Angiogenesis: An organizing principle for drug discovery?

Nature Reviews Drug Discovery

Volumn 6, Issue 4, 2007, Pages 273-286

  Folkman, Judah ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHOXYESTRADIOL; 3 (4 AMINO 1,3 DIHYDRO 1,3 DIOXO 2H ISOINDOL 2 YL)GLUTARIMIDE; 4 (4 FLUORO 2 METHYL 5 INDOLYLOXY) 6 METHOXY 7 [3 (1 PYRROLIDINYL)PROPOXY]QUINAZOLINE; ANGIOGENESIS INHIBITOR; AP 23573; AXITINIB; BEVACIZUMAB; BORTEZOMIB; CELECOXIB; CETUXIMAB; CILENGITIDE; COMBRETASTATIN; CYCLOPHOSPHAMIDE; ENDOSTAR; ENDOSTATIN; ERLOTINIB; EVEROLIMUS; LENALIDOMIDE; N (3,3 DIMETHYL 6 INDOLINYL) 2 (4 PYRIDINYLMETHYLAMINO)NICOTINAMIDE; N ACETYLSARCOSYLGLYCYLVALYL DEXTRO ALLOISOLEUCYLTHREONYLNORVALYLISOLEUCYLARGINYLPROLINE ETHYLAMIDE; PEGAPTANIB; PLACEBO; RANIBIZUMAB; REBIMASTAT; REGULATOR PROTEIN; SORAFENIB; SUNITINIB; TEMSIROLIMUS; THALIDOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB;

ABSENCE OF SIDE EFFECTS; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW SUPPRESSION; BRAIN TUMOR; CANCER; CANCER CHEMOTHERAPY; CANCER LOCALIZATION; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; COLORECTAL CANCER; CONSTIPATION; DIARRHEA; DOSE RESPONSE; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENTIATION; DRUG RESEARCH; DRUG WITHDRAWAL; GENETIC REGULATION; HAIR LOSS; HUMAN; LOW DRUG DOSE; METABOLIC REGULATION; METASTASIS; MOLECULAR DYNAMICS; MULTIPLE MYELOMA; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OFF LABEL DRUG USE; ONCOGENE; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; RETINA MACULA AGE RELATED DEGENERATION; THROMBOEMBOLISM; THROMBOSIS; TUMOR VASCULARIZATION; UNSPECIFIED SIDE EFFECT; VISUAL ACUITY; WEAKNESS;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; BLOOD PLATELETS; ENDOTHELIUM; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC;

EID: 33947732977     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2115     Document Type: Article

References (142)

1. Sholley, M. M., Ferguson, G. P., Seibel, H. R., Montour, J. L., & Wilson, J. D. Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells. Lab. Invest. 51, 624-634 (1984).
2. Folkman, J. Angiogenesis. in Harrison's Textbook of Internal Medicine (eds Braunwald, E. et al.) (McGraw-Hill. New York, 2001).
3. Moulton, K. S. et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc. Natl Acad. Sci. USA 100, 4736-4741 (2003).
4. Folkman, J. Angiogenesis in psoriasis: Therapeutic implications. J. Invest. Dermatol. 59, 40-43 (1972).
5. Zeng, X., Chen, J., Miller, Y. I., Javaherian, K. & Moulton, K. S. Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis. J. Lipid Res. 46, 1849-1859 (2005).
6. Ezekowitz, A., Mulliken, J. & Folkman, J. Interferon-α therapy of haemangiomas in newborns and infants. Br. J. Haematol. 79 (Suppl. 1), 67-68 (1991).
7. Szabo, S. et al. Accelerated healing of duodenal ulcers by oral administration of a mutein of basic fibroblast growth factor in rats. Gastroenterology 106, 1106-1111 (1994).
8. Miller, J. W. et al. Vascular endothelial growth factor/ vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am. J. Pathol. 145, 574-584 (1994).
9. Folkman J. in Targeted Therapies in Rheumatology (eds Smolen, J. S. & Lipsky P. E.) 111-131 (Martin Dunitz, London, 2003).
10. Moulton, K. S. et al. Angiogenesis inhibitors endostatin or TN P-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99, 1726-1732 (1999).
11. Moulton, K. S. Angiogenesis in atherosclerosis: Gathering evidence beyond speculation. Curr. Opin. Lipidol. 17, 548-555 (2006).
12. Gimbrone, M. A., Jr., Cotran, R. S. & Folkman, J. Human vascular endothelial cells in culture. Growth and DNA synthesis. J. Cell Biol. 60, 673-684 (1974).
13. Ausprunk, D. H., Knighton, D. R. & Folkman, J. Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Role of host and preexisting graft blood vessels. Am. J. Pathol. 79, 597-628 (1975).
14. Langer, R. & Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature 263, 797-800 (1976).
15. Gimbrone, M. A. Jr., Cotran, R. S., Leapman, S. B. & Folkman, J. Tumor growth and neovascularization: An experimental model using the rabbit cornea. J. Natl Cancer Inst. 52, 413-427 (1974).
16. Auerbach, R., Arensman, R., Kubai, L. & Folkman, J. Tumor-induced angiogenesis: Lack of inhibition by irradiation. Int. J. Cancer 15, 241-245 (1975).
17. Taylor, S. & Folkman, J. Protamine is an inhibitor of angiogenesis. Nature 297, 307-312 (1982).
18. Crum, R., Szabo, S. & Folkman, J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230, 1375-1378 (1985).
19. Folkman, J. Tumor angiogenesis: Therapeutic implications. N. Engl. J. Med. 285, 1182-1186 (1971).
20. Ausprunk, D. H., Falterman, K. & Folkman, J. The sequence of events in the regression of corneal capillaries. Lab. Invest. 38, 284-294 (1978).
21. Maeshima, Y. et al. Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295, 140-143 (2002).
22. O'Reilly, M. S. et al. Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79, 315-328 (1994).
23. Frater-Schroder, M., Risau, W., Hallmann. R., Gautschi, P. & Bohlen, P. Tumor necrosis factor type α, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc. Natl Acad. Sci. USA 84, 5277-5281 (1987).
24. Folkman, J. Endogenous angiogenesis inhibitors. Acta Pathol. Microbiol. Immunol. Scand. 112, 496-507 (2004).
25. Nyberg, P., Xie, L. & Kalluri, R. Endogenous inhibitors of angiogenesis. Cancer Res. 65, 3967-3979 (2005).
26. Folkman, J. in Cancer Medicine 7th Edn (eds Kufe, D. W. et al) (B.C. Decker, Hamilton, Ontario, 2006).
27. O'Reilly, M. S. et al. Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 88, 277-285 (1997).
28. Abdollahi, A. et al. Endostatin's antiangiogenic signaling network. Mol. Cell 13, 649-663 (2004).
29. Inoue, K., Korenaga, H., Tanaka, N. G., Sakamoto, N. & Kadoya, S. The sulfated polysaccharide - peptidoglycan complex potently inhibits embryonic angiogenesis and tumor growth in the presence of cortisone acetate. Carbohydr. Res. 181, 135-142 (1988).
30. Hurwitz, H. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335-2342 (2004).
31. Udagawa, T. et al. Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: Contribution of local and bone marrow-derived host cells. FASEB J. 20, 95-102 (2006).
32. Higgins, K.J., Abdelrahim, M., Liu, S., Yoon, K. & Safe, S. Regulation of vascular endothelial growth factor receptor-2 expression in pancreatic cancer cells by Sp proteins. Biochem. Biophys. Res. Commun. 345, 292-301 (2006).
33. Yasui, H., Hideshima. T, Richardson, P. G. & Anderson, K. C. Recent advances in the treatment of multiple myeloma. Curr. Pharm. Biotechnol. 7, 381-393 (2006).
34. Ranieri, G. et al. Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: From the biology to the clinic. Curr. Med. Chem. 13, 1845-1857 (2006).
35. Rosenfeld, P. J. Intravitreal bevacizumab: The low cost alternative to lucentis? Am. J. Ophthalmol. 142, 141-143 (2006).
36. Rosenfeld, P. J., Heier, J. S., Hantsbarger, G. & Shams, N. Tolerability and efficacy of multiple escalating doses of ranibizumab (lucentis) for neovascular age-related macular degeneration. Ophthalmology 113, 623-632 (2006).
