Year-2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology 113:1508.e1–1508.e25CrossRef
71.
Ciulla TA, Rosenfeld PJ (2009) Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. Curr Opin Ophthalmol 20:158–165PubMedCrossRef
72.
Moussa S, Ansari-Shahrezaei S, Smretschnig E, Hagen S, Steindl-Kuscher K, Krebs I, Binder S (2010) Contrast sensitivity after intravitreal antivascular endothelial growth factor therapy for myopic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 248:1087–1090PubMedCrossRef
73.
Yao J, Wu X, Kasman IM, Vogt T, Phan V, Shibuya M, Ferrara N, Bais C (2011) Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci USA 108:11590–11595PubMedCrossRef
74.
Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8:831–840PubMed
75.
Miyamoto N, de Kozak Y, Jeanny JC, Glotin A, Mascarelli F, Massin P, BenEzra D, Behar-Cohen F (2007) Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy. Diabetologia 50:461–470PubMedCrossRef
76.
Zhong X, Huang H, Shen J, Zacchigna S, Zentilin L, Giacca M, Vinores SA (2011) Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation. Mol Vis 17:492–507PubMed
77.
Van Cutsem E, Tabernero J, Lakomy R et al. Intravenous (IV) aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second-line treatment of metastatic colorectal cancer (MCRC): Results of a multinational phase III trial (EFC10262-VELOUR). Ann Oncol 22(supplement 5): v10–v18. Abstract O-0024
78.
Kopetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY, Adinin R, Overman MJ, Valero V, Wen S, Lieu C, Yan S, Tran HT, Ellis LM, Abbruzzese JL, Heymach JV (2010) Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 28:453–459PubMedCrossRef
79.
Lieu C, Tran H, Jian Z, Mao M, Overman M, Eng C, Morris J, Ellis L, Heymach J, Kopetz S. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer (mCRC). J Clin Oncol 29:suppl. abstr 3533
Metadata
Title
Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab
Authors
Nicholas Papadopoulos
Joel Martin
Qin Ruan
Ashique Rafique
Michael P. Rosconi
Ergang Shi
Erica A. Pyles
George D. Yancopoulos
Neil Stahl
Stanley J. Wiegand
Publication date
01-06-2012
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 2/2012
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-011-9249-6

Other articles of this Issue 2/2012

Angiogenesis 2/2012 Go to the issue

Original Paper

Angiogenic properties of myofibroblasts isolated from normal human skin wounds

Erratum

Erratum to: MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway

Original Paper

Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction

Original Paper

Over-expression of BMP4 inhibits experimental choroidal neovascularization by modulating VEGF and MMP-9

Original Paper

Calpain-mediated vimentin cleavage occurs upstream of MT1-MMP membrane translocation to facilitate endothelial sprout initiation

Original Paper

Matrix composition regulates three-dimensional network formation by endothelial cells and mesenchymal stem cells in collagen/fibrin materials
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits