Antiangiogenic peptides and proteins: From experimental tools to clinical drugs

Hanahan, 2000, The hallmarks of cancer, Cell, 100, 57, 10.1016/S0092-8674(00)81683-9 Folkman, 2000, Cancer: looking outside the genome, Nat. Rev., Mol. Cell Biol., 1, 76, 10.1038/35036100 De Wever, 2003, Role of tissue stroma in cancer cell invasion, J. Pathol., 200, 429, 10.1002/path.1398 Folkman, 1971, Tumor angiogenesis: therapeutic implications, N. Engl. J. Med., 285, 1182, 10.1056/NEJM197111182852108 Carmeliet, 2000, Angiogenesis in cancer and other diseases, Nature, 407, 249, 10.1038/35025220 Holmgren, 1995, Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression, Nat. Med., 1, 149, 10.1038/nm0295-149 Fidler, 2000, Angiogenesis and cancer metastasis, Cancer J., 6, 134 Achen, 2005, Focus on lymphangiogenesis in tumor metastasis, Cancer Cell, 7, 121, 10.1016/j.ccr.2005.01.017 Folkman, 2002, Role of angiogenesis in tumor growth and metastasis, Semin. Oncol., 29, 15, 10.1053/sonc.2002.37263 Carmeliet, 2003, Angiogenesis in health and disease, Nat. Med., 9, 653, 10.1038/nm0603-653 Cavallaro, 2000, Molecular mechanisms of tumor angiogenesis and tumor progression, J. Neuro-Oncol., 50, 63, 10.1023/A:1006414621286 Ruegg, 2003, Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis, Cell. Mol. Life Sci., 60, 1135, 10.1007/s00018-003-2297-3 Bicknell, 2004, Novel angiogenic signaling pathways and vascular targets, Annu. Rev. Pharmacol. Toxicol., 44, 219, 10.1146/annurev.pharmtox.44.101802.121650 Autiero, 2005, Role of neural guidance signals in blood vessel navigation, Cardiovasc. Res., 65, 629, 10.1016/j.cardiores.2004.09.013 Neufeld, 2005, Semaphor ins in cancer, Front. Biosci., 10, 751, 10.2741/1569 Chen, 2005, Roles of neuropilins in neuronal development, angiogenesis, and cancers, World J. Surg., 29, 271, 10.1007/s00268-004-7818-1 Carmeliet, 2005, Common mechanisms of nerve and blood vessel wiring, Nature, 436, 193, 10.1038/nature03875 Eichmann, 2005, Guidance of vascular and neural network formation, Curr. Opin. Neurobiol., 15, 108, 10.1016/j.conb.2005.01.008 Acevedo, 2004, A new role for Nogo as a regulator of vascular remodeling, Nat. Med., 10, 382, 10.1038/nm1020 Raines, 2004, Nogo puts the brake on vascular lesions, Nat. Med., 10, 348, 10.1038/nm0404-348 Karkkainen, 2002, Lymphatic endothelium: a new frontier of metastasis research, Nat. Cell Biol., 4, E2, 10.1038/ncb0102-e2 Alitalo, 2002, Molecular mechanisms of lymphangiogenesis in health and disease, Cancer Cell, 1, 219, 10.1016/S1535-6108(02)00051-X Makinen, 2002, Molecular mechanisms of lymphangiogenesis, Cold Spring Harbor Symp. Quant. Biol., 67, 189, 10.1101/sqb.2002.67.189 Lohela, 2003, Lymphangiogenic growth factors, receptors and therapies, Thromb. Haemost., 90, 167, 10.1160/TH03-04-0200 Tammela, 2005, Molecular lymphangiogenesis: new players, Trends Cell Biol., 15, 434, 10.1016/j.tcb.2005.06.004 He, 2004, Role of lymphangiogenic factors in tumor metastasis, Biochim. Biophys. Acta, 1654, 3 Saharinen, 2004, Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation, Trends Immunol., 25, 387, 10.1016/j.it.2004.05.003 Nisato, 2003, Lymphangiogenesis and tumor metastasis, Thromb. Haemost., 90, 591, 10.1160/TH03-04-0206 Tille, 2004, Lymphangiogenesis and tumour metastasis, Novartis Found. Symp., 256, 112, 10.1002/0470856734.ch9 Stacker, 2004, Lymphangiogenic growth factors as markers of tumor metastasis, APMIS, 112, 539, 10.1111/j.1600-0463.2004.apm11207-0812.x Folkman, 1992, Inhibition of angiogenesis, Semin. Cancer Biol., 3, 89 Ingber, 1990, Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth, Nature, 348, 555, 10.1038/348555a0 Kerbel, 2002, Clinical translation of angiogenesis inhibitors, Nat. Rev., Cancer, 2, 727, 10.1038/nrc905 Rüegg, 2003, Translational research in tumor angiogenesis: from bench to bedside and back to the bench, Bull. Suisse Cancer, 23, 3 Bouma-ter Steege, 2001, Angiostatic proteins and peptides, Crit. Rev. Eukaryot. Gene Expr., 11, 319 Carswell, 1975, An endotoxin-induced serum factor that causes necrosis of tumors, Proc. Natl. Acad. Sci. U. S. A., 72, 3666, 10.1073/pnas.72.9.3666 Aggarwal, 1996, Tumor necrosis factors: developments during the last decade, Eur. Cytokine Netw., 7, 93 Moss, 1997, Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha, Nature, 385, 733, 10.1038/385733a0 Black, 