Angiogenesis pp 389-405 | Cite as

Tumoral Vascularity: What Does It Tell Us About the Growth and Spread of Cancer?

  • Noel Weidner
Chapter
Part of the NATO ASI Series book series (NSSA, volume 298)

Abstract

Without blood vessels, tumor cells continue to grow until passive diffusion no longer allows enough nutrients to enter or metabolic waste products to exit (1–17). Furthermore, intratumoral endothelial cells proliferate faster than those in the adjacent benign stroma (45-fold faster in breast carcinoma and 30-fold in prostate carcinoma) (18, 19), and the rate of tumor progression increases with increased intratumoral vascularity (19–92). Also, different techniques to specifically inhibit angiogenesis (i.e., not cytostatic to tumor cells in vitro) clearly inhibit tumor growth in vivo (93–104). For example, an analog of fumagillin (a.k.a. AGM-1470 or TNP-470) inhibits endothelial proliferation in vitro and tumor-induced angiogenesis in vivo (95) TNP-470 and other angiogenesis inhibitors are now in various phases of clinical trials as therapeutic agents for a variety of malignant solid tumors, leukemias, and infantile hemangiomas (1,93,94). Moreover, Kim et al. (97) found that inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis suppressed tumor growth in vivo. This group injected human malignant cell lines into nude mice followed by treatment with a monoclonal antibody specific for VEGF. The antibody inhibited the tumor growth and reduced tumor vessel density, but had no effect on the growth rate of the tumor cells in vitro. Millauer et al. (99) noted marked suppression of tumor growth with the introduction of defective VEGF receptors into tumor endothelial cells. He also noted that a single intravascular injection of antagonists of the ν3 integrin disrupted ongoing angiogenesis in the chick chorioallantoic membrane.

Keywords

Vascular Endothelial Growth Factor Breast Carcinoma Tumor Angiogenesis Microvessel Density Invasive Breast Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Folkman J. Clinical applications of angiogenesis research. N Engl J Med 1995; 333, 1757–1763.PubMedCrossRefGoogle Scholar
  2. 2.
    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285:1182–1186.PubMedCrossRefGoogle Scholar
  3. 3.
    Folkman J, Hochberg M, Knighton D. Self-regulation of growth in three dimensions: the role of surface area limitations. In: Clarkson B, Baserga R, eds, Control of Proliferation in Animal Cells, Cold Spring Harbor: Cold Spring Harbor Laboratory, 1974; pp 833–842.Google Scholar
  4. 4.
    Sutherland RM. Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 1988; 240:177–184.PubMedCrossRefGoogle Scholar
  5. 5.
    Sutherland RM, McCredie JA, Inch WR. Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 1971; 46:113–120.PubMedGoogle Scholar
  6. 6.
    Blood CH, Zetter BR. Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochimica et Biophysica Acta 1990; 1032:89–118.PubMedGoogle Scholar
  7. 7.
    Gimbrone MA, Leapman SB, Cotran RS, Folkman J. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 1972; 136:261–276.PubMedCrossRefGoogle Scholar
  8. 8.
    Gimbrone MA, Cotran RS, Leapman SB, Folkman J. Tumor growth neovascularization: An experimental model using rabbit cornea. J Natl Canc Inst 1974; 52:413–427.Google Scholar
  9. 9.
    Folkman J. What is the evidence that tumors are angiogenesis-dependent? J Natl Cancer Instit 1990; 82:4–6.CrossRefGoogle Scholar
  10. 10.
    Antonelli-Orlidge A, Saunders KB, Smith SR, D’Amore PA. An activated form of transforming growth factor-beta is produced by co-cultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 1989; 86:4544–4588.PubMedCrossRefGoogle Scholar
  11. 11.
    Ausprunk DH, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977; 14:53–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Adam JA, Maggelakis AA. Diffusion of regulated growth characteristics of a spherical prevascular carcinoma. Bull Math Biol 1990; 52:549–582.PubMedGoogle Scholar
  13. 13.
    Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS. Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Aca Sci USA 1986; 83:4167–4171.CrossRefGoogle Scholar
  14. 14.
    Knighton D, Ausprunk D, Tapper D, Folkman J. Avascular and vascular phases of tumor growth in the chick embryo. Brit J Canc 1977; 35:347–356.CrossRefGoogle Scholar
  15. 15.
    Lien W, Ackerman N. The blood supply of experimental liver metastases. II. A microcirculatory study of normal and tumor vessels of the liver with the use of perfused silicone rubber. Surgery 1970; 68:334–340.PubMedGoogle Scholar
  16. 16.
    Thompson WD, Shiach KJ, Fraser RA, Mcintosh LC, Simpson JG. Tumors acquire their vasculature by vessel incorporation, not vessel ingrowth. J Pathol 1987; 151:323–332.PubMedCrossRefGoogle Scholar
  17. 17.
    Skinner SA, Tutton PJM, O’Brien PE. Microvascular architecture of experimental colon tumors in the rat. Cancer Res 1990; 50: 2411–2417.PubMedGoogle Scholar
  18. 18.
    Vartanian R, Weidner N. Correlation of intratumoral endothelial-cell proliferation with microvessel density (tumor angiogenesis) and tumor-cell proliferation in breast carcinoma. Am JPathol 1994; 144:1188–1194.Google Scholar
  19. 19.
    Vartanian RK, Weidner N. Endothelial cell proliferation in human prostatic carcinoma and hyperplasia: correlation with microvessel density, epithelial cell proliferation, and Gleason’s score. Lab Invest 1995; 73:844–850.PubMedGoogle Scholar
  20. 20.
    Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1–8, 1991.PubMedCrossRefGoogle Scholar
  21. 21.
    Bosari S, Lee AKC, DeLellis RA, et al. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 23:755–761, 1992.PubMedCrossRefGoogle Scholar
  22. 22.
    Horak E, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340:1120–1124, 1992.PubMedCrossRefGoogle Scholar
  23. 23.
    Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84:1875–1887, 1992.PubMedCrossRefGoogle Scholar
  24. 24.
    Visscher DW, Smilanetz S, Drozdowicz S, Wykes SM. Prognostic significance of image morphometric microvessel enumeration in breast carcinoma. Anal Quant Cytolol Histol 15:88–92, 1993.Google Scholar
  25. 25.
    Toi M, Kashitani J, Tominaga T. Tumor angiogenesis is an independent prognostic indicator of primary breast carcinoma. Int J Cancer 55:371–374, 1993.PubMedCrossRefGoogle Scholar
  26. 26.
    Gasparini G, Weidner N, Bevilacqua P, Maluta S, Dalla Palma P, Caffo O, Barbareschi M, Boracchi P, Marubini E, Pozza F. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol 12:454–466, 1994.PubMedGoogle Scholar
  27. 27.
    Obermair A, Czerwenka K, Kurz C, Buxbaum P, Schemper M, Sevela P. Influenceof Tumoral Microvessel Density on the Recurrence-Free Survival in Human Breast Cancer: Preliminary Results. Onkologie 17:44–49, 1994.CrossRefGoogle Scholar
  28. 28.
    Gasparini G, Bevilacqua P, Boracchi P, Maluta S, Pozza F, Barbareschi M, Dalla Palma P, Mezzetti M, Harris AL. Prognostic value of p53 expression in early-stage breast carcinoma compared with tumour angiogenesis, epidermal growth factor receptor, c-erbB2, cathepsin D, DNA ploidy, parameters of cell kinetics and conventional features. Int J Oncol 4:155–162, 1994.PubMedGoogle Scholar
  29. 29.
    Fox SB, Leek AK, DeLellis RA, et al. Tumor angiogenesis in node-negative breast carcinomas: relationship with epidermal growth factor receptor, estrogen receptor, and survival. Breast Can Res Treat 29:109–116, 1994.CrossRefGoogle Scholar
  30. 30.
    Gasparini G, Barbareschi M, Boracchi P, Bevilacqua P, Verderio P, Dalla Palma P, Menard S. 67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer. Int J Cancer 60:7604–610, 1995.CrossRefGoogle Scholar
  31. 31.
    Inada K, Toi M, Hoshina S, Hayashi K, Tominaga T. Significance of tumor angiogenesis as an independent prognostic factor in axillary node-negative breast cancer. Gan To Kagaku Jap J Cancer Chemo 22 (suppl l):59–65, 1995.Google Scholar
  32. 32.
    Charpin C, Devictor B, Bergeret D, Andrac L, Boulat J, Horschowski N, Lavaut MN, Piana L. CD 31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors. Am J Clin Pathol 103:443–448, 1995.PubMedGoogle Scholar
  33. 33.
    Barbareschi M, Gasparini G, Weidner N, Morelli L, Forti S, Eccher C, Fina P, Leonardi E, Mauri F, Bevilacqua P, Dalla Palma P. Microvessel density quantification in breast carcinomas: assessment by manual vs. a computer-assisted image analysis system. Appl Immunohistochern 3:75–84, 1995.Google Scholar
  34. 34.
    Obermair A, Czerwenka K, Kurz C, Kaider A, Sevelda P. Tumor vascular density in breast tumors and their effect on recurrence free survival. Chirurg 65:611–615, 1994.PubMedGoogle Scholar
  35. 35.
    Toi M, Hoshina S, Yamamoto Y, Ishiit, Hayashi K, Tominaga T. Tumor angiogenesis in breast carcinoma: significance of vessel density as a prognostic indicator. Gan To Kagaku Ryoho Japanese J Cancer Chemo 21 (Suppl 2): 178–182, 1994.Google Scholar
  36. 36.
    Gasparini G, Barbareschi M, Boracchi P, Verderio P, Caffo O, Meli S, Palma PD, Marubini E, Bevilacqua P. Tumor angiogenesis may predict clinical outcome of node-positive breast cancer patients treated either with adjuvant hormone therapy or chemotherapy. Cancer J Sci Am 1:131–141, 1995.PubMedGoogle Scholar
  37. 37.
    Ogawa Y, Chung Y-S, Nakata B, Takatsuka S, Maeda K, Sawada T, Kato Y, Yoshikawa K, Sakurai M, Sowa M. Microvessel quantitation in invasive beast cancer by staining for factor VIII-related antigen. Brit J Cancer 1995; 71: 1297–1301.PubMedCrossRefGoogle Scholar
  38. 38.
    Obermair A, Kurz C, Czervenka K, Thoma M, Kaider A, Wagner T, Gitsch G, Sevelda P. Microvessel density and vessel invasion in lymph node negative breast cancer: effect on recurrence-free survival. Int J Cancer 62:126–130, 1995.PubMedCrossRefGoogle Scholar
  39. 39.