37. Kim, I. K. et al. Effect of intravitreal injection of ranibizumab in combination with verteporfin PDT on normal primate retina and choroid. Invest. Ophthalmol. Vis. Sci. 47, 357-363 (2006).
38. Husain, D. et al. Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey. Arch. Ophthalmol. 123, 509-516 (2005).
39. Michels, S. & Rosenfeld. P. J. [Treatment of neovascular age-related macular degeneration with ranibizumab/lucentis]. Klin. Monatsbl. Augenheilkd. 222, 480-484 (2005) (in German).
40. Pieramici, D. J. & Avery, R. L. Ranibizumab: Treatment in patients with neovascular age-related macular degeneration. Expert Opin. Biol. Ther. 6, 1237-1245 (2006).
41. Shima, D. T. et al. Hypoxic induction of endothelial cell growth factors in retinal cells: Identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol. Med. 1, 182-193 (1995).
42. Ng. E. W. & Adamis, A. P. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can. J. Ophthalmol. 40, 352-368 (2005).
43. Lim, M. S. Re: Correlational of oral tongue cancer inversion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor [VEGF) expression, by Kim S-H, Cho NH, Kim K, et al. J. Surg. Oncol. 93, 253-254 (2006).
44. Des Guetz, G. et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br. J. Cancer 94, 1823-1832 (2006).
45. Kerbel, R. S., Viloria-Petit, A., Klement, G. & Rak, J. "Accidental" anti-angiogenic drugs. Anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples. Eur. J. Cancer 36, 1248-1257 (2000).
46. Morelli, M.P. et al. Anti-tumor activity of the combination of cetuximab, and anti-EGFR blocking monoclonal antibody and ZD6474. an inhibitor of BEGFR and EGFR tyrosine kinases. J. Cell Physiol. 208, 344-353 (2006).
47. Pinedo, H.M. et al. Involvement of platelets in tumour angiogenesis? Lancet 352, 1775-1777 (1998).
48. Greene, A. K. et al. Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial hepatectomy. Transplantation 78, 1139-1144 (2004).
49. Rupnick, M. A. et al. Adipose tissue mass can be regulated through the vasculature. Proc. Natl Acad. Sci. USA 99, 10730-10735 (2002).
50. Giuriato, S. et al. Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc. Natl Acad. Sci. USA 103, 16266-16271 (2006).
51. Klagsbrun, M. & Eichmann, A. A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev. 16, 535-548 (2005).
52. Yang, O., Rasmussen, S. A. & Friedman, J. M. Mortality associated with Down's syndrome in the USA from 1983 to 1997: A population-based study. Lancet 359, 1019-1025 (2002).
53. Soker, S., Takashima, S., Miao, H. Q., Neufeld, G. & Klagsbrun, M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92, 735-745 (1998).
54. Vogel, G. Developmental biology. The unexpected brains behind blood vessel growth. Science 307, 665-667 (2005).
55. Mukouyama, Y. S., Shin. D., Britsch, S., Taniguchi, M. & Anderson, D. J. Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 109, 693-705 (2002).
56. Kutcher, M. E., Klagsbrun, M. & Mamluk, R. VEGF is required for the maintenance of dorsal root ganglia blood vessels but not neurons during development. FASEB J. 18, 1952-1954 (2004).
57. Folkman, J., Browder, T. & Palmblad, J. Angiogenesis research: guidelines for translation to clinical application. Thromb. Haemost. 86, 23-33 (2001).
58. Klement, G. et al. Early tumor detection using platelet uptake of angiogenesis regulators. Blood 104 (ASH Annual Meeting Abstracts), 839 (2004).
59. Naumov, G. N. et al. A model of human tumor dormancy: An angiogenic switch from the nonangiogenic phenotype. J. Natl Cancer Inst. 98, 316-325 (2006).
60. Almog, N. et al. Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. FASEB J. 20, 947-949 (2006).
61. Verheul, H. M. et al. Uptake of bevacizumab by platelets blocks the biological activity of platelet-derived vascular endothelial growth factor [VEGF]. Proc. Amer. Assoc. Cancer Res. 47, Abstract #5708 (2006).
