Vascular Endothelial Growth Factor and Angiogenesis

Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro- and antiangiogenic molecules have already been discovered. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF in physiological and pathological processes is reviewed. We also discuss how modulation of VEGF expression creates new therapeutic possibilities and describe recent developments in this field.

[1]  C. Dinney,et al.  Treatment of human metastatic transitional cell carcinoma of the bladder in a murine model with the anti-vascular endothelial growth factor receptor monoclonal antibody DC101 and paclitaxel. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[2]  H. Dvorak,et al.  Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. , 1995, International archives of allergy and immunology.

[3]  J. Isner,et al.  Randomized, Single-Blind, Placebo-Controlled Pilot Study of Catheter-Based Myocardial Gene Transfer for Therapeutic Angiogenesis Using Left Ventricular Electromechanical Mapping in Patients With Chronic Myocardial Ischemia , 2001, Circulation.

[4]  E C Nice,et al.  Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF‐C/D receptor VEGFR‐3 , 2001, The EMBO journal.

[5]  S. Rafii,et al.  The Id proteins and angiogenesis , 2001, Oncogene.

[6]  L. Claesson‐Welsh,et al.  VEGF receptor signal transduction. , 2003, Science's STKE : signal transduction knowledge environment.

[7]  C. Dinney,et al.  Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  J. Pouysségur,et al.  Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. , 2000, The Journal of biological chemistry.

[9]  M Ancukiewicz,et al.  Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. , 2000, Cancer research.

[10]  T. Fojo,et al.  p53 Inhibits Hypoxia-inducible Factor-stimulated Transcription* , 1998, The Journal of Biological Chemistry.

[11]  S. Rafii,et al.  Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells , 2001, The Journal of experimental medicine.

[12]  H. Blau,et al.  VEGF gene delivery to muscle: potential role for vasculogenesis in adults. , 1998, Molecular cell.

[13]  J. Isner,et al.  Therapeutic Angiogenesis for Coronary Artery Disease , 2002, Annals of Internal Medicine.

[14]  H. Dvorak,et al.  Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. , 1995, The American journal of pathology.

[15]  G. Batist,et al.  AE-941 (Neovastat): a novel multifunctional antiangiogenic compound. , 2001, Expert review of anticancer therapy.

[16]  J. Folkman,et al.  Vascular endothelial growth factor expression and tumor angiogenesis are regulated by androgens in hormone responsive human prostate carcinoma: evidence for androgen dependent destabilization of vascular endothelial growth factor transcripts. , 2001, The Journal of urology.

[17]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[18]  S. Soker,et al.  Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[19]  J. M. Arbeit,et al.  Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. , 2000, Cancer research.

[20]  H. Yoshiji,et al.  Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. , 1997, Cancer research.

[21]  P. Hewett,et al.  Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. , 2002, Cancer research.

[22]  R. Weichselbaum,et al.  Blockade of the Vascular Endothelial Growth Factor Stress Response Increases the Antitumor Effects of Ionizing Radiation , 1999 .

[23]  M. Post,et al.  Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. , 1999, Circulation.

[24]  S. Fox,et al.  Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. , 2001, The Lancet. Oncology.

[25]  B Landuyt,et al.  Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11 , 2003, British Journal of Cancer.

[26]  K. Alitalo,et al.  VEGF‐C and VEGF‐D expression in neuroendocrine cells and their receptor, VEGFR‐3, in fenestrated blood vessels in human tissues , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  I. Endo,et al.  Diurnal fluctuation of edema synchronized with plasma VEGF concentration in a patient with POEMS syndrome. , 2002, Internal medicine.

[28]  M. Aglietta,et al.  Platelet activating factor produced in vitro by Kaposi's sarcoma cells induces and sustains in vivo angiogenesis. , 1995, The Journal of clinical investigation.

[29]  D. Carbone,et al.  Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells , 1996, Nature Medicine.

[30]  M. Shibuya,et al.  Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Dvorak Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  D. Carbone,et al.  Clinical significance of defective dendritic cell differentiation in cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  S. Rafii,et al.  Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Y. Matsumura,et al.  TAp63gamma (p51A) and dNp63alpha (p73L), two major isoforms of the p63 gene, exert opposite effects on the vascular endothelial growth factor (VEGF) gene expression. , 2002, Oncogene.

[35]  S. Ramakrishnan,et al.  Inhibition of angiogenesis and tumour growth by VEGF121–toxin conjugate: differential effect on proliferating endothelial cells , 2000, British Journal of Cancer.

[36]  J. Folkman,et al.  Clinical translation of angiogenesis inhibitors , 2002, Nature Reviews Cancer.