1997, A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells, Nature, 385, 729, 10.1038/385729a0 Wallach, 1999, Tumor necrosis factor receptor and Fas signaling mechanisms, Annu. Rev. Immunol., 17, 331, 10.1146/annurev.immunol.17.1.331 Lienard, 1992, High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma, J. Clin. Oncol., 10, 52, 10.1200/JCO.1992.10.1.52 Lejeune, 1998, Clinical applications of TNF-alpha in cancer, Curr. Opin. Immunol., 10, 573, 10.1016/S0952-7915(98)80226-4 Ruegg, 2000, Tumor necrosis factor: clinical use and mechanisms of action, Drug Resist. Updat., 3, 271, 10.1054/drup.2000.0154 Folli, 1993, Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability, Int. J. Cancer, 53, 829, 10.1002/ijc.2910530521 van der Veen, 2000, TNF-alpha augments intratumoural concentrations of doxorubicin in TNF-alpha-based isolated limb perfusion in r at sarcoma models and enhances anti-tumour effects, Br. J. Cancer, 82, 973, 10.1054/bjoc.1999.1027 Blum, 1997, Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines, Am. J. Physiol., 273, H286 Petrache, 2003, The role of the microtubules in tumor necrosis factor-alpha-induced endothelial cell permeability, Am. J. Respir. Cell Mol. Biol., 28, 574, 10.1165/rcmb.2002-0075OC Romer, 1995, IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells, J. Immunol., 154, 6582, 10.4049/jimmunol.154.12.6582 Lampugnani, 1992, A novel endothelial-specific membrane protein is a marker of cell–cell contacts, J. Cell Biol., 118, 1511, 10.1083/jcb.118.6.1511 Ruegg, 1998, Evidence for the involvement of endothelial cell integrin alpha-v-beta-3 in the disruption of the tumor vasculature induced by tnf and ifn-gamma, Nat. Med., 4, 408, 10.1038/nm0498-408 Halin, 2003, Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to inter leukin 12 and to tumor necrosis factor alpha, Cancer Res., 63, 3202 Curnis, 2002, Improving chemotherapeutic drug penetration in tumors by vascular targeting and barrier alteration, J. Clin. Invest., 110, 475, 10.1172/JCI0215223 Lejeune, 2002, Clinical use of TNF revisited: improving penetration of anti-cancer agents by increasing vascular permeability, J. Clin. Invest., 110, 433, 10.1172/JCI0216493 Zhai, 1999, VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo, FASEB J., 13, 181, 10.1096/fasebj.13.1.181 Ezekowitz, 1992, Interferon alfa-2a therapy for life-threatening hemangiomas of infancy, N. Engl. J. Med., 326, 1456, 10.1056/NEJM199205283262203 Hong, 2000, Efficient inhibition of in vivo human malignant glioma growth and angiogenesis by interferon-beta treatment at early stage of tumor development, Clin. Cancer Res., 6, 3354 Dinney, 1998, Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration, Cancer Res., 58, 808 Watanabe, 1988, Antitumor synergism between recombinant human tumor necrosis factor and recombinant human interferon-r, J. Biol. Response Modif., 7, 24 Kohno, 2003, Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer, Cancer Res., 63, 5091 Cervenak, 2000, Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10, Blood, 96, 2568, 10.1182/blood.V96.7.2568 Stearns, 1999, Interleukin 10 (IL-10) inhibition of primary human prostate cell-induced angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and inhibition of matrix metalloproteinase (MMP)-2/MMP-9 secretion, Clin. Cancer Res., 5, 189 Voest, 1995, Inhibition of angiogenesis in vivo by interleukin 12, J. Natl. Cancer Inst., 87, 581, 10.1093/jnci/87.8.581 Strasly, 2001, IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk, J. Immunol., 166, 3890, 10.4049/jimmunol.166.6.3890 Mitola, 2003, IL-12 regulates an endothelial cell-lymphocyte network: effect on metalloproteinase-9 production, J. Immunol., 171, 3725, 10.4049/jimmunol.171.7.3725 Wong, 2004, Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12, Clin. Cancer Res., 10, 4509, 10.1158/1078-0432.CCR-04-0081 Baggiolini, 1997, Human chemokines: an update, Annu. Rev. Immunol., 15, 675, 10.1146/annurev.immunol.15.1.675 Balkwill, 2003, Chemokine biology in cancer, Semin. Immunol., 15, 49, 10.1016/S1044-5323(02)00127-6 Romagnani, 2004, CXC chemokines: the regulatory link between inflammation and angiogenesis, Trends Immunol., 25, 201, 10.1016/j.it.2004.02.006 Rosenkilde, 2004, The chemokine system—A major regulator of angiogenesis in health and disease, APMIS, 112, 481, 10.1111/j.1600-0463.2004.apm11207-0808.x Daly, 1995, High activity suppression