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Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro

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Abstract

Bevacizumab (Avastin™, Genentech) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), a critical angiogenic factor involved in both physiological and pathological conditions. It has been recently approved by the US FDA as a first-line therapy for widespread metastatic colorectal cancer. This report is a detailed biological characterization of bevacizumab in a variety of in vitro models. It is shown that bevacizumab potently neutralizes VEGF and blocks its signal transduction through both the VEGFR-1 and VEGFR-2 receptors, as demonstrated by the inhibition of VEGF-induced cell proliferation, survival, permeability, nitric oxide production, as well as migration and tissue factor production. Although bevacizumab retains the ability to bind to human Fcγ receptors and complement protein C1q, it does not demonstrate cell or complement-mediated cytotoxicity in either VEGF producing or targeting cells. Thus the mechanism of anti-tumor activity of bevacizumab is most likely due to its anti-angiogenesis effect through binding and neutralization of secreted VEGF.

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References

  1. W Risau V Lemmon (1988) ArticleTitleChanges in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis Dev Biol 125 IssueID2 441–450 Occurrence Handle10.1016/0012-1606(88)90225-4 Occurrence Handle1:CAS:528:DyaL1cXpt1Whug%3D%3D Occurrence Handle3338622

    Article  CAS  PubMed  Google Scholar 

  2. W Risau H Sariola HG Zerwes et al. (1988) ArticleTitleVasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies Development 102 IssueID3 471–478 Occurrence Handle1:STN:280:BiaD3s%2FjtlM%3D Occurrence Handle2460305

    CAS  PubMed  Google Scholar 

  3. N Ferrara (2001) ArticleTitleRole of vascular endothelial growth factor in regulation of physiological angiogenesis Am J Physiol Cell Physiol 280 IssueID6 C1358–C1366 Occurrence Handle1:CAS:528:DC%2BD3MXksFKntbk%3D Occurrence Handle11350730

    CAS  PubMed  Google Scholar 

  4. KH Plate PC Warnke (1997) ArticleTitleVascular endothelial growth factor J Neuro-Oncol 35 IssueID3 363–370 Occurrence Handle10.1023/A:1005845307160

    Article  Google Scholar 

  5. Z Zhou J Wang R Cao et al. (2004) ArticleTitleImpaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice Cancer Res 64 IssueID14 4699–4702 Occurrence Handle1:CAS:528:DC%2BD2cXls1Oms7g%3D Occurrence Handle15256433

    CAS  PubMed  Google Scholar 

  6. P Taylor (2002) ArticleTitleVEGF and imaging of vessels in rheumatoid arthritis Arthritis Res 4 IssueIDSuppl 3 S99–S107 Occurrence Handle10.1186/ar582 Occurrence Handle12110128

    Article  PubMed  Google Scholar 

  7. E Paleolog (2002) ArticleTitleAngiogenesis in rheumatoid arthritis Arthritis Res 4 IssueIDSuppl 3 S81–S90 Occurrence Handle10.1186/ar575 Occurrence Handle12110126

    Article  PubMed  Google Scholar 

  8. AN Witmer GFJM Vrensen CJF Van Noorden RO Schlingemann (2003) ArticleTitleVascular endothelial growth factors and angiogenesis in eye disease Prog Retinal Eye Res 22 IssueID1 1–29 Occurrence Handle10.1016/S1350-9462(02)00043-5 Occurrence Handle1:CAS:528:DC%2BD3sXht1Cqsb0%3D

    Article  CAS  Google Scholar 

  9. N Ferrara WJ Henzel (1989) ArticleTitlePituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells Biochem Biophys Res Commun 161 IssueID2 851–858 Occurrence Handle10.1016/0006-291X(89)92678-8 Occurrence Handle1:CAS:528:DyaL1MXkslWhtbY%3D Occurrence Handle2735925

    Article  CAS  PubMed  Google Scholar 

  10. P Carmeliet YS Ng D Nuyens et al. (1999) ArticleTitleImpaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188 Nat Med 5 IssueID5 495–502 Occurrence Handle10.1038/8379 Occurrence Handle1:CAS:528:DyaK1MXivVKks70%3D Occurrence Handle10229225