[37]  Jacques Landry,et al.  p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells , 1997, Oncogene.

[38]  J. Wood,et al.  Targeting Vascular Endothelial Growth Factor (VEGF) for Anti-tumor Therapy, by Anti-VEGF Neutralizing Monoclonal Antibodies or by VEGF Receptor Tyrosine-kinase Inhibitors , 2004, Cancer and Metastasis Reviews.

[39]  R. Paridaens,et al.  Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo? , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[40]  G. Gasparini,et al.  Clinical significance of determination of surrogate markers of angiogenesis in breast cancer. , 2001, Critical reviews in oncology/hematology.

[41]  R. Crystal,et al.  Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. , 1998, Journal of vascular surgery.

[42]  M A Moses,et al.  Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Ulf Eriksson,et al.  Vascular endothelial growth factors VEGF‐B and VEGF‐C , 1997, Journal of cellular physiology.

[44]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[45]  L. Wilkinson,et al.  Demonstration of lymphatics in human synovial tissue , 2004, Rheumatology International.

[46]  K. Alitalo,et al.  Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors. , 1998, The American journal of pathology.

[47]  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. , 1996, The Journal of clinical endocrinology and metabolism.

[48]  S. Oliviero,et al.  In Fibroblasts Vegf-D Expression Is Induced by Cell-Cell Contact Mediated by Cadherin-11* , 2001, The Journal of Biological Chemistry.

[49]  H. Kawanaka,et al.  Von Hippel‐Lindau tumor suppressor and HIF‐1α: new targets of NSAID inhibition of hypoxia‐induced angiogenesis , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[50]  W Blumenfeld,et al.  Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. , 1993, The American journal of pathology.

[51]  J. Isner,et al.  Endothelial Progenitor Cell Vascular Endothelial Growth Factor Gene Transfer for Vascular Regeneration , 2002, Circulation.

[52]  B. Curry,et al.  ZD4190: an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. , 2000, Cancer research.

[53]  P. Baker,et al.  Elevated Serum Levels of Vascular Endothelial Growth Factor in Patients With Preeclampsia , 1995, Obstetrics and gynecology.

[54]  R. Weichselbaum,et al.  Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. , 1999, Cancer research.

[55]  L. Ellis,et al.  Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis , 2002, Oncogene.

[56]  W. Sessa,et al.  Suppression of vascular endothelial growth factor-mediated endothelial cell protection by survivin targeting. , 2001, The American journal of pathology.

[57]  M. Karkkainen,et al.  Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells , 1999, Molecular and Cellular Endocrinology.

[58]  R. Kerbel Tumor angiogenesis: past, present and the near future. , 2000, Carcinogenesis.

[59]  J. M. Arbeit,et al.  Hypoxia-inducible Factor-1α Is a Positive Factor in Solid Tumor Growth , 2000 .

[60]  T. Lindahl,et al.  The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer. , 2001, Cancer research.

[61]  J. Mestan,et al.  PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. , 2000, Cancer research.

[62]  Jessica Lo,et al.  HIF‐1α is required for solid tumor formation and embryonic vascularization , 1998 .

[63]  C E Griffiths,et al.  Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis , 1999, The British journal of dermatology.

[64]  M. Gassmann,et al.  Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. , 1998, Genes & development.

[65]  J. Keski‐Oja,et al.  Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair. , 2002, The Journal of investigative dermatology.

[66]  S. Hirohashi,et al.  Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[67]  G. Koehl,et al.  Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor , 2002, Nature Medicine.

[68]  P. Carmeliet,et al.  Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis , 1998, Nature.

[69]  D. Gospodarowicz,et al.  VEGF receptor subtypes KDR and FLT1 show different sensitivities to heparin and placenta growth factor. , 1994, Growth factors.

[70]  Joseph B. Kearney,et al.  Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. , 2002, Blood.

[71]  S. Stacker,et al.  The vascular endothelial growth factor family; proteins which guide the development of the vasculature , 1998, International journal of experimental pathology.

[72]  I. Greer,et al.  Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre‐eclampsia , 1997, British journal of obstetrics and gynaecology.

[73]  A. Yuan,et al.  Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  C. Logothetis,et al.  Phase I trial of the angiogenesis inhibitor TNP-470 for progressive androgen-independent prostate cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[75]  Satoru Koyanagi,et al.  A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells. , 2003, Cancer research.

[76]  V. V. van Hinsbergh,et al.  Analysis of Coagulation Cascade and Endothelial Cell Activation During Inhibition of Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Pathway in Cancer Patients , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[77]  A. MacKenzie,et al.  The inhibitors of apoptosis (IAPs) and their emerging role in cancer , 1998, Oncogene.