of myeloid progenitor proliferation by chimeric mutants of interleukin 8 and platelet factor 4, J. Biol. Chem., 270, 23282, 10.1074/jbc.270.40.23282 Lasagni, 2003, An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4, J. Exp. Med., 197, 1537, 10.1084/jem.20021897 Perollet, 1998, Platelet factor 4 modulates fibroblast growth factor 2 (FGF-2) activity and inhibits FGF-2 dimerization, Blood, 91, 3289, 10.1182/blood.V91.9.3289 Jouan, 1999, Inhibition of in vitro angiogenesis by platelet factor-4-derived peptides and mechanism of action, Blood, 94, 984, 10.1182/blood.V94.3.984.415k31_984_993 Bikfalvi, 2004, The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules, Semin. Thromb. Hemost., 30, 137, 10.1055/s-2004-822978 Gengrinovitch, 1995, Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms, J. Biol. Chem., 270, 15059, 10.1074/jbc.270.25.15059 Neville, 1997, The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C–X–C chemokine superfamily, Cytokine Growth Factor Rev., 8, 207, 10.1016/S1359-6101(97)00015-4 Yang, 2004, The angiostatic activity of interferon-inducible protein-10/ CXCL10 in human melanoma depends on binding to CXCR3 but not to glycosaminoglycan, Mol. Ther., 9, 846, 10.1016/j.ymthe.2004.01.010 Sgadari, 1996, Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10, Blood, 87, 3877, 10.1182/blood.V87.9.3877.bloodjournal8793877 Cao, 2001, Interferon-inducible protein 10 induction and inhibition of angiogenesis in vivo by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), Cancer Res., 61, 1517 Arenberg, 1996, Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases, J. Exp. Med., 184, 981, 10.1084/jem.184.3.981 Feldman, 2002, Retroviral gene transfer of interferon inducible protein 10 inhibits growth of human melanoma xenografts, Int. J. Cancer, 99, 149, 10.1002/ijc.10292 Regulier, 2001, Adenovirus-mediated delivery of antiangiogenic genes as an antitumor approach, Cancer Gene Ther., 8, 45, 10.1038/sj.cgt.7700278 Shellenberger, 2004, BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells, Cancer Res., 64, 8262, 10.1158/0008-5472.CAN-04-2056 Frazier, 1991, Thrombospondins, Curr. Opin. Cell Biol., 3, 792, 10.1016/0955-0674(91)90052-Z Bornstein, 1992, Thrombospondins: structure and regulation of expression, FASEB J., 6, 3290, 10.1096/fasebj.6.14.1426766 Asch, 1993, Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain, Science, 262, 1436, 10.1126/science.7504322 Dawson, 1997, CD36 mediates the in vitro inhibitory effects of thrombospondin-1 on endothelial cells, J. Cell Biol., 138, 707, 10.1083/jcb.138.3.707 Lagadec, 2003, Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow, Blood, 101, 4836, 10.1182/blood-2002-11-3483 Patel, 1997, Thrombospondin-1 is a potent mitogen and chemoattractant for human vascular smooth muscle cells, Arterioscler. Thromb. Vasc. Biol., 17, 2107, 10.1161/01.ATV.17.10.2107 Nicosia, 1994, Matrix-bound thrombospondin promotes angiogenesis in vitro, J. Cell Biol., 124, 183, 10.1083/jcb.124.1.183 Vailhe, 2003, Thrombospondins as anti-angiogenic therapeutic agents, Curr. Pharm. Des., 9, 583, 10.2174/1381612033391342 Iruela-Arispe, 2004, Thrombospondin modules and angiogenesis, Int. J. Biochem. Cell Biol., 36, 1070, 10.1016/j.biocel.2004.01.025 Lymn, 1999, Phosphatidylinositol 3-kinase and focal adhesion kinase are early signals in the growth factor-like responses to thrombospondin-1 seen in human vascular smooth muscle, Arterioscler. Thromb. Vasc. Biol., 19, 2133, 10.1161/01.ATV.19.9.2133 Chen, 2000, The cell biology of thrombospondin-1, Matrix Biol., 19, 597, 10.1016/S0945-053X(00)00107-4 Volpert, 2000, Modulation of endothelial cell survival by an inhibitor of angiogenesis thrombospondin-1: a dynamic balance, Cancer Metastasis Rev., 19, 87, 10.1023/A:1026560618302 Nor, 2000, Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway, J. Vasc. Res., 37, 209, 10.1159/000025733 Simantov, 2003, CD36: a critical anti-angiogenic receptor, Front. Biosci., 8, s874, 10.2741/1168 Freyberg, 2000, Integrin-associated protein and thrombospondin-1 as endothelial mechanosensitive death mediators, Biochem. Biophys. Res. Commun., 271, 584, 10.1006/bbrc.2000.2678 Noh, 2003, An N-terminal 80 kDa recombinant fragment of human thrombospondin-2 inhibits vascular endothelial growth factor induced endothelial cell migration in vitro and tumor growth and angiogenesis in