    Article  CAS  PubMed  Google Scholar 

  11. GD Yancopoulos S Davis Nw Gale et al. (2000) ArticleTitleVascular-specific growth factors and blood vessel formation Nature 407 IssueID6801 242–248 Occurrence Handle10.1038/35025215 Occurrence Handle1:CAS:528:DC%2BD3cXmvVSlsrY%3D Occurrence Handle11001067

    Article  CAS  PubMed  Google Scholar 

  12. N Ferrara HP Gerber J LeCouter (2003) ArticleTitleThe biology of VEGF and its receptors Nat Med 9 IssueID6 669–676 Occurrence Handle1:CAS:528:DC%2BD3sXktFOnur4%3D Occurrence Handle12778165

    CAS  PubMed  Google Scholar 

  13. N Ferrara K Alitalo (1999) ArticleTitleClinical applications of angiogenic growth factors and their inhibitors Nat Med 5 IssueID12 1359–1364 Occurrence Handle10.1038/70928 Occurrence Handle1:CAS:528:DyaK1MXnvFCqtrw%3D Occurrence Handle10581076

    Article  CAS  PubMed  Google Scholar 

  14. N Ferrara (2002) ArticleTitleRole of vascular endothelial growth factor in physiologic and pathologic angiogenesis: Therapeutic implications Semin Oncol 29 IssueID6 Suppl 16 10–14 Occurrence Handle10.1053/sonc.2002.37264 Occurrence Handle1:CAS:528:DC%2BD3sXlvFSqsQ%3D%3D

    Article  CAS  Google Scholar 

  15. J Folkman (2002) ArticleTitleRole of angiogenesis in tumor growth and metastasis Semin Oncol 29 IssueID6 15–18 Occurrence Handle10.1053/sonc.2002.37263 Occurrence Handle1:CAS:528:DC%2BD3sXlvFSqtg%3D%3D

    Article  CAS  Google Scholar 

  16. HS Rugo (2004) ArticleTitleBevacizumab in the treatment of breast cancer: Rationale and current data Oncologist 9 IssueIDsuppl 1 43–49 Occurrence Handle10.1634/theoncologist.9-suppl_1-43 Occurrence Handle1:CAS:528:DC%2BD2cXlsFOju74%3D

    Article  CAS  Google Scholar 

  17. R Longo R Sarmiento M Fanelli et al. (2001) ArticleTitleAnti-angiogenic therapy: Rationale, challenges and clinical studies Angiogenesis 5 IssueID4 237–256 Occurrence Handle10.1023/A:1024532022166

    Article  Google Scholar 

  18. Zondor SD, Medina PJ. Bevacizumab: An angiogenesis inhibitor with efficacy in colorectal and other malignancies (CE) (July/August). Ann Pharmacother 2004: aph.1D470

  19. N Ferrara KJ Hillan H-P Gerber W Novotny (2004) ArticleTitleDiscovery and development of Bevacizumab, an anti-vegf antibody for treating cancer Nature Rev Drug Discov 3 IssueID5 391–400 Occurrence Handle10.1038/nrd1381 Occurrence Handle1:CAS:528:DC%2BD2cXktlCrt78%3D

    Article  CAS  Google Scholar 

  20. CA Boocock DS Charnock-Jones AM Sharkey et al. (1995) ArticleTitleExpression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma J Natl Cancer Inst 87 IssueID7 506–516 Occurrence Handle1:CAS:528:DyaK2MXlsVequrc%3D Occurrence Handle7707437

    CAS  PubMed  Google Scholar 

  21. TVM Pietsch HK Wolf A Deimling Particlevon et al. (1997) ArticleTitleExpression and distribution of vascular endothelial growth factor protein in human brain tumors Acta Neuropathol (Berl). 93 IssueID2 109–117 Occurrence Handle10.1007/s004010050591 Occurrence Handle1:CAS:528:DyaK2sXhvVertbk%3D

    Article  CAS  Google Scholar 

  22. KJLB Kim K Houck J Winer N Ferrara (1992) ArticleTitleThe vascular endothelial growth factor proteins: Identification of biologically relevant regions by neutralizing monoclonal antibodies Growth Factors 7 IssueID1 53–64 Occurrence Handle1:STN:280:By2A28fmsFA%3D Occurrence Handle1380254

