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The Biology of Vascular Endothelial Growth Factor

Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080

I. Introduction

II. Biological Activities of VEGF

III. Organization of the VEGF Gene

IV. Properties of the VEGF Isoforms

V. Regulation of VEGF Gene Expression

A. Hypoxia

B. Cytokines

C. Differentiation and transformation

VI. The VEGF Receptors

A. Characterization and distribution of VEGF-binding sites

B. The Flt-1 and Flk-1/KDR tyrosine kinases

1. Binding characteristics

2. Signal transduction

3. Regulation

4. Structural requirements for ligand binding in Flt-1 and Flk-1/KDR

5. VEGF determinants for binding Flt-1 and Flk-1/KDR

VII. VEGF-Related Molecules

VIII. Role of VEGF and Its Receptors in Physiological Angiogenesis

A. Distribution of VEGF, Flk-1/KDR and Flt-1 mRNA

B. Analysis of Flk-1/KDR, Flt-1 and VEGF gene knockouts

IX. Role of VEGF in Pathological Angiogenesis

A. Tumor angiogenesis

1. Expression of VEGF in human tumors

2. Inhibition of VEGF action in vivo

B. Intraocular neovascular syndromes

C. Other pathological conditions

X. Therapeutic Applications of VEGF-Induced Angiogenesis

XI. Perspectives

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				R. P.M. Dings, M. Loren, H. Heun, E. McNiel, A. W. Griffioen, K. H. Mayo, and R. J. Griffin Scheduling of Radiation with Angiogenesis Inhibitors Anginex and Avastin Improves Therapeutic Outcome via Vessel Normalization Clin. Cancer Res., June 1, 2007; 13(11): 3395 - 3402. [Abstract] [Full Text] [PDF]

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				R. R. Langley and I. J. Fidler Tumor Cell-Organ Microenvironment Interactions in the Pathogenesis of Cancer Metastasis Endocr. Rev., May 1, 2007; 28(3): 297 - 321. [Abstract] [Full Text] [PDF]

				V L Bosquiazzo, J G Ramos, J Varayoud, M Munoz-de-Toro, and E H Luque Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis Reproduction, May 1, 2007; 133(5): 1045 - 1055. [Abstract] [Full Text] [PDF]

				S. M. Meeran, S. Katiyar, C. A. Elmets, and S. K. Katiyar Interleukin-12 Deficiency Is Permissive for Angiogenesis in UV Radiation-Induced Skin Tumors Cancer Res., April 15, 2007; 67(8): 3785 - 3793. [Abstract] [Full Text] [PDF]

				D. Kong, Y. Li, Z. Wang, S. Banerjee, and F. H. Sarkar Inhibition of Angiogenesis and Invasion by 3,3'-Diindolylmethane Is Mediated by the Nuclear Factor-{kappa}B Downstream Target Genes MMP-9 and uPA that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer Cancer Res., April 1, 2007; 67(7): 3310 - 3319. [Abstract] [Full Text] [PDF]

				J. Fang, Q. Zhou, L.-Z. Liu, C. Xia, X. Hu, X. Shi, and B.-H. Jiang Apigenin inhibits tumor angiogenesis through decreasing HIF-1{alpha} and VEGF expression Carcinogenesis, April 1, 2007; 28(4): 858 - 864. [Abstract] [Full Text] [PDF]

				S. Jesmin, S. Zaedi, N. Shimojo, M. Iemitsu, K. Masuzawa, N. Yamaguchi, C. N. Mowa, S. Maeda, Y. Hattori, and T. Miyauchi Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1030 - E1040. [Abstract] [Full Text] [PDF]

				M. J. Nijland, N. E. Schlabritz-Loutsevitch, G. B. Hubbard, P. W. Nathanielsz, and L. A. Cox Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway J. Physiol., March 15, 2007; 579(3): 643 - 656. [Abstract] [Full Text] [PDF]

				M. Buraczynska, P. Ksiazek, I. Baranowicz-Gaszczyk, and L. Jozwiak Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients Nephrol. Dial. Transplant., March 1, 2007; 22(3): 827 - 832. [Abstract] [Full Text] [PDF]

				J. A. Garcia and B. I. Rini Recent Progress in the Management of Advanced Renal Cell Carcinoma CA Cancer J Clin, March 1, 2007; 57(2): 112 - 125. [Abstract] [Full Text] [PDF]

				Y. Li, S. Hazarika, D. Xie, A. M. Pippen, C. D. Kontos, and B. H. Annex In Mice With Type 2 Diabetes, a Vascular Endothelial Growth Factor (VEGF)-Activating Transcription Factor Modulates VEGF Signaling and Induces Therapeutic Angiogenesis After Hindlimb Ischemia Diabetes, March 1, 2007; 56(3): 656 - 665. [Abstract] [Full Text] [PDF]

				D. Manau, F. Fabregues, J. Penarrubia, M. Creus, F. Carmona, G. Casals, W. Jimenez, and J. Balasch Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF Hum. Reprod., March 1, 2007; 22(3): 669 - 675. [Abstract] [Full Text] [PDF]

				M. Bergman Jungestrom, L. U. Thompson, and C. Dabrosin Flaxseed and Its Lignans Inhibit Estradiol-Induced Growth, Angiogenesis, and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Xenografts In vivo Clin. Cancer Res., February 1, 2007; 13(3): 1061 - 1067. [Abstract] [Full Text] [PDF]

				D. J. George Phase 2 Studies of Sunitinib and AG013736 in Patients with Cytokine-Refractory Renal Cell Carcinoma Clin. Cancer Res., January 15, 2007; 13(2): 753s - 757s. [Abstract] [Full Text] [PDF]

				B. Fu, J. Xue, Z. Li, X. Shi, B.-H. Jiang, and J. Fang Chrysin inhibits expression of hypoxia-inducible factor-1{alpha} through reducing hypoxia-inducible factor-1{alpha} stability and inhibiting its protein synthesis Mol. Cancer Ther., January 1, 2007; 6(1): 220 - 226. [Abstract] [Full Text] [PDF]