Skip to main content
SpringerLink
Log in

Tumor Angiogenesis as a Target for Early Intervention and Cancer Prevention

  • Chapter
Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 249 Accesses

Abstract

Cancer now affects as many as 22 million people worldwide, and results in six million deaths each year (1). Men have a 43% chance, and women a 38% chance, of being diagnosed with any type of cancer during their lifetime (2,3). Despite advances in the early detection of cancer, most malignancies are still diagnosed and treated at advanced stages, with a limited range of therapeutic options and poor overall survival. Cancer prevention and early intervention are thus important long-range strategies for managing the cancer pandemic.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Schwartsmann G, Ratain MJ, Cragg GM, et al. Anticancer drug discovery and development throughout the world. J Clin Oncol 2002;20:47S-59S.

    PubMed  CAS  Google Scholar 

  2. Ries LAG, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review, 1973–1998, National Cancer Institute, Bethesda, MD. http://seer.cancer.gov/Publications/CSR 1973–1998, 2001.

    Google Scholar 

  3. Lifetime risk of being diagnosed with cancer. J Natl Cancer Inst 2001;93:742.

    Google Scholar 

  4. Chemoprevention Working Group. Prevention of cancer in the next millennium: report of the Chemoprevention Working Group to the American Association for Cancer Research. Cancer Res 1999;59:4743–4758.

    Google Scholar 

  5. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990;82:4–6.

    Article  PubMed  CAS  Google Scholar 

  6. Folkman J, Merler E, Abernathy C, et al. Isolation of a tumor fraction responsible for angiogenesis. J Exp Med 1971;133:275–288.

    Article  PubMed  CAS  Google Scholar 

  7. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–1186.

    Article  PubMed  CAS  Google Scholar 

  8. Ribatti D, Vacca A, Dammacco F. The role of the vascular phase in solid tumor growth: a historical review. Neoplasia 1999.1(4):293–302.

    Article  PubMed  CAS  Google Scholar 

  9. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–31.

    Article  PubMed  CAS  Google Scholar 

  10. Kerbel RS. Tumor angiogenesis: past, present, and the near future. Carcinogenesis 2000;21:505–515.

    Article  PubMed  CAS  Google Scholar 

  11. Weidner N. Angiogenesis as a predictor of clinical outcome in cancer patients. Hum Pathol 2000;31(4):403–405.

    Article  PubMed  CAS  Google Scholar 

  12. Folkman J. Tumor angiogenesis, in Harrison’s Textbook of Internal Medicine, 15th ed. Braunwald E, Fauci AS, Kasper DL, et al., eds. McGraw-Hill, New York, NY, 2000 pp.132–152.

    Google Scholar 

  13. Mangi MH, Newland AC. Angiogenesis and angiogenic markers in haematological malignancies. Br J Haematol 2000:111:43–51

    Article  PubMed  CAS  Google Scholar 

  14. Brandvold KA, Neiman P, Rudell A. Angiogenesis is an early event in the generation of myc-induced lymphomas. Oncogene 2000;19:2780–2785.

    Article  PubMed  CAS  Google Scholar 

  15. Padro T, Ruiz S, Bieker R, et al. Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood 2000;95:2637–2644.

    PubMed  CAS  Google Scholar 

  16. Rajkumar SV, Greipp PR. Angiogenesis in multiple myeloma. Br J Haematol 2001;113:565.

    Article  PubMed  CAS  Google Scholar 

  17. Pruneri G, Bertolini F, Soligo D, et al. Angiogenesis in myelodysplastic syndromes. Br J Cancer 1999;81:1398–1401.

    Article  PubMed  CAS  Google Scholar 

  18. Rak J, Filmus J, Kerbel RS. Reciprocal paracrine interactions between tumour cells and endothelial cells: the ‘angiogenesis progression’ hypothesis. Eur J Cancer 1996;32A:2438–2450.

    Article  PubMed  CAS  Google Scholar 

  19. Folkman J. Angiogenesis-dependent diseases. Semin Oncol 2001;28:536–542.

    Article  PubMed  CAS  Google Scholar 

  20. Singhal S, Mehta J, Desikan R et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565–1571.

    Article  PubMed  CAS  Google Scholar 

  21. DeVore RF, Fehrenbacher L, Herbst RS, et al. A randomized phase II trial comparing rhuMab VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxel (CP) to CP alone in patients with stage IIIB/IV NSCL. Proc Am Soc Clin Oncol 2000;19:485a, abst. no. 1896.

    Google Scholar 

  22. Batist G, Patenaude F, Champagne P, et al. (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 2002;13:1259–1263.

    Article  PubMed  CAS  Google Scholar 

  23. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nature Rev Cancer 2002;2:727–739.

    Article  CAS  Google Scholar 

  24. Tosetti F, Ferrari N, De Flora S, et al. Angioprevention: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002;16:2–14.

    Article  PubMed  CAS  Google Scholar 

  25. Helmlinger G, Yuan F, Dellian M, et al. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 1997;3:177–182.

    Article  PubMed  CAS  Google Scholar 

  26. Gargett CE, Rogers PA. Human endometrial angiogenesis. Reproduction 2001;121:181–186.

    Article  PubMed  CAS  Google Scholar 

  27. Hazzard TM, Stouffer RL. Angiogenesis in ovarian follicular and luteal development. Baillieres Clin Obstet Gynaecol 2000;14:883–900.

    Article  CAS  Google Scholar 

  28. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod 2001;64:1033–1040.

    Article  PubMed  CAS  Google Scholar 

  29. Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Investig Dermatol Symp Proc 2000;5:40–46.

    Article  PubMed  CAS  Google Scholar 

  30. Shing Y, Folkman J, Sullivan R, et al. Heparin affinity: purification of a tumor-derived capillary endothelial growth factor. Science 1984;223:1296–1298.

    Article  PubMed  CAS  Google Scholar 

  31. Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983–985.

    Article  PubMed  CAS  Google Scholar 

  32. Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306–1309.

    Article  PubMed  CAS  Google Scholar 

  33. Nor JE, Christensen J, Mooney DJ, et al. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol 1999;154:375–384.

    Article  PubMed  CAS  Google Scholar 

  34. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671–674.

    Article  PubMed  CAS  Google Scholar 

  35. Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res 2002;62:2749–2752.

    PubMed  CAS  Google Scholar 

  36. Hattori K, Heissig B, Wu Y, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002;8:841–849.

    PubMed  CAS  Google Scholar 

  37. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987.235:442–447.

    Article  PubMed  CAS  Google Scholar 

  38. Thommen R, Humar R, Misevic G, et al. PDGF-BB increases endothelial migration on cord movements during angiogenesis in vitro. J Cell Biochem 1997;64:403–413.

    Article  PubMed  CAS  Google Scholar 

  39. Russell KS, Stern DF, Polverini PJ, et al. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol 1999;277:H2205-H2211.

    PubMed  CAS  Google Scholar 

  40. Gillis P, Savla U, Volpert OV, et al. Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function. J Cell Sci 1999;112:2049–2057.

    PubMed  CAS  Google Scholar 

  41. Nguyen M. Angiogenic factors as tumor markers. Investig New Drugs 1997;15:29–37.

    Article  CAS  Google Scholar 

  42. Brem H, Folkman J. Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med 1975;141:427–439.

    Article  PubMed  CAS  Google Scholar 

  43. Moses MA, Wiederschain D, Wu I, et al. Troponin I is present in human cartilage and inhibits angiogenesis. Proc Natl Acad Sci USA 1999;96:2645–2650.

    Article  PubMed  CAS  Google Scholar 

  44. Feldman L, Rouleau C. Troponin I inhibits capillary endothelial cell proliferation by interaction with the cell’s bFGF receptor. Microvasc Res 2002;63:41–49.

    Article  PubMed  CAS  Google Scholar 

  45. Inoki I, Shiomi T, Hashimoto G, et al. Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J 2002;16:219–221.

    PubMed  CAS  Google Scholar 

  46. Kusafuka K, Hiraki Y, Shukunami C, et al. Cartilage-specific matrix protein, chondromodulin-I (ChM-I), is a strong angioinhibitor in endochondral ossification of human neonatal vertebral tissues in vivo: relationship with angiogenic factors in cartilage. Acta Histochem 2002;104:167–175.

    Article  PubMed  CAS  Google Scholar 

  47. Davies C, de L, Melder RJ, Munn LL, et al. Decorin inhibits endothelial migration and tube-like structure formation: role of thrombospondin-1. Microvasc Res 2001;62(1):26–42.

    Article  CAS  Google Scholar 

  48. Liu N, Lapcevich RK, Underhill CB, et al. Metastatin: a hyaluronan-binding complex from cartilage that inhibits tumor growth. Cancer Res 2001;61:1022–1028.

    PubMed  CAS  Google Scholar 

  49. Dawson DW, Volpert OV, Gillis P, et al. Pigment epitheliumderived factor: a potent inhibitor of angiogenesis. Science 1999:285:245–24R.

    Article  PubMed  CAS  Google Scholar 

  50. Lutty GA, Thompson DC, Gallup JY, et al. Vitreous: an inhibitor of retinal extract-induced neovascularization. Invest Ophthalmol Vis Sci 1983;24:52.

    PubMed  CAS  Google Scholar 

  51. Williams GA, Eisenstein R, Schumacher B, et al. Inhibitor of vascular endothelial cell growth in the lens. Am J Ophthalmol 1984;97:366–371.

    PubMed  CAS  Google Scholar 

  52. Mun EC, Doctrow SR, Carter R, et al. An angiogenesis inhibitor from the cornea. Investig Ophthalmol Vis Sci 1989;30(Suppl):151.

    Google Scholar 

  53. Auerbach W, Auerbach R. Angiogenesis inhibition: a review. Pharmacol Ther 1994;63:265–311.

    Article  PubMed  CAS  Google Scholar 

  54. Dameron KM, Volpert OV, Tainsky MA, et al. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 1994;265:1582–1584.

    Article  PubMed  CAS  Google Scholar 

  55. Nor JE, Mitra RS, Sutorik MM, et al. Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway. J Vasc Res 2000;37:209–218.

    Article  PubMed  CAS  Google Scholar 

  56. Streit M, Riccardi L, Velasco P, et al. Thrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis. Proc Natl Acad Sci USA 1999;96:14,888–14,893.

    Article  CAS  Google Scholar 

  57. Singh RK, Gutman M, Bucana CD, et al. Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad Sci USA 1995;92:4562–4566.

    Article  PubMed  CAS  Google Scholar 

  58. Friesel R, Komoriya A, Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol 1987;104:689–696.

    Article  PubMed  CAS  Google Scholar 

  59. Kamphaus GD, Colorado PC, Panka DJ, et al. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 2000;275:1209–1215.

    Article  PubMed  CAS  Google Scholar 

  60. Maeshima Y, Manfredi M, Reimer C, et al. Identification of the anti-angiogenic site within vascular basement membranederived tumstatin. J Biol Chem 2001;276:15240–15248.

    Article  PubMed  CAS  Google Scholar 

  61. Colorado PC, Torre A, Kamphaus G, et al. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 2000;60:2520–2526.

    PubMed  CAS  Google Scholar 

  62. O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994;79:315–328.

    Article  PubMed  Google Scholar 

  63. Heidtmann HH, Nettelbeck DM, Mingels et al. Generation of angiostatin-like fragments from plasminogen by prostatespecific antigen. Br J Cancer 1999;81:1269–1272.

    Article  PubMed  CAS  Google Scholar 

  64. Gately S, Twardowski P, Stack MS, et al. The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin. Proc Natl Acad Sci USA 1997;94:10868–10872.

    Article  PubMed  CAS  Google Scholar 

  65. O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277–285.

    Article  PubMed  Google Scholar 

  66. Dixelius J, Larsson H, Sasaki T, et al. Endostatin-induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis. Blood 2000;95:3403–3411.

    PubMed  CAS  Google Scholar 

  67. O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth. Cold Spring Harb Symp Quant Biol 1994;59:471–482.

    Article  PubMed  Google Scholar 

  68. Herbst RS, Hess KR, Tran HT, et al. Phase I study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2002;20:3792–3803.

    Article  PubMed  CAS  Google Scholar 

  69. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353–364.

    Article  PubMed  CAS  Google Scholar 

  70. Plate KH, Breier G, Millauer B, et al. Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 1993;53:5822–5827.

    PubMed  CAS  Google Scholar 

  71. Rastinejad F, Polverini PJ, Bouck NP. Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 1989;56:345–355.

    Article  PubMed  CAS  Google Scholar 

  72. Ohno-Matsui K, Morita I, Tombran-Tink J, et al. Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF. J Cell Physiol 2001;189:323–333.

    Article  PubMed  CAS  Google Scholar 

  73. Lyden D, Young AZ, Zagzag D, et al. Idl and Id3 are required for neurogenesis, angiogenesis and vascularization of tumor xenografts. Nature 1999;401:670–677.

    Article  PubMed  CAS  Google Scholar 

  74. Baudino TA, McKay C, Pendeville-Samain H, et al. c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev 2002;16:2530–2543.

    Article  PubMed  CAS  Google Scholar 

  75. Vikhanskaya F, Bani MR, Borsotti P, et al. p73 Overexpression increases VEGF and reduces thrombospondin-1 production: implications for tumor angiogenesis. Oncogene 2001;20:7293–7300.

    Article  PubMed  CAS  Google Scholar 

  76. Lu L, Holmqvist K, Cross M, et al. Role of the src homology 2 domain-containing protein Shb in murine brain endothelial cell proliferation and differentiation. Cell Growth Differ 2002;13:141–148.

    PubMed  CAS  Google Scholar 

  77. Rak J, Mitsuhashi Y, Bayko L, Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumour angiogenesis. Cancer Res 1995;55:4575–4580.

    PubMed  CAS  Google Scholar 

  78. Grugel D, Finkenzeller G, Weindel K, et al. Both v-Ha-ras and v-raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J Biol Chem 1995;270:25915–25919.