    CAS  PubMed  Google Scholar 

  23. Kim KJLB, Winer J, Armanini M. et al.(1993). Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 841–4

  24. LG Presta H Chen SJ O’Connor et al. (1997) ArticleTitleHumanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders Cancer Res 57 IssueID20 4593–4599 Occurrence Handle1:CAS:528:DyaK2sXmslKqtLg%3D Occurrence Handle9377574

    CAS  PubMed  Google Scholar 

  25. PBM Borgstrom KJ Hillan P Sriramarao N Ferrara (1998) ArticleTitleNeutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo Prostate 35 IssueID1 1–10 Occurrence Handle10.1002/(SICI)1097-0045(19980401)35:1<1::AID-PROS1>3.0.CO;2-O Occurrence Handle1:CAS:528:DyaK1cXisFCks74%3D Occurrence Handle9537593

    Article  CAS  PubMed  Google Scholar 

  26. PHK Borgstrom P Sriramarao N Ferrara (1996) ArticleTitleComplete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: Novel concepts of angiostatic therapy from intravital videomicroscopy Cancer Res 56 IssueID17 4032–4039 Occurrence Handle1:STN:280:BymA2Mvmt1M%3D Occurrence Handle8752175

    CAS  PubMed  Google Scholar 

  27. EY Soh MS Eigelberger KJ Kim et al. (2000) ArticleTitleNeutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo Surgery 128 IssueID6 1059–1066 Occurrence Handle10.1067/msy.2000.110430 Occurrence Handle1:STN:280:DC%2BD3M%2FnsFehug%3D%3D Occurrence Handle11114643

    Article  CAS  PubMed  Google Scholar 

  28. F Yuan Y Chen M Dellian (1996) ArticleTitleTime-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody PNAS 93 IssueID25 14765–14770 Occurrence Handle10.1073/pnas.93.25.14765 Occurrence Handle1:CAS:528:DyaK28XnsVOht78%3D Occurrence Handle8962129

    Article  CAS  PubMed  Google Scholar 

  29. AMED Ryan KE Hagler Rh Bruner et al. (1999) ArticleTitlePreclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody Toxicol Pathol 27 IssueID1 78–86 Occurrence Handle1:CAS:528:DyaK1MXhtlSitL8%3D Occurrence Handle10367678

    CAS  PubMed  Google Scholar 

  30. H Hurwitz L Fehrenbacher W Novotny et al. (2004) ArticleTitleBevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer N Engl J Med 350 IssueID23 2335–2342 Occurrence Handle10.1056/NEJMoa032691 Occurrence Handle1:CAS:528:DC%2BD2cXks1Gjt74%3D Occurrence Handle15175435

    Article  CAS  PubMed  Google Scholar 

  31. N Ferrara T Davis-Smyth (1997) ArticleTitleThe biology of vascular endothelial growth factor Endocr Rev 18 IssueID1 4–25 Occurrence Handle10.1210/er.18.1.4 Occurrence Handle1:CAS:528:DyaK2sXhsFCiu7s%3D Occurrence Handle9034784

    Article  CAS  PubMed  Google Scholar 

  32. BA Keyt HV Nguyen LT Berleau et al. (1996) ArticleTitleIdentification of vascular endothelial growth factor determinants for binding KDR and FLT-1 receptors J Biol Chem 271 IssueID10 5638–46 Occurrence Handle10.1074/jbc.271.10.5638 Occurrence Handle1:CAS:528:DyaK28XhsFehtrw%3D Occurrence Handle8621427

    Article  CAS  PubMed  Google Scholar 

  33. S Ansar Ahmed J Gogal M Robert JE Walsh (1994) ArticleTitleA new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: An alternative to [3H]thymidine incorporation assay J Immunol Meth 170 IssueID2 211–24 Occurrence Handle10.1016/0022-1759(94)90396-4 Occurrence Handle1:CAS:528:DyaK2MXnvFKl