[78]  R K Jain,et al.  Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. , 1998, The Journal of investigative dermatology.

[79]  D. Ruiter,et al.  Design of a Variant of Vascular Endothelial Growth Factor-A (VEGF-A) Antagonizing KDR/Flk-1 and Flt-1 , 2002, Laboratory Investigation.

[80]  S. S. Lee,et al.  Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. , 2001, Clinical and experimental rheumatology.

[81]  Steven A. Stacker,et al.  VEGF-D promotes the metastatic spread of tumor cells via the lymphatics , 2001, Nature Medicine.

[82]  R. Busse,et al.  Vascular endothelial growth factor activates nuclear factor-kappaB and induces monocyte chemoattractant protein-1 in bovine retinal endothelial cells. , 1999, Diabetes.

[83]  R Bicknell,et al.  Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. , 2000, Cancer research.

[84]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[85]  Masanori Tanaka,et al.  Microvessel Morphology and Vascular Endothelial Growth Factor Expression in Human Colonic Carcinoma With or Without Metastasis , 2002, Laboratory Investigation.

[86]  A. Mantovani,et al.  Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. , 1996, Blood.

[87]  Bruno C. Hancock,et al.  Suppression of Intestinal Polyposis in Apc Δ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2) , 1996, Cell.

[88]  J. Nelson,et al.  Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[89]  C. Wernstedt,et al.  Identification of Vascular Endothelial Growth Factor Receptor-1 Tyrosine Phosphorylation Sites and Binding of SH2 Domain-containing Molecules* , 1998, The Journal of Biological Chemistry.

[90]  Paul Martin,et al.  Wound Healing--Aiming for Perfect Skin Regeneration , 1997, Science.

[91]  M. Feldmann,et al.  Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. , 2001, Arthritis and rheumatism.

[92]  R. Jaffe,et al.  Angiogenesis in the human female reproductive tract. , 1995, Obstetrical & gynecological survey.

[93]  J. Winer,et al.  Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. , 1992, The Journal of biological chemistry.

[94]  M. Trikha,et al.  Platelets and Cancer: Implications for Antiangiogenic Therapy , 2002, Seminars in thrombosis and hemostasis.

[95]  R. Coffey,et al.  Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. , 1994, Gastroenterology.

[96]  J. Ware,et al.  Therapeutic Angiogenesis in Ischemic Heart Disease , 1999, Thrombosis and Haemostasis.

[97]  M. Toi,et al.  Tumor angiogenesis in breast cancer: Its importance as a prognostic indicator and the association with vascular endothelial growth factor expression , 2004, Breast Cancer Research and Treatment.

[98]  C. Dinney,et al.  Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[99]  G M Tozer,et al.  Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation. , 2000, European journal of cancer.

[100]  L. Fabri,et al.  Purification and refolding of vascular endothelial growth factor‐B , 2000, Protein science : a publication of the Protein Society.

[101]  Cynthia Cohen,et al.  Reactive oxygen generated by Nox1 triggers the angiogenic switch , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[102]  S. Arii,et al.  Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma , 2000, Cancer.

[103]  P. Campochiaro,et al.  Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. , 2000, The American journal of pathology.

[104]  E. Paleolog,et al.  New vessels, new approaches: angiogenesis as a therapeutic target in musculoskeletal disorders , 1999, International journal of experimental pathology.

[105]  J. Isner,et al.  Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. , 1998, Journal of vascular surgery.

[106]  T. Ishiwata,et al.  Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue. , 2002, The Journal of rheumatology.

[107]  Peter Bohlen,et al.  Complete inhibition of vascular endothelial growth factor (VEGF) activities with a bifunctional diabody directed against both VEGF kinase receptors, fms-like tyrosine kinase receptor and kinase insert domain-containing receptor. , 2001, Cancer research.

[108]  H. Fraser,et al.  Angiogenesis and its control in the female reproductive system. , 2000, British medical bulletin.

[109]  L. Water,et al.  VEGF expression by epithelial and stromal cell compartments: resolving a controversy. , 2000, The American journal of pathology.

[110]  E. Ingham,et al.  Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. , 1998, British Journal of Cancer.

[111]  S. Szabó,et al.  Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury. , 1998, The American journal of physiology.

[112]  M. Nomura,et al.  Placenta Growth Factor and Vascular Endothelial Growth Factor B and C Expression in Microvascular Endothelial Cells and Pericytes , 1999, The Journal of Biological Chemistry.