vivo, J. Invest. Dermatol., 121, 1536, 10.1046/j.1523-1747.2003.12643.x Haviv, 2005, Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities, J. Med. Chem., 48, 2838, 10.1021/jm0401560 O'Reilly, 1994, Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma, Cell, 79, 315, 10.1016/0092-8674(94)90200-3 Folkman, 1995, Angiogenesis inhibitors generated by tumors, Mol. Med., 1, 120, 10.1007/BF03401559 O'Reilly, 1996, Angiostatin induces and sustains dormancy of human primary tumor sin mice, Nat. Med., 2, 689, 10.1038/nm0696-689 Soff, 2000, Angiostatin and angiostatin-related proteins, Cancer Metastasis Rev., 19, 97, 10.1023/A:1026525121027 Beerepoot, 2003, Recombinant human angiostatin by twice-daily subcutaneous injection in advanced cancer: a pharmacokinetic and long-term safety study, Clin. Cancer Res., 9, 4025 O'Reilly, 1997, Endostatin: an endogenous inhibitor of angiogenesis and tumor growth, Cell, 88, 277, 10.1016/S0092-8674(00)81848-6 Sorensen, 2002, Delivery of endostatin in experimental cancer therapy, Int. J. Exp. Pathol., 83, 265, 10.1046/j.1365-2613.2002.00240.x Herbst, 2002, Phase I study of recombinant human endostatin in patients with advanced solid tumors, J. Clin. Oncol., 20, 3792, 10.1200/JCO.2002.11.061 Hansma, 2005, Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer, Ann. Oncol., 16, 1695, 10.1093/annonc/mdi318 Wickstrom, 2002, Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells, Cancer Res., 62, 5580 Wickstrom, 2003, Endostatin associates with lipid rafts and induces reorganization of the actin cytoskeleton via down-regulation of RhoA activity, J. Biol. Chem., 278, 37895, 10.1074/jbc.M303569200 Wickstrom, 2005, Endostatin signaling and regulation of endothelial cell–matrix interactions, Adv. Cancer Res., 94, 197, 10.1016/S0065-230X(05)94005-0 Sasaki, 1999, Structural basis and potential role of heparin/heparan sulfate binding to the angiogenesis inhibitor endostatin, EMBO J., 18, 6240, 10.1093/emboj/18.22.6240 Karihaloo, 2001, Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud, Proc. Natl. Acad. Sci. U. S. A., 98, 12509, 10.1073/pnas.221205198 Kreuger, 2002, Role of heparan sulfate domain organization in endostatin inhibition of endothelial cell function, EMBO J., 21, 6303, 10.1093/emboj/cdf638 Olsson, 2004, The minimal active domain of endostatin is a heparin-binding motif that mediates inhibition of tumor vascularization, Cancer Res., 64, 9012, 10.1158/0008-5472.CAN-04-2172 Karumanchi, 2001, Cell surface glypicans are low-affinity endostatin receptors, Mol. Cell, 7, 811, 10.1016/S1097-2765(01)00225-8 Hanai, 2002, Endostatin is a potential inhibitor of Wnt signaling, J. Cell Biol., 158, 529, 10.1083/jcb.200203064 Hanai, 2002, Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1, J. Biol. Chem., 277, 16464, 10.1074/jbc.M112274200 Maeshima, 2000, Distinct antitumor properties of a type IV collagen domain derived from basement membrane, J. Biol. Chem., 275, 21340, 10.1074/jbc.M001956200 Maeshima, 2001, Identification of the anti-angiogenic site within vascular basement membrane-derived tumstatin, J. Biol. Chem., 276, 15240, 10.1074/jbc.M007764200 Maeshima, 2002, Tumstatin, an endothelial cell-specific inhibitor of protein synthesis, Science, 295, 140, 10.1126/science.1065298 Kaur, 2005, Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor, Oncogene, 24, 3632, 10.1038/sj.onc.1208317 Rehn, 2001, Interaction of endostatin with integrins implicated in angiogenesis, Proc. Natl. Acad. Sci. U. S. A., 98, 1024, 10.1073/pnas.031564998 Sudhakar, 2003, Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins, Proc. Natl. Acad. Sci. U. S. A., 100, 4766, 10.1073/pnas.0730882100 Bix, 2005, Matrix revolutions: “tails” of basement-membrane components with angiostatic functions, Trends Cell Biol., 15, 52, 10.1016/j.tcb.2004.11.008 Eder, 2002, Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily, J. Clin. Oncol., 20, 3772, 10.1200/JCO.2002.02.082 Dell'Eva, 2002, Inhibition of tumor angiogenesis by angiostatin: from recombinant protein to gene therapy, Endothelium, 9, 3, 10.1080/10623320210712 Folkman, 2004, Endogenous angiogenesis inhibitors, APMIS, 112, 496, 10.1111/j.1600-0463.2004.apm11207-0809.x Nyberg, 2005, Endogenous inhibitors of angiogenesis, Cancer Res., 65, 3967, 10.1158/0008-5472.CAN-04-2427 Abdollahi, 2005, Endostatin: the logic of antiangiogenic therapy, Drug