62. Klement, G., Cervi, D., Yip, T. T., Folkman, J. & Italiano, J. Platelet PF-4 is an early marker of tumor angiogenesis. Blood 108 (ASH Annual Meeting Abstract), 1476 (2006).
63. Italiano, J., Richardson, J. L. Folkman, J. & Klement, G. Blood platelets organize pro- and anti-angiogenic factors into separate, distinct alpha granules: Implications for the regulation of angiogenesis. Blood 108 (ASH Annual Meeting Abstracts), 393 (2006).
64. Volpert, O. V., Lawler. J. & Bouck, N. P. A human fibrosarcoma inhibits systemic angiogenesis and the growth of experimental metastases via thrombospondin-1. Proc. Natl Acad. Sci USA 95, 6343-6348 (1998).
65. Rastinejad. F., Polverini, P. J. & Bouck, N. P. Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56, 345-355 (1989).
66. Dameron, K. M., Volpert, O. V., Tainsky, M. A. & Bouck, N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265, 1582-1584 (1994).
67. Kang, S. -Y. et al. Repression of stromal thrombospondin-1 is a determinant for metastatic tissue specificity. Proc. Amer. Assoc. Cancer Res. 47, Abstract #2798 (2006).
68. Iruela-Arispe, M. L., Porter, P., Bornstein, P. & Sage, E. H. Thrombospondin-1. an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium. J. Clin. Invest. 97, 403-412 (1996).
69. North, P. E. et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch. Dermatol. 137, 559-570 (2001).
70. Barnes, C. M. et al. Evidence by molecular profiling for a placental origin of infantile hemangioma. Proc. Natl Acad. Sci USA 102, 19097-19102 (2005).
71. Greene, A. K. et al. Endothelial-directed hepatic regeneration after partial hepatectomy. Ann. Surg. 237, 530-535 (2003).
72. Kolonin, M. G., Saha, P. K., Chan, L, Pasqualini, R. & Arap, W. Reversal of obesity by targeted ablation of adipose tissue. Nature Med. 10, 625-632 (2004).
73. Folkman, J. Is tissue mass regulated by vascular endothelial cells? Prostate as the first evidence. Endocrinology 139, 441-442 (1998).
74. Street, J. et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Natl Acad. Sci. USA 99, 9656-9661 (2002).
75. Gerber, H. P., & Ferrara, N. The role of VEGF in normal and neoplastic hematopoiesis. J. Mol. Med. 81, 20-31 (2003).
76. Kaplan, F. et al. Urinary basic fibroblast growth factor. A biochemical marker for preosseous fibroproliferative lesions in patients with fibrodysplasia ossificans progressiva. Clin. Orthop. 346, 59-65 (1998).
77. Ferrara, N., LeCouter, J. Lin, R., & Peale, F. EG-VEGF and Bv8: A novel family of tissue-restricted angiogenic factors. Biochim. Biophys. Acta 1654, 69-78 (2004).
78. Chin, L. & DePinho, R. A. Flipping the oncogene switch: Illumination of tumor maintenance and regression. Trends Genet. 16, 147-150 (2000).
79. Felsher, D. W. & Bishop, J. M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell. 4, 199-207 (1999).
80. Felsher, D. W. & Bishop, J. M. Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc. Natl Acad. Sci. USA 96, 3940-3944 (1999).
81. Shachaf, C. M. et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431, 1112-1117 (2004).
82. Jang, J. W., Boxer, R. B. & Chodosh, L. A. Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol. Cell. Biol. 26, 8109-8121 (2006).
83. Folkman, J. & Ryeom, S. Is oncogene addiction angiogenesis-dependent? Cold Spring Harb. Symp. Quant. Biol. 70, 389-397 (2005).
84. Weinstein, I. B. & Joe, A. K. Mechanisms of disease: Oncogene addiction - a rationale for molecular targeting in cancer therapy. Nat. Clin. Pract. Oncol. 3, 448-457 (2006).
85. Demetri, G. D. Targeting c-kit mutations in solid tumors: Scientific rationale and novel therapeutic options. Semin. Oncol. 28, 19-26 (2001).
