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Vol. 52, Issue 2, 237-268, June 2000
Tumor Angiogenesis Laboratory (A.W.G.), Department of Internal
Medicine, University Hospital Maastricht, Maastricht; Groningen
University Institute for Drug Exploration (G.M.), Department of
Pathology and Laboratory Medicine, Tumor Immunology Laboratory, and
Department of Pharmacokinetics and Drug Delivery, Groningen, The
Netherlands
I. General Aspects of Angiogenesis
A. Introduction
B. Function of Endothelial Cells in Normal Physiology
C. Molecular Control of Angiogenesis
1. Initiation of the Angiogenic Response.
2. Endothelial Cell Migration and Proliferation.
3. Maturation of the Neovasculature.
4. Other Mechanisms Implicated in Angiogenesis Control.
II. Angiogenesis Stimulation
A. Target Diseases for Angiogenesis Stimulation
B. Proangiogenic Compounds
1. Vascular Endothelial Growth Factor.
2. Fibroblast Growth Factors.
3. Angiopoietin-1.
C. Effects of Angiogenesis Stimulation in Preclinical Studies
D. First Clinical Studies on Angiogenesis Stimulation
III. Angiogenesis Inhibition
A. Angiogenesis and Cancer
B. In Vitro and in Vivo Models to Study Angiogenesis
C. Ways to Interfere with Angiogenesis
1. Intervention with Endothelial Cell Growth.
2. Intervention with Endothelial Cell Adhesion and
Migration.
3. Intervention with Metalloproteinases.
D. Preclinical Use of Angiogenesis Inhibitors in Cancer
E. Clinical Trials with Inhibitors of Angiogenesis for Cancer
Treatment
F. Novel Approaches to Interfere with Tumor Blood Flow
1. Targeted Strategies to Induce Tumor Blood Coagulation.
2. Targeted Strategies to Kill Tumor Endothelial
Cells.
3. The Quest for New Targets on Tumor Endothelium.
IV. The Interplay between Angiogenesis and Cells of the Immune
System
A. Angiogenesis Regulates Leukocyte Recruitment
B. The Role of Angiogenesis in Chronic Inflammation
C. Inhibition of Angiogenesis in Chronic Inflammation
D. Clinical Trials with Inhibitors of Angiogenesis for Noncancerous
Diseases
V. Back to the Drawing Board
A. Angiogenesis Stimulation
B. Antiangiogenic Strategies in Cancer Therapy
C. Antiangiogenic Strategies in Chronic Inflammation
VI. Concluding Remarks
Acknowledgments
References
Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is a sequence of events that is fundamental to many physiologic and pathologic processes such as cancer, ischemic diseases, and chronic inflammation. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor, the fibroblast growth factors (like in FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Whereas inhibition of angiogenesis can prevent diseases with excessive vessel growth such as cancer, diabetes retinopathy, and arthritis, stimulation of angiogenesis would be beneficial in the treatment of diseases such as coronary artery disease and critical limb ischemia in diabetes. In this review we highlight the current knowledge on angiogenesis regulation and report on the recent findings in angiogenesis research and clinical studies. We also discuss the potentials, limitations, and challenges within this field of research, in light of the development of new therapeutic strategies for diseases in which angiogenesis plays an important role.