    Article  PubMed  CAS  Google Scholar 

  79. Arbiser JL, Moses MA, Fernandez CA, et al. Oncogenic H-ras stimulates tumour angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 1997;94:861–866.

    Article  PubMed  CAS  Google Scholar 

  80. Schlessinger J. New roles for Src kinases in control of cell survival and angiogenesis. Cell 2000; 100: 293–296.

    Article  PubMed  CAS  Google Scholar 

  81. Kumar R, Yarmand-Bagheri R. The role of HER2 in angiogenesis. Semin Oncol 2001;28(Suppl 16):27–32.

    Article  PubMed  CAS  Google Scholar 

  82. Giri D, Ittmann M. Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma. Hum Pathol 1999;30:419–424.

    Article  PubMed  CAS  Google Scholar 

  83. Claudio PP, Stiegler P, Howard CM, et al. RB2/p130 geneenhanced expression down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo. Cancer Res 2001;6:462–468.

    Google Scholar 

  84. Blancher C, Moore JW, Robertson N et al. Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxiainducible factor (HIF)-1 alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3’-kinase/Akt signaling pathway. Cancer Res 2001;61:7349–7355.

    PubMed  CAS  Google Scholar 

  85. Li CY, Shan S, Huang O, et al. Initial stages of tumor cellinduced angiogenesis: evaluation via skin window chambers in rodent models. J Nall Cancer Inst 2000;92:143–147.

    Article  CAS  Google Scholar 

  86. Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF.Science 1999;284:1994–1998.

    Article  CAS  Google Scholar 

  87. Folkman J. Incipient angiogenesis. J Nall Cancer Inst 2000;92:94–95.

    Article  CAS  Google Scholar 

  88. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995;1:149–153.

    Article  PubMed  CAS  Google Scholar 

  89. Li W. Tumor angiogenesis: molecular pathology, therapeutic targeting and imaging. Acad Radiol 2000;7:800–811.

    Article  PubMed  CAS  Google Scholar 

  90. Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 1985;315:115–122.

    Article  PubMed  CAS  Google Scholar 

  91. Folkman J, Hanahan D. Expression of the angiogenic phenotype during development of murine and human cancer, in Origins of Human Cancer: A Comprehensive Review. Brugge J, Curran T, Harlow E, et al, eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1991:pp.803–814.

    Google Scholar 

  92. Folkman J, Watson K, Ingber D, et al. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989;339:58–61.

    Article  PubMed  CAS  Google Scholar 

  93. Lacey M, Alpert S, Hanahan D. Bovine papillomavirus genome elicits skin tumours in transgenic mice. Nature 1986;322:609–612.

    Article  PubMed  CAS  Google Scholar 

  94. Kandel J, Bossy-Wetzel E, Radvanyi F, et al. Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell 1991;66:1095–1104.

    Article  PubMed  CAS  Google Scholar 

  95. Bergers G, Hanahan D, Coussens LM. Angiogenesis and apoptosis are cellular parameters of neoplastic progression in transgenic mouse models of tumorigenesis. Int J Dev Biol 1998;42(7 Spec No):99S-1002.

    Google Scholar 

  96. Coussens LM, Raymond WW, Bergers G, et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 1999;13:1382–1397.

    Article  PubMed  CAS  Google Scholar 

  97. Norrby K. Mast cells and angiogenesis. APMIS 2002;110:355–371.

    Article  PubMed  CAS  Google Scholar 

  98. Ribatti D, Crivellato E, Candussio L, et al. Mast cells and their secretory granules are angiogenic in the chick embryo chorioallantoic membrane. Clin Exp Allergy 2001;31:602–608.

    Article  PubMed  CAS  Google Scholar 

  99. Smith-McCune K, Zhu YH, Hanahan D, et al. Crossspecies comparison of angiogenesis during the premalignant stages of squamous carcinogenesis in the human cervix and K14-HPV16 transgenic mice. Cancer Res 1997;57:1294–1300.

    PubMed  CAS  Google Scholar 

  100. Folkman J. Tumor angiogenesis, in Cancer Biology, Vol 3: Biology of Tumors. FF Becker, ed. Plenum Press, New York, NY; 1975, pp.355–388.

    Chapter  Google Scholar 

  101. Wurschmidt F, Beck-Bornholdt HP, Vogler H. Radiobiology of the rhabdomyosarcoma R 1 H of the rat: influence of the size of irradiation field on tumor response, tumor bed effect, and neovascularization kinetics. Int J Radiat Oncol Biol Phvs 1990:18:879–882.

    Article  CAS  Google Scholar 

  102. Yamaura H, Yamada K, Matsuzawa T. Radiation effect on the proliferating capillaries in rat transparent chamber. Int J Radiat Biol 1976;30:179.

    Article  CAS  Google Scholar 

  103. Gimbrone MA Jr, Cotran R, Leapman S, et al. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 1972;136:261–276.

    Article  PubMed  Google Scholar 

  104. Folkman J. Tumor angiogenesis and tissue factor. Nat Med 1996;2:167–168.

    Article  PubMed  CAS  Google Scholar 

  105. Modzelewski RA, Davies P, Watkins SC, et al. Isolation and purification of fresh tumor-derived endothelial cells from a murine RIF-1 fibrosarcoma. Cancer Res 1994;54:336–339.

    PubMed  CAS  Google Scholar 

  106. Thompson WD, Shiach KJ, Fraser RA, et al. Tumours acquire their vasculature by vessel incorporation, not vessel ingrowth. J Pathol 1987;151:323–332.

    Article  PubMed  CAS  Google Scholar 

  107. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994;79:185–188.

    Article  PubMed  CAS  Google Scholar 

  108. Butler TP, Gullino PM. Quantitation of cell shedding into efferent blood of mammary adenocarcinoma. Cancer Res 1975;35:512–516.

    PubMed  CAS  Google Scholar 

  109. Folkman J. Antiangiogenesis Agents, in Cancer: Principles & Practice of Oncology, 6th ed. DeVita VT, Hellman S, Rosenberg SA, eds. Lippincott Williams & Wilkins, Philadelphia, PA, 2001, pp.509–519.

    Google Scholar 

  110. Engerman RL, Pfaffenbach D, Davis MD. Cell turnover in capillaries. Lab Investig 1967;17:738–743.

    PubMed  CAS  Google Scholar 

  111. Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer 1984;49:405–413.

    Article  PubMed  CAS  Google Scholar 

  112. Tannock IF. Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res 1970;30:2470–2476.

    PubMed  CAS  Google Scholar 

  113. Ausprunk D, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977;14:53–65.

    Article  PubMed  CAS  Google Scholar 

  114. Carmeliet P, Dor Y, Herbert JM, et al. Role of HIF-1 in hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. Nature 1998;394:485–490.

    Article  PubMed  CAS  Google Scholar 

  115. Polverini PJ, Leibovich SJ. Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Investig 1984;51:635–642.

    PubMed  CAS  Google Scholar 

  116. Dias S, Choy M, Rafii S. The role of CXC chemokines in the regulation of tumor angiogenesis. Cancer Investig 2001;19:732–738.