86. Duensing, A. et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene 23, 3999-4006 (2004).
87. Ritchie, E. & Nichols, G. Mechanisms of resistance to imatinib in CML patients: A paradigm for the advantages and pitfalls of molecularly targeted therapy. Curr. Cancer Drug Targets 6, 645-657 (2006).
88. Rak, J. et al. Oncogenes and tumor angiogenesis: Differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res. 60, 490-498 (2000).
89. Rak, J., Yu, J. L., Klement, G. & Kerbel, R. S. Oncogenes and angiogenesis: Signaling three-dimensional tumor growth. J. Investig. Dermatol. Symp. Proc. 5, 24-33 (2000).
90. Yoshioka, M. et al. Chondromodulin-1 maintains cardiac valvular function by preventing angiogenesis. Nature Med. 12, 1151-1159 (2006).
91. Zorick, T. S. et al. High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. Eur. J. Hum. Genet. 9, 811-814 (2001).
92. Hesser, B. A. et al. Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells. Blood 104, 149-158 (2004).
93. Lourenco, G. J. et al. A high risk of occurrence of sporadic breast cancer in individuals with the 104NN polymorphism of the COL18A1 gene. Breast Cancer Res. Treat. 100, 335-338 (2006).
94. Sund, M. et al. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Proc. Natl Acad. Sci. USA 102, 2934-2939 (2005).
95. Sommer, A. et al. Racial differences in the cause-specific prevalence of blindness in east Baltimore. N. Engl. J. Med. 325, 1412-1417 (1991).
96. Rohan, R. M., Fernandez, A., Udagawa, T., Yuan, J. & D'Amato, R. J. Genetic heterogeneity of angiogenesis in mice. FASEB J. 14, 871-876 (2000).
97. Rogers, M. S., Rohan, R. M., Birsner, A. E. & D'Amato, R. J. Genetic loci that control vascular endothelial growth factor-induced angiogenesis, FASEB J. 17, 2112-2114 (2003).
98. Beecken, W. D. et al. Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in mice. J. Natl Cancer Inst. 93, 382-387 (2001).
99. Schuch, G., Kisker, O., Atala, A. & Soker, S. Pancreatic tumor growth is regulated by the balance between positive and negative modulators of angiogenesis. Angiogenesis 5, 181-190 (2002).
100. Kisker, O. et al. Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model. Cancer Res. 61, 7669-7674 (2001).
101. Roy, R., Wewer, U. M., Zurakowski, D., Pories, S. E. & Moses, M. A. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J. Biol. Chem. 279, 51323-51330 (2004).
102. In "Washington Post". (February 28, 2004).
103. Satchi-Fainaro, R. et al. Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin. Cancer Cell. 7, 251-261 (2005).
104. Satchi-Fainaro, R. et al. Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470. Nature Med. 10, 255-261 (2004).
105. Pore, N. et al. EGFR tyrosine kinase inhibitors decrease VEGF expression by both hypoxia-inducible factor (HIF)-1-independent and HIF-1-dependent mechanisms. Cancer Res. 15, 3197-3204 (2006).
106. Wood, J. et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J. Pharmacol. Exp. Ther. 302, 1055-1061 (2002).
107. Giraudo, E., Inoue, M., and Hanahan, D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J. Clin. Invest 114, 623-633 (2004).
108. Ferretti, G. et al. Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients. Oncology 69, 35-43 (2005).
109. Santini, D. et al. Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin. Cancer Res. 9, 2893-2897 (2003).
110. Boehm, T. et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390, 404-407 (1997).
111. Kulke, M.H. et al. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J. Clin. Oncol. 24, 3555-3561 (2006).
112. Mehta, P. Thalidomide and thrombosis. Clin. Adv. Hematol. Oncol. 1, 464-465 (2003).
113. Fernandez, P. M. & Rickles, F. R. Tissue factor and angiogenesis in cancer. Curr. Opin. Hematol. 9, 401-406 (2002).
114. Jain, R.K. Antiangiogenic therapy for cancer: Current and emerging concepts. Oncology 9, 7-16 (2005).
115. Jain, R.K. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 307, 58-62 (2006).
116. Teicher, B.A. et al. Antiangiogenic agents can increase tumor oxygenation and response to radiation therapy. Radiat. Oncol. Investig. 2, 269-176 (1995).