Resist. Updat., 8, 59, 10.1016/j.drup.2005.03.001 Cao, 2004, Angiostatin, Semin. Thromb. Hemost., 30, 83, 10.1055/s-2004-822973 Shibuya, 2001, Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1), Int. J. Biochem. Cell Biol., 33, 409, 10.1016/S1357-2725(01)00026-7 Shibuya, 1995, Role of VEGF-flt receptor system in normal and tumor angiogenesis, Adv. Cancer Res., 67, 281, 10.1016/S0065-230X(08)60716-2 Lin, 1998, Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor, Cell Growth Differ., 9, 49 Chen, 2000, Inhibition of vascular endothelial growth factor activity by transfection with the soluble FLT-1 gene, J. Cardiovasc. Pharmacol., 36, 498, 10.1097/00005344-200010000-00013 Lai, 2001, Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization, Hum. Gene Ther., 12, 1299, 10.1089/104303401750270959 Hasumi, 2002, Soluble FLT-1 expression suppresses carcinomatous ascites in nude mice bearing ovarian cancer, Cancer Res., 62, 2019 Ye, 2004, sFlt-1 gene therapy of follicular thyroid carcinoma, Endocrinology, 145, 817, 10.1210/en.2003-1106 Kou, 2004, In vivo inhibition of tumor angiogenesis by a soluble VEGFR-2 fragment, Exp. Mol. Pathol., 76, 129, 10.1016/j.yexmp.2003.10.010 Gerber, 2000, Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor, Cancer Res., 60, 6253 Holash, 2002, VEGF-Trap: a VEGF blocker with potent antitumor effects, Proc. Natl. Acad. Sci. U. S. A., 99, 11393, 10.1073/pnas.172398299 Huang, 2003, Regression of established tumors and metastases by potent vascular endothelial growth factor blockade, Proc. Natl. Acad. Sci. U. S. A., 100, 7785, 10.1073/pnas.1432908100 Konner, 2004, Use of soluble recombinant decoy receptor vascular endothelial growth factor trap (VEGF Trap) to inhibit vascular endothelial growth factor activity, Clin. Colorectal Cancer, 4, S81, 10.3816/CCC.2004.s.013 Makinen, 2001, Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3, Nat. Med., 7, 199, 10.1038/84651 He, 2002, Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling, J. Natl. Cancer Inst., 94, 819, 10.1093/jnci/94.11.819 He, 2005, 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, 10.1158/0008-5472.CAN-04-4576 Ross, 2004, Targeted therapies for cancer 2004, Am. J. Clin. Pathol., 122, 598, 10.1309/5CWPU41AFR1VYM3F Presta, 1997, Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders, Cancer Res., 57, 4593 Ferrara, 2004, Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer, Nat. Rev., Drug Discov., 3, 391, 10.1038/nrd1381 Yang, 2002, A randomized double-blind placebo-controlled trial of bevacizumab (anti-VEGF antibody) demonstrating a prolongation in time to progression in patients with metastatic. renal cancer Kabbinavar, 2003, 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, 10.1200/JCO.2003.10.066 Hurwitz, 2004, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N. Engl. J. Med., 350, 2335, 10.1056/NEJMoa032691 Olszewski, 2005, The horizon of antiangiogenic therapy for colorectal cancer, Oncology (Huntingt), 19, 297 Jayson, 2005, Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer, Eur. J. Cancer, 41, 555, 10.1016/j.ejca.2004.11.021 Prewett, 1999, Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors, Cancer Res., 59, 5209 Shaheen, 2001, Effects of an antibody to vascular endothelial growth factor receptor-2 on survival, tumor vascularity, and apoptosis in a murine model of colon carcinomatosis, Int. J. Oncol., 18, 221 Zhang, 2002, Combined anti-fetal liver kinase 1 monoclonal antibody and continuous low-dose doxorubicin inhibits angiogenesis and growth of human soft tissue sarcoma xenografts by induction of endothelial cell apoptosis, Cancer Res., 62, 2034 Bruns, 2002, Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice, Int. J. Cancer, 102, 101, 10.1002/ijc.10681 Witte, 1998, Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy, Cancer Metastasis Rev., 17, 155, 10.1023/A:1006094117427 Hunt, 2001, Technology evaluation: IMC-1C11, ImClone Systems, Curr. Opin. Mol. Ther., 3, 418 Posey, 2003, A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma, Clin. Cancer Res., 9, 1323 Pytowski, 2005, Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody, J. Natl. Cancer Inst., 97, 14, 10.1093/jnci/dji003 Brooks, 1994, Requirement of vascular integrin alpha v beta 3 for angiogenesis, Science, 264, 569, 10.1126/science.7512751 Brooks, 1994, Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels, Cell, 