Molecular and biological properties of vascular endothelial growth factor

Journal of Molecular Medicine

Volumn 77, Issue 7, 1999, Pages 527-543

  Ferrara, Napoleone ^a  

^a GENENTECH INC   (United States)

Author keywords

Angiogenesis; Retinopathy; Tumor growth; Tyrosine kinases; Vascular endothelial growth factor

Indexed keywords

VASCULOTROPIN;

ANGIOGENESIS; ANIMAL TISSUE; BLOOD VESSEL PERMEABILITY; DIABETIC RETINOPATHY; GENE TRANSFER; NONHUMAN; OSSIFICATION; PATHOGENESIS; PROLIFERATIVE RETINOPATHY; REVIEW;

ANIMALS; ENDOTHELIAL GROWTH FACTORS; ENDOTHELIUM, VASCULAR; FEMALE; GENE EXPRESSION REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LYMPHOKINES; MALE; MICE; MICE, KNOCKOUT; MODELS, BIOLOGICAL; MULTIGENE FAMILY; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS;

EID: 0032852528     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s001099900019     Document Type: Review

References (230)

1. 1. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27-31
2. 2. Garner A (1994) Vascular diseases. In: Garner A, Klintworth GK (eds) Pathobiology of ocular diseases, 2nd edn. Dekker, New York, pp 1625-1710
3. 3. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931-10934
4. 4. Risau W (1997) Mechanisms of angiogenesis. Nature 386: 671-674
5. 5. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Duvis S, Sato TN, Yancopoulos GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87:1171-1180
6. 6. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegend SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science 277:55-60
7. 7. Good D, Polverini P, Rastinejad F, Beau M, Lemons R, Frazier W, Bouck N (1990) A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci USA 87:6624-6628
8. 8. DiPietro LA (1997) Thrombospondin as a regulator of angiogenesis. In: Rosen E, Goldberg ID (eds) Regulation of angiogenesis. Springer, Berlin Heidelberg New York, pp 295-314
9. 9. Ferrara N, Clapp C, Weiner R (1991) The 16 K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells. Endocrinology 129:896-900
10. 10. O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315-328
11. 11. O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277-285
12. 12. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983-985
13. 13. Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851-8518
14. 14. Ploüet J, Schilling J, Gospodarowicz D (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT20 cells. EMBO J 8:3801-3808
15. 15. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306-1309
16. 16. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309-1312
17. 17. Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88:9267-9271
18. 18. Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U (1996) Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA 93:2576-2581
19. 19. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 15:1751
20. 20. Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI (1996) Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci USA 93:1988-1992
21. 21. Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA (1998) Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk 1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA 95:548-553
22. 22. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4-25
23. 23. Enholm B, Jussila L, Karkkainen M, Alitalo K (1998) Vascular endothelial growth factor-C: a growth factor for lymphatic and blood vessel endothelial cells. Trends Cardiovasc Med 8:292-296
24. 24. Carmeliet P, Collen D (1998) Vascular development and disorders: molecular analysis and pathogenic insights. Kidney Int 53:1519-1549
25. 25. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9-22
26. 26. Ferrara N, Carver Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439-442
27. 27. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435-439
28. 28. Gerber HP, Dixit V, Ferrara N (1998) Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 273:13313-13316
29. 29. Gerber HP, McMurtrey A, Kowalski J, Van M, Keyl BA, Dixit V, Ferrara N (1998) VEGF regulates endothelial cell survival by the PI3-kinase/Akt signal transduction pathway requirement for Flk-1/KDR activation. J Biol Chem 273:30366-30343
30. 30. Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024-1028
31. 31. Benjamin L, Hemo I, Keshet H (1998) A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGFB and VEGF. Development 125:1591-1598
32. 32. Pepper MS, Ferrara N, Orci L, Montesano R (1991) Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem Biophys Res Commun 181: 902-906
33. 33. Unemori EN, Ferrara N, Bauer FA Amento EP (1992) Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol 153: 557-562