    Article  CAS  Google Scholar 

  117. Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000; 60:1306–1311.

    PubMed  CAS  Google Scholar 

  118. Leahy KM, Koki AT, Masferrer JL. Role of cyclooxygenases in angiogenesis. Curr Med Chem 2000;7:1163–1170.

    Article  PubMed  CAS  Google Scholar 

  119. Nor JE, Christensen J, Liu J, et al. Up-regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. Cancer Res 2001;61:2183–2188.

    PubMed  CAS  Google Scholar 

  120. Mignatti P, Tsuboi R, Robbins E, et al. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases. J Cell Biol 1989;108:671–682.

    Article  PubMed  CAS  Google Scholar 

  121. Brooks PC, Montgomery AM, Rosenfeld M, et al. Integrin α033 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994;79(7):1157–1164.

    Article  PubMed  CAS  Google Scholar 

  122. Van Der Schaft DW, Dings RP, De Lussanet QG, et al. The designer anti-angiogenic peptide anginex targets tumor endothelial cells and inhibits tumor growth in animal models. FASEB J 2002;16:1991–1993.

    PubMed  Google Scholar 

  123. Huang S, Pettaway CA, Uehara H, et al. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 2001;20:4188–4197.

    Article  PubMed  CAS  Google Scholar 

  124. Nelson AR, Fingleton B, Rothenberg ML, et al. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 2000;18:1135–1149.

    PubMed  CAS  Google Scholar 

  125. Sang QXA. Complex role of matrix metalloproteinases in angiogenesis. Cell Res 1998;8:171–177.

    Article  PubMed  CAS  Google Scholar 

  126. Koolwijk P, Sidenius N, Peters E, et al. Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12: implication for angiogenesis in fibrin matrices. Blood 2001;97:3123–3131.

    Article  PubMed  CAS  Google Scholar 

  127. Nguyen M, Folkman J, Bischoff J. 1-Deoxymannojirimycin inhibits capillary tube formation in vitro. Analysis of N-linked oligosaccharides in bovine capillary endothelial cells. J Biol Chem 1992;267:26157–26165.

    PubMed  CAS  Google Scholar 

  128. Nguyen M, Strubel NA, Bischoff J. A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis. Nature 1993;365:267–269.

    Article  PubMed  CAS  Google Scholar 

  129. Nangia-Makker P, Honjo Y, Sarvis R, et al. Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol 2000;156:899–909.

    Article  PubMed  CAS  Google Scholar 

  130. DeLisser HM, Christofidou-Solomidou M, Strieter RM, et al. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 1997;151:671–677.

    PubMed  CAS  Google Scholar 

  131. Bach TL, Barsigian C, Chalupowicz DG, et al. VE-Cadherin mediates endothelial cell capillary tube formation in fibrin and collagen gels. Exp Cell Res 1998;238:324–334.

    Article  PubMed  CAS  Google Scholar 

  132. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interactions between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998;93:741–753.

    Article  PubMed  CAS  Google Scholar 

  133. Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis and growth factors: ephrins enter the fray at the border. Cell 1998;93:661–664.

    Article  PubMed  CAS  Google Scholar 

  134. Adams RH, Wilkinson GA, Weiss C, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 1999;13:295–306.

    Article  PubMed  CAS  Google Scholar 

  135. Shin D, Garcia-Cardena G, Hayashi S, et al. Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels as sites of adult neovascularization. Dev Biol 2001;230:139–150.

    Article  PubMed  CAS  Google Scholar 

  136. Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell 1996;87:1153–1155.

    Article  PubMed  CAS  Google Scholar 

  137. Hayes AJ, Huang WQ, Mallah J, et al. Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc Res 1999;58:224–237.

    Article  PubMed  CAS  Google Scholar 

  138. Benjamin LE, Golijanin D, Itin A, et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Investig 1999;103:159–165.

    Article  PubMed  CAS  Google Scholar 

  139. Lindahl P, Johansson BR, Leveen P, et al. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997;277:242–245.

    Article  PubMed  CAS  Google Scholar 

  140. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.

    Article  PubMed  CAS  Google Scholar 

  141. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.

    Article  PubMed  CAS  Google Scholar 

  142. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001:1194–1201.

    Google Scholar 

  143. Iwaguro H, Yamaguchi J-I, Kalka C, et al. Endothelial progenitor cell vascular endothelial growth factor transfer for vascular regeneration. Circulation 2002;105:732–738.

    Article  PubMed  CAS  Google Scholar 

  144. White CW, Sondheimer HM, Crouch EC, et al. Treatment of pulmonary hemangiomatosis with recombinant interferon alpha-2a. N Engl J Med 1989;320:1197–1200.

    Article  PubMed  CAS  Google Scholar 

  145. Kruger EA, Figg WD. TNP-470: an angiogenesis inhibitor in clinical development for cancer. Expert Opin Invest Drugs 2000:9:1383–1396.

    Article  CAS  Google Scholar 

  146. Ezekowitz RBA, Mulliken JB, Folkman J. Interferon alpha-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992;326:1456–1463.

    Article  PubMed  CAS  Google Scholar 

  147. Li WW, Li VW, Tsakayannis D. Angiogenesis therapies: concepts, clinical trials, and considerations for new drug development, in The New Angiotherapy. Fan T PD, Kohn EC, eds. Humana Press, Totowa, NJ, 2002, pp. 547–571.

    Google Scholar 

  148. Watson JC, Sutanto-Ward E, Osaku M, et al. Importance of timing and length of administration of angiogenesis inhibitor TNP-470 in the treatment of K12/TRb colorectal hepatic metastases in BD-IX rats. Surgery 1999;126:358–363.

    Article  PubMed  CAS  Google Scholar 

  149. Boehm T, Folkman J, Browder T, et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997;390:404–407.

    Article  PubMed  CAS  Google Scholar 

  150. Pluda JM. Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin Oncol 1997;24:203–218.

    PubMed  CAS  Google Scholar 

  151. Folkman J, Hahnfeldt P, Hlatky L. The logic of anti-angiogenic gene therapy, in The Development of Human Gene Therapy. Friedman T, ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 1998. on. 527–543.

    Google Scholar 

  152. Herbst RS, Lee AT, Tran HT, Abbruzzese JL. Clinical studies of angiogenesis inhibitors: the University of Texas MD Anderson Center Trial of Human Endostatin. Curr Oncol Rep 2001;3:131–140.

    Article  PubMed  CAS  Google Scholar 

  153. Teicher BA, Sotomayor EA, Huang ZD. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res 1992;52:6702–6704.

    PubMed  CAS  Google Scholar 

  154. Mauceri HJ, Hanna NN, Beckett MA, et al. Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 1998;394:287–291.

    Article  PubMed  CAS  Google Scholar 

  155. Bergsland E, Hurwitz H, Fehrenbacher L, et al. A randomized phase II trial comparing rhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus 5-fluorouracil/leucovorin (FU/LV) to FU/LV alone in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 2000;19:939a, abst. no 939.