[113]  H. Dvorak Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. , 1986, The New England journal of medicine.

[114]  P. Carmeliet Mechanisms of angiogenesis and arteriogenesis , 2000, Nature Medicine.

[115]  D A Hilton,et al.  Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. , 1999, Cancer research.

[116]  G. Semenza,et al.  Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. , 2000, Genes & development.

[117]  A. Harris,et al.  The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[118]  U. Hellman,et al.  Differential Binding of Vascular Endothelial Growth Factor B Splice and Proteolytic Isoforms to Neuropilin-1* , 1999, The Journal of Biological Chemistry.

[119]  G. Stancel,et al.  Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen. , 1996, Cancer research.

[120]  G. Watanabe,et al.  Vascular endothelial growth factor expression in airways of patients with lung cancer: a possible diagnostic tool of responsive angiogenic status on the host side. , 2002, Chest.

[121]  J. Breed,et al.  Phase Ib 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. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[122]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[123]  D. Carbone,et al.  Vascular Endothelial Growth Factor Effects on Nuclear Factor-κB Activation in Hematopoietic Progenitor Cells , 2001 .

[124]  H. Hutchings,et al.  Signal relays in the VEGF system. , 1999, Frontiers in bioscience : a journal and virtual library.

[125]  J. Isner,et al.  Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[126]  S. Soker,et al.  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. , 1998, The Journal of biological chemistry.

[127]  N. Ferrara,et al.  A repressor sequence in the juxtamembrane domain of Flt‐1 (VEGFR‐1) constitutively inhibits vascular endothelial growth factor‐dependent phosphatidylinositol 3′‐kinase activation and endothelial cell migration , 2000, The EMBO journal.

[128]  S. Gately The Contributions of Cyclooxygenase-2 to Tumor Angiogenesis , 2004, Cancer and Metastasis Reviews.

[129]  J. Cherrington,et al.  The Antiangiogenic Agents SU5416 and SU6668 Increase the Antitumor Effects of Fractionated Irradiation , 2002, Radiation research.

[130]  D. Hicklin,et al.  Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. , 1999, Cancer research.

[131]  R. Bing Myocardial ischemia and infarction: growth of ideas. , 2001, Cardiovascular research.

[132]  A. Luttun,et al.  Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1 , 2002, Nature Medicine.

[133]  R. DuBois,et al.  Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[134]  D. Collins,et al.  Inhibition of angiogenesis by antiestrogens. , 1993, Cancer research.

[135]  R. Henriksson,et al.  Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[136]  K. Alitalo,et al.  Proinflammatory Cytokines Regulate Expression of the Lymphatic Endothelial Mitogen Vascular Endothelial Growth Factor-C* , 1998, The Journal of Biological Chemistry.

[137]  S. Fan,et al.  Clinical implications of circulating angiogenic factors in cancer patients. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[138]  R. Stouffer,et al.  Angiogenesis in ovarian follicular and luteal development. , 2000, Bailliere's best practice & research. Clinical obstetrics & gynaecology.

[139]  L. Presta,et al.  The second immunoglobulin‐like domain of the VEGF tyrosine kinase receptor Flt‐1 determines ligand binding and may initiate a signal transduction cascade. , 1996, The EMBO journal.

[140]  I. Zachary Vascular Endothelial Growth Factor: How It Transmits Its Signal , 1998, Nephron Experimental Nephrology.

[141]  C. Meuleman,et al.  Angiogenic activity of peritoneal fluid from women with endometriosis. , 1993, Fertility and sterility.

[142]  David R. Nadeau,et al.  Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[143]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[144]  Kenneth J. Hillan,et al.  Vascular endothelial growth factor is essential for corpus luteum angiogenesis , 1998, Nature Medicine.

[145]  Shigeyoshi Itohara,et al.  Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis , 2000, Nature Cell Biology.

[146]  L. Aiello,et al.  Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[147]  Sabita Roy,et al.  Targeting the tumor vasculature: Inhibition of tumor growth by a vascular endothelial growth factor‐toxin conjugate , 1997, International journal of cancer.

[148]  J. Cherrington,et al.  SU6668 inhibits Flk‐1/KDR and PDGFRβ in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[149]  J. Schlessinger,et al.  Identification of a novel contactin‐associated transmembrane receptor with multiple domains implicated in protein–protein interactions , 1997, The EMBO journal.

[150]  David E. Housman,et al.  Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours , 1996, Nature.

[151]  N. Tamura,et al.  Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. , 1998, Circulation.

[152]  L. Rubbia‐Brandt,et al.  Elevated levels of angiogenic cytokines in the plasma of cancer patients , 2000, International journal of cancer.