    Bevilacqua P, Barbareschi M, Verderio P, Boracchi P, Caffo O, Dalla Palma P, Meli S, Weidner N, Gasparini G. Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma — results of a multiparametric study. Breast Cancer Res Treat 1995; 36:205–217.PubMedCrossRefGoogle Scholar
  40. 40.
    Toi M, Inada K, Suzuki H, Tominaga T. Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. Breast Cancer Res Treat 1995; 36:193–204.PubMedCrossRefGoogle Scholar
  41. 41.
    Gasparini G, Barbareschi M, Boracchi P, Bevilacqua P, Verderio P, Calla Palma P, Menard S. 67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer. In J Cancer 1995; 60:604–610.Google Scholar
  42. 42.
    Fox SB, Turner GDH, Leek RD, Whitehouse RM, Gatter KC, Harris AL. The prognostic value of quantitative angiogenesis in breast cancer and role of adhesion molecule expression in tumor endothelium. Breast Cancer Res Treat 1995; 36:219–226.PubMedCrossRefGoogle Scholar
  43. 43.
    Scopinaro F, Schillaci O, Scarpini M, Mingazzini PL, diMacio L, Banci M, Danieli R, Zerilli M, Limiti MR, Centi Colella A. Technetium-99m sestamibi: an indicator of breast cancer invasiveness. Eur J Nucl Med 1994; 21:984–987.PubMedCrossRefGoogle Scholar
  44. 44.
    Lipponen P, Ji H, Aaltomaa S, Syrjanen K. Tumor vascularity and basement membrane structure in breast cancer as related to tumor histology and prognosis. J Cancer Res Clin Oncol 1994; 120:645–650.PubMedCrossRefGoogle Scholar
  45. 45.
    Wakui S, Furusato M, Itoh T, Sasaki H, Akiyama A, Kinoshita I, Asano K, Tokuda T, Aizawa S, Ushigome S. Tumor angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study. J Pathol 168:257–262, 1992.PubMedCrossRefGoogle Scholar
  46. 46.
    Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143:401–409, 1993.PubMedGoogle Scholar
  47. 47.
    Fregene TA, Khanuja PS, Noto AC, Gehani SK, Van Egmont EM, Luz DA, Pienta KJ. Tumor- associated angiogenesis in prostate cancer. Anticancer Res 13:2377–2381, 1993.PubMedGoogle Scholar
  48. 48.
    Brawer MK, Deering RE, Brown M, Preston SD, Bigler SA. Predictors of pathologic stage in prostate carcinoma. Cancer 73:678–687, 1994.PubMedCrossRefGoogle Scholar
  49. 49.
    Vesalainen S, Lipponen P, Talja M, Alhava E, Syrjanen K. Tumor vascularity and basement membrane structure as prognostic factors in T1–2M0 prostatic adenocarcinoma. Anticancer Res 14:709–714, 1994.PubMedGoogle Scholar
  50. 50.
    Hall MC, Troncoso P, Pollack A, Zhau HY, Zagars GK, Chung LW, von Eschenbach AC. Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy. Urology 44:869–875, 1994.PubMedCrossRefGoogle Scholar
  51. 51.
    Mikami Y, Tsukuda M, Mochimatsu I, Kokatsu T, Yago T, Sawaki S. Angiogenesis in head and neck tumors. Nip Jib Gak Kai 96:645–50, 1991.CrossRefGoogle Scholar
  52. 52.
    Gasparini G, Weidner N, Bevilacqua P, Maluta S, Boracchi P, Testolin A, Pozza F, Folkman J. Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma. Int J Cancer 1993; 55:739–744.PubMedCrossRefGoogle Scholar
  53. 53.
    Albo D, Granick MS, Jhala N, Atkinson B, Solomon MP. The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck. Ann Plast Surg 32:588–594, 1994.PubMedCrossRefGoogle Scholar
  54. 54.
    Williams JK, Carlson GW, Cohen C, Derose PB, Hunter S, Jurkiewicz MJ. Tumor angiogenesis as a prognostic factor in oral cavity tumors. Am J Surg 168:373–380, 1994.PubMedCrossRefGoogle Scholar
  55. 55.
    Alcalde RE, Shintani S, Yoshihama Y, Matsumura T. Cell proliferation and tumor angiogenesis in oral squamous cell carcinomas. Anticancer Res 1995; 15:1417–1422.PubMedGoogle Scholar
  56. 56.
    Macchiarini P, Fontanini G, Hardin MJ, Hardin MJ, Squartini F, Angeletti CA. Relation of neovasculature to metastasis of non-small-cell lung cancer. Lancet 340:145–146, 1992PubMedCrossRefGoogle Scholar
  57. 57.
    Macchiarini P, Fontanini G, Dulmet E, de Montpreville V, Chapelier AR, Cerrin J, Le Roy Ladurie F, Dartevelle PG. Angiogenesis: an indicator of metastasis in non-small-cell lung cancer invading the thoracic inlet. Ann Thorac Surg 57:1534–1539, 1994.PubMedCrossRefGoogle Scholar
  58. 58.
    Yamazaki K, Abe S, Takekawa H, Sukoh N, Watanabe N, Ogura S, Nakajima I, Isobe H, Inoue K, Kawakami Y. Tumor angiogenesis in human lung adenocarcinoma. Cancer 1994; 74:2245–2250.PubMedCrossRefGoogle Scholar
  59. 59.