    Article  CAS  Google Scholar 

  34. JW Breslin PJ Pappas JJ Cerveira et al. (2003) ArticleTitleVEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide Am J Physiol Heart Circ Physiol 284 IssueID1 H92–H100 Occurrence Handle1:CAS:528:DC%2BD3sXmvFyqsQ%3D%3D Occurrence Handle12388327

    CAS  PubMed  Google Scholar 

  35. J Friedl M Puhlmann DL Bartlett et al. (2002) ArticleTitleInduction of permeability across endothelial cell monolayers by tumor necrosis factor (TNF) occurs via a tissue factor-dependent mechanism: Relationship between the procoagulant and permeability effects of TNF Blood 100 IssueID4 1334–1339 Occurrence Handle1:CAS:528:DC%2BD38Xmt12itb0%3D Occurrence Handle12149215

    CAS  PubMed  Google Scholar 

  36. J Kroll J Waltenberger (1999) ArticleTitleA novel function of VEGF receptor-2 (KDR): Rapid release of nitric oxide in response to VEGF-A stimulation in endothelial cells Biochem Biophys Res Commun 265 IssueID3 636–639 Occurrence Handle10.1006/bbrc.1999.1729 Occurrence Handle1:CAS:528:DyaK1MXnvFaqtLk%3D Occurrence Handle10600473

    Article  CAS  PubMed  Google Scholar 

  37. A Papapetropoulos G Garcia-Cardena JA Madri WC Sessa (1997) ArticleTitleNitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells J Clin Invest 100 IssueID12 3131–3139 Occurrence Handle1:CAS:528:DyaK2sXotVyrs70%3D Occurrence Handle9399960

    CAS  PubMed  Google Scholar 

  38. RL Shields AK Namenuk K Hong et al. (2001) ArticleTitleHigh resolution mapping of the binding site on human IgG1 for Fcgamma RI, Fcgamma RII, Fcgamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fcgamma R J Biol Chem 276 IssueID9 6591–6604 Occurrence Handle10.1074/jbc.M009483200 Occurrence Handle1:CAS:528:DC%2BD3MXhslShurs%3D Occurrence Handle11096108

    Article  CAS  PubMed  Google Scholar 

  39. EE Idusogie LG Presta H Gazzano-Santoro et al. (2000) ArticleTitleMapping of the C1q binding site on Rituxan, a chimeric antibody with a human IgG1 Fc J Immunol 164 IssueID8 4178–84 Occurrence Handle1:CAS:528:DC%2BD3cXis1WksrY%3D Occurrence Handle10754313

    CAS  PubMed  Google Scholar 

  40. BK Lal S Varma PJ. Pappas et al. (2001) ArticleTitleVEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways Microvas Res 62 IssueID3 252–262 Occurrence Handle10.1006/mvre.2001.2338 Occurrence Handle1:CAS:528:DC%2BD3MXnvVSitrs%3D

    Article  CAS  Google Scholar 

  41. B Barleon S Sozzani D. Zhou et al. (1996) ArticleTitleMigration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1 Blood 87 IssueID8 3336–3343 Occurrence Handle1:CAS:528:DyaK28Xit1Krs7k%3D Occurrence Handle8605350

    CAS  PubMed  Google Scholar 

  42. M Clauss F Pipp K. Issbrucker et al. (2003) ArticleTitleDissection of monocyte and endothelial activities by using VEGF-receptor specific ligands Adv Exp Med Biol 522 75–82 Occurrence Handle1:CAS:528:DC%2BD3sXmsVWjt7w%3D Occurrence Handle12674212

    CAS  PubMed  Google Scholar 

  43. F Pipp M Heil K. Issbrucker et al. (2003) ArticleTitleVEGFR-1-selective VEGF homologue PlGF Is arteriogenic: Evidence for a monocyte-mediated mechanism Circ Res 92 IssueID4 378–385 Occurrence Handle10.1161/01.RES.0000057997.77714.72 Occurrence Handle1:CAS:528:DC%2BD3sXhsValtb4%3D Occurrence Handle12600898

    Article  CAS  PubMed  Google Scholar 

  44. A Sawano S Iwai Y. Sakurai et al. (2001) ArticleTitleFlt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans Blood 97 IssueID3 785–791 Occurrence Handle10.1182/blood.V97.3.785 Occurrence Handle1:CAS:528:DC%2BD3MXhtVSjtr0%3D Occurrence Handle11157498