    Google Scholar 

  156. Burke PA, DeNardo SJ, Miers LA, et al. Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res 2002;62:4263–4272.

    PubMed  CAS  Google Scholar 

  157. Boucher Y, Leunig M, Jain RK. Tumor angiogenesis and interstitial hypertension. Cancer Res 1996;56:4264–4266.

    PubMed  CAS  Google Scholar 

  158. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7:987–989.

    Article  PubMed  CAS  Google Scholar 

  159. Kumar R, Kuniyasu H, Bucana CP, et al. Spatial and temporal expression of angiogenic molecules during tumor growth and progression. Oncol Res 1998;10:301–311.

    PubMed  CAS  Google Scholar 

  160. Kumar R, Yoneda J, Bucana CP, et al. Regulation of distinct steps of angiogenssis by different angiogenic molecules. Int J Oncol 1998;12:749–757.

    PubMed  CAS  Google Scholar 

  161. Relf M, LeJeune S, Scott PA, et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor b-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 1997;57:963–969.

    PubMed  CAS  Google Scholar 

  162. Friedlander M, Brooks PC, Shaffer RW, et al. Definition of two angiogenic pathways by distinct alpha v integrins. Science 1995;270:1500–1502.

    Article  PubMed  CAS  Google Scholar 

  163. Kaban LB, Mulliken JB, Ezekowitz RA, et al. Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics 1999;103:1145–1149.

    Article  PubMed  CAS  Google Scholar 

  164. Fine HA, Figg WD, Jaeckle K, et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 2000;18:708–715.

    PubMed  CAS  Google Scholar 

  165. Tulpule A, Scadden DT, Espina BM, et al. Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi’s sarcoma. J Clin Oncol 2000;18:716–723.

    PubMed  CAS  Google Scholar 

  166. Kudelka AP, Verschraegen CF, Loyer E. Complete remission of metastatic cervical cancer with the angiogenesis inhibitor TNP-470. N Engl J Med 1998;338:991–992.

    Article  PubMed  CAS  Google Scholar 

  167. Marler JJ, Rubin JB, Trede NS, et al. Successful antiangiogenic therapy of giant cell angioblastoma with interferon alfa 2b: report of 2 cases. Pediatrics 2002;109:E37.

    Article  PubMed  Google Scholar 

  168. Patt YZ, Hassan MM, Lozano RD, et al. Durable clinical response of refractory hepatocellular carcinoma to orally administered thalidomide. Am J Clin Oncol (CCT) 2000;23:319–321.

    Article  CAS  Google Scholar 

  169. Mesters RM, Padro T, Bieker R, et al. Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood 2001.98:241–243.

    Article  PubMed  CAS  Google Scholar 

  170. Barlogie B, Desikan R, Eddlemon P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001;98:492–494.

    Article  PubMed  CAS  Google Scholar 

  171. Tatum JL, Hoffman JM. Role of imaging in clinical trials of antiangiogenesis therapy in oncology. Acad Radiol 2000;7:798–799.

    Article  PubMed  CAS  Google Scholar 

  172. Sipkins DA, Cheresh DA, Kazemi MR, et al. Detection of tumor angiogenesis in vivo by alpha-Vbeta3-targeted magnetic resonance imaging. Nat Med 1998;4:623–626.

    Article  PubMed  CAS  Google Scholar 

  173. Jayson GC, Zweit J, Jackson A, et al. Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design for antiangiogenic antibodies. J Natl Cancer Inst 2002;94:1484–1493.

    Article  PubMed  CAS  Google Scholar 

  174. Hill SA, Toze GM, Petit GR, et al. Preclinical evaluation of the antitumor activity of the novel vascular targeting agent Oxi 4503. Anticancer Res 2002;22:1453–1458.

    PubMed  CAS  Google Scholar 

  175. Goto H, Yano S, Zhang H, et al. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice. Cancer Res 2002;62:3711–3715.

    PubMed  CAS  Google Scholar 

  176. Siemann DW, Mercer E, Lepler S, et al. Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int J Cancer 2002;99:1–6.

    Article  PubMed  CAS  Google Scholar 

  177. Brem H, Folkman J. Analysis of experimental antiangiogenic therapy. J Pediatr Surg 1993;28:445–451.

    Article  PubMed  CAS  Google Scholar 

  178. Li, WW, Li VW, Casey R, et al. Clinical trials of angiogenesisbased therapies: overview and new guiding principles, in Angiogenesis: Models, Modulators and Clinical Application. Maragoudakis M, ed. Plenum Press, New York, NY, 1998, pp.475–492.

    Google Scholar 

  179. Teo NB, Shoker BS, Martin L, et al. Angiogenesis in preinvasive cancers. Anticancer Res 2002;22:2061–2072.

    PubMed  CAS  Google Scholar 

  180. Vajkoczy P, Farhadi M, Gaumann A, et al. Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2. J Clin Investig 2002;109:777–785.

    PubMed  CAS  Google Scholar 

  181. Lee AH, Happerfield LC, Bobrow LG, et al. Angiogenesis and inflammation in ductal carcinoma in situ of the breast. J Pathol 1997;181:200–206.

    Article  PubMed  CAS  Google Scholar 

  182. Fisseler-Ecichoff A, Rothstein D, Muller KM. Neovascularization in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa. Virchows Arch 1996;429:95–100.

    Google Scholar 

  183. Wong MP, Cheung N, Yuen ST, et al. Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression. Int J Cancer 1999;81(6):845–850.

    Article  PubMed  CAS  Google Scholar 

  184. Dellas A, Moch H, Schultheiss E. Angiogenesis in cervical neoplasia: microvessel quantification in precancerous lesions and invasive carcinomas with clinicopathological correlations. Gynecol Oncol 1997;67:27–33.

    Article  PubMed  CAS  Google Scholar 

  185. Smith-McCune KK, Weidner N. Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 1994;54:800–804.

    PubMed  CAS  Google Scholar 

  186. Chodak GW, Haudenschild C, Gittes RF, et al. Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder. Ann Surg 1980;192(6):762–771.

    Article  PubMed  CAS  Google Scholar 

  187. Fong Y, Blumgart L, Cohen A. Surgical treatment of colorectal metastases to liver. CA Cancer J Clin 1995;45:50–62.

    Article  PubMed  CAS  Google Scholar 

  188. Paku S, Lapis K. Morphological aspects of angiogenesis in experimental liver metastases. Am J Pathol 1993;143:926–936.

    PubMed  CAS  Google Scholar 

  189. Ingber D, Fujita T, Kishimoto S, et al. Synthetic analogs of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 1990;348:555–557.

    Article  PubMed  CAS  Google Scholar 

  190. Suganuma Y, Takahashi T, Taniguchi H, et al. Inhibitory effect of anti-angiogenic agent TNP-470 (AGM-1470) on liver metastasis of VX2 carcinoma in rabbits. Reg Cancer Treat 1994;7:160–162.

