Expertos Invitados





EL PAPEL DEL FACTOR DE CRECIMIENTO DEL ENDOTELIO VASCULAR EN LA ANGIOGENESIS

(especial para SIIC © Derechos reservados)
Dado que la angiogénesis es un acontecimiento clave en el crecimiento tumoral, invasión y metástasis, se ha propuesto al factor de crecimiento del endotelio vascular como blanco terapéutico en varios tipos de tumores.
Autor:
Nicola Maruotti
Columnista Experto de SIIC

Institución:
University of Foggia Medical School

Artículos publicados por Nicola Maruotti
Coautor
Domenico Ribatti* 
University of Bari Medical School, Bari, Italia*
Recepción del artículo
2 de Mayo, 2007 		Aprobación
17 de Septiembre, 2007
Primera edición
10 de Abril, 2008 		Segunda edición, ampliada y corregida
7 de Junio, 2021

EL PAPEL DEL FACTOR DE CRECIMIENTO DEL ENDOTELIO VASCULAR EN LA ANGIOGENESIS

Resumen
El factor de crecimiento del endotelio vascular (VEGF) es un factor angiogénico importante. La familia de los VEGF incluye VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E y el factor de crecimiento placentario (PlGF), los cuales, mediante diferentes interacciones con tres receptores de tirosina quinasa, que incluyen VEGFR-1/Flt-1, VEGFR-2/Flk-1 y VEGFR-3/Flt-4 y dos receptores de tirosina quinasa no proteicos, incluidos neuropilina 1 y neuropilina 2, son responsables de la proliferación de células endoteliales, migración y expresión de quimioquinas, citoquinas y metaloproteinasas de la matriz. Se ha detectado VEGF, que se expresa en respuesta a citoquinas, factores de crecimiento, hormonas, proteasas extracelulares e hipoxia, en diferentes tejidos como encéfalo, hígado, bazo, riñón y piel, donde es producido por varios citotipos, que incluyen células endoteliales, fibroblastos, queratinocitos, macrófagos, mastocitos y células tumorales. El VEGF participa en varias condiciones fisiológicas y patológicas, que incluyen desarrollo del embrión, vasculogénesis y hematopoyesis temprana, ovulación, reparación de heridas, psoriasis, endometriosis, aterosclerosis, retinopatía diabética, degeneración macular neovascular del ojo relacionada con la edad, enfermedades inflamatorias crónicas y tumores. Dado que la angiogénesis es un acontecimiento clave en el crecimiento tumoral, invasión y metástasis, se ha propuesto al VEGF como blanco terapéutico de varios tipos tumorales, como cáncer de mama, de células renales, colorrectal y de pulmón de células no pequeñas. Además, el VEGF puede ser un agente terapéutico interesante en las enfermedades cardíacas y periféricas isquémicas.

Palabras clave
angiogénesis, antiangiogénesis, célula endotelial, crecimiento tumoral


Artículo completo
(castellano)
Extensión:  +/-10.73 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

The role of vascular endothelial growth factor in angiogenesis

Abstract
Vascular endothelial growth factor (VEGF) is an important angiogenic factor. VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor (PlGF) which by different interactions with three tyrosine kinase receptors, including VEGFR-1/Flt-1, VEGFR-2/Flk-1 and VEGFR-3/Flt-4, and two non protein tyrosine kinase receptors, including neuropilin-1 and -2, are responsible for endothelial cells proliferation, migration and expression of chemokines, cytokines and matrix metalloproteinases. VEGF, expressed in response to cytokines, growth factors, hormones, extracellular proteases, and hypoxia, has been detected in different tissues, such as brain, liver, spleen, kidney and skin, where it is produced by several cytotypes, including endothelial cells, fibroblasts, keratinocytes, macrophages, mast cells and tumor cells. VEGF is involved in several physiological and pathological conditions, including embryo development, vasculogenesis and early hematopoiesis, ovulation, wound repair, psoriasis, endometriosis, arteriosclerosis, diabetic retinophathy, neovascular age-related macular degeneration of the eye, chronic inflammatory diseases, and tumors. Since angiogenesis is a key event in tumor growth, invasion and metastasis, VEGF has been proposed as a therapeutic target in several tumor types, such as breast cancer, renal cell cancer, colorectal cancer and non small cells lung cancer. Furthermore, VEGF may be an interesting therapeutic agent in ischemic heart and peripheral diseases.