34. 34. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029-1039
35. 35. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650-1659
36. 36. Dvorak HF, Harvey VS, Estrella P, Brown LF, McDonagh J, Dvorak AM (1987) Fibrin containing gels induce angiogenesis. Implications for tumor stroma generation and wound healing. Lab Invest 57:673-686
37. 37. Bates DO, Curry FE (1996) Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels. Am J Physiol 271:H2520-H2528
38. 38. Bates DO, Curry FE (1997) Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway. Am J Physiol 273:H687-H694
39. 39. Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369-2379
40. 40. Roberts WG, Palade GE (1997) Neovasculature induced by vascular endothelial growth factor is fenestrated. Cancer Res 57:765-772
41. 41. Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W (1998) Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140:947-959
42. 42. Melder RJ, Koenig GC, Witwer BP, Safabakhsh N, Munn LL, Jain RK (1996) During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Nat Med 2: 992-927
43. 43. Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D (1990) Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172:1535-1545
44. 44. Broxmeyer HE, Cooper S, Li ZH, Lu L, Song HY, Kwon BS, Warren RE, Donner DB (1995) Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor. Int J Hematol 62:203-215
45. 45. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1096-103
46. 46. Ku DD, Zaleski JK, Liu S, Brock TA (1993) Vascular endothelial growth Factor induces EDRF-dependent relaxation in coronary arteries. Am J Physiol 265:11586-11592
47. 47. Yang R, Thomas GR, Bunting S, Ko A, Ferrara N, Keyt B, Ross J, Jin H (1996) Effects of vascular endothelial growth factor on hemodynamics and cardiac performance. J Cardiovasc Pharmacol 27:838-844
48. 48. Cuevas P, Carceller F, Ortega S, Zazo M, Nielo I, Gimenez-Gallego G (1991) Hypotensive activity of fibroblast growth factor. Science 254:1208-1210
49. 49. Cuevas P, Garcia-Calvo M, Carceller F, Reimers D, Zazo M, Cuevas B, Munoz-Willery I, Martinez-Coso V, Lamas S, Gimenez-Gallego G (1996) Correction of hypertension by normalization of endothelial levels of fibroblast growth factor and nitric oxide synthase in spontaneously hypertensive rats. Proc Natl Acad Sci USA 93:11996-12001
50. 50. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW (1991) The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5:1806-1814
51. 51. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA (1991) The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing J Biol Chem 266:11947-11954
52. 52. Vincenti V, Cassano C, Rocchi M, Persico G (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93:1493-1495
53. 53. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N (1992) Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 267:26031-26037
54. 54. Park JE, Keller, IL-A, Ferrara N (1993) The vascular endothelial growth factor isoforms (VEGF): differential deposition into the subepithelial extracellular matrix and bioactivily of extracellular matrix-bound VEGF. Mol Biol Cell 4:1317-1326
55. 55. Keyt BA, Berleau LT, Nguyen HV, Chen H, Heinsohn H, Vandlen R, Ferrara N (1996) The carboxyl-terminal domain (111-165) of vascular endothelial growth factor is critical for its mitogenic potency. J Biol Chem 271:7788-7795
56. 56. Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G (1997) VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem 272:7151-7158
57. 57. Ploüet J, Moro F, Bertagnolli S, Coldeboeuf N, Mazarguil H, Clamens S, Bayard F (1997) Extracellular cleavage of the vascular endothelial growth factor 189-amino acid form by urokinase is required for its mitogenic effect. J Biol Chem 272: 13390-13396
58. 58. Muller YA, Li B, Christinger HW, Wells JA, Cunningham BC, de Vos AM (1997) Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc Natl Acad Sci USA 94:7192-7197
59. 59. Minchenko A, Bauer t, Salceda S, Caro J (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vivo and in vitro. Lab Invest 71:374-379
60. 60. Shima DT, Adamis AP, Ferrara N, Yeo KT, Yeo TK, Allende R, Folkman J, D'Amore PA (1995) Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med 1:182-193
61. 61. Banai S, Shweiki D, Pinson A, Chandra M, Lazarovich G, Keshet E (1994) Upregulation of vascular endothelial growth factor expression induced by myocardial ischemia: implications for coronary angiogenesis. Cardiovasc Res 28:1176-1179
62. 62. Hashimoto F, Ogita T, Nakaoka T, Matsuoka R, Takao A, Kira Y (1994) Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart. Am J Physiol 267:H1948-H1954