    Google Scholar 

  191. Shusterman S, Grupp SA, Barr R, et al. The angiogenesis inhibitor TNP-470 effectively inhibits human neuroblastoma xenograft growth, especially in the setting of subclinical disease. Clin Cancer Res 2001;7:977–984.

    PubMed  CAS  Google Scholar 

  192. Bergers G, Javaherian K, Lo K-M, et al. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 1999;284:808–812.

    Article  PubMed  CAS  Google Scholar 

  193. Joseph IB, Vukanovic J, Isaacs JT. Antiangiogenic treatment with linomide as chemoprevention for prostate, seminal vesicle, and breast carcinogenesis in rodents. Cancer Res 1996;56:3404–3408.

    PubMed  CAS  Google Scholar 

  194. Marson LP, Kurian KM, Millere WR, et al. The effect of tamoxifen on breast tumour vascularity. Breast Cancer Res Treat 2001;66:9–15.

    Article  PubMed  CAS  Google Scholar 

  195. Ruggeri BA, Robinson C, Angeles T, et al. The chemopreventive agent oltipraz possesses potent antiangiogenic activity in vitro, ex vivo, and in vivo and inhibits tumor xenograft growth. Clin Cancer Res 2002;8:267–274.

    PubMed  CAS  Google Scholar 

  196. Lingen MW, Polverini PJ, Bouck NP. Inhibition of squamous cell carcinoma angiogenesis by direct interaction of retinoic acid with endothelial cells. Lab Investig 1996;74:476–483.

    PubMed  CAS  Google Scholar 

  197. Takahashi Y, Mai M, Nishioka K. Alpha-difluoromethylornithine induces apoptosis as well as antiangiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model. Int J Cancer 2000;85:243–247.

    PubMed  CAS  Google Scholar 

  198. Jiang C, Jiang W, Ip C, et al. Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Mol Carcinog 1999;26:213–225.

    Article  PubMed  CAS  Google Scholar 

  199. Cai T, Fassina G, Morini M, et al. N-acetylcysteine inhibits endothelial cell invasion and angiogenesis. Lab Investig 1999;79:1151–1159.

    PubMed  CAS  Google Scholar 

  200. Ebeler SE, Brenneman CA, Kim GS, et al. Dietary catechin delays tumor onset in a transgenic model. Am J Clin Nutr 2002;76:865–872.

    PubMed  CAS  Google Scholar 

  201. Wang Z, Fuentes CF, Shapshay SM. Antiangiogenic and chemopreventive activities of celecoxib in oral carcinoma cell. Laryngoscope 2002;112:839–842.

    Article  PubMed  CAS  Google Scholar 

  202. Sharma S, Ghoddoussi M, Gao P, et al. A quantitative angiogenesis model for efficacy testing of chemopreventive agents. Anticancer Res 2001;21:3829–3837.

    PubMed  CAS  Google Scholar 

  203. Kruger EA, Duray PH, Price DK, et al. Approaches to preclinical screening of antiangiogenic agents. Semin Oncol 2001;28:570–576.

    Article  PubMed  CAS  Google Scholar 

  204. Perletti G, Concari P, Giardini R, et al. Antitumor activity of endostatin against carcinogen-induced rat primary mammary tumors. Cancer Res 2000;60:1793–1796.

    PubMed  CAS  Google Scholar 

  205. Hong WK, Lippman SM, Itri LM, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 1995;332:1405–1410.

    Article  PubMed  Google Scholar 

  206. Hong WK, Endicott J, Itri LM. 13-cis-Retinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986;315:1501–1505.

    Article  PubMed  CAS  Google Scholar 

  207. Singh DK, Lippman SM. Cancer chemoprevention, part 1: retinoids and carotenoids and other classic antioxidants. Oncology 1998;12:1643–1660.

    PubMed  CAS  Google Scholar 

  208. Petkovich M, Brand NJ, Krust A, et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 1987; 330:444–450.

    Article  PubMed  CAS  Google Scholar 

  209. Lotan R. Retinoids in cancer chemoprevention. FASEB J 1996;10:1031–1039.

    PubMed  CAS  Google Scholar 

  210. Braunhut SJ, Palomares M. Modulation of endothelial cell shape and growth by retinoids. Microvasc Res 1991;41:47–62.

    Article  PubMed  CAS  Google Scholar 

  211. Ingber DE. Extracellular matrix and cell shape: potential control points for inhibition of angiogenesis. J Cell Biochem 1991;87:3579–3583.

    Google Scholar 

  212. Imcke E, Ruszczak Z, Mayer-Da Silva A, et al. Cultivation of human dermal microvascular endothelial cells in vitro: immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermato Res 1991;283:149–157.

    Article  CAS  Google Scholar 

  213. Arensman RM and Stolar CJH. Vitamin A effect on tumor angiogenesis. J Ped Surg 1979;14:809–812.

    Article  CAS  Google Scholar 

  214. Liaudet-Coopman EDE, Berchem GJ, Wellstein A. In vivo inhibition of angiogenesis and induction of apoptosis by retinoid acid in squamous cell carcinoma. Clin Cancer Res 1997;3:179–84.

    PubMed  CAS  Google Scholar 

  215. Majewski S, Szmurlo A, Marczak M, et al. Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination. Cancer Lett 1993;75:35–39.

    Article  PubMed  CAS  Google Scholar 

  216. Yasuda Y, Nishi N, Takahashi JA, et al. Induction of avascular yolk sac due to reduction of basic fibroblast growth factor by retinoic acid in mice. Dev Biol 1992;150:397–413.

    Article  PubMed  CAS  Google Scholar 

  217. Kirkpatrick K, Ogunkolade W, Elkak A, et al. The mRNA expression of cyclo-oxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human breast cancer. Curr Med Res Opin 2002;18:237–241.

    Article  PubMed  CAS  Google Scholar 

  218. Changching DL, Kenyon L, Hyslop T, et al. Cyclooxygenase-2 (COX-2) expression in human meningioma: correlation with malignant progression and potential target. Proc Am Soc Clin Oncol 2002: Abstract #296.

    Google Scholar 

  219. Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 2000;89:2637–2645.

    Article  PubMed  CAS  Google Scholar 

  220. Krishnan K, Arnett D, Youngberg G. Expression of Bcl-2, CD95, VEGF, Ki-67 and COX-2 in Barrett’s esophagus and esophageal carcinoma: markers for esophageal cancer chemoprevention trials. Proc Am Soc Clin Oncol 2002: Abstract #2276.

    Google Scholar 

  221. Kang, J, Kim E, Shin H, et al. The overexpression of cyclooxygenase-2 (COX-2) and antitumor effect of selective COX-2 inhibitor (SC-236) in gastric cancer. Proc Am Soc Clin Oncol 2000; Abstract #1279.

    Google Scholar 

  222. Half E, Tang XM, Gwyn K, et al. Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 2002;62:1676–1681.

    PubMed  CAS  Google Scholar 

  223. Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2001;2:544–551.

