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Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080
Correspondence: Address all correspondence and requests for reprints to: Napoleone Ferrara, M.D., Department of Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080. E-mail: nf{at}gene.com
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. Hypoxia has been shown to be a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality. VEGF is critical also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. In situ hybridization studies demonstrate expression of VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with various VEGF inhibitors in a variety of malignancies are ongoing. Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.
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N. Korsisaari, J. Ross, X. Wu, M. Kowanetz, N. Pal, L. Hall, J. Eastham-Anderson, W. F. Forrest, N. Van Bruggen, F. V. Peale, et al. Blocking Vascular Endothelial Growth Factor-A Inhibits the Growth of Pituitary Adenomas and Lowers Serum Prolactin Level in a Mouse Model of Multiple Endocrine Neoplasia Type 1 Clin. Cancer Res., January 1, 2008; 14(1): 249 - 258. [Abstract] [Full Text] [PDF]
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 G. Zhang, N. Dmitrieva, Y. Liu, K. A. McGinty, and K. J. Berkley Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R162 - R171. [Abstract] [Full Text] [PDF]
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 C. Liu, G. M. Balanos, M. Fatemian, T. G. Smith, K. L. Dorrington, and P. A. Robbins Effects of hydralazine on the pulmonary vasculature and respiratory control in humans Exp Physiol, January 1, 2008; 93(1): 104 - 114. [Abstract] [Full Text] [PDF]
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H. Rossiter, C. Barresi, M. Ghannadan, F. Gruber, M. Mildner, D. Fodinger, and E. Tschachler Inactivation of VEGF in mammary gland epithelium severely compromises mammary gland development and function FASEB J, December 1, 2007; 21(14): 3994 - 4004. [Abstract] [Full Text] [PDF]
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 N. C. Rath, W. E. Huff, and G. R. Huff Thiram-Induced Changes in the Expression of Genes Relating to Vascularization and Tibial Dyschondroplasia Poult. Sci., November 1, 2007; 86(11): 2390 - 2395. [Abstract] [Full Text] [PDF]
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 K. Fizazi The role of Src in prostate cancer Ann. Onc., November 1, 2007; 18(11): 1765 - 1773. [Abstract] [Full Text] [PDF]
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 H. Izuta, Y. Chikaraishi, M. Shimazawa, S. Mishima, and H. Hara 10-Hydroxy-2-decenoic Acid, a Major Fatty Acid from Royal Jelly, Inhibits VEGF-induced Angiogenesis in Human Umbilical Vein Endothelial Cells Evid. Based Complement. Altern. Med., October 22, 2007; (2007) nem152v1. [Abstract] [Full Text] [PDF]
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 L. B. Saltz, H.-J. Lenz, H. L. Kindler, H. S. Hochster, S. Wadler, P. M. Hoff, N. E. Kemeny, E. M. Hollywood, M. Gonen, M. Quinones, et al. Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared With Cetuximab and Bevacizumab Alone in Irinotecan-Refractory Colorectal Cancer: The BOND-2 Study J. Clin. Oncol., October 10, 2007; 25(29): 4557 - 4561. [Abstract] [Full Text] [PDF]
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 J. Klubo-Gwiezdzinska, R. Junik, E. Kopczynska, O. Juraniec, and H. Kardymowicz The comparison of serum vascular endothelial growth factor levels between patients with metastatic and non-metastatic thyroid cancer, and patients with nontoxic multinodular goiter Eur. J. Endocrinol., October 1, 2007; 157(4): 521 - 527. [Abstract] [Full Text] [PDF]
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T. Ostendorf, A. S. De Vriese, and J. Floege Renal side effects of anti-VEGF therapy in man: a new test system Nephrol. Dial. Transplant., October 1, 2007; 22(10): 2778 - 2780. [Full Text] [PDF]