63. 63. Goldberg MA, Schneider TJ (1994) Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem 269:4355-4361
64. 64. Levy AP, Levy NS, Wegner S, Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270:13333-13340
65. 65. Liu Y, Cox SR, Morita T, Kourembanas S (1995) Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ Res 77:638-643
66. 66. Madan A, Curtin PT (1993) A 24-base-pair sequence 3′ to the human erythropoietin gene contains a hypoxia-responsive transcriptional enhancer. Proc Natl Acad Sci USA 90:3928-3932
67. 67. Wang GL, Semetua GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230-1237
68. 2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12: 149-162
69. 69. Ryan HE, Lo J, Johnson RS (1998) HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J 17:3005-3015
70. 70. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshet E (1998) Role of HTF-1 alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485-490
71. 71. Ikeda E, Achen MG, Breier G, Risau W (1995) Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 270:19761-19766
72. 72. Levy AP, Levy NS, Goldberg MA (1996) Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 271:2746-2753
73. 73. Frank S, Hubner G, Breier G, Longaker MT, Greenhalg DG, Werner S (1995) Regulation of VEGF expression in cultured keratinocytes. Implications for normal and impaited wound healing. J Biol Chem 270:12607-12613
74. 74. Goldman C, Kim J, Wonf, W.-L, King V, Brock T, Gillespie Y (1993) Epidermal growth factor stimulates vascular endothelial growth factor production by malignant glioma cells. A model of glioblastoma multiforme pathophysiology. Mol Biol Cell 4:121-133
75. 75. Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K (1994) Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem 269:6271-6274
76. 76. Ben-Av P, Crofford LJ, Wilder RL, Hla T (1995) Induction of vascular endothelial growth factor expression in synovial fibroblasts. FEBS Lett 372:83-87
77. 77. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ (1996) Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271:736-741
78. 78. Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB (1996) Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem 271: 29483-29488
79. 79. Soh EY, Sobhi SA, Wong MG, Meng YG, Siperstein AE, Clark OH, Duh QY (1996) Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines. Surgery 120:944-947
80. 80. Shifren JL, Mesiano S, Taylor RN, Ferrara N, Jaffe RB (1998) Corticotropin regulates vascular endothelial growth factor expression in human fetal adrenal cortical cells. J Clin Endocrinol Metab 83:1342-1347
81. 81. Claffey KP, Wilkison WO, Spiegelman BM (1992) Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways. J Biol Chem 267: 16317-16322
82. 82. Rak J, Mitsuhashi Y, Bayko L, Filmus J, Shirasawa S, Sasazuki T, Kerbel RS (1995) Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 55:4575-4580
83. 83. Grugel S, Finkenzeller G, Weindel K, Barleon B, Marme D (1995) Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NTH 3T3 cells. J Biol Chem 270:25915-25919
84. 84. Okada F, Rak JW, Croix BS, Lieubeau B, Kaya M, Roncari L, Shirasawa S, Sasazuki T, Kerbel RS (1998) Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci USA 95:3609-3614
85. 85. Siemeister G, Weindel K, Mohrs K, Barleon B, Martiny Baron G, Marme D (1996) Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein. Cancer Res 56:2299-2301
86. 86. Hiopoulos O, Levy AF, Jiang C, Kaelin WG, Jr, Goldberg MA (1996) Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci USA 93: 10595-10599
87. 87. Gnarra JR, Zhou S, Merrill MJ, Wagner JR, Krumm A, Papavassiliou E, Oldfield EH, Klausner RD, Linehan WM (1996) Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci USA 93:10589-10594
88. 88. Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP (1997) The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 17:5629-5639
89. 89. Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N (1992) Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 89:244-253
90. 90. Jakeman LB, Armanini M, Philips HS, Ferrara N (1993) Developmental expression of binding sites and mRNA for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 133:848-859
91. 91. Vries de C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989-991
92. 92. Terman BI, Dougher Vermazen M, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, Bohlen P (1992) Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 187:1579-1586
93. 93. Matthews W, Jordan CT, Gavin M, Jenkins NA, Copeland NG, Lemischka IR (1991) A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc Natl Acad Sci USA 88:9026-9030