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Y. Qian, J. Luo, S. S. Leonard, G. K. Harris, L. Millecchia, D. C. Flynn, and X. Shi Hydrogen Peroxide Formation and Actin Filament Reorganization by Cdc42 Are Essential for Ethanol-induced in Vitro Angiogenesis J. Biol. Chem., April 25, 2003; 278(18): 16189 - 16197. [Abstract] [Full Text] [PDF]
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 K. Howell, R. J Preston, and P. McLoughlin Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation J. Physiol., February 15, 2003; 547(1): 133 - 145. [Abstract] [Full Text] [PDF]
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S. Sengupta, E. Gherardi, L. A. Sellers, J. M. Wood, R. Sasisekharan, and T.-P. D. Fan Hepatocyte Growth Factor/Scatter Factor Can Induce Angiogenesis Independently of Vascular Endothelial Growth Factor Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 69 - 75. [Abstract] [Full Text] [PDF]
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 T.-N. Lin, S.-W. Sun, W.-M. Cheung, F. Li, and C. Chang Dynamic Changes in Cerebral Blood Flow and Angiogenesis After Transient Focal Cerebral Ischemia in Rats: Evaluation With Serial Magnetic Resonance Imaging Stroke, December 1, 2002; 33(12): 2985 - 2991. [Abstract] [Full Text] [PDF]
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 Y.-J. Lee, N. Nagai, C.-H. Siar, K. Nakano, H. Nagatsuka, H. Tsujigiwa, C.-H. Roan, and M. Gunduz Angioarchitecture of Primary Oral Malignant Melanomas J. Histochem. Cytochem., November 1, 2002; 50(11): 1555 - 1562. [Abstract] [Full Text] [PDF]
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 N. Cheng, D. M. Brantley, H. Liu, Q. Lin, M. Enriquez, N. Gale, G. Yancopoulos, D. P. Cerretti, T. O. Daniel, and J. Chen Blockade of EphA Receptor Tyrosine Kinase Activation Inhibits Vascular Endothelial Cell Growth Factor-Induced Angiogenesis Mol. Cancer Res., November 1, 2002; 1(1): 2 - 11. [Abstract] [Full Text] [PDF]
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T. Tarui, M. Majumdar, L. A. Miles, W. Ruf, and Y. Takada Plasmin-induced Migration of Endothelial Cells. A POTENTIAL TARGET FOR THE ANTI-ANGIOGENIC ACTION OF ANGIOSTATIN J. Biol. Chem., September 6, 2002; 277(37): 33564 - 33570. [Abstract] [Full Text] [PDF]
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 I. M. B. Francischetti, J. G. Valenzuela, V. M. Pham, M. K. Garfield, and J. M. C. Ribeiro Toward a catalog for the transcripts and proteins (sialome) from the salivary gland of the malaria vector Anopheles gambiae J. Exp. Biol., August 15, 2002; 205(16): 2429 - 2451. [Abstract] [Full Text] [PDF]
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M. Trikha, Z. Zhou, J. Timar, E. Raso, M. Kennel, E. Emmell, and M. T. Nakada Multiple Roles for Platelet GPIIb/IIIa and {alpha}v{beta}3 Integrins in Tumor Growth, Angiogenesis, and Metastasis Cancer Res., May 1, 2002; 62(10): 2824 - 2833. [Abstract] [Full Text] [PDF]
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 O. Devuyst New insights in the molecular mechanisms regulating peritoneal permeability Nephrol. Dial. Transplant., April 1, 2002; 17(4): 548 - 551. [Full Text] [PDF]
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 M. Weis, C. Heeschen, A. J. Glassford, and J. P. Cooke Statins Have Biphasic Effects on Angiogenesis Circulation, February 12, 2002; 105(6): 739 - 745. [Abstract] [Full Text] [PDF]
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B. A. Ruggeri, C. Robinson, T. Angeles, J. Wilkinson IV, and M. L. Clapper The Chemopreventive Agent Oltipraz Possesses Potent Antiangiogenic Activity in Vitro, ex Vivo, and in Vivo and Inhibits Tumor Xenograft Growth Clin. Cancer Res., January 1, 2002; 8(1): 267 - 274. [Abstract] [Full Text] [PDF]
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A. Otani, B. M. Slike, M. I. Dorrell, J. Hood, K. Kinder, K. L. Ewalt, D. Cheresh, P. Schimmel, and M. Friedlander A fragment of human TrpRS as a potent antagonist of ocular angiogenesis PNAS, January 1, 2002; (2002) 12601899. [Abstract] [Full Text] [PDF]