[153]  D. Gingras,et al.  The antiangiogenic agent neovastat (AE-941) inhibits vascular endothelial growth factor-mediated biological effects. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[154]  Interferon alfa‐2a therapy for life‐threatening hemangiomas of infancy , 1993, The New England journal of medicine.

[155]  Y. Hirata,et al.  Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. , 1997, Genomics.

[156]  U. Mirastschijski,et al.  Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds. , 2002, Human pathology.

[157]  Y. Okada,et al.  Expression of vascular endothelial growth factor isoforms and their receptors Flt‐1, KDR, and neuropilin‐1 in synovial tissues of rheumatoid arthritis , 2000, The Journal of pathology.

[158]  L. Nanney,et al.  Cell biology of wound healing. , 1996, International review of cytology.

[159]  M. Shibuya,et al.  A Novel Type of Vascular Endothelial Growth Factor, VEGF-E (NZ-7 VEGF), Preferentially Utilizes KDR/Flk-1 Receptor and Carries a Potent Mitotic Activity without Heparin-binding Domain* , 1998, The Journal of Biological Chemistry.

[160]  D. Carbone,et al.  Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. , 1999, Journal of immunology.

[161]  S. Rodan,et al.  Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. , 1994, The Journal of clinical investigation.

[162]  M A Konerding,et al.  Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. , 1999, Circulation.

[163]  E. Keshet,et al.  A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. , 1998, Development.

[164]  M. Pla,et al.  Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AGM-1470 in a transgenic mouse model of rheumatoid arthritis. , 2000, Arthritis and rheumatism.

[165]  J. Becker,et al.  A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth , 2002, Nature Network Boston.

[166]  S. Cory,et al.  The Bcl-2 protein family: arbiters of cell survival. , 1998, Science.

[167]  K. Alitalo,et al.  A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. , 1996, The EMBO journal.

[168]  M. Gassmann,et al.  Up-regulation of hypoxia-inducible factor-1alpha is not sufficient for hypoxic/anoxic p53 induction. , 1998, Cancer research.

[169]  Yung‐Chie Lee,et al.  Aberrant p53 expression correlates with expression of vascular endothelial growth factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[170]  G. Semenza,et al.  Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1 , 1996, Molecular and cellular biology.

[171]  F. Santilli,et al.  Role of Growth Factors in the Development of Diabetic Complications , 2000, Hormone Research in Paediatrics.

[172]  J. Caro,et al.  Hypoxia-inducible factor 1alpha (HIF-1alpha) is a non-heme iron protein. Implications for oxygen sensing. , 1998, The Journal of biological chemistry.

[173]  J. Isner,et al.  Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. , 1998, The American journal of pathology.

[174]  Peter Carmeliet,et al.  Molecular mechanisms of lymphangiogenesis in health and disease. , 2002, Cancer cell.

[175]  F. Selheim,et al.  Identification of functional VEGF receptors on human platelets , 2002, FEBS letters.

[176]  A J Warner,et al.  The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells. , 2000, The Biochemical journal.

[177]  M. Shibuya,et al.  VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells , 1999, Oncogene.

[178]  Shay Soker,et al.  Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor , 1998, Cell.

[179]  K. Alitalo,et al.  Signalling properties of FLT4, a proteolytically processed receptor tyrosine kinase related to two VEGF receptors. , 1994, Oncogene.

[180]  D. Walsh,et al.  Angiogenesis and arthritis. , 1999, Rheumatology.

[181]  A. Hsu,et al.  The Cyclooxygenase-2 Inhibitor Celecoxib Induces Apoptosis by Blocking Akt Activation in Human Prostate Cancer Cells Independently of Bcl-2* , 2000, The Journal of Biological Chemistry.

[182]  A. Ristimäki,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Differential Hormonal Regulation of Vascular Endothelial Growth Factors VEGF, VEGF-B, and VEGF-C Messenger Ribonucleic Acid Levels in Cultured Human , 2022 .

[183]  K. Alitalo,et al.  Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium. , 2002, The Journal of rheumatology.

[184]  G. Strassmann,et al.  Potential involvement of IL-10 in suppressing tumor-associated macrophages. Colon-26-derived prostaglandin E2 inhibits TNF-alpha release via a mechanism involving IL-10. , 1995, Journal of immunology.

[185]  Napoleone Ferrara,et al.  Clinical applications of angiogenic growth factors and their inhibitors , 1999, Nature Medicine.

[186]  D. Marmé,et al.  Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease , 1999, Cancer.