Key words
angiogenesis, antiangiogenesis, endothelial cell, tumor growth


Full text
(english)
 para suscriptores/ assinantes
Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Bioquímica, Oncología
Relacionadas: Cardiología, Farmacología, Inmunología, Medicina Interna



Comprar este artículo
Extensión: 10.73 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Domenico Ribatti, University of Bari Medical School Department of Human Anatomy and Histology, I-70124, Piazza Giulio Cesare, 11, Bari, Italia
Patrocinio y reconocimiento:
Financiado por la Associazione Italiana per la Ricerca sul Cancro (AIRC, National and Regional Funds) Milán, Ministerio de Educación, Universidades e Investigación (Proyecto CARSO n. 72/2; FIRB 2001 and PRIN 2005), Roma, y Fondazione Italiana per la Lotta al Neuroblastoma, Génova, Italia.
Bibliografía del artículo
1. Ribatti D, Vacca A, Dammacco F. The role of the vascular phase in solid tumor growth: a historical review. Neoplasia 1:293-302, 1999.
2. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353-64, 1996.
3. O'Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315-28, 1994.
4. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277-85, 1997.
5. Dameron KM, Volpert OV, Tainsky MA, Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265:1582-4, 1994.
6. Risau W. Mechanisms of angiogenesis. Nature 386:671-4, 1987.
7. Patan S, Munn LL, Jain RK. Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 51:260-72, 1996.
8. Chang YS, Di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA 97:14608-13, 2000.
9. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739-52, 1999.
10. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 21:4368-80, 2002.
11. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581-611, 2004.
12. Hoeben A, Landuyt B, Highley MS, Wildiers, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549-80, 2004.
13. Meyer M, Clauss M, Lepple-Wienhues A, et al. A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signaling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. EMBO J 18:363-74, 1999.
14. Roskoski R. Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol 2007.
15. Veikkola T, AlitaloK. VEGFs, receptors and angiogenesis. Semin Cancer Biol 9:211-20, 1999.
16. Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 269:26988-95, 1994.
17. Park JE, Chen HH, Winer J, Houck KA, Ferrara N. 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 269:25646-54, 1994.
18. Olofsson B, Korpelainen E, Pepper MS, et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA 95:11709-14, 1998.
19. Gille H, Kowalski J, Li B, et al. Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). J Biol Chem 276:3222-30, 2001.
20. Takahashi T, Yamaguchi S, Chida K, Shibuya M. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-? and DNA synthesis in vascular endothelial cells. EMBO J 20:2768-78, 2001.
21. Bernatchez PN, Soker S, Sirois MG. Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent. J Biol Chem 274:31047-54, 1999.
22. Kukk E, Lymboussaki A, Taira S, et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 122:3829-37, 1996.
23. Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 312:584-93, 2006.
24. Ellis LM. The role of neuropilins in cancer. Mol Cancer Ther 5:1099-107, 2006.
25. Kärpänen T, Heckman CA, Keskitalo S, et al. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J 20:1462-72, 2006.
26. Migdal M, Huppertz B, Tessler S, et al. Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem 273:22272-8, 1998.
27. Makinen T, Olofsson B, KärpänenT, et al. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem 274:21217-22, 1999.
28. Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165. J Biol Chem 275:18040-5, 2000.
29. Li J, Perrella MA, Tsai JC, et al. Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells. J Biol Chem 270:308-312, 1995.
30. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271:736-41, 1996.
31. Deroanne CF, Hajitou A, Calberg-Bacq CM, Nusgens BV, Lapiere CM. Angiogenesis by fibroblast growth factor 4 is mediated through an autocrine up-regulation of vascular endothelial growth factor expression. Cancer Res 57:5590-7, 1997.
32. Finkenzeller G, Marme D, Weich HA, Hug H. Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C. Cancer Res 52:4821-3, 1992.