    Yuan A, Yang P-C, Yu C-J, Yao Y-T, Lee Y-C, Kuo S-H, Luh K-T. Tumor angiogenesis correlates with histologic type and nodal metastasis in non-small cell lung carcinoma. Amer J Resp Critical Care Med Dec. 1995, 152(6 Pt 1): 2157–62.CrossRefGoogle Scholar
  60. 60.
    Fontanini G, Bigini D, Vignati S, Basolo F, Mussi A, Lucchi M, Chine S, Angeletti CA, Bevilacqua G. Recurrence and death in non small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products. J Pathol 1995; 177:57–63.PubMedCrossRefGoogle Scholar
  61. 61.
    Angeletti, CA, Lucchi M, Fontanini G, Mussi A, Chella A, Ribechini A, Vignati S, Bevilacqua G. Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence. CA, Aug 1, 1996; 78(3):409–15.Google Scholar
  62. 62.
    Srivastava A, Laidler P, Hughes LE, Woodcock J, Shedden EJ. Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study. Eur J Cancer Clin Oncol 22:1205–1209, 1986.PubMedCrossRefGoogle Scholar
  63. 63.
    Srivastava A, Laidler P, Davies R, Horgan K, Hughes LE. The prognostic significance of tumor vascularity in intermediate-thickness (0.76–4.0 mm thick) skin melanoma. Am J Pathol 133:419–23, 1988.PubMedGoogle Scholar
  64. 64.
    Smolle J, Soyer H-P, Hofmann-Wellenhof R, Smolle-Juettner FM, Kerl H. Vascular architecture of melanocytic skin tumors. A quantitative immunohistochemical study using automated image analysis. Path Res Pract 185:740–745, 1989.PubMedCrossRefGoogle Scholar
  65. 65.
    Fallowfield ME, Cook MG. The vascularity of primary cutaneous melanoma. J Pathol 1991; 164:241–244.PubMedCrossRefGoogle Scholar
  66. 66.
    Barnhill RL, Levy MA. Regressing thin cutaneous malignant melanomas (<1.0 mm) are associated with angiogenesis. Am J Pathol 1993; 143:99–104.PubMedGoogle Scholar
  67. 67.
    Vacca A, Ribatti D, Roncali L, Lospalluti M, Serio G, Carrel S, Dammacco F. Melanocyte tumor progression is associated with changes in angiogenesis and expression of the 67-kilodalton laminin receptor. Cancer 72:455–461, 1993.PubMedCrossRefGoogle Scholar
  68. 68.
    Graham CH, Rivers J, Kerbel RS, Stankiewicz KS, White WL. Extent of vascularization as a prognostic indicator in thin (<0.76 mm) malignant melanomas. Am J Pathol 145:510–514, 1994PubMedGoogle Scholar
  69. 69.
    Saclarides TJ, Speziale NJ, Drab E, Szeluga DJ, Rubin DB. Tumor angiogenesis and rectal carcinoma. Dis Colon Rectum 37:921–926, 1994.PubMedCrossRefGoogle Scholar
  70. 70.
    Maeda K, Chung Y-S, Takatsuka S, Ogawa Y, Sawada T, Yamashito Y, Onoda N, Kato Y, Nitta A, Arimoto Y, Kondo Y, Sowa M. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. J Clin Oncol 13:477–481, 1995.PubMedGoogle Scholar
  71. 71.
    Maeda K, Chung YS, Takatsuka S, Ogawa Y, Onoda N, Sawada T, Kato Y, Nitta A, Arimoto Y, Kondo Y, Sowa M. Tumor angiogenesis and tumor cell proliferation as prognostic indicators in gastric carcinoma. Br J Cancer 1995; 72:319–323.PubMedCrossRefGoogle Scholar
  72. 72.
    Takebayashi Y, Akiyama S-I, Yamada K, Akiba S, Aikou T. Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma. Cancer 1996; 78(2):226–31.PubMedCrossRefGoogle Scholar
  73. 73.
    Olivarez D, Ulbright T, DeRiese W, Foster R, Reister T, Einhorn L, Sledge G. Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease. Cancer Res 54:2800–2802, 1994.PubMedGoogle Scholar
  74. 74.
    Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F, Dammacco F. Bone marrow angiogenesis and progression in multiple myeloma. Brit J Haematol 87:503–508, 1994.CrossRefGoogle Scholar
  75. 75.
    Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PM, Sallan SE, Folkman J. Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet 334:82–86, 1994.CrossRefGoogle Scholar
  76. 76.
    Leon SP, Folkerth RD, Black PM. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 1996; 77(2):362–72.PubMedCrossRefGoogle Scholar
  77. 77.
    Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147:33–41, 1995.PubMedGoogle Scholar
  78. 78.
    Volm M, Koomagi R, Kaufmann M, Mattern J, Stammler G. Microvessel density, expression of proto- oncogenes, and resistance-related proteins and incidence of metastases in primary ovarian carcinomas. Clin Exp Met 1996; (In press).Google Scholar
  79. 79.
    Wiggins DL, Granai CO, Steinhoff MM, Calabresi P. Tumor angiogenesis as a prognostic factor in cervical carcinoma. Gynecol Oncol 56:353–356, 1995.PubMedCrossRefGoogle Scholar
  80. 80.