[187]  A. Harris,et al.  Relation of vascular endothelial growth factor production to expression and regulation of hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in human bladder tumors and cell lines. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[188]  A. Harris,et al.  PROGNOSTIC VALUE OF ANGIOGENESIS IN OPERABLE NON‐SMALL CELL LUNG CANCER , 1996, The Journal of pathology.

[189]  A. Harris,et al.  The angiogenic pathway ‘vascular endothelial growth factor/flk‐1(KDR)‐receptor’ in rheumatoid arthritis and osteoarthritis , 2001, The Journal of pathology.

[190]  E. Levin,et al.  Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome. , 1998, The Journal of clinical investigation.

[191]  S H Lee,et al.  Early expression of angiogenesis factors in acute myocardial ischemia and infarction. , 2000, The New England journal of medicine.

[192]  Shay Soker,et al.  Relative effects of VEGF‐A and VEGF‐C on endothelial cell proliferation, migration and PAF synthesis: Role of neuropilin‐1 , 2002, Journal of cellular biochemistry.

[193]  J. Vaillant,et al.  Vegf, vegf‐B, vegf‐C and their receptors KDR, FLT‐1 and FLT‐4 during the neoplastic progression of human colonic mucosa , 2000, International journal of cancer.

[194]  W. Sessa,et al.  Regulation of endothelium-derived nitric oxide production by the protein kinase Akt , 1999, Nature.

[195]  R K Jain,et al.  Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha--> hypoxia response element--> VEGF cascade differentially regulates vascular response and growth rate in tumors. , 2000, Cancer research.

[196]  H. Fujii,et al.  Correlation of Vascular Endothelial Growth Factor-C Expression with Tumor-Infiltrating Dendritic Cells in Gastric Cancer , 2002, Oncology.

[197]  S. Hunt Technology evaluation: IMC-1C11, ImClone Systems. , 2001, Current opinion in molecular therapeutics.

[198]  S. Ylä-Herttuala,et al.  Gene therapy for therapeutic angiogenesis in critically ischaemic lower limb – on the way to the clinic , 2001, European journal of clinical investigation.

[199]  L. Orci,et al.  Vascular endothelial growth factor‐C‐mediated lymphangiogenesis promotes tumour metastasis , 2001, The EMBO journal.

[200]  O. Cussenot,et al.  VEGF overexpression in clinically localized prostate tumors and neuropilin‐1 overexpression in metastatic forms , 2000, International journal of cancer.

[201]  K. Alitalo,et al.  Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[202]  J. Pober,et al.  Control of apoptosis during angiogenesis by survivin expression in endothelial cells. , 2000, The American journal of pathology.

[203]  W. Parks,et al.  Epilysin, a Novel Human Matrix Metalloproteinase (MMP-28) Expressed in Testis and Keratinocytes and in Response to Injury* , 2001, The Journal of Biological Chemistry.

[204]  Leonard,et al.  Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. , 1997, Cancer research.

[205]  J. Monson,et al.  Pre-operative serum vascular endothelial growth factor can select patients for adjuvant treatment after curative resection in colorectal cancer , 2000, British Journal of Cancer.

[206]  Y. Matsumura,et al.  TAp63γ (p51A) and dNp63α (p73L), two major isoforms of the p63 gene, exert opposite effects on the vascular endothelial growth factor (VEGF) gene expression , 2002, Oncogene.

[207]  Barbara Mayer,et al.  Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[208]  K. Alitalo,et al.  A novel vascular endothelial growth factor, VEGF‐C, is a ligand for the Flt4 (VEGFR‐3) and KDR (VEGFR‐2) receptor tyrosine kinases. , 1996, The EMBO journal.

[209]  H. Dvorak,et al.  Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. , 1992, Molecular biology of the cell.

[210]  D. Hallahan,et al.  Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. , 2001, Cancer research.

[211]  Y. Sasaki,et al.  Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[212]  Josef Korinek,et al.  Proceedings of the American Society of Clinical Oncology , 1982 .

[213]  R K Jain,et al.  Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor. , 1999, Cancer research.

[214]  D. Papamichael Prognostic role of angiogenesis in colorectal cancer. , 2001, Anticancer research.

[215]  M. Dake,et al.  Vascular endothelial growth factor enhances atherosclerotic plaque progression , 2001, Nature Medicine.

[216]  J. Folkman,et al.  How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. , 1986, Cancer research.

[217]  R. Ali,et al.  Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1 , 2002, Gene Therapy.

[218]  D. Carbone,et al.  Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. , 1998, Journal of immunology.