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D. GOUKASSIAN, A. DIEZ-JUAN, T. ASAHARA, P. SCHRATZBERGER, M. SILVER, T. MURAYAMA, J. M. ISNER, and V. ANDRES Overexpression of p27Kip1 by doxycycline-regulated adenoviral vectors inhibits endothelial cell proliferation and migration and impairs angiogenesis FASEB J, September 1, 2001; 15(11): 1877 - 1885. [Abstract] [Full Text] [PDF]
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 N. Hopkins, E. Cadogan, S. Giles, and P. McLoughlin Chronic airway infection leads to angiogenesis in the pulmonary circulation J Appl Physiol, August 1, 2001; 91(2): 919 - 928. [Abstract] [Full Text] [PDF]
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E. Pillebout, M. Burtin, H. T. Yuan, P. Briand, A. S. Woolf, G. Friedlander, and F. Terzi Proliferation and Remodeling of the Peritubular Microcirculation after Nephron Reduction : Association with the Progression of Renal Lesions Am. J. Pathol., August 1, 2001; 159(2): 547 - 560. [Abstract] [Full Text]
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M. S. Pepper Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis Arterioscler. Thromb. Vasc. Biol., July 1, 2001; 21(7): 1104 - 1117. [Abstract] [Full Text] [PDF]
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 C. E. Gargett, F. Lederman, B. Heryanto, L. S. Gambino, and P. A.W. Rogers Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils Hum. Reprod., June 1, 2001; 16(6): 1065 - 1075. [Abstract] [Full Text] [PDF]
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 S. M. Moghimi, A. C. Hunter, and J. C. Murray Long-Circulating and Target-Specific Nanoparticles: Theory to Practice Pharmacol. Rev., June 1, 2001; 53(2): 283 - 318. [Abstract] [Full Text] [PDF]
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C.-H. Yeh, H.-C. Peng, R.-S. Yang, and T.-F. Huang Rhodostomin, A Snake Venom Disintegrin, Inhibits Angiogenesis Elicited by Basic Fibroblast Growth Factor and Suppresses Tumor Growth by A Selective alpha vbeta 3 Blockade of Endothelial Cells Mol. Pharmacol., April 16, 2001; 59(5): 1333 - 1342. [Abstract] [Full Text]
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C. D. Kim, H. H. Kim, Y. K. Kim, Y. K. Kwak, S.-O. Kim, S.-E. Yoo, and K. W. Hong Antiangiogenic Effect of KR31372 in Rat Sponge Implant Model J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 1085 - 1090. [Abstract] [Full Text]
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E. Middleton Jr., C. Kandaswami, and T. C. Theoharides The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer Pharmacol. Rev., December 1, 2000; 52(4): 673 - 751. [Abstract] [Full Text] [PDF]
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R. C. Savani, G. Cao, P. M. Pooler, A. Zaman, Z. Zhou, and H. M. DeLisser Differential Involvement of the Hyaluronan (HA) Receptors CD44 and Receptor for HA-mediated Motility in Endothelial Cell Function and Angiogenesis J. Biol. Chem., September 21, 2001; 276(39): 36770 - 36778. [Abstract] [Full Text] [PDF]
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L. C. Boujaoude, C. Bradshaw-Wilder, C. Mao, J. Cohn, B. Ogretmen, Y. A. Hannun, and L. M. Obeid Cystic Fibrosis Transmembrane Regulator Regulates Uptake of Sphingoid Base Phosphates and Lysophosphatidic Acid. MODULATION OF CELLULAR ACTIVITY OF SPHINGOSINE 1-PHOSPHATE J. Biol. Chem., September 14, 2001; 276(38): 35258 - 35264. [Abstract] [Full Text] [PDF]
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A. Otani, B. M. Slike, M. I. Dorrell, J. Hood, K. Kinder, K. L. Ewalt, D. Cheresh, P. Schimmel, and M. Friedlander A fragment of human TrpRS as a potent antagonist of ocular angiogenesis PNAS, January 8, 2002; 99(1): 178 - 183. [Abstract] [Full Text] [PDF]
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