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O. Sawada, H. Kawamura, M. Kakinoki, T. Sawada, and M. Ohji Vascular Endothelial Growth Factor in Aqueous Humor Before and After Intravitreal Injection of Bevacizumab in Eyes With Diabetic Retinopathy Arch Ophthalmol, October 1, 2007; 125(10): 1363 - 1366. [Abstract] [Full Text] [PDF]
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D. Krilleke, A. DeErkenez, W. Schubert, I. Giri, G. S. Robinson, Y.-S. Ng, and D. T. Shima Molecular Mapping and Functional Characterization of the VEGF164 Heparin-binding Domain J. Biol. Chem., September 21, 2007; 282(38): 28045 - 28056. [Abstract] [Full Text] [PDF]
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 F. A. Scappaticci, J. R. Skillings, S. N. Holden, H.-P. Gerber, K. Miller, F. Kabbinavar, E. Bergsland, J. Ngai, E. Holmgren, J. Wang, et al. Arterial Thromboembolic Events in Patients with Metastatic Carcinoma Treated with Chemotherapy and Bevacizumab J Natl Cancer Inst, August 15, 2007; 99(16): 1232 - 1239. [Abstract] [Full Text] [PDF]
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A. Silvestri and H. M Fraser Oestrogen and progesterone receptors in the marmoset endometrium: changes during the ovulatory cycle, early pregnancy and after inhibition of vascular endothelial growth factor, GnRH or ovariectomy Reproduction, August 1, 2007; 134(2): 341 - 353. [Abstract] [Full Text] [PDF]
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W. B. Nagengast, E. G. de Vries, G. A. Hospers, N. H. Mulder, J. R. de Jong, H. Hollema, A. H. Brouwers, G. A. van Dongen, L. R. Perk, and M. N. Lub-de Hooge In Vivo VEGF Imaging with Radiolabeled Bevacizumab in a Human Ovarian Tumor Xenograft J. Nucl. Med., August 1, 2007; 48(8): 1313 - 1319. [Abstract] [Full Text] [PDF]
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 R Zhai, M N Gong, W Zhou, T B Thompson, P Kraft, L Su, and D C Christiani Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower VEGF plasma levels in patients with ARDS Thorax, August 1, 2007; 62(8): 718 - 722. [Abstract] [Full Text] [PDF]
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 D. J. Kelly, D. Buck, A. J. Cox, Y. Zhang, and R. E. Gilbert Effects on protein kinase C-beta inhibition on glomerular vascular endothelial growth factor expression and endothelial cells in advanced experimental diabetic nephropathy Am J Physiol Renal Physiol, August 1, 2007; 293(2): F565 - F574. [Abstract] [Full Text] [PDF]
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M. Luke, K. Januschowski, M. Warga, J. Beutel, M. Leitritz, F. Gelisken, S. Grisanti, T. Schneider, C. Luke, K. U. Bartz-Schmidt, et al. The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator Br J Ophthalmol, August 1, 2007; 91(8): 1077 - 1082. [Abstract] [Full Text] [PDF]
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 A view on new drugs for macular degeneration DTB, July 1, 2007; 45(7): 49 - 52. [Full Text] [PDF]
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 J. H. Chidlow Jr., D. Shukla, M. B. Grisham, and C. G. Kevil Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G5 - G18. [Abstract] [Full Text] [PDF]
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M. Jinushi and G. Dranoff Triggering Tumor Immunity through Angiogenesis Targeting Clin. Cancer Res., July 1, 2007; 13(13): 3762 - 3764. [Full Text] [PDF]
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 E. Liu, M. Morimoto, S. Kitajima, T. Koike, Y. Yu, H. Shiiki, M. Nagata, T. Watanabe, and J. Fan Increased Expression of Vascular Endothelial Growth Factor in Kidney Leads to Progressive Impairment of Glomerular Functions J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2094 - 2104. [Abstract] [Full Text] [PDF]
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N. Shimojo, S. Jesmin, S. Zaedi, T. Otsuki, S. Maeda, N. Yamaguchi, K. Aonuma, Y. Hattori, and T. Miyauchi Contributory role of VEGF overexpression in endothelin-1-induced cardiomyocyte hypertrophy Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H474 - H481. [Abstract] [Full Text] [PDF]
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