94. 94. Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (1990) Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase (flt) closely related to the fms family. Oncogene 8:519-527
95. 95. Terman BI, Carrion MF, Kovacs E, Rasmussen BA, Eddy RL, Shows TB (1991) Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene 6:1677-1683
96. 96. Kendall RL, Thomas KA (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705-10709
97. 97. Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor. FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226:324-328
98. 98. Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Perlovaara L, Alitalo R, Alitalo K (1992) FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res 52:5738-5743
99. 99. Galland F, Karamysheva A, Mattei MG, Rosnet O, Marchello S, Birnbaum D (1992) Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene. Genomics 13: 475-478
100. 100. Finnerty H, Kelleher K, Morris GE, Bean K, Merberg DM, Kriz R, Morris JC, Sookdeo H, Turner KJ, Wood CR (1993) Molecular cloning of murine FLT and FLT4. Oncogene 8:2293-2298
101. 101. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Awartz M, Fukumura D, Jain RK, Alitalo K (1997) Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 276:1423-1425
102. 102. Davis-Smyth T, Chen H, Park J, Presta LG, Ferrara N (1996) The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade. HMBO J 15:4919-4927
103. 103. Barleon B, Totzke F, Herzog C, Blanke S, Kremmer E, Siemeister G, Marme D, Martiny-Baron G (1997) Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1. J Biol Chem 272:10382-10328
104. 104. Fuh G, Li B, Crowley C, Cunningham B, Wells JA (1998) Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor. J Biol Chem 272:11197-11204
105. 105. Wiesmann C, Fuh G, ChrisLinger HW, Eigenbrot C, Wells JA, de Vos AM (1997) Crystal structure at 1.7 a resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell 91:695-704
106. 106. Davis-Smyth T, Presta LG, Ferrara N (1998) Mapping the charged residues in the second immunoglobulin-like domain of the vascular endothelial growth factor/placenta growth factor receptor Flt-1 required for binding and structural stability. J Biol Chem 273:3216-3222
107. 107. Guo D, Jia Q, Song HY, Warren RS, Donner DB (1995) Vascular endothelial cell growth factor promotes tyrosine phosphorylation of mediators of signal transduction that contain SH2 domains. Association with endothelial cell proliferation. J Biol Chem 270:6729-6733
108. 108. Morbidelli L, Chang CH, Douglas JG, Granger HJ, Ledda F, Ziehe M (1996) Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol 270:H411-H415
109. 109. 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 269:26988-26995
110. 110. Seetharam L, Gotoh N, Maru Y, Neufeld G, Yamaguchi S, Shibuya MA (1995) unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene 10:135-147
111. 111. Albini A, Soldi R, Giunciuglio D, Giraudo E, Benelli R, Primo L, Noonan D, Salio M, Camussi G, Rockl W, Bussolino F (1996) The angiogenesis induced by HIV-1 tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat Med 2:1371-1375
112. 112. Park JE, Chen H, Winer J, Houck KA, Ferrara N (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646-25654
113. 113. Cunningham SA, Waxham MN, Arrate PM, Brock TA (1995) Interaction of the Flt-1 tyrosine kinase receptor with the p85 subunit of phosphatidylinositol 3-kinase. Mapping of a novel site involved in binding. J Biol Chem 270: 20254-20257
114. 114. Landgren F, Schiller P, Cao Y, Claesson-Welsh L (1998) Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1. Oncogene 16:359-367
115. 115. Maru Y, Yamaguchi S, Shibuya M (1998) Flt-1, a receptor for vascular endothelial growth factor, has transtforming and morphogenic potentials. Oncogcne 16:2585-2595
116. 116. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M (1998) Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 95:9349-9354
117. 117. Keyt BA, Nguyen HV, Berleau LT, Duarte CM, Park J, Chen H, Ferrara N (1996) Identification of vascular endothelial growth factor determinants for binding KDR and FLT-1 receptors. Generation of receptor-selective VEGF variants by site-directed mutagenesis. J Biol Chem 271:5638-5646
118. 118. Ortega N, Jonca F, Vincent S, Favard C, Ruchoux MM, Ploüet J (1997) Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype. Am J Pathol 151:1215-1224
119. 119. Lyttle DJ, Fraser KM, Flemings SB, Mercer AA, Robinson AJ (1994) Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus. J Virol 68:84-92