    Bremer GL, Tiebosch ATMG, van der Putten HWHM, Schouten HJA, de Haan J, Arends J-W. Tumor angiogenesis: an independent prognostic parameter in cervical cancer. Amer J Obstet Gynecol, Jan 1996; 174(1 Pt 1): 126–31.CrossRefGoogle Scholar
  81. 81.
    Schlenger K, Hockel M, Mitze M, Schaffer U, Weikel W, Knapstein PG, Lambert A. Tumor vascularity — A novel prognostic factor in advanced cervical carcinoma. Gynecol Oncol 1995; 59:57–66.PubMedCrossRefGoogle Scholar
  82. 82.
    Abulafia O, Triest WE, Sherer DM, Hansen CC, Ghezzi F. Angiogenesis in endometrial hyperplasia and stage I endometrial carcinoma. Obstet Gynecol 1995; 86:479–485.PubMedGoogle Scholar
  83. 83.
    Shimoyama S, Gansauge F, Gansauge S, Negri G, Oohara T, Beger HG. Increased Angiogenin Expression in Pancreatic Cancer Is Related to Cancer Aggressiveness. CA Res June 1996; 56: 2703–2706.Google Scholar
  84. 84.
    Egawa S, Tsutsumi M, Konishi Y, Kobari M, Matsuni S, Nagasaki K, Futami H, Yamaguchi K. The role of Angiogenesis in the Tumor Growth of Syrian Hamster Pancreatic Cancer Cell Line HPD-NR. Gastroenterology 1995; 108:1536–1533.CrossRefGoogle Scholar
  85. 85.
    Konno H, Tanaka T, Matsuda I, Kanai T, Maruo Y, Nishino N, Nakamura S, Baba S. Comparison of the Inhibitory Effect of the Angiogenesis Inhibitor TNP-470 and Mitomycin C on the Growth and Liver Metastasis of Human Colon Cancer. Int J Ca 1995; 61:268–271.CrossRefGoogle Scholar
  86. 86.
    Tomisaki S, Ohno S, Ichiyoshi Y, Kuwano H, Maehara Y, Sugimachi K. Microvessel Quantification and Its Possible Relation with Liver Metastasis is Colorectal Cancer. CA (Suppl) April 15, 1996; 77(8):1722–1728.Google Scholar
  87. 87.
    Maeda K, Chung Y, Ogawa Y, Takatsuka S, Kang S, Ogawa M, Sawada T, Sowa M. Prognostic Value of Vascular Endothelial Growth Factor Expression in Gastric Carcinoma. CA, March 1, 1996; 77(5):858–863.Google Scholar
  88. 88.
    Jaeger TM, Weidner N, Chew K, Moore DH, Kerschmann RL, Waldman FM, Carroll PR. Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer. J Urol 154:59–71; 1995.CrossRefGoogle Scholar
  89. 89.
    Bochner BH, Cote RJ, Weidner N, Groshen S, Chen S-C, Skinner DG, Nichols PW. Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Instit 1995; 87:1603–1612.CrossRefGoogle Scholar
  90. 90.
    Dickinson AJ, Fox SB, Persad RA, Hollyer J, Sibley GN, Harris AL. Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br J Urol 1994; 74:762–766.PubMedCrossRefGoogle Scholar
  91. 91.
    Kohno Y, Iwanari O, Kitao M. Prognostic importance of histologic vascular density in cervical cancer treated with hypertensive intraarterial chemotherapy. Cancer 1993; 72:2394–2400.PubMedCrossRefGoogle Scholar
  92. 92.
    Zatterstrom UK, Brun E, Willen R, Kjellen E, Wennerberg J. Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck. Head & Neck 1995; 17:312–318.CrossRefGoogle Scholar
  93. 93.
    Folkman J. Angiogenesis and its inhibitors. In: DeVita VT, Hellman S, Rosenberg SA, eds, Important Advances in Oncology. Philadelphia: J.B. Lippincott Co, 1985; pp 42–62.Google Scholar
  94. 94.
    Harris AL, Fox S, Bicknell R, Leek R, Relf M, LeJeune S, Kaklamanis L. Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer. Cancer 1994; 74(3 Suppl): 1021–1025.PubMedCrossRefGoogle Scholar
  95. 95.
    Ingber D, Fujita T, Kishimoto S, Katsuichi S, Kanamaru T, Brem H, Folkman J. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumor growth. Nature 1990; 348:555–557.PubMedCrossRefGoogle Scholar
  96. 96.
    Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond M, Dexter DL. Modulation of solid tumor growth in vivo by bFGF. Proc Am Assoc Cancer Res 1990; 31:79(Abst).Google Scholar
  97. 97.
    Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993; 362:841–844.PubMedCrossRefGoogle Scholar
  98. 98.
    Hori A, Sasada R, Matsutani E, Naito K, Sakura Y, Fujita T, Kozai Y. Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor. Cancer Res 1991; 51:6180–6184.PubMedGoogle Scholar
  99. 99.
    Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 1994; 367:576–579.PubMedCrossRefGoogle Scholar
  100. 100.
    Brooks PC, Montgomery AMP, Rosenfeld M, Reisfeld RA, Hu T, Ilier G, Cheresh DA. Integrin alphavbeta3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994; 79:1157–1164.PubMedCrossRefGoogle Scholar
  101. 101.
    O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79:315–328.PubMedCrossRefGoogle Scholar
  102. 102.