117. Calabrese, E. J., Staudenmayer, J. W. & Stanek, E. J. Drug development and hormesis: Changing conceptual understanding of the dose response creates new challenges and opportunities for more effective drugs. Curr. Opin. Drug Discov. Devel. 9, 117-123 (2006).
118. Slaton, J. W., Perrotte, P., Inoue, K., Dinney, C. P. & Fidler, I. J. Interferon-α-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin. Cancer Res. 5, 2726-2734 (1999).
119. Celik, I. et al. Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve. Cancer Res. 65, 11044-11050 (2005).
120. Tjin Tham Sjin, R. M. et al. Endostatin therapy reveals a U-shaped curve for antitumor activity. Cancer Gene Ther. (2006).
121. Panigrahy, D. et al. PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J. Clin. Invest. 110, 923-932 (2002).
122. Kuo, C. J. et al. Comparative evaluation of the antitumor activity of antiangiogenic proteins delivered by gene transfer. Proc. Natl Acad. Sci USA 98, 4605-4610 (2001).
123. Marshall, E. Cancer therapy. Setbacks for endostatin. Science 295, 2198-2199 (2002).
124. Folkman, J. Antiangiogenesis in cancer therapy - endostatin and its mechanisms of action. Exp. Cell Res. 312, 594-607 (2006).
125. Hida, K. et al. Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res. 64, 8249-8255 (2004).
126. Dorrell, M.I., Aguilar, E., Scheppke, L. Barnett, F. H. & Friedlander, M. Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc. Natl Acad. Sci. USA 8 Jan 2007 (doi:10.1073/ pnas.0607542104).
127. Kaban, L. B. et al. Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon α-2a. Pediatrics 103, 1145-1149 (1999).
128. Marler, J. J. et al. Successful antiangiogenic therapy of giant cell angioblastoma with interferon α 2b: Report of 2 cases. Pediatrics 109, e37 (2002).
129. Kaban, L. B. et al. Antiangiogenic therapy with interferon α for giant cell lesions of the jaws. J. Oral Maxillofac. Surg. 60, 1103-1111 (2002).
130. Folkman, J. The Harvey Lectures, Series 92, 1996-1997. 65-82 (John Wiley & Sons, New York, 1998).
131. Browder, T. et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 60, 1878-1886 (2000).
132. Klement, G. et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J. Clin. Invest. 105, R15-R24 (2000).
133. Bocci, G., Francia. G., Man, S., Lawler, J. & Kerbel, R. S. Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc. Natl Acad. Sci. USA 100, 12917-12922 (2003).
134. Hanahan, D., Bergers, G. & Bergsland, E. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J. Clin. Invest. 105, 1045-1047 (2000).
135. Kieran, M. W. et al. A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J. Pediatr. Hematol. Oncol. 27, 573-581 (2005).
136. Nilsson, U. W. & Dabrosin, C. Estradiol and tamoxifen regulate endostatin generation via matrix metalloproteinase activity in breast cancer in vivo. Cancer Res. 66, 4789-4794 (2006).
137. Ma, L., del Soldato, P. & Wallace, J. L. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance. Proc. Natl Acad. Sci. USA 99, 13243-13247 (2002).
138. Nagashima, M., Asano, G. & Yoshino, S. Imbalance in production between vascular endothelial growth factor and endostatin in patients with rheumatoid arthritis. J. Rheumatol. 27, 2339-2342 (2000).
139. Kalas, W. et al. Restoration of thrombospondin 1 expression in tumor cells harbouring mutant ras oncogene by treatment with low doses of doxycycline. Biochem. Biophys. Res. Commun. 310, 109-114 (2003).
140. Carmeliet, P. Angiogenesis in life, disease and medicine. Nature 438, 932-936 (2005).
141. Marx, J. Angiogenesis. A boost for tumor starvation. Science 301, 452-454 (2003).
142. Relf, M. et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor β1 platelet-derived endothelail cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 57(5), 963-969 (1997).