[219]  Megumi Baba,et al.  Anti‐tumor and anti‐metastatic effects of human‐vascular‐endothelial‐growth‐factor‐neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice , 1998, International journal of cancer.

[220]  M. Longaker,et al.  Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes. , 1995, The Journal of Biological Chemistry.

[221]  J. Minna,et al.  Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. , 2000, Cancer research.

[222]  C. Angeletti,et al.  Bcl2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma. , 1998, European journal of cancer.

[223]  Till Acker,et al.  Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration , 2001, Nature Genetics.

[224]  H. Joensuu,et al.  Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[225]  W. Jelkmann,et al.  Prediction of severe ovarian hyperstimulation syndrome by free serum vascular endothelial growth factor concentration on the day of human chorionic gonadotrophin administration. , 1999, Human reproduction.

[226]  K. Alitalo,et al.  Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. , 2000, The American journal of pathology.

[227]  A. Giaccia,et al.  Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. , 1997, Blood.

[228]  J. M. Arbeit,et al.  Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. , 2000, Cancer research.

[229]  F. Dieterlen‐Lièvre,et al.  Blood-borne seeding by hematopoietic and endothelial precursors from the allantois. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[230]  J. Isner Myocardial gene therapy , 2002, Nature.

[231]  B. Echtenacher,et al.  Lysis of tumor cells by natural killer cells in mice is impeded by platelets. , 1999, Cancer research.

[232]  A. Genazzani,et al.  Changes in vascular endothelial growth factor levels and the risk of ovarian hyperstimulation syndrome in women enrolled in an in vitro fertilization program. , 1998, Fertility and sterility.

[233]  A. Harris,et al.  Relationship of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines. , 2000, Cancer research.

[234]  Y. Maehara,et al.  Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues , 2000, British Journal of Cancer.

[235]  G. Neufeld,et al.  VEGF145, a Secreted Vascular Endothelial Growth Factor Isoform That Binds to Extracellular Matrix* , 1997, The Journal of Biological Chemistry.

[236]  H. Ryan,et al.  HIF-1 alpha is required for solid tumor formation and embryonic vascularization. , 1998, The EMBO journal.

[237]  L. Ellis,et al.  Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. , 1998, Cancer research.

[238]  G. Palade,et al.  Neovasculature induced by vascular endothelial growth factor is fenestrated. , 1997, Cancer research.

[239]  H. Verheul,et al.  Platelet: transporter of vascular endothelial growth factor. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[240]  R. Kerbel,et al.  Possible Mechanisms of Acquired Resistance to Anti-angiogenic Drugs: Implications for the Use of Combination Therapy Approaches , 2004, Cancer and Metastasis Reviews.

[241]  Xuri Li,et al.  Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D. , 2001, The international journal of biochemistry & cell biology.

[242]  K. Alitalo,et al.  Vascular endothelial growth factor B, a novel growth factor for endothelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[243]  L. Aiello,et al.  Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. , 1999, Diabetes.

[244]  F. Bayard,et al.  Extracellular Cleavage of the Vascular Endothelial Growth Factor 189-Amino Acid Form by Urokinase Is Required for Its Mitogenic Effect* , 1997, The Journal of Biological Chemistry.

[245]  J C Reed,et al.  IAP family proteins--suppressors of apoptosis. , 1999, Genes & development.

[246]  H. Dvorak,et al.  Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis , 1994, The Journal of experimental medicine.

[247]  H. Dvorak,et al.  Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. , 1989, Biochimica et biophysica acta.

[248]  Makoto Murakami,et al.  Regulation of Prostaglandin E2 Biosynthesis by Inducible Membrane-associated Prostaglandin E2 Synthase That Acts in Concert with Cyclooxygenase-2* , 2000, The Journal of Biological Chemistry.

[249]  P. Hahnfeldt,et al.  Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us. , 2002, Journal of the National Cancer Institute.

[250]  J. Gallo,et al.  Cells designed to deliver anticancer drugs by apoptosis. , 2002, Cancer research.

[251]  R. Eisenstein Angiogenesis in arteries: review. , 1991, Pharmacology & therapeutics.

[252]  D. Hanahan,et al.  Tumor-derived expression of vascular endothelial growth factor is a critical factor in tumor expansion and vascular function. , 1999, Cancer research.

[253]  M. Moses,et al.  HIF-1alpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis. , 2001, Cancer research.

[254]  C. Thompson,et al.  Phosphatidylinositol 3-Kinase/Akt Signaling Is Neither Required for Hypoxic Stabilization of HIF-1α nor Sufficient for HIF-1-dependent Target Gene Transcription* , 2002, The Journal of Biological Chemistry.