79, 1157, 10.1016/0092-8674(94)90007-8 Brooks, 1995, Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin, J. Clin. Invest., 96, 1815, 10.1172/JCI118227 Wu, 1998, Stepwise in vitro affinity maturation of Vitaxin, an alphav beta3-specific humanized mAb, Proc. Natl. Acad. Sci. U. S. A., 95, 6037, 10.1073/pnas.95.11.6037 Wilder, 2002, Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases, Ann. Rheum. Dis., 61, ii96, 10.1136/ard.61.suppl_2.ii96 Gutheil, 2000, Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3, Clin. Cancer Res., 6, 3056 Posey, 2001, A pilot trial of Vitaxin, a humanized anti-vitronectin receptor (anti alpha v beta 3) antibody in patients with metastatic cancer, Cancer Biother. Radiopharm., 16, 125, 10.1089/108497801300189218 Liao, 2000, Monoclonal antibody to vascular endothelial-cadherin is a potent inhibitor of angiogenesis, tumor growth, and metastasis, Cancer Res., 60, 6805 Corada, 2002, A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability, Blood, 100, 905, 10.1182/blood.V100.3.905 Lamagna, 2005, Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth, Cancer Res., 65, 5703, 10.1158/0008-5472.CAN-04-4012 McCafferty, 1990, Phage antibodies: filamentous phage displaying antibody variable domains, Nature, 348, 552, 10.1038/348552a0 Pini, 2000, Phage display of antibody fragments, Curr. Protein Pept. Sci., 1, 155, 10.2174/1389203003381397 Wu, 2000, Designer genes: recombinant antibody fragments for biological imaging, Q. J. Nucl. Med., 44, 268 Adams, 1999, Generating improved single-chain Fv molecules for tumor targeting, J. Immunol. Methods, 231, 249, 10.1016/S0022-1759(99)00161-1 Kriangkum, 2001, Bispecific and bifunctional single chain recombinant antibodies, Biomol. Eng., 18, 31, 10.1016/S1389-0344(01)00083-1 Castellani, 1994, The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis, Int. J. Cancer, 59, 612, 10.1002/ijc.2910590507 Pini, 1998, Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel, J. Biol. Chem., 273, 21769, 10.1074/jbc.273.34.21769 Tarli, 1999, A high-affinity human antibody that targets tumoral blood vessels, Blood, 94, 192, 10.1182/blood.V94.1.192.413k22_192_198 Demartis, 2001, Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin, Eur. J. Nucl. Med., 28, 534, 10.1007/s002590100480 Santimaria, 2003, Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer, Clin. Cancer Res., 9, 571 Carnemolla, 2002, Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix, Blood, 99, 1659, 10.1182/blood.V99.5.1659 Borsi, 2003, Selective targeted delivery of TNFalpha to tumor blood vessels, Blood, 102, 4384, 10.1182/blood-2003-04-1039 Ebbinghaus, 2005, Engineered vascular-targeting antibody–interferon–gamma fusion protein for cancer therapy, Int. J. Cancer, 116, 304, 10.1002/ijc.20952 Vitaliti, 2000, Inhibition of tumor angiogenesis by a single-chain antibody directed against vascular endothelial growth factor, Cancer Res., 60, 4311 Cai, 2003, Single chain Fv antibody against angiopoietin-2 inhibits VEGF-induced endothelial cell proliferation and migration in vitro, Biochem. Biophys. Res. Commun., 309, 946, 10.1016/j.bbrc.2003.08.086 Zhu, 1999, Inhibition of vascular endothelial growth factor induced mitogenesis of human endothelial cells by a chimeric anti-kinase insert domain-containing receptor antibody, Cancer Lett., 136, 203, 10.1016/S0304-3835(98)00324-3 Sanz, 2002, Single-chain antibody-based gene therapy: inhibition of tumor growth by in situ production of phage-derived human antibody fragments blocking functionally active sites of cell-associated matrices, Gene Ther., 9, 1049, 10.1038/sj.gt.3301725 Bloemendal, 2004, Activated vitronectin as a target for anticancer therapy with human antibodies, Cancer Immunol. Immunother., 53, 799, 10.1007/s00262-004-0506-z Ruoslahti, 1987, New perspectives in cell adhesion: RGD and integrins, Science, 238, 491, 10.1126/science.2821619 Ruoslahti, 1996, RGD and other recognition sequences for integrins, Annu. Rev. Cell Dev. Biol., 12, 697, 10.1146/annurev.cellbio.12.1.697 Gurrath, 1992, Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides, Eur. J. Biochem., 210, 911, 10.1111/j.1432-1033.1992.tb17495.x Aumailley, 1991, Arg–Gly–Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1, FEBS Lett., 291, 50, 10.1016/0014-5793(91)81101-D Pfaff, 1994, Selective recognition of cyclic RGD peptides of NMR defined