120. 120. Ogawa S, Oku A, Sawano A, Yamaguchi S, Yazaki Y, Shibuya MA (1998) novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KUR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem 273: 31273-31282
121. 121. Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336-3343
122. 122. Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI (1998) Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160:1224-1232
123. 123. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735-745
124. 124. Morishita K, Johnson DE, Williams LT (1995) A novel promoter for vascular endothelial growth factor receptor (flt-1) that confers endothelial-specific gene expression. J Biol Chem 270:27948-27953
125. 125. Patterson C, Perrella MA, Hsieh CM, Yoshizumi M, Lee ME, Haber E (1995) Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem 270:23111-23118
126. 126. Tuder RM, Flook BE, Voelkel NF (1995) Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95:1798-1807
127. 127. Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP, Simons M (1996) VEGF, flk-1, and flk-1 expression in a rat myocardial infarction model of angiogenesis. Am J Physiol 270:H1803-H1811
128. 128. Takagi H, King GL, Ferrara N, Aiello LP (1996) Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells. Invest Ophthalmol Vis Sci 37:1311-1321
129. 129. Brogi E, Schatteman G, Wu T, Kim EA, Varticovski L, Keyt B, Isner JM (1996) Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest 97:469-476
130. 130. Gerber HP, Condorelli F, Park J, Ferrara N (1997) Differential transcriptional regulation of the two VEGF receptor genes. Flt-I, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem 22:23659-23667
131. 131. Kremer C, Breier G, Risau W, Plate KH (1997) Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system. Cancer Res 57:3852-3859
132. 132. Shen BQ, Lee DY, Gerher HP, Keyt BA, Ferrara N, Zioncheck TF (1998) Homologous up-regulation of KDR/Flk-1 receptor expression by vascular endothelial growth factor in vitro. J Biol Chem 273:29979-29985
133. 133. Barleon B, Siemeister G, Martiny-Baron G, Weindel K, Herzog C, Marme D (1997) Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinasc 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res 57:5421-5425
134. 134. Mandriota SJ, Menoud PA, Pepper MS (1996) Transforming growth factor beta 1 down-regulates vascular endothelial growth factor receptor 2/flk-1 expression in vascular endothelial cells. J Biol Chem 271:11500-11505
135. 135. Patterson C, Perrella MA, Endege WO, Yoshizumi M, Lee ME, Haber E (1996) Downregulation of vascular endothelial growth factor receptors by tumor necrosis factor-alpha in cultured human vascular endothelial cells. J Clin Invest 98:490-496
136. 136. Giraudo E, Primo L, Audero E, Gerber HP, Koolwijk P, Soker S, Klagsbrun M, Ferrara N, Bussolino F (1998) Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells. J Biol Chem 273:22128-22135
137. 137. Fong GH, Rossam J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66-70
138. 138. Shalaby F, Rossant J, Yamagtiehi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62-66
139. 139. Brandon EP, Idzerda RL, McKnight GS (1995) Targeting the mouse genome: a compendium of knockouts. III. Curr Biol 5:873-881
140. 140. Gerber HP, Hillan KJ, Ryan AM, Kowalski J, Keller, G.-A, Rangell L, Wright BD, Radtke F, Aguet M, Ferrara N (1999) VEGF is required for growth and survival in neonatal mice. Development 126:1149-1159
141. 141. Simon M, Grone HJ, Johren O, Kullmer J, Plate KH, Risau W, Fuchs E (1995) Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol 268:F240-F250
142. 142. Kitamoto Y, Tokunaga H, Tomita K (1997) Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis. J Clin Invest 99:2351-2357
143. 143. Tufro-McReddie A, Norwood VF, Aylor KW, Botkin SJ, Carcy RM, Gomez RA (1997) Oxygen regulates vascular endothelial growth factor-mediated vasculogenesis and tubulogencsis. Dev Biol 183:139-149
144. 144. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623-628
145. 145. Bassett DL (1943) The changes in the vascular pattern of the ovary of the albino rat during the estrous cycle. Am J Anat 73:251-264
146. 146. Gospodarowicz D, Takral TK (1978) Production of a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. Proc Natl Acad Sci USA 75:847-851
147. 147. Phillips HS, Hains J, Leung DW, Ferrara N (1990) Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology 127:965-967
148. 148. Ravindranath N, Little-Ihrig L, Phillips HS, Ferrara N, Zeleznik AJ (1992) Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary. Endocrinology 131:254-260
149. 149. Shweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E (1993) Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally-mediated angiogenesis. J Clin Invest 91:2235-2243