    Article  PubMed  CAS  Google Scholar 

  224. Amano H, Hayashi I, Yoshida S, et al. Cyclooxygenase-2 and adenylate cyclase/protein kinase A signaling pathway enhances angiogenesis through induction of vascular endothelial growth factor in rat sponge implants. Hum Cell 2002;15:13–24.

    Article  PubMed  Google Scholar 

  225. Leahy KM, Ornberg RL, Wang Y, et al. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 2002;62:625–631.

    PubMed  CAS  Google Scholar 

  226. Fosslien E. Review: molecular pathology of cyclooxygenase2 in cancer-induced angiogenesis. Ann Clin Lab Sci 2001;31:325–348.

    PubMed  CAS  Google Scholar 

  227. Dormand O, Bezzi M, Mariotti A, et al. Prostaglandin E2 promotes integrin avb3-dependent endothelial cell adhesion, Rac activation and spreading through cAMP/PKA-dependent signaling. J Biol Chem 2002;277:4S838–4S846.

    Google Scholar 

  228. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc 716 knockout mice by inhibition of cyclooxygenase-2 (COX-2). Cell 1996;87:803–809.

    Article  PubMed  CAS  Google Scholar 

  229. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946–1952.

    Article  PubMed  CAS  Google Scholar 

  230. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–1388.

    Article  PubMed  CAS  Google Scholar 

  231. Hershman D, Sundararajan V, Jacobson JS, et al. Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost effectiveness analysis. J Clin Oncol 2002;20:9–16.

    Article  PubMed  CAS  Google Scholar 

  232. Gelmann EP. Tamoxifen induction of apoptosis in estrogen receptor-negative cancers: new tricks for an old dog? J Natl Cancer Inst 1996;88:224–226.

    Article  PubMed  CAS  Google Scholar 

  233. McNamara DA, Harmey J, Wang JH, et al. Tamoxifen inhibits endothelial cell proliferation and attenuates VEGFmediated angiogenesis and migration in vivo. Eur J Surg Oncol 2001;27:714–718.

    Article  PubMed  CAS  Google Scholar 

  234. Blackwell KL, Haroon ZA, Shan S, et al. Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res 2000;6(11):4359–4364.

    PubMed  CAS  Google Scholar 

  235. Gagliardi A, Collins DC. Inhibition of angiogenesis by antiestrogens. Cancer Res 1993;53(3):533–535.

    PubMed  CAS  Google Scholar 

  236. Haran EF, Maretzek AF, Goldberg I, et al. Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. Cancer Res 1994;54:5511–5514.

    PubMed  CAS  Google Scholar 

  237. Gagliardi AR, Hennig B, Collins DC. Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors. Anticancer Res 1996;16:1101–1106.

    PubMed  CAS  Google Scholar 

  238. Buteau-Lozano H, Ancelin M, Lardeux B, et al. Transcriptional regulation of vascular endothelial growth factor by estradiol and tamoxifen in breast cancer cells: a complex interplay between estrogen receptors alpha and beta. Cancer Res 2002;62:4977–4984.

    PubMed  CAS  Google Scholar 

  239. Thamrongwittawatpong L, Sirivatanauksorn Y, Batten JJ, et al. The effect of N(G)-monomethyl-L-arginine and tamoxifen on nitric oxide production in breast cancer cells stimulated by estrogen and progesterone. Eur J Surg 2001;167:484–489.

    Article  PubMed  CAS  Google Scholar 

  240. Gallo O, Masini E, Morbidelli L, et al. Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J Natl Cancer Inst 1998;90(8):587–596.

    Article  PubMed  CAS  Google Scholar 

  241. Garcia-Cardena G, Folkman J. Is there a role for nitric oxide in tumor angiogenesis? J Natl Cancer Inst 1998;90:560–561.

    Article  PubMed  CAS  Google Scholar 

  242. Hyder SM, Stancel GM, Chiappetta C, et al. Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen. Cancer Res 1996;56:3954–3960.

    PubMed  CAS  Google Scholar 

  243. Hague S, Manek S, Oehler MK, et al. Tamoxifen induction of angiogenic factor expression in endometrium. Br J Cancer 2002;86:761–767.

    Article  PubMed  CAS  Google Scholar 

  244. Neis KJ, Brandner P, Schlenker M. Tamoxifen-induced hyperplasia of the endometrium. Contrib Gynecol Obstet 2000;20:60–68.

    Article  PubMed  CAS  Google Scholar 

  245. Maugeri G, Nardo LG, Campione C, et al. Endometrial lesions after tamoxifen therapy in breast cancer women. Breast J 2001;7:240–244.

    Article  PubMed  CAS  Google Scholar 

  246. Deligdisch L, Kalir T, Cohen CJ, et al. Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer. Gynecol Oncol 2000;78:181–186.

    Article  PubMed  CAS  Google Scholar 

  247. Gail MH, Costantino JP, Bryant J, et al. Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 1999;91:1829–1846.

    Article  PubMed  CAS  Google Scholar 

  248. Yang CS, Wang Z-Y. Tea and cancer. J Natl Cancer Inst 1993:85:1038–1049.

    Article  PubMed  CAS  Google Scholar 

  249. Wang ZY, Wang LD, Lee MJ, et al. Inhibition of N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in rats by green and black tea. Carcinogenesis 1995;16:2143–2148.

    Article  PubMed  CAS  Google Scholar 

  250. Yang U, Wang ZY, Kim S, et al. Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice. Cancer Res 1997;57:1889–1894.

    PubMed  CAS  Google Scholar 

  251. Wang ZY, Cheng SI, Zhou ZC, et al. Antimutagenic activity of green tea polyphenols. Mutat Res 1989;223:273–285.

    Article  PubMed  CAS  Google Scholar 

  252. Wang ZY, Hong JY, Huang MT, et al. Inhibition of N-nitrosodiethylamine- and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mice by green tea and black tea. Cancer Res 1992;52:1943–1947.

    PubMed  CAS  Google Scholar 

  253. Sazuka M, Murakami S, Isemura M, et al. Inhibitory effects of green tea infusion on in vitro invasion and in vivo metastasis of mouse lung carcinoma cells. Cancer Lett 1995;98:27–31.

    PubMed  CAS  Google Scholar 

  254. Taniguchi S, Fujiki H, Kobayashi K, et al. Effect of (-)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. Cancer Lett 1992;65:51–54.

    Article  PubMed  CAS  Google Scholar 

  255. Cao Y, Cao R. Angiogenesis inhibited by drinking green tea. Nature 1999;398:381.

    Article  PubMed  CAS  Google Scholar 

  256. Garbisa S, Biggin S, Cavallarin N, et al. Tumor invasion: molecular shears blunted by green tea. Nat Med 1999;5:1216.

    Article  PubMed  CAS  Google Scholar 

  257. Garbisa S, Sartor L, Biggin S, et al. Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin3-gallate. Cancer 2001;91:822–832.

    Article  PubMed  CAS  Google Scholar 

  258. Lu YP, Lou YR, Xie JG, et al. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tmors in mice. Proc Natl Acad Sci USA 2002;99:12455–12460.