conformation by alpha IIb beta 3, alpha V beta 3, and alpha 5 beta 1 integrins, J. Biol. Chem., 269, 20233, 10.1016/S0021-9258(17)31981-6 Dechantsreiter, 1999, N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists, J. Med. Chem., 42, 3033, 10.1021/jm970832g Smith, 2003, Cilengitide Merck, Curr. Opin. Investig. Drugs, 4, 741 Mitjans, 2000, In vivo therapy of malignant melanoma by means of antagonists of alphav integrins, Int. J. Cancer, 87, 716, 10.1002/1097-0215(20000901)87:5<716::AID-IJC14>3.0.CO;2-R Taga, 2002, Alpha v-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin, Int. J. Cancer, 98, 690, 10.1002/ijc.10265 Burke, 2002, Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts, Cancer Res., 62, 4263 Burkhart, 2004, Doxorubicin–formaldehyde conjugates targeting alphavbeta3 integrin, Mol. Cancer Ther., 3, 1593, 10.1158/1535-7163.1593.3.12 Eskens, 2003, Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours, Eur. J. Cancer, 39, 917, 10.1016/S0959-8049(03)00057-1 Koivunen, 1993, Selection of peptides binding to the alpha 5 beta 1 integrin from phage display library, J. Biol. Chem., 268, 20205, 10.1016/S0021-9258(20)80715-7 Pasqualini, 1995, A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins, J. Cell Biol., 130, 1189, 10.1083/jcb.130.5.1189 Livant, 2000, Anti-invasive, antitumorigenic, and antimetastatic activities of the PHSCN sequence in prostate carcinoma, Cancer Res., 60, 309 Schreiner, 1991, Expression and role of integrins in adhesion of human colonic carcinoma cells to extracellular matrix components, Clin. Exp. Metastasis, 9, 163, 10.1007/BF01756387 Stoeltzing, 2003, Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice, Int. J. Cancer, 104, 496, 10.1002/ijc.10958 Blaschuk, 2000, Cadherins as modulators of angiogenesis and the structural integrity of blood vessels, Cancer Metastasis Rev., 19, 1, 10.1023/A:1026522216059 Gerhardt, 1999, N-cadherin expression in endothelial cells during early angiogenesis in the eye and brain of the chicken: relation to blood–retina and blood–brain barrier development, Eur. J. Neurosci., 11, 1191, 10.1046/j.1460-9568.1999.00526.x Gerhardt, 2000, N-cadherin mediates pericytic–endothelial interaction during brain angiogenesis in the chicken, Dev. Dyn., 218, 472, 10.1002/1097-0177(200007)218:3<472::AID-DVDY1008>3.0.CO;2-# Paik, 2004, Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization, Genes Dev., 18, 2392, 10.1101/gad.1227804 Luo, 2005, N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis, J. Cell Biol., 169, 29, 10.1083/jcb.200411127 Williams, 2000, A novel family of cyclic peptide antagonists suggests that N-cadherin specificity is determined by amino acids that flank the HAV motif, J. Biol. Chem., 275, 4007, 10.1074/jbc.275.6.4007 Bayes, 2004, Gateways to clinical trials, Methods Find. Exp. Clin. Pharmacol., 26, 587 Griffioen, 2001, Anginex, a designed peptide that inhibits angiogenesis, Biochem. J., 354, 233, 10.1042/0264-6021:3540233 Dings, 2003, The designed angiostatic peptide anginex synergistically improves chemotherapy and antiangiogenesis therapy with angiostatin, Cancer Res., 63, 382 Dings, 2005, Anginex synergizes with radiation therapy to inhibit tumor growth by radiosensitizing endothelial cells, Int. J. Cancer, 115, 312, 10.1002/ijc.20850 Ruoslahti, 2000, Targeting tumor vasculature with homing peptides from phage display, Semin. Cancer Biol., 10, 435, 10.1006/scbi.2000.0334 Pasqualini, 1999, Vascular targeting with phage peptide libraries, Q. J. Nucl. Med., 43, 159 Ruoslahti, 2004, Vascular zip codes in angiogenesis and metastasis, Biochem. Soc. Trans., 32, 397, 10.1042/bst0320397 Arap, 1998, Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model, Science, 279, 377, 10.1126/science.279.5349.377 Pasqualini, 2000, Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis, Cancer Res., 60, 722 Curnis, 2002, Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells, Cancer Res., 62, 867 Corti, 2004, Tumor vascular targeting with tumor necrosis factor alpha and chemotherapeutic drugs, Ann. N. Y. Acad. Sci., 1028, 104, 10.1196/annals.1322.011 A. Sacchi, A. Gasparri, C. Gallo Stampino, S. Toma, F. Curnis, A. Corti, Synergistic anti-tumor activity of cisplatin, paclitaxel and gemcitabine with tumor vasculature-targeted Tumor Necrosis Factor-alpha (NGR-TNF), Cancer Res. (in press). ten Hagen, 2003, Solid tumor therapy: manipulation of the vasculature with TNF, Technol. Cancer Res. Treat., 2, 195, 10.1177/153303460300200303 Brouckaert, 2004, Tumor necrosis factor-alpha augmented tumor response in B16BL6 melanoma-bearing mice treated with stealth liposomal doxorubicin (Doxil) correlates with altered Doxil pharmacokinetics, Int. J. Cancer, 109, 442, 10.1002/ijc.11703 Jain, 2005, Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy, Science, 307, 58, 10.1126/science.1104819 Ruegg, 2003, The quest for surrogate markers of angiogenesis: a paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials, Curr. Mol. Med., 3, 673, 10.2174/1566524033479410 Zucker, 2000, Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment, Oncogene, 19, 6642, 10.1038/sj.onc.1204097 Freije, 2003, Matrix metalloproteinases and tumor progression, Adv. Exp. Med. Biol., 532, 91, 10.1007/978-1-4615-0081-0_9 Bergers, 1999, Effects of angiogenesis inhibitors on multistage carcinogenesis in mice, Science, 284, 808, 10.1126/science.284.5415.808 Hurwitz, 2005, Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer, J. Clin. Oncol., 23, 3502, 10.1200/JCO.2005.10.017 Hurwitz, 2004, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N. Engl. J. Med., 350, 2335, 10.1056/NEJMoa032691 Laird, 2002, J.M. Cherrington, SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice, FASEB J., 16, 681, 10.1096/fj.01-0700com Farhadi, 2005, Combined inhibition of vascular endothelial growth factor and platelet-derived growth factor signaling: effects on the angiogenesis, microcirculation, and growth of orthotopic malignant gliomas, J. Neurosurg., 102, 363, 10.3171/jns.2005.102.2.0363 George, 2001, Prognostic significance of vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B9480, Clin. Cancer Res., 7, 1932 Ranuncolo, 2003, Plasma MMP-9 (92 kDa-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients, Int. J. Cancer, 106, 745, 10.1002/ijc.11288 Shaked, 2005, Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis, Cancer Cell, 7, 101, 10.1016/S1535-6108(04)00369-1 Schneider, 2005, A surrogate marker to monitor angiogenesis at last, Cancer Cell, 7, 3, 10.1016/j.ccr.2004.12.014 LaFlamme, 1997, Integrin cytoplasmic domains as connectors to the cell's signal transduction apparatus, Matrix Biol., 16, 153, 10.1016/S0945-053X(97)90003-2 LaFlamme, 1994, Single subunit chimeric integrins as mimics and inhibitors of endogenous integrin functions in receptor localization, cell spreading and migration, and matrix assembly, J. Cell Biol., 126, 1287, 10.1083/jcb.126.5.1287 Lukashev, 1994, Disruption of integrin function and induction of tyrosine phosphorylation by the autonomously expressed beta 1 integrin cytoplasmic domain, J. Biol. Chem., 269, 18311, 10.1016/S0021-9258(17)32307-4 Smilenov, 1994, Integrin beta 1 cytoplasmic domain dominant negative effects revealed by lysophosphatidic acid treatment, Mol. Biol. Cell, 5, 1215, 10.1091/mbc.5.11.1215 Oguey, 2000, Disruption of integrin-dependent adhesion and survival of endothelial cells by recombinant adenovirus expressing isolated beta integrin cytoplasmic domains, Gene Ther., 7, 1292, 10.1038/sj.gt.3301236 M. Hasmim, G. Vassalli, G. Alghisi, J. Bamat, L. Ponsonnet, G. Bieler, C. Bonnard, C. Paroz, D. Oguey, C. Rüegg, Expressed isolated integrin beta1 subunit cytodomain induces endothelial cell death secondary to detachment and reveals an essential role for integrins in the survival of quiescent endothelium. Thromb. Haemost. (in press). Console, 2003, Antennapedia and HIV transactivator of transcription (TAT) “protein transduction domains” promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans, J. Biol. Chem., 278, 35109, 10.1074/jbc.M301726200 Bonny, 2001, Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death, Diabetes, 50, 77, 10.2337/diabetes.50.1.77 Fujihara, 2005, Inhibition of NF-kappa B by a cell permeable form of I kappa B alpha induces apoptosis in eosinophils, Biochem. Biophys. Res. Commun., 326, 632, 10.1016/j.bbrc.2004.11.090 Foletti, 2005, Isolated integrin beta3 subunit cytoplasmic domains require membrane anchorage and the NPXY motif to recruit to adhesion complexes but do not discriminate between beta1- and beta3-positive complexes, Thromb. Haemost., 94, 155, 10.1160/TH04-12-0792 Aronheim, 1994, Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway, Cell, 78, 949, 10.1016/0092-8674(94)90271-2