150. 150. Cullinan-Bove K, Koos RD (1993) Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology 133:829-837
151. 151. Ferrara N, Chen H, Davis-Smyth T, Gerber, H.-P, Nguyen, T.-N, Peers D, Chisholm V, Hillan KJ, Schwall RH (1998) Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 4:336-340
152. 152. Goldziher JW, Green JA (1962) The polycistic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab 22:325-332
153. 153. Kamat BR, Brown LF, Manseau HJ, Senger DR, Dvorak HF (1995) Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development. Am J Pathol 146:157-165
154. 154. Engel T, Jewelewicz R, Dyrenfurth I, Speroff L, Vande Wiele RL (1972) Ovarian hyperstimulation syndrome: report of one case with notes on pathogenesis and treatment. Am J Obstet Gynecol 112:1052-1057
155. 155. McClure N, Healy DL, Rogers PA, Sullivan J, Beaton L, Haning RV, Connolly DT, Robertson DM (1994) Vascular endothelial growth factor as a capillary permeability agent in ovarian hyperstimulation syndrome. Lancet 344:235-269
156. 156. Agrawal R, Conway G, Sladkevicius P, Tan SL, Engmann L, Payne N, Bekir J, Campbell S, Jacobs H (1998) Serum vascular endothelial growth factor and Doppler blood flow velocities in in vitro fertilization: relevance to ovarian hyperstimulation syndrome and polycystic ovaries. Fertil Steril 70:651-658
157. 157. Murthy YS, Arronet GH, Pareck MC (1970) Luteal phase inadequacy. Obstet Gynecol 36:758-772
158. 158. Algire GH, Chalkley HW (1945) Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6:73-85
159. 159. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182-1186
160. 160. Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442-447
161. 161. Dennis PA, Rifkin DB (1990) Studies on the role of basic fibroblast growth factor in vivo: inability of neutralizing antibodies to block tumor growth. J Cell Physiol 144:84-98
162. 162. Ferrara N, Houck K, Jakeman L, Leung DW (1992) Molecular and biological properties of the vascular endothelial growth facmily of proteins. Endocr Rev 32:18-32
163. 163. Volm M, Koomagi R, Mattern J, Stammler G (1997) Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro. Anticancer Res 17:99-103
164. 164. Volm M, Koomagi R, Mattern J (1997) Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in sqimmous cell lung cancer. Int J Cancer 74:64-68
165. 165. Brown LF, Berse B, Jackman RW, Tognazzi K, Guidi AJ, Dvorak HF, Senger DR, Connolly JL, Schnitt SJ (1995) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 26:86-91
166. 166. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP (1996) Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res 56:2013-2016
167. 167. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF (1993) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53:4727-4735
168. 168. Ellis LM, Takahashi Y, Fcnoglio CJ, Cleary KR, Bucana CD, Evans DB (1998) Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. Eur J Cancer 34:337-340
169. 169. Uchida S, Shimada Y, Watanabe G, Tanaka H, Shibagaki I, Miyahara T, Ishigaini S, Imamura M (1998) In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis. Br J Cancer 77:1704-1709
170. 170. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR (1993) Increased expression of vascular permeability factor (vascular endothelial growth lactor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143:1255-1262
171. 171. Olson TA, Mohanraj D, Carson LH, Ramakrishnan S (1994) Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res 54:276-280
172. 172. Guidi AJ, Abu Jawdeh G, Tognazzi K, Dvorak HF, Brown LF (1996) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma. Cancer 78:454-460
173. 173. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843-845
174. 174. Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845-848
175. 175. Phillips HS, Armanini M, Stavrou D, Ferrara N, Westphal M (1993) Intense focal expression of vascular endothelial growth factor mRNA in human intracranial neoplasms: association with regions of necrosis. Int J Oncol 2:913-919
176. 176. Berkman RA, Merrill MJ, Reinhold WC, Monacci WT, Saxena A, Clark WC, Robertson JT, Ali IU, Oldfield EH (1993) Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin Invest 91:153-159
177. 177. Wizigmann Voos S, Breier G, Risau W, Plate KH (1995) Upregulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res 55:1358-1364
178. 178. Fukumura D, Xavier R, Sugiura T, Chen Y, Park EC, Lu N, Selig M, Nielsen G, Taksir T, Jain RK, Seed B (1998) Tumor induction of VEGF promoter activity in stromal cells. Cell 94:715-725