    O’Reilley MS, Holmgren L, Chen K, Folkman J. Suppression of angiogenesis in mice by angiostatin inhibits murine and human primary tumor growth. (Submitted).Google Scholar
  103. 103.
    Nicosia RF, Tchao R, Leighton J. Interactions between newly formed endothelial channels and carcinoma cells in plasma clot culture. Clin Exp Metast 1986; 4:91–104.CrossRefGoogle Scholar
  104. 104.
    Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 1995; 95:1789–1797.PubMedCrossRefGoogle Scholar
  105. 105.
    Rak JW, Hegmann EJ, Lu C, Kerbel RS. Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression. J Cell Physiol 1994; 159:245–255.PubMedCrossRefGoogle Scholar
  106. 106.
    Hamada J, Cavanaugh PG, Lotan O. Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer 1992; 66:349–354.PubMedCrossRefGoogle Scholar
  107. 107.
    Folkman J. Angiogenesis and breast cancer. J Clin Oncol 1994; 12:441–443.PubMedGoogle Scholar
  108. 108.
    Pepper MS, Vassalli JD, Montesano R, Orci L. Urokinase type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 1987; 105:2535–2541.PubMedCrossRefGoogle Scholar
  109. 109.
    Fox SB, Stuart N, Smith K, Brunner N, Harris AL. High levels of uPA and PA-1 are associated with highly angiogenic breast carcinomas. J Pathol 993; 170 (Suppl):388a.Google Scholar
  110. 110.
    Hildenbrand R, Dilger I, Horlin A, Stutte HJ. Urokinase and macrophages in tumor angiogenesis. Br J Cancer 1995; 72:818–823.PubMedCrossRefGoogle Scholar
  111. 111.
    Moscatelli D, Gross J, Rifkin D. Angiogenic factors stimulate plasminogen activator and collagenase production by capillary endothelial cells. J Cell Biol 1981; 91:201a.CrossRefGoogle Scholar
  112. 112.
    Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315:1650–1659.PubMedCrossRefGoogle Scholar
  113. 113.
    Folkman J, Klagsbrun M. Angiogenic factors. Science 1987; 235:442–7.PubMedCrossRefGoogle Scholar
  114. 114.
    Polverini PJ, Leibovich SJ. Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor associated macrophages. Lab Invest 1984; 51:635–42.PubMedGoogle Scholar
  115. 115.
    Guidi AJ, Fischer L, Harris JR, Schnitt SJ. Microvessel density and distribution in ductal carcinoma in situ of the breast. J Natl Cancer Inst 1994; 86:614–619.PubMedCrossRefGoogle Scholar
  116. 116.
    Smith-McCune KK, Weidner N. Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 1994; 54:800–804.PubMedGoogle Scholar
  117. 117.
    Kandel J, Bossy-Wetzel E, Radvani F, Klagsburn M, Folkman J, Hanahan D. Neovascularization is associated with a switch to the export of bFGF in the multi-step development of fibrosarcoma. Cell 1991; 66:1095–1104.PubMedCrossRefGoogle Scholar
  118. 118.
    Nguyen M, Watanabe H, Budson AE, Richie JP, Folkman J. Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Nati Cancer Instit 1993; 85:241–242.CrossRefGoogle Scholar
  119. 119.
    Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146:1029–1039.PubMedGoogle Scholar
  120. 120.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 1993; 143:1255–1262.PubMedGoogle Scholar
  121. 121.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 1993; 53:4727–4735.PubMedGoogle Scholar
  122. 122.
    Senger DR, Van De Water L, Brown LF, Nagy JA, Yeo K-T, Yeo T-K, Berse B, Jackman RW, Dvorak AM, Dvorak HF. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Met Rev 1993; 12:303–324.CrossRefGoogle Scholar
  123. 123.
    Thompson WD, Campbell R, Evans T. Fibrin degradation and angiogenesis: quantitative analysis of the angiogenic response in the chick chorioallantoic membranes. J Pathol 1985; 145:27–37.PubMedCrossRefGoogle Scholar
  124. 124.
    Toi M, Hoshina S, Takayanagi T, Tominaga T. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res 1994; 85:1045–1049.PubMedCrossRefGoogle Scholar
  125. 125.
    Goto F, Goto K, Weindel K, Folkman J. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. LabInvest 1993; 69:508–517.Google Scholar
  126. 126.
    Maeda K, Chung Y-S, Ogawa Y, Takatsuka S, Kang S-M, Ogawa M, Sawada T, Onoda N, Kato Y, Sowa M. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer 1996; 73:884–888.PubMedCrossRefGoogle Scholar
  127. 127.
    Leibovich SJ, Polverini PJ, Fong TW, Harlow LA, Koch AE. Production of angiogenic acitivity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci USA 1994; 91:4190–4194.PubMedCrossRefGoogle Scholar
  128. 128.
    Laniado-Schwartzman M, Lavrovsky Y, Stotlz RA, Conners MS, Falck JR, Chauhan K, Abraham NG. Activation of nuclear factor kappa B and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells. J Biol Chem 1994; 269 (39): 2432–2437.Google Scholar
  129. 129.
    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.PubMedCrossRefGoogle Scholar
  130. 130.
    Bouck NP. Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. Cancer Cells 1990; 2:179–185.PubMedGoogle Scholar
  131. 131.