33. Goad DL, Rubin J, Wang H, Tashjian AH, Patterson C. Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I. Endocrinology 137:2262-8, 1996.
34. Pertovaara L, Kaipainen A, Mustonen T, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-ß in fibroblastic and epithelial cells. J Biol Chem 269:6271-4, 1994.
35. Ongusaha PP, Kwak JC, Zwible AJ, et al. HB-EGF is a potent inducer of tumor growth and angiogenesis. Cancer Res 64:5283-90, 2004.
36. Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes-implications for normal and impaired wound healing. J Biol Chem 270:12607-13, 1995.
37. Ryuto M, Ono M, Izumi H, et al. Induction of vascular endothelial growth factor by tumor necrosis factor a in human glioma cells. Possible roles of SP-1. J Biol Chem 271:28220-8, 1996.
38. Kawaguchi M, Akagi M, Gray MJ, Liu W, Fan F, Ellis LM. Regulation of vascular endothelial growth factor expression in human gastric cancer cells by interleukin-1ß. Surgery 136:686-92, 2004.
39. Matsumoto K, Ohi H, Kanmatsuse K. Interleukin 10 and interleukin 13 synergize to inhibit vascular permeability factor release by peripheral blood mononuclear cells from patients with lipoid nephrosis. Nephron 77:212-8, 1997.
40. Haggstrom S, Lissbrant IF, Bergh A, Damber JE. Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats. J Urol 161:1620-5, 1999.
41. Wang J, Luo F, Lu JJ, Chen PK, Liu P, Zheng W. VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors. Int J Cancer 97:163-7, 2002.
42. Hyder SM, Murthy L, Stancel GM. Progestin regulation of vascular endothelial growth factor in human breast cancer cells. Cancer Res 58:392-5, 1998.
43. Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21:1104-7, 2001.
44. Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 169:681-91, 2005.
45. Flaumenhaft R, Rifkin DB. The extracellular regulation of growth factor action. Mol Biol Cell 3:1057-65, 1992.
46. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 267:26031-7, 1992.
47. Keyt BA, Berleau LT, Nguyen HV, et al. The carboxyl-terminal domain (111-165) of vascular endothelial growth factor is critical for its mitogenic potency. J Biol Chem 271:7788-95, 1996.
48. Plouët J, Moro F, Bertagnolli S, et al. Extracellular cleavage of the vascular endothelial growth factor 189-amino acid form by urokinase is required for its mitogenic effect. J Biol Chem 272:13390-6, 1997.
49. Ashikari-Hada S, Habuchi H, Kariya Y, Kimata K. Heparin regulates vascular endothelial growth factor165-dependent mitogenic activity, tube formation, and its receptor phosphorylation of human endothelial cells. Comparison of the effects of heparin and modified heparins. J Biol Chem 280:31508-15, 2005.
50. Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol 59:15-26, 2006.
51. Zhou J, Schmid T, Schnitzer S, Brune B. Tumor hypoxia and cancer progression. Cancer Lett 237:10-21, 2006.
52. Berra E, Ginouves A, Pouyssegur J. The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling. EMBO Rep 7:41-5, 2006.
53. Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266:11947-54, 1991.
54. Levy NS, Chung S, Furneaux H, Levy AP. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem 273:6417-23, 1998.
55. Stein I, Itin A, Einat P, Skaliter R, Grossman Z, Keshet E. Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia. Mol Biol Cell 18:3112-9, 1998.
56. Akiri G, Nahari D, Finkelstein Y, Le S, Elroy-Stein O, Levi B. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene 12:227-36, 1998.
57. Manalo DJ, Rowan A, Lavoie T, et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood 105:659-69, 2005.
58. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435-9, 1996.
59. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inacitivation of the VEGF gene. Nature 380:439-42, 1996.
60. Eichmann A, Corbel C, Najaf V, Vaigot P, Breant C, Le Douarin NM. Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor-2. Proc Natl Acad Sci USA 94:5141-6, 1997.
61. Shalaby F, Ho J, Stanford WL, et al. A requirement for flk-1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89:981-90, 1997.
62. Schuh AC, Faloon P, Hu RL, Bhimani M, Choi K. In vitro hematopoietic and endothelial potential of flk-1 -/- embryonic stem cells and embryos. Proc Natl Acad Sci USA 96:2159-64, 1999.
63. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99:11946-50, 2002.
64. Khaibullina AA, Rosenstein JM, Krum JM. Vascular endothelial growth factor promotes neurite maturation in primary CNS neuronal cultures. Dev Brain Res 148:59-68, 2004.
65. Ferrara N, Cehn H, Davis-Smyth T, et al. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nature Med 4:336-40, 1998.
66. Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, Di Pietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 152:1445-52, 1998.
67. Salven P, Heikkila P, Joensuu H. Enhanced expression of vascular endothelial growth factor in metastatic melanoma. Br J Cancer 76:930-4, 1997.
68. Straume O, Akslen LA. Expression of vascular endothelial growth factor, its receptors (Flt-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. Am J Pathol 159:223-35, 2001.
69. Dvorak HF. Tumors: wounds that not heal. Similarity between tumor stroma generation and wound healing. N Engl J Med 315:1650-8, 1986.
70. Dvorak HF, Harvey VS, Estrella P, Brown LF, Mc Donagh J, Dvorak AM. Fibrin containing gels induce angiogenesis: implication for tumor stroma generation and wound healing. Lab Invest 57:673-86, 1987.
71. Kondo S, Asano M, Matsuo K, Ohmori I, Suzuki H. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta 1221:211-4, 1994.
72. Yamamoto Y, Toi M, Kondo S, et al. Concentrations of vascular endothelial growth factor in the sera of normal controls and cancer patients. Clin Cancer Res 2:821-6, 1996.
73. Nuefeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9-22, 1999.
74. Vlaykova T, Laurila P, Muhonen T, et al. Prognostic value of tumour vascularity in metastatic melanoma and association of blood vessel density with vascular endothelial growth factor expression. Melanoma Res 9:59-68, 1999.
75. Nicosia RF. What is the role of vascular endothelial growth factor-related molecules in tumor angiogenesis? Am J Pathol 153:11-6, 1998.
76. Ribatti D, Vacca A, Nico B, Crivellato E, Roncali L, Dammacco F. The role of mast cells in tumor angiogenesis. Br J Haematol 115:514-21, 2001.
77. Senger DR, Brown L, Claffey K, Dvorak A. Vascular permeability factor, tumor angiogenesis and stroma generation. Invasion Metastasis 14:385-94, 1995.
78. Claffey KP, Brown LF, Del Aguila LF, et al. Expression of vascular permeability/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res 56:172-81, 1996.
79. Lymboussaki A, Partanen TA, Olofsson B, et al. Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors. Am J Pathol 153:395-403, 1998.
80. Kerbel RS, Viloria-Petit A, Okada F, Rak J. Establishing a link between oncogenes and tumor angiogenesis. Mol Med 4:286-95, 1998.
81. Kieser A, Welch HA, Brandner G, Marme D, Kolck W. Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene 9:963-9, 1994.
82. Siemeister G, Weindel K, Mohrs K, Barleon B, Martinybaron G, Marme D. Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein. Cancer Res 56:2299-301, 1996.
83. Stratmann R, Krieg M, Haas R, Plate KH. Putative control of angiogenesis in hemangioblastomas by the von Hippel-Lindau tumor suppressor gene. J Neuropathol Exp Neurol 56:1242-52, 1997.
84. Zhang L, Yu D, Hu M, et al. Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression. Cancer Res 60:3655-61, 2000.
85. Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP. The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 17:5629-39, 1997.
86. Iliopoulos O, Levy AP, Jiang C, Kaelin WG, Goldberg MA. Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein. Proc Natl Acad Sci USA 93:10595-9, 1996.
87. Pal S, Claffey KP, Dvorak HF, Mukhopadhyay D. The von Hippel-Lindau gene product inhibits vascular permeability factor vascular endothelial growth factor expression in renal cell carcinoma by blocking protein kinase C pathways. J Biol Chem 272:27509-12, 1997.
88. Chin K, Kurashima Y, Ogura T, Tajiri H, Yoshida S, Esumi H. Induction of vascular endothelial growth factor/vascular permeability factor by nitric oxide in human glioblastoma and hepatocellular cell lines. Oncogene 15:437-42, 1997.
89. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial cell growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843-5, 1992.
90. Carmeliet P, Dor Y, Herbert JM, et al. Role of HIF-1a in hypoxia-mediated angiogenesis, cell proliferation and tumour angiogenesis. Nature 394:485-90, 1998.
91. Jiang BH, Agani F, Passaniti A, Semenza GL. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res 57:5328-35, 1997.
92. Detmar M, Yeo KT, Nagy JA, et al. Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 105:44-50, 1995.
93. Shifren JL, Tseng JF, Zaloudek CJ, et al. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J Clin Endocrinol Metab 81:3112-8, 1996.
94. Couffinhal T, Kearney M, Witzenbichler B, et al. Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in normal and atherosclerotic human arteries. Am J Pathol 150:1673-85, 1997.
95. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480-7, 1994.
96. Malecaze F, Clemens S, Simorer-Pinotel V, et al. Detection of vascular endothelial growth factor mRNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 112:1476-82, 1994.
97. Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. 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 37:855-68, 1996.
98. Lee SS, Joo YS, Kim WU, et al. Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 19:321-4, 2001.
99. Bousvaros A, Leichtner A, Zurakowski D, et al. Elevated serum vascular endothelial growth factor in children and young adults with Crohn's disease. Dig Dis Sci 44:424-30, 1999.
100. Namiki A, Brogi E, Kearney M, et al. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J Biol Chem 270:31189-95, 1995.
101. Bjornheden T, Levin M, Evaldsson M, Wiklund O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler Thromb Vasc Biol 19:870-6, 1999.
102. Luttun A, Tjwa M, Moons L, et al. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8:831-40, 2002.
103. Taylor PC. VEGF and imaging of vessels in rheumatoid arthritis. Arthritis Res 4:S99-S107, 2002.
104. Takeshita S, Zheng LP, Brogi E, et al. Therapeutic angiogenesis. A single intra-arterial bolus of vascular endothelial growth factor augments neovascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662-70, 1994.
105. Takeshita S, Tsurumi Y, Couffinahl T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 75:487-501, 1996.
106. Pearlman JD, Hibberd MG, Chuang ML, et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nature Med 1:1085-9, 1995.
107. Henry TD, Abraham JA. Review of preclinical and clinical results with vascular endothelial growth factors for therapeutic angiogenesis. Curr Interv Cardiol Rep 2:228-41, 2000.
108. Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 107:1359-65, 2003.
109. Makinen K, Manninen H, Hedman M, et al. Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther 6:127-33, 2002.
110. Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841-4, 1993.
111. Saleh M, Stacker SA, Wilks AF. Inibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res 56:393-401, 1996.
112. Millauer B, Shawver KL, Plate KH, Risau W, Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367:576-9, 1994.
113. Skobe M, Rockwell P, Goldstein N, Vossler S, Fusenig NE. Halting angiogenesis suppresses carcinoma cell invasion. Nature Med 11:1222-7, 1997.
114. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593-9, 1997.
115. Muller YA, Chen Y, Christinger HW, et al. VEGF and the Fab fragment of a humanized neutralizing antibody: crystal structure of the complex at 2.4 Å resolution and mutational analysis of the interface. Structure 6:1153-67, 1998.
116. Cobleigh MA, Langmuir VK, Sledge GW, et al. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117-24, 2003.
117. Yang JC, Harworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427-34, 2003.
118. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60-5, 2003.
119. Margolin K, Gordon MS, Holmgren E, et al. Phase I trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol 19:851-6, 2001.
120. Smith JK, Mamoon NM, Duhe RJ. Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy. Oncol Res 14:175-225, 2004.
121. Holash J, Davis S, Papadopoulos N, et al. Yancopoulos and J.S. Rudge, VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Nat Acad Sci USA 99:11393-8, 2002.
122. He T, Rajantie I, Pajusola K, et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res 65:4739-46, 2005.
 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008