179. 179. Toi M, Kondo S, Suzuki H, Yamamoto Y, Inada K, Imazawa T, Taniguchi T, Tominaga T (1996) Quantitative analysis of vascular endothelial growth factor in primary breast cancer. Cancer 77:1101-1106
180. 180. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T (1997) Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89:139-147
181. 181. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Sowa M (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77:858-683
182. 182. Kondo S, Asano M, Matsuo K, Ohmori I, Suzuki H (1994) Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta 1221:211-214
183. 183. Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin s lymphoma. Blood 90:3167-3172
184. 184. Salven P, Ruotsalainen T, Mattson K, Joensuu H (1998) High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer. Int J Cancer 79:144-146
185. 185. Takigawa N, Segawa Y, Fujimoto N, Hotta K, Eguchi K (1998) Elevated vascular endothelial growth factor levels in sera of patients with lung cancer. Anticancer Res 18: 1251-1254
186. 186. Kim KJ, Li B, Houck K, Winer J, Ferrara N (1992) The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors 7:53-64
187. 187. Kim KJ, Li B, Winer J, Armanini M, Gillet N, Phillips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 362:841-844
188. 188. Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N (1995) Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95:1789-1797
189. 189. Melnyk O, Shuman MA, Kim KJ (1996) Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth. Cancer Res 56:921-924
190. 190. Asano M, Yukita A, Matsumoto T, Kondo S, Suzuki H (1998) Inhibition of tumor growth and metastasis by an immunoncutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121. Cancer Res 55:5296-5301
191. 191. Borgstrom P, Bourdon MA, Hillan KJ, Sriramarao P, Ferrara N (1998) Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate 35:1-10
192. 192. Borgstrom P, Hillan KJ, Sriramarao P, Ferrara N (1996) Complete 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 56:4032-4039
193. 193. Yuan F, Chen Y, Dellian M, Safabakhsh N, Ferrara N, Jain RK (1996) Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc Natl Acad Sci USA 93: 14765-14770
194. 194. Shi, Y.-P, Ferrara N (1999) Oncogenic ras fails to restore an in vivo oncogenic phenotype in embryonic stem cells lacking VEGF, Biochem Biophys Res Commun 254:480-483
195. 195. Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A (1994) Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367:576-579
196. 196. Millauer B, Longhi MP, Plate KH, Shawver LK, Risau W, Ullrich A, Strawn LM (1996) Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Cancer Res 56:1615-1620
197. 197. Kong HL, Hecht D, Song W, Kovesdi I, Hackett NR, Yayon A, Crystal RG (1998) Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor. Hum Gene Ther 9:823-833
198. 198. Goldman CK, Kendall RL, Cabrera G, Soroceanu L, Heike Y, Gillespie GY, Siegal GP, Mao X, Bett AJ, Huckle WR, Thomas KA, Curiel DT (1998) Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc Natl Acad Sci USA 95:8795-8800
199. 199. Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-VEGF monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593-4599
200. 200. Strawn LM, McMahon G, App H, Schreck R, Kuchler WR, Longhi MP, Hui TH, Tang C, Levitzki A, Gazit A, Chen I, Keri U, Orfi L, Risau W, Flamme I, Ullrich A, Hirth KP, Shawver LK (1996) Flk-1 as a target for tumor growth inhibition. Cancer Res 56:3540-3545
201. 201. Olk RJ, Lee CM (1993) Diabetic retinopathy: practical management. Lippincott, Philadelphia
202. 202. Patz A (1980) Studies on retinal neovascularization. Invest Ophthalmol Vis Sci 19:1133-1138
203. 203. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen H, Aiello LM, Ferrara N, King GL (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopalhy and other retinal disorders. N Engl J Med 331:1480-1487
204. 204. Adamis AP, Miller JW, Bernal MT, D'Amico DJ, Folkman J, Yco TK, Yeo KT (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118:445-450
205. 205. Malecaze F, Clemens S, Simorer-Pinotel V, Mathis A, Chollet P, Favard P, Bayard F, Ploüet J (1994) Detection of vascular endothelial growth factor mRNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 112:1476-1482
206. 206. Okamoto N, Tobe T, Hacked SF, Ozaki H, Vinores MA, LaRochelle W, Zack DJ, Campochiaro PA (1997) Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subrctinal neovascularization. Am J Pathol 151:281-291
207. 207. Miller JW, Adamis AP, Shima DT, D'Amore PA, Moulton RS, O'Reilly MS, Folkman J, Dvorak HF, Brown LF, Berse B, et al (1994) Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol 145:574-584