    Zajchowski DA, Band V, Trask DK, Kling D, Connoly JL, Sager R. Suppression of tumor-forming ability and related traits in MCF -7 human breast cancer cells by fusion with immortal mammary epithelial cells. Proc Natl Acad Sci USA 1990; 87:2314–2318.PubMedCrossRefGoogle Scholar
  132. 132.
    Dameron KM, Volpert OV, Tainsky MS, Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 1994; 265:1582–1584.PubMedCrossRefGoogle Scholar
  133. 133.
    Folkman J. Angiogenesis in cancer, vascular, rheumatoid, and other disease. Nature Medicine 1995; 1:27–31.PubMedCrossRefGoogle Scholar
  134. 134.
    Fidler IJ, Gersten DM, Hart IR. The biology of cancer invasion and metastasis. Adv Cancer Res 1978; 28:149–250.PubMedCrossRefGoogle Scholar
  135. 135.
    Nicolson G. Cancer metastasis. Sci Am 1979; 240:66–76.PubMedCrossRefGoogle Scholar
  136. 136.
    Weiss L. “Biophysical aspects of the metastatic cascade.” In: Weiss L, ed, Fundamental Aspects of Metastasis, Amsterdam: N. Holland, 1976; pp. 51–70.Google Scholar
  137. 137.
    Bernstein LR, Liotta LA. Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis. Curr Opin Oncol 1994; 6:106–113.PubMedCrossRefGoogle Scholar
  138. 138.
    Liotta L, Kleinerman J, Saidel G. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 1974; 34:997–1004.PubMedGoogle Scholar
  139. 139.
    Liotta L, Saidel G, Kleinerman J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 1976; 36:889–894.PubMedGoogle Scholar
  140. 140.
    McCulloch P, Choy A, Martin L. Association between tumour angiogenesis and tumour cell shedding into effluent venous blood during breast cancer surgery. Lancet 1995; 346:1334–1335.PubMedCrossRefGoogle Scholar
  141. 141.
    Nagy JA, Brown LF, Senger DR, Lanir N, Van de Water L, Dvorak AM, Dvorak HF. Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta 1989; 948:305–26.PubMedGoogle Scholar
  142. 142.
    Sugino T, Kawaguchi T, Suzuki T. Stromal invasion is not essential to blood-borne metastasis in mouse mammary carcinoma. In: Scientific Program Booklet of the Pathological Society of Great Britain and Ireland; 170th Meeting, January 1995; (Abstract #161).Google Scholar
  143. 143.
    Smolin G. Hyundiuk RA. Lymphatic drainage from vascularized rabbit cornea. Am J Ophthalmol 1971; 72:147–151.PubMedGoogle Scholar
  144. 144.
    Folkman J. Angiogenesis. In: Verstraete M, Vermylen J, Lijnan R, Arnout J, eds, Thrombosis and Haemostasis, Leuven: Leuven University Press. 1987; 24:583–96.Google Scholar
  145. 145.
    Liotta LA, Stracke ML. “Tumor invasion and metastasis: biochemical mechanisms” In: Lippman, ME and Dickson RB, eds, Breast Cancer: Cellular and Molecular Biology, Boston: Kluwer Academic Publishers, 1988, pp.223–238.CrossRefGoogle Scholar
  146. 146.
    Brem S, Cotran R, Folkman J. Tumor angiogenesis: a quantitative method for histologic grading. J Natl Cancer Inst 1972; 48:347–356.PubMedGoogle Scholar
  147. 147.
    Folkman J, Watson K, Ingber D, Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989; 339:58–61.PubMedCrossRefGoogle Scholar
  148. 148.
    Weidner N. “The relationship of tumor angiogenesis and metastasis with emphasis on invasive breast carcinoma.” In: Advances in Pathology and Laboratory Medicine, Weinstein RS (ed), Mosby Year Book, Chicago, Vol. 1992; 5:101–121.Google Scholar
  149. 149.
    Hall NR, Fish DE, Hunt N, Goldin RD, Guillou PJ, Monson JRT. Is the relationship between angiogenesis and metastasis in breast cancer real? Surg Oncol 1:223–229, 1992.PubMedCrossRefGoogle Scholar
  150. 150.
    Van Hoef MEHM, Knox WF, Dhesi SS, Howell A, Schor AM. Assessment of tumor vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer 29A:1141–1145, 1993.CrossRefGoogle Scholar
  151. 151.
    Miliaras D, Kamas A, Kalekou H. Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance? Histopathol 26:165–169, 1995.CrossRefGoogle Scholar
  152. 152.
    Axelsson K, Ljung BME, Moore DH, Thor AD, Chew KL, Edgerton SM, Smith HS, Mayall BH. Tumor angiogenesis as a prognostic assay for invasive ductal carcinoma. J Natl Cancer Instit 87:997–1008, 1995.CrossRefGoogle Scholar
  153. 153.
    Carnochan P, Briggs JC, Westbury G, Davies AJ. The vascularity of cutaneous melanoma: a quantitative histologic study of lesions 0.85–1.25 mm in thickness. Br J Cancer 1991; 64:102–107.PubMedCrossRefGoogle Scholar
  154. 154.
    Leedy DA, Trune DR, Kronz JD, Weidner N, Cohen JI. Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma. Otolaryngol Head Neck Surg 1994; 111:417–422.PubMedGoogle Scholar
  155. 155.