[255]  H. Cai,et al.  Cloning and Characterization of Neuropilin-1-Interacting Protein: A PSD-95/Dlg/ZO-1 Domain-Containing Protein That Interacts with the Cytoplasmic Domain of Neuropilin-1 , 1999, The Journal of Neuroscience.

[256]  M. Karkkainen,et al.  Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. , 2001, Cancer research.

[257]  Cherrington,et al.  SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. , 2000, Cancer research.

[258]  B. Olffson Vascular endothelial grouth facter B, a novel growth facter for endothelial cells , 1996 .

[259]  A. Lassar,et al.  Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. , 1994, Current opinion in cell biology.

[260]  K. Seibert,et al.  COX‐2 Inhibitors: A New Class of Antiangiogenic Agents , 1999, Annals of the New York Academy of Sciences.

[261]  B Z Levi,et al.  VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells , 1995, The Journal of Biological Chemistry.

[262]  M. Highley,et al.  Immuno affinity purification combined with mass spectrometry detection for the monitoring of VEGF isoforms in patient tumor tissue , 2003 .

[263]  M. Shibuya,et al.  Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. , 1994, The Journal of biological chemistry.

[264]  Bing Li,et al.  Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo , 1993, Nature.

[265]  L. Mayo,et al.  VRAP Is an Adaptor Protein That Binds KDR, a Receptor for Vascular Endothelial Cell Growth Factor* , 2000, The Journal of Biological Chemistry.

[266]  D. Pode,et al.  Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. , 1999, The Journal of clinical investigation.

[267]  L. Aiello,et al.  Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. , 1994, The New England journal of medicine.

[268]  K. Alitalo,et al.  Vascular endothelial growth factor-C and its receptor VEGFR-3 in the nasal mucosa and in nasopharyngeal tumors. , 2000, The American journal of pathology.

[269]  M. Shibuya,et al.  Vascular Endothelial Growth Factor Is Necessary in the Development of Arteriosclerosis by Recruiting/Activating Monocytes in a Rat Model of Long-Term Inhibition of Nitric Oxide Synthesis , 2002, Circulation.

[270]  A. Stopeck,et al.  Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[271]  K Walsh,et al.  Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. , 1998, Circulation.

[272]  M. Droller Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. , 2000, The Journal of urology.

[273]  K. Alitalo,et al.  Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia , 1997, Oncogene.

[274]  K. Honn,et al.  Adhesion molecules and tumor metastasis: an update. , 1994, Invasion & metastasis.

[275]  D. Charnock-Jones,et al.  Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. , 1996, The Journal of clinical investigation.

[276]  K. Alitalo,et al.  VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. , 1999, The American journal of pathology.

[277]  R. Stouffer,et al.  Vascular endothelial growth factor levels in serum and follicular fluid of patients undergoing in vitro fertilization. , 1997, Fertility and sterility.

[278]  G. Neufeld,et al.  Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. , 1993, The Journal of clinical investigation.

[279]  S. Chakrabarti,et al.  Role of vasoactive factors in the pathogenesis of early changes in diabetic retinopathy , 2000, Diabetes/metabolism research and reviews.

[280]  S. Baruchel,et al.  Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. , 2000, The Journal of clinical investigation.

[281]  G. Stancel,et al.  Regulation of angiogenic growth factors in the female reproductive tract by estrogens and progestins. , 1999, Molecular endocrinology.

[282]  S. Kawashima,et al.  Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus , 1999, The British journal of ophthalmology.

[283]  M. Shibuya,et al.  A single autophosphorylation site on KDR/Flk‐1 is essential for VEGF‐A‐dependent activation of PLC‐γ and DNA synthesis in vascular endothelial cells , 2001, The EMBO journal.

[284]  G. Neufeld,et al.  Vascular endothelial growth factor (VEGF) and its receptors , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[285]  D. Carbone,et al.  Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[286]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[287]  T. Sawada,et al.  Prognostic value of vascular endothelial growth factor expression in gastric carcinoma , 1996, Cancer.

[288]  D J Mooney,et al.  Up-Regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. , 2001, Cancer research.

[289]  N. Ahn,et al.  Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. , 2000, Cancer Research.

[290]  G. Zimmerman,et al.  Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[291]  P Lavie,et al.  Interindividual heterogeneity in the hypoxic regulation of VEGF: significance for the development of the coronary artery collateral circulation. , 1999, Circulation.

[292]  H. Esumi,et al.  Regulation of vascular endothelial growth factor expression by insulin‐like growth factor‐I in endometrial adenocarcinoma cells , 2000, International journal of cancer.