208. 208. Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE (1995) Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA 92:905-909
209. 209. Adamis AP, Shima DT, Tolentino MJ, Gragoudas ES, Ferrara N, Folkman J, D'Amore PA, Miller JW (1996) Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol 114:66-71
210. 210. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-recepltor chimeric proteins. Proc Natl Acad Sci USA 92: 10457-10461
211. 211. Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR (1996) Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci 37:855-868
212. 212. Kvanta A, Algvere PV, Berglin L, Seregard S (1996) Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci 37:1929-1934
213. 213. Koch AE, Harlow L, Haines GK, Amento EP, Unemori EN, Wong W-L, Pope RM, Ferrara N (1994) Vascular endothelial growth factor: a cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152:4149-4156
214. 214. Fava RA, Olsen NJ, Spencer-Green G, Yeo KT, Yeo TK, Berse B, Jaekman RW, Senger DR, Dvorak HF, Brown LF (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180:341-346
215. 215. Takeshita S, Zhung L, Brogi E, Kearney M, Pu, L.-Q, Bunting S, Ferrara N, Symes JF, Isner JM (1994) Therapeutic angiogenesis: a single intra-arterial bolus of vascular endothelial growth factor augments collateral vessel formation in a rabbit ischemic hind-limb model. J Clin Invest 93:662-670
216. 216. Takeshita S, Tsurumi Y, Couffinahl T, Asahara T, Banters C, Symes J, Ferrara N, Isner JM (1996) Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 75:487-501
217. 217. Takeshita S, Weir L, Chen D, Zheng LP, Riessen R, Banters C, Symes JF, Ferrara N, Isner JM (1996) Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227:628-635
218. 218. Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1995) Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor. Circulation 91:2802-2809
219. 219. Mack CA, Magovern CJ, Budenhender KT, Patel SR, Schwarz EA, Zanzonico P, Ferris B, Sanborn T, Isorn P, Ferris B, Sanbom T, Isom OW, Crystal RG, Rosengart TK (1998) Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. J Vasc Surg 27: 699-709
220. 220. Banai S, Jaktlish MT, Shou M, Lazarous D, Scheinowitz M, Biro S, Epstein S, Unger E (1994) Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor. Circulation 89: 2183-2189
221. 221. Maradu K, Friedman M, Lopez JJ, Wang SY, Li J, Prasad PV, Pearlman JD, Edelman ER, Sellke FW, Simons M (1996) Vascular endothelial growth factor administration in chronic myocardial ischemia. Am J Physiol 270:H1791-H1802
222. 222. Mack CA, Patel SR, Schwarz EA, Zanzonico P, Hahn RT, Ilercil A, Devereux RB, Goldsmith SJ, Christian TF, Sanborn TA, Kovesdi I, Haekett N, Isom OW, Crystal RG, Rosengart TK (1998) Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. I Thorac Cardiovasc Surg 115:168-176
223. 223. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF (1996) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348: 370-374
224. 224. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97:1114-1123
225. 225. Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Asharc AB, Lathi K, Isner JM (1998) Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800-2804
226. 226. Henry TD, Rocha-Singh K, Isner JM, Kereiakcs DJ, Giordano FJ, Simons M, Losordo DW, Hendel RC, Bonow RO, Rothman JM, Barbas ER, McCluskey ER (1998) Results of intracoronary recombinant human vascular endothelial growth factor (rhVEGF) administration trial. J Am Coll Cardiol 31 [2 Suppl A]:810-811
227. 227. Henry TD, Annex BH, Azrin MA, McKendall GR, Willerson JT, Hendel RC, Giordano FJ, Klein R, Gibson CM, Berman DS, Luce CA McCluskey ER (1999) Double blind, placebo controlled trial of recombinant human vascular endothelial growth factor: the VIVA Trial. J Am Coll Cardiol 33 [2 Suppl A]:384A874-874
228. 228. Deroanne CF, Hajitou A, Calberg-Bacq CM, Nusgens BV, Lapiere CM (1997) Angiogenesis by fibroblast growth factor 4 is mediated through an autocrine up-regulation of vascular endothelial growth factor expression. Cancer Res 57:5590-5597
229. 229. Seghezzi G, Patel S, Ren CJ, Gualandris A, Pintucci G, Robbins ES, Shapiro RL, Galloway AC, Rifkin DB, Mignatti P (1998) Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis. J Cell Biol 141:1659-1673
230. 230. Gordon MS, Talpaz M, Margolin K, Holmgren E, Sledge GW, Benjamin R, Staller S, Shak S, Adelman D (1998) Phase I trial of recombinant humanized monoclonal antivascular endothelial growth factor in patients with metastatic cancer. Presented at the 34th Annual Meeting of the American Society of Clinical Oncologists, Los Angeles, 16-19 May