    Rutger JL, Mattox TF, Vargas MP. Angiogenesis in uterine cervical squamous cell carcinoma. Int J Gyn Path 1995; 14:114–118.CrossRefGoogle Scholar
  156. 156.
    van Diest PJ, Zevering JP, Zevering LC, Baak JPA. Prognostic value of microvessel quantitation in cisplatin treated Figo 3 and 4 ovarian cancer patients. Path Res Pract 1995; 191:25–30.PubMedCrossRefGoogle Scholar
  157. 157.
    Siitonen SM, Haapasalo HK, Rantala IS, Helin HJ, Isola JJ. Comparison of different immunohistochemical methods in the assessment of angiogenesis: lack of prognostic value in a group of 77 selected node-negative breast carcinomas. Mod Pathol 1995; 8:745–752.PubMedGoogle Scholar
  158. 158.
    Goulding H, Rashid NFNA, Robertson JF, Bell JA, Elston CW, Blarney RW, Ellis IO. Assessment of angiogenesis in breast carcinoma: An important factor in prognosis? Hum Pathol 1995; 26:1196–1200.PubMedCrossRefGoogle Scholar
  159. 159.
    Costello P, McCann A, Carney DN, Dervan PA. Prognostic significance of microvessel density in lymph node negative breast carcinoma. Hum Pathol 1995; 26:1181–1184.PubMedCrossRefGoogle Scholar
  160. 160.
    MacLennan GT, Bostwick DG. Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology 1995; 46:27–30.PubMedCrossRefGoogle Scholar
  161. 161.
    Tahan SR, Stein AL. Angiogenesis in invasive squamous cell carcinoma of the lip: tumor vascularity is not an indicator of metastatic risk. J Cut Pathol 1995; 22:236–240.CrossRefGoogle Scholar
  162. 162.
    Dray TG, Hardin NJ, Sofferman RA. Angiogenesis as a prognostic marker in early head and neck cancer. Ann Otol Rhinol Laryngol 1995; 104:724–729.PubMedGoogle Scholar
  163. 163.
    Barnhill RL, Busam KJ, Berwick M, Blessing K, Cochran AJ, Elder DE, Fandrey K, Daraoli T, White WL. Tumor vascularity is not a prognostic factor for cutaneous melanoma [letter]. Lancet 1994; 344:1237–1238.PubMedCrossRefGoogle Scholar
  164. 164.
    Kainz C, Speiser P, Wanner C, Obermair A, Tempfer C, Sliutz G, Reinthaller A, Breitenecker G. Prognostic value of tumor microvessel density in cancer of the uterine cervix stage IB to IIB. Anticancer Res 1995; 15:1549–1551.PubMedGoogle Scholar
  165. 165.
    DeYoung BR, Wick MR, Fitzgibbon JF, Sirgi KE, Swanson PE. CD31: An immunospecific marker for endothelial differentiation in human neoplasms. Appl Immunohistochem 1993; 1:97–100.Google Scholar
  166. 166.
    Longacre TA, Rouse RV. CD31: A new marker for vascular neoplasia. Advan Anat Pathol 1994; 1:16–20.CrossRefGoogle Scholar
  167. 167.
    van de Rijn M, Rouse RV. CD34: A review. Appl Immunohistochern 1994; 2:71–80.Google Scholar
  168. 168.
    Traweek ST, Kandalaft PL, Mehta P, Battifora H. The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. Am J Clin Pathol 1991; 96:25–31.PubMedGoogle Scholar
  169. 169.
    Schlingemann RO, Rietveld FJR, Kwaspen F, van de Kerkhof PCM, de Waal RMW, Ruiter DJ. Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. Am J Pathol 1991; 138:1335–1347.PubMedGoogle Scholar
  170. 170.
    Wang JM, Kumar S, Pye D, Haboubi N, Al-Nakib L. Breast carcinoma: comparative study of tumor vasculature using two endothelial-cell markers. J Natl Cancer Inst 1994; 86:386–388.PubMedCrossRefGoogle Scholar
  171. 171.
    Wang JM, Kumar S, Pye D, van Agthoven AJ, Krupinski J, Hunter RD. A monoclonal antibody detects heterogeneity in vascular endothelium of tumors and normal tissues. Int J Cancer 1993; 54:363–370.PubMedCrossRefGoogle Scholar
  172. 172.
    Watanabe II, Nguyen M, Schizer M. Basic fibroblast growth factor in human serum — a prognostic test for breast cancer. Mol Biol Cell 1992; 3:324a.Google Scholar
  173. 173.
    Nguyen M, Watanabe II, Budson AE. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 1994; 86:356.PubMedCrossRefGoogle Scholar
  174. 174.
    Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PM, Sallan SE, Folkman J. Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet 334:82–86, 1994.CrossRefGoogle Scholar
  175. 175.
    Esserman L, Hylton N, George T, Yassa L, Weidner N. Constrast-enhanced magnetic resonance imaging (cMRI) provides a window to visualize anatomic extent and tumor angiogenesis in breast carcinoma. Cancer Res (submitted).Google Scholar
  176. 176.
    Herlyn M, Clark WH, Rodeck U, Mancianti ML, Jambrosic J, Koprowski H. Biology of tumor progression in human melanocytes. Lab Invest 1987; 56:461–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Noel Weidner
    • 1
  1. 1.Department of PathologyUniversity of California, San FranciscoSan FranciscoUSA

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