    Article  CAS  PubMed  Google Scholar 

  45. P Ben-Av LJ Crofford RL Wilder T. Hla (1995) ArticleTitleInduction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: A potential mechanism for inflammatory angiogenesis FEBS Lett 372 IssueID1 83–87 Occurrence Handle10.1016/0014-5793(95)00956-A Occurrence Handle1:CAS:528:DyaK2MXosVOit74%3D Occurrence Handle7556649

    Article  CAS  PubMed  Google Scholar 

  46. T Cohen D Nahari LW. Cerem et al. (1996) ArticleTitleInterleukin 6 Induces the expression of vascular endothelial growth factor J Biol Chem 271 IssueID2 736–741 Occurrence Handle10.1074/jbc.271.2.736 Occurrence Handle1:STN:280:BymC3s3otVU%3D Occurrence Handle8557680

    Article  CAS  PubMed  Google Scholar 

  47. S Frank G Hübner G. Breier et al. (1995) ArticleTitleRegulation of vascular endothelial growth factor expression in cultured keratinocytes J Biol Chem 270 IssueID21 12607–12613 Occurrence Handle1:CAS:528:DyaK2MXlvFOiurw%3D

    CAS  Google Scholar 

  48. AP Levy NS Levy S Wegner MA. Goldberg (1995) ArticleTitleTranscriptional regulation of the rat vascular endothelial growth factor gene by hypoxia J Biol Chem 270 IssueID22 13333–13340 Occurrence Handle10.1074/jbc.270.22.13333 Occurrence Handle1:CAS:528:DyaK2MXmtV2hsr4%3D Occurrence Handle7768934

    Article  CAS  PubMed  Google Scholar 

  49. Y Liu SR Cox T Morita S. Kourembanas (1995) ArticleTitleHypoxia regulates vascular endothelial growth factor gene expression in endothelial cells: Identification of a 5’ enhancer Circ Res 77 IssueID3 638–643 Occurrence Handle1:CAS:528:DyaK2MXns1altLs%3D Occurrence Handle7641334

    CAS  PubMed  Google Scholar 

  50. RS Warren H Yuan MR. Matli et al. (1996) ArticleTitleInduction of vascular endothelial growth factor by insulin-like growth factor in colorectal carcinoma J Biol Chem 271 IssueID46 29483–29488 Occurrence Handle10.1074/jbc.271.46.29483 Occurrence Handle1:CAS:528:DyaK28XntFOhtrs%3D Occurrence Handle8910616

    Article  CAS  PubMed  Google Scholar 

  51. H Wang JA. Keiser (1998) ArticleTitleVascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells : Role of flt-1 Circ Res 83 IssueID8 832–840 Occurrence Handle1:CAS:528:DyaK1cXntVCrtrw%3D Occurrence Handle9776730

    CAS  PubMed  Google Scholar 

  52. WJ Lamoreaux ME Fitzgerald A. Reiner et al. (1998) ArticleTitleVascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro Microvasc Res 55 IssueID1 29–42 Occurrence Handle10.1006/mvre.1997.2056 Occurrence Handle1:CAS:528:DyaK1cXhsF2nt7s%3D Occurrence Handle9473407

    Article  CAS  PubMed  Google Scholar 

  53. M Prewett J Huber Y. Li et al. (1999) ArticleTitleAntivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors Cancer Res 59 IssueID20 5209–5218 Occurrence Handle1:CAS:528:DyaK1MXmvFelsLo%3D Occurrence Handle10537299

    CAS  PubMed  Google Scholar 

  54. Willett CG, Boucher Y, di Tomaso E. et al.(2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. 10(2): 145–147

  55. H Zeng HF Dvorak D. Mukhopadhyay (2001) ArticleTitleVascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) receptor-1 down-modulates VPF/VEGF receptor-2-mediated endothelial cell proliferation, but not migration, through phosphatidylinositol 3-kinase-dependent Pathways J Biol Chem 276 IssueID29 26969–26979 Occurrence Handle10.1074/jbc.M103213200 Occurrence Handle1:CAS:528:DC%2BD3MXlsV2jt7o%3D Occurrence Handle11350975

    Article  CAS  PubMed  Google Scholar 

  56. M Clauss H Weich G. Breier et al. (1996) ArticleTitleThe vascular endothelial growth factor receptor Flt-1 mediates biological activities. implications for a functional role of placenta growth factor in monocyte activation and chemotaxis J Biol Chem 271 IssueID30 17629–17634 Occurrence Handle10.1074/jbc.271.30.17629 Occurrence Handle1:CAS:528:DyaK28XksFyisLY%3D Occurrence Handle8663424

    Article  CAS  PubMed  Google Scholar 

  57. RL Kendall G Wang J Disalvo KA. Thomas (1994) ArticleTitleSpecificity of vascular endothelial cell growth factor receptor ligand binding domains Biochem Biophys Res Commun 201 IssueID1 326–330 Occurrence Handle10.1006/bbrc.1994.1705 Occurrence Handle1:CAS:528:DyaK2cXktVWhsrc%3D Occurrence Handle8198591

    Article  CAS  PubMed  Google Scholar 

  58. J Waltenberger L Claesson-Welsh A. Siegbahn et al. (1994) ArticleTitleDifferent signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor J Biol Chem 269 IssueID43 26988–26995 Occurrence Handle1:CAS:528:DyaK2cXmt1artb4%3D Occurrence Handle7929439

    CAS  PubMed  Google Scholar 

  59. RT-P Poon CP-Y Lau JW-Y. Ho et al. (2003) ArticleTitleTissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma Clin Cancer Res 9 IssueID14 5339–5345 Occurrence Handle1:CAS:528:DC%2BD3sXovVOnsrs%3D Occurrence Handle14614019

    CAS  PubMed  Google Scholar 

  60. DF Altomare MT Rotelli V. Memeo et al. (2003) ArticleTitleExpression of tissue factor and vascular endothelial growth factor in colorectal carcinoma Tumori 89 IssueID4 Suppl 5–6 Occurrence Handle1:STN:280:DC%2BD3szmvFygsQ%3D%3D Occurrence Handle12903530

    CAS  PubMed  Google Scholar 

  61. Creasey AARK. Tissue factor pathway inhibitor activity in severe sepsis. Crit Care Med 2001; 29(7).

  62. HH Versteeg MP Peppelenbosch CA. Spek (2003) ArticleTitleTissue factor signal transduction in angiogenesis Carcinogenesis 24 IssueID6 1009–1013 Occurrence Handle10.1093/carcin/bgg039 Occurrence Handle1:CAS:528:DC%2BD3sXkvVSnurc%3D Occurrence Handle12807741

    Article  CAS  PubMed  Google Scholar 

  63. BC Kuenen M Levi JC. Meijers et al. (2002) ArticleTitleAnalysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients Arterioscler Thromb Vasc Biol 22 IssueID9 1500–1505 Occurrence Handle10.1161/01.ATV.0000030186.66672.36 Occurrence Handle1:CAS:528:DC%2BD38XntVKkurs%3D Occurrence Handle12231573

    Article  CAS  PubMed  Google Scholar 

  64. M Belting MI Dorrell S. Sandgren et al. (2004) ArticleTitleRegulation of angiogenesis by tissue factor cytoplasmic domain signaling Nat Med 10 IssueID5 502–509 Occurrence Handle10.1038/nm1037 Occurrence Handle1:CAS:528:DC%2BD2cXjsF2jtL0%3D Occurrence Handle15098027

    Article  CAS  PubMed  Google Scholar 

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  1. David Fei

    Present address: Analytical Development, BioPharmaceuticals, Chiron Corporation, Emeryville, California, USA

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  1. Department of BioAnalytical Research & Development, Genentech, Mail Stop 38, 1 DNA Way, San Francisco, CA, 94080, USA

    Yaning Wang, David Fei, Martin Vanderlaan & An Song

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Wang, Y., Fei, D., Vanderlaan, M. et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 7, 335–345 (2004). https://doi.org/10.1007/s10456-004-8272-2

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