    Article  PubMed  CAS  Google Scholar 

  259. Lamartiniere CA, Cotroneo MS, Fritz WA, et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J Nutr 2002;132:5525–558S.

    Google Scholar 

  260. Cotroneo MS, Wang J, Fritz WA, et al. Genistein action in the prepubertal mammary gland in a chemoprevention model. Carcinogenesis 2002;23:1467–1474.

    Article  PubMed  CAS  Google Scholar 

  261. Constantinou AI, Lantvit D, Hawthorne M, et al. Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats. Nutr Cancer 2001;41:75–81.

    PubMed  CAS  Google Scholar 

  262. Brown A, Jolly P, Wei H. Genistein modulates neuroblastoma cell proliferation and differentiation through induction of apoptosis and regulation of tyrosine kinase activity and N-myc expression. Carcinogenesis 1998;19:991–997.

    Article  PubMed  CAS  Google Scholar 

  263. Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer 1999;35:167–174.

    Article  PubMed  CAS  Google Scholar 

  264. Dixon RA, Ferreira D. Genistein. Phytochemistry 2002;60:205–211.

    Article  PubMed  CAS  Google Scholar 

  265. Adlercreutz H, Honjo H, Higashi A, et al. Urinary excretion of lignans and isoflavanoid phytoestrogens in Japanese men and women consuming traditional Japanese diet. Am J Clin Nutr 1991;54:1093–1100.

    PubMed  CAS  Google Scholar 

  266. Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 1993;90:2690–2694.

    Article  PubMed  CAS  Google Scholar 

  267. Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary ingested isoflavanoid, inhibits cell proliferation and in vitro angiogenesis. J Nutr 1995;125:790S-797S.

    PubMed  CAS  Google Scholar 

  268. Muir C, Waterhouse J, Mack T, et al. Cancer Incidence in Five Continents, Vol. 5. Lyon France: International Agency for Research on Cancer, 1987.

    Google Scholar 

  269. Severson RK, Nomura AMY, Grove JS, et al. A prospective study of demographics and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 1989;49:1857–1860.

    PubMed  CAS  Google Scholar 

  270. Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987;262:5592–5595.

    PubMed  CAS  Google Scholar 

  271. Guo D, Jia Q, Song HY, et al. Vascular endothelial growth factor promotes tyrosine phosphorylation of mediators of signal transduction that contain SH2 domains. Association with endothelial cell proliferation. J Biol Chem 1995;270:6729–6733.

    Article  PubMed  CAS  Google Scholar 

  272. Levy AP, Levy NS, Goldberg MA. Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 1996;271:113–131.

    Google Scholar 

  273. Xia P, Aiello LP, Ishii H, et al. Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Investig 1996;988:2018–2026.

    Article  Google Scholar 

  274. Angiogenesis Foundation Clinical Trials Database, 2003. http:// www.clinicaltrials.gov

  275. Perkins S, Verschoyle RD, Hill K, et al. Chemopreventive efficacy and pharmacokinetics of curcumin in the mink mouse, a model of familial adenomatous polyposis. Cancer Epidemiol Biomark Prey 2002;11:535–540.

    CAS  Google Scholar 

  276. Goel A, Boland CR, Chauhan DP. Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. Cancer Lett 2001;172:111–118.

    Article  PubMed  CAS  Google Scholar 

  277. Dorai T, Cao YC, Dorai B, et al. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 2001;47:293–303.

    Article  PubMed  CAS  Google Scholar 

  278. Gururaj A, Belakavadi M, Venkatesh D, et al. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Commun 2002;297:934–942.

    Article  PubMed  CAS  Google Scholar 

  279. Shao ZM, Shen ZZ, Liu CH, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int J Cancer 2002;98:234–240.

    Article  PubMed  CAS  Google Scholar 

  280. Mohan R, Sivak J, Ashton P, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem 2000;275:10405–10412.

    Article  PubMed  CAS  Google Scholar 

  281. Shin EY, Kim SY, Kim EG. c-Jun N-terminal kinase is involved in motility of endothelial cells. Exp Mol Med 2001;33:276–283.

    Article  PubMed  CAS  Google Scholar 

  282. Thaloor D, Singh AK, Sidhu GS, et al. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell Growth Differ 1998;9:305–312.

    PubMed  CAS  Google Scholar 

  283. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895–2900.

    PubMed  CAS  Google Scholar 

  284. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218–220.

    Article  PubMed  CAS  Google Scholar 

  285. Kimura Y, Okuda H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr 2001;13:1844–1849.

    Google Scholar 

  286. Brakenhielm E, Cao R, Cao Y. Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J 2001;10:1798–1800.

    Google Scholar 

  287. Bertelli AA, Baccalini R, Battaglia E, et al. Resveratrol inhibits TNF alpha-induced endothelial cell activation. Therapie 2001;56:613–616.

    Article  PubMed  CAS  Google Scholar 

  288. Igura K, Ohta T, Kuroda Y, et al. Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Lett 2001;171:11–16.

    Article  PubMed  CAS  Google Scholar 

  289. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbez(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 2002;62:4945–4954.

    PubMed  CAS  Google Scholar 

  290. Masso-Welch PA, Zangani D, Ip C, et al. Inhibition of angiogenesis by the chemopreventive agents conjugated linoleic acid. Cancer Res 2002;62:4383–4389.

    PubMed  CAS  Google Scholar 

  291. Mehta RG, Liu J, Constaritinou A, et al. Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage. Carcinogenesis 1995;16:399–404.

    Article  PubMed  CAS  Google Scholar 

  292. Garg A, Garg S, Zaneveld LJ, et al. Chemistry and pharmacology of the citrus bioflavanoid herperidin. Phytother Res 2001;15:655–669.

    Article  PubMed  CAS  Google Scholar 

  293. So FV, Guthrie N, Chambers AF, et al. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavanoids and citrus juices. Nutr Cancer 1996;26:167–181.

    Article  PubMed  CAS  Google Scholar 

  294. Akagi K, Hirose M, Hoshiya T, et al. Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model. Cancer Lett 1995;94:113–121.

    Article  PubMed  CAS  Google Scholar 

  295. Kohno H, Tanaka T, Kawabata K, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavanoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 2002;101:461–468.

    Article  PubMed  CAS  Google Scholar 

  296. Kwon KB, Yoo SJ, Ryu DG, et al. Induction of apoptosis by allul disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol 2002;63:41–47.

    Article  PubMed  CAS  Google Scholar 

  297. Panigrahy D, Singer S, Shen LQ, et al. PPARy ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Investig 2002;110:923–932.

    PubMed  CAS  Google Scholar 

  298. Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis. Circulation 2002;105:739–745.

    Article  PubMed  CAS  Google Scholar 

  299. Niethammer AG, Xiang R, Becker JC, et al. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 2002;8(12):1369–1375.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. William W. Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Li, W.W. (2004). Tumor Angiogenesis as a Target for Early Intervention and Cancer Prevention. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_40

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-767-3_40

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-342-8

  • Online ISBN: 978-1-59259-767-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation