Home LiteratureArticle Details
PMID: 9195286 Published · ppublish English Journal Article Review

Markers of tumor angiogenesis: clinical applications in prognosis and anti-angiogenic therapy.

Investigational new drugs ·Vol. 15 ·No. 1 ·1997-00-00 ·Pages 15-28

Fox SB, Harris AL

Abstract

Numerous studies in many tumor types have demonstrated that quantitation by microvessel as a measure of angiogenesis is a powerful prognostic tool. However, the ability to exploit tumor angiogenesis as a prognostic marker is limited by the methods currently used for capillary identification and quantitation. This report critically evaluates all aspects of the techniques and their associated problems used for assessing tumor angiogenesis in tissue sections including the area of tumor assessed, the vascular parameter measured, the method of quantitation, the stratification of patients and the practical utility of computer image analysis systems. The potential of angiogenic factors assays, proteolytic enzymes, and cell adhesion molecules as surrogate endpoints for quantifying tumor angiogenesis are discussed and other methods for quantifying tumor angiogenesis are described. The potential clinical applications of these angiogenic markers in prognosis, stratification for adjuvant treatments (both cytotoxic and anti-angiogenic/vascular targeting) and other aspects of patient management is also discussed, particularly design of phase I and II trials.

MeSH Terms
Antibodies Antigen-Antibody Reactions Antineoplastic Agents/standards,therapeutic use Biomarkers, Tumor/metabolism Cell Adhesion Molecules/metabolism Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Drugs, Investigational/standards,therapeutic use Humans Image Processing, Computer-Assisted Neoplasms/blood supply,drug therapy,pathology Neovascularization, Pathologic/diagnosis,drug therapy Peptide Hydrolases/metabolism Prognosis Randomized Controlled Trials as Topic
Chemicals
Antibodies Antineoplastic Agents Biomarkers, Tumor Cell Adhesion Molecules Drugs, Investigational Peptide Hydrolases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Fox S B
Department of Cellular Science, University of Oxford, John Radcliffe Hospital, UK.
Harris A L
References (158)
158 references, click to expand
  1. Angiogenesis induced by "normal" human breast tissue: a probable marker for precancer.
    Science. 1982 Oct 15;218(4569):293-5 PMID: 6181563
  2. Comparative analysis of neovascularization in primary cutaneous melanoma and Spitz nevus.
    Am J Dermatopathol. 1994 Feb;16(1):9-13 PMID: 7512803
  3. Tumor-associated urokinase-type plasminogen activator: biological and clinical significance.
    Biol Chem Hoppe Seyler. 1992 Jul;373(7):611-22 PMID: 1515091
  4. Tumour vascularity and basement membrane structure in breast cancer as related to tumour histology and prognosis.
    J Cancer Res Clin Oncol. 1994;120(11):645-50 PMID: 7962040
  5. Requirement of vascular integrin alpha v beta 3 for angiogenesis.
    Science. 1994 Apr 22;264(5158):569-71 PMID: 7512751
  6. Regulation of in vitro capillary tube formation by anti-integrin antibodies.
    J Cell Biol. 1993 May;121(4):931-43 PMID: 8491784
  7. Distribution of urokinase-type plasminogen activator immunoreactivity in the mouse.
    J Cell Biol. 1984 Mar;98(3):894-903 PMID: 6365928
  8. Integrins as dynamic regulators of vascular function.
    FASEB J. 1994 Sep;8(12):929-38 PMID: 7522194
  9. Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms.
    Mod Pathol. 1992 May;5(3):303-7 PMID: 1495934
  10. Angiogenesis in uterine cervical squamous cell carcinoma.
    Int J Gynecol Pathol. 1995 Apr;14(2):114-8 PMID: 8601522
  11. Identification of basic fibroblast growth factor in papillary carcinoma of the thyroid.
    Acta Pathol Jpn. 1993 Oct;43(10):582-9 PMID: 8291446
  12. Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumours.
    Lancet. 1994 Jul 9;344(8915):82-6 PMID: 7516992
  13. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5277-81 PMID: 2440047
  14. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.
    Am J Pathol. 1993 Aug;143(2):401-9 PMID: 7688183
  15. Comparison of microscopic vascularity in benign and malignant prostate tissue.
    Hum Pathol. 1993 Feb;24(2):220-6 PMID: 8432518
  16. Urinary basic fibroblast growth factor in patients with bladder cancer and benign prostatic hypertrophy.
    Br J Urol. 1995 Sep;76(3):311-4 PMID: 7551838
  17. 4A11, a monoclonal antibody recognizing a novel antigen expressed on aberrant vascular endothelium. Upregulation in an in vivo model of contact dermatitis.
    Am J Pathol. 1994 Feb;144(2):244-59 PMID: 8311112
  18. Tumor interactions with the vasculature: angiogenesis and tumor metastasis.
    Biochim Biophys Acta. 1990 Jun 1;1032(1):89-118 PMID: 1694687
  19. Tumor angiogenesis and rectal carcinoma.
    Dis Colon Rectum. 1994 Sep;37(9):921-6 PMID: 7521279
  20. Thrombosis and cancer.
    Hum Pathol. 1987 Mar;18(3):275-84 PMID: 3546076
  21. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.
    Nature. 1995 Aug 10;376(6540):517-9 PMID: 7543654
  22. Prognostic significance of image morphometric microvessel enumeration in breast carcinoma.
    Anal Quant Cytol Histol. 1993 Apr;15(2):88-92 PMID: 7686372
  23. Increased serum levels of basic fibroblast growth factor in patients with renal cell carcinoma.
    Biochem Biophys Res Commun. 1991 Oct 15;180(1):386-92 PMID: 1718278
  24. Tumor angiogenesis as a prognostic factor in oral cavity tumors.
    Am J Surg. 1994 Nov;168(5):373-80 PMID: 7526718
  25. Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier.
    Am J Pathol. 1988 May;131(2):361-72 PMID: 2451889
  26. Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor.
    J Natl Cancer Inst. 1994 Aug 17;86(16):1234-8 PMID: 7518876
  27. VLA-2 mediates the interaction of collagen with endothelium during in vitro vascular tube formation.
    Cell Biol Int. 1994 Sep;18(9):859-67 PMID: 7528076
  28. Vascularization of carcinomas of the esophagus and its correlation with tumor proliferation.
    Cancer Res. 1994 Jan 15;54(2):587-91 PMID: 8275498
  29. Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis.
    J Pathol. 1995 Nov;177(3):275-83 PMID: 8551390
  30. Expression of HGF-SF in normal and malignant human tissues.
    EXS. 1993;65:181-99 PMID: 8380737
  31. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer.
    Lancet. 1992 Nov 7;340(8828):1120-4 PMID: 1279332
  32. 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 Mar 2;86(5):356-61 PMID: 7508518
  33. Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms.
    J Cell Biol. 1993 Apr;121(1):163-70 PMID: 7681432
  34. Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer.
    Cancer Res. 1990 Nov 1;50(21):6827-9 PMID: 2119883
  35. Human endothelial cells contain one type of plasminogen activator.
    FEBS Lett. 1984 Mar 12;168(1):33-7 PMID: 6538515
  36. Tumor stroma as a regulator of neoplastic behavior. Agonistic and antagonistic elements embedded in the same connective tissue.
    Lab Invest. 1995 Aug;73(2):157-60 PMID: 7637316
  37. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review.
    Cancer Res. 1989 Dec 1;49(23):6449-65 PMID: 2684393
  38. 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(2):193-204 PMID: 8534867
  39. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
    Cancer Res. 1995 Sep 15;55(18):3964-8 PMID: 7664263
  40. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease.
    Cancer Res. 1992 Dec 1;52(23):6702-4 PMID: 1384969
  41. Barriers to drug delivery in solid tumors.
    Sci Am. 1994 Jul;271(1):58-65 PMID: 8066425
  42. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia.
    J Natl Cancer Inst. 1995 Aug 16;87(16):1237-45 PMID: 7563170
  43. The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck.
    Ann Plast Surg. 1994 Jun;32(6):588-94 PMID: 7521149
  44. Microvessel quantitation and prognosis in invasive breast carcinoma.
    Hum Pathol. 1992 Jul;23(7):755-61 PMID: 1377162
  45. Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients.
    J Natl Cancer Inst. 1993 Feb 3;85(3):241-2 PMID: 8423630
  46. Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10832-6 PMID: 1438285
  47. Involvement of extracellular matrix constituents in breast cancer.
    Semin Cancer Biol. 1995 Jun;6(3):165-73 PMID: 7495985
  48. Tumor angiogenesis as a prognostic factor in cervical carcinoma.
    Gynecol Oncol. 1995 Mar;56(3):353-6 PMID: 7535719
  49. Angiogenesis and risk of breast cancer in women with fibrocystic disease.
    J Natl Cancer Inst. 1994 Apr 20;86(8):635-6 PMID: 7511694
  50. Tumor necrosis factor inhibits the proliferation of cultured capillary endothelial cells.
    Biochem Biophys Res Commun. 1987 Mar 30;143(3):997-1004 PMID: 2436621
  51. Comparative morphometric study of tumor vasculature in human squamous cell carcinomas and their xenotransplants in athymic nude mice.
    Cancer Res. 1989 Aug 15;49(16):4557-61 PMID: 2743340
  52. A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis.
    Nature. 1993 Sep 16;365(6443):267-9 PMID: 7690465
  53. Monoclonal antibody PAL-E specific for endothelium.
    Lab Invest. 1985 Jan;52(1):71-6 PMID: 3880842
  54. Thrombospondin and other possible related matrix proteins in malignant and benign breast disease. An immunohistochemical study.
    Am J Pathol. 1992 Jun;140(6):1473-82 PMID: 1351369
  55. Thymidine phosphorylase is angiogenic and promotes tumor growth.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):998-1002 PMID: 7532308
  56. Urokinase receptor and colorectal cancer survival.
    Lancet. 1994 Aug 6;344(8919):401-2 PMID: 7914317
  57. The vascularity of cutaneous melanoma: a quantitative histological study of lesions 0.85-1.25 mm in thickness.
    Br J Cancer. 1991 Jul;64(1):102-7 PMID: 1854608
  58. Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study.
    J Pathol. 1992 Nov;168(3):257-62 PMID: 1281874
  59. Breast cancer angiogenesis: a quantitative morphologic and Doppler imaging study.
    Ann Surg Oncol. 1995 May;2(3):246-51 PMID: 7543800
  60. Angiogenesis research yields new approaches to cancer treatment and prognosis.
    J Natl Cancer Inst. 1993 Oct 20;85(20):1629-30 PMID: 7692073
  61. Morphometric evaluation of microvessels surrounding hyperplastic and neoplastic mammary lesions.
    Breast Cancer Res Treat. 1988 Jul;11(3):241-8 PMID: 2458784
  62. Tumor-related angiogenesis.
    Crit Rev Oncol Hematol. 1989;9(3):197-242 PMID: 2480145
  63. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels.
    Cell. 1994 Dec 30;79(7):1157-64 PMID: 7528107
  64. Are tumours innervated? Immunohistological investigations using antibodies against the neuronal marker protein gene product 9.5 (PGP 9.5) in benign, malignant and experimental tumours.
    Tumour Biol. 1994;15(5):269-74 PMID: 7991987
  65. Correlation between contrast enhancement in dynamic magnetic resonance imaging of the breast and tumor angiogenesis.
    Invest Radiol. 1994 Dec;29(12 ):1043-9 PMID: 7536719
  66. Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease.
    Cancer Res. 1994 May 15;54(10):2800-2 PMID: 7513256
  67. The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium.
    J Pathol. 1995 Dec;177(4):369-76 PMID: 8568591
  68. Angiogenesis in malignant fibrous histiocytoma.
    Oncology. 1995 Jan-Feb;52(1):51-4 PMID: 7528371
  69. Vascular and interstitial barriers to delivery of therapeutic agents in tumors.
    Cancer Metastasis Rev. 1990 Nov;9(3):253-66 PMID: 2292138
  70. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.
    Cell. 1994 Oct 21;79(2):315-28 PMID: 7525077
  71. Tumor angiogenesis in node-negative breast carcinomas--relationship with epidermal growth factor receptor, estrogen receptor, and survival.
    Breast Cancer Res Treat. 1994 Jan;29(1):109-16 PMID: 7517221
  72. Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies.
    Br J Cancer. 1993 Jul;68(1):122-4 PMID: 7686390
  73. Biologic and clinical significance of basic fibroblast growth factor immunostaining in breast carcinoma.
    Mod Pathol. 1995 Aug;8(6):665-70 PMID: 8532703
  74. Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer.
    Int J Cancer. 1995 Apr 21;64(2):79-82 PMID: 7542228
  75. Tumour angiogenesis in latent prostatic carcinoma.
    Br J Cancer. 1994 Dec;70(6):1244-6 PMID: 7526886
  76. Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation.
    Int J Cancer. 1995 Apr 21;64(2):117-23 PMID: 7615354
  77. The prognostic value of tumor blood vessel morphology in primary uveal melanoma.
    Ophthalmology. 1993 Sep;100(9):1389-98 PMID: 8371929
  78. The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium.
    Br J Cancer. 1996 Feb;73(3):275-80 PMID: 8562330
  79. Microvessel quantitation in invasive breast cancer by staining for factor VIII-related antigen.
    Br J Cancer. 1995 Jun;71(6):1297-301 PMID: 7779727
  80. Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading the thoracic inlet.
    Ann Thorac Surg. 1994 Jun;57(6):1534-9 PMID: 7516646
  81. Colour and pulsed Doppler US and tumour marker CA 125 in differentiation between benign and malignant ovarian masses.
    Anticancer Res. 1995 Jul-Aug;15(4):1527-32 PMID: 7654041
  82. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma.
    J Clin Oncol. 1995 Feb;13(2):477-81 PMID: 7531224
  83. Is the relationship between angiogenesis and metastasis in breast cancer real?
    Surg Oncol. 1992 Jun;1(3):223-9 PMID: 1285217
  84. Angiogenesis and regressing cutaneous malignant melanoma.
    Lancet. 1992 Apr 18;339(8799):991-2 PMID: 1373461
  85. JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections.
    J Clin Pathol. 1990 Sep;43(9):752-7 PMID: 2212067
  86. A novel role for E- and P-selectins: shape control of endothelial cell monolayers.
    J Cell Sci. 1994 Sep;107 ( Pt 9):2449-57 PMID: 7531200
  87. Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer.
    J Urol. 1995 Jul;154(1):69-71 PMID: 7539869
  88. Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma.
    J Natl Cancer Inst. 1995 Jul 5;87(13):997-1008 PMID: 7543156
  89. Assessment of tumour vascularity as a prognostic factor in lymph node negative invasive breast cancer.
    Eur J Cancer. 1993;29A(8):1141-5 PMID: 8390846
  90. Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation.
    Cancer Res. 1993 Mar 15;53(6):1444-9 PMID: 7680286
  91. Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas.
    Br J Urol. 1994 Dec;74(6):762-6 PMID: 7530131
  92. In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins.
    J Cell Physiol. 1992 Dec;153(3):437-49 PMID: 1280276
  93. Vascular permeability factor (VPF, VEGF) in tumor biology.
    Cancer Metastasis Rev. 1993 Sep;12(3-4):303-24 PMID: 8281615
  94. Angiogenesis and tumor progression of melanoma. Quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma.
    Lab Invest. 1992 Sep;67(3):331-7 PMID: 1383607
  95. Localization of basic fibroblast growth factor and transforming growth factor beta 1 in the human mammary gland.
    Cancer Res. 1991 Sep 1;51(17):4685-92 PMID: 1873813
  96. CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors.
    Am J Clin Pathol. 1995 Apr;103(4):443-8 PMID: 7726141
  97. Tumour vascularity is not a prognostic factor for cutaneous melanoma.
    Lancet. 1994 Oct 29;344(8931):1237-8 PMID: 7934572
  98. Identification of a role of the vitronectin receptor and protein kinase C in the induction of endothelial cell vascular formation.
    J Cell Biochem. 1993 Feb;51(2):206-18 PMID: 7680047
  99. Proteolytic balance and capillary morphogenesis.
    Cell Differ Dev. 1990 Dec 2;32(3):319-27 PMID: 1711917
  100. Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy.
    Urology. 1994 Dec;44(6):869-75 PMID: 7527168
  101. Tumor vascularization, mitotic index, histopathologic grade, and DNA ploidy in the assessment of 114 head and neck squamous cell carcinomas.
    Cancer. 1995 Apr 1;75(7):1649-56 PMID: 8826923
  102. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.
    J Natl Cancer Inst. 1992 Dec 16;84(24):1875-87 PMID: 1281237
  103. Multiparametric prognostic evaluation of biological factors in primary breast cancer.
    J Natl Cancer Inst. 1992 Aug 19;84(16):1266-72 PMID: 1640487
  104. Tumor angiogenesis in advanced stage ovarian carcinoma.
    Am J Pathol. 1995 Jul;147(1):33-41 PMID: 7541612
  105. Myometrial blood flow studies in carcinoma of the corpus uteri. A preliminary report on the clearance method using xenon 133.
    Acta Radiol Ther Phys Biol. 1969 Jun;8(3):193-8 PMID: 5822263
  106. Association with clinical outcome of expression of VLA-4 in primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels.
    J Natl Cancer Inst. 1995 Mar 1;87(5):366-71 PMID: 7531774
  107. Vascular density and the response of breast carcinomas to mastectomy and adjuvant chemotherapy.
    Eur J Cancer. 1993;29A(10):1391-3 PMID: 8398265
  108. Relationship of endothelial cell proliferation to tumor vascularity in human breast cancer.
    Cancer Res. 1993 Sep 15;53(18):4161-3 PMID: 7689928
  109. Heterogeneity of vascular endothelial cells with relevance to diagnosis of vascular tumours.
    J Clin Pathol. 1992 Feb;45(2):143-8 PMID: 1371777
  110. Angiogenesis as a marker of preneoplastic lesions of the human breast.
    Cancer. 1978 Jan;41(1):239-44 PMID: 626933
  111. Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma.
    Cancer Res. 1993 Oct 15;53(20):4927-32 PMID: 8104688
  112. Vascular targeting--a new approach to the therapy of solid tumors.
    Pharmacol Ther. 1994 Oct;64(1):155-74 PMID: 7846113
  113. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer.
    Jpn J Cancer Res. 1994 Oct;85(10):1045-9 PMID: 7525523
  114. The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0 mm thick) skin melanoma. A quantitative histologic study.
    Am J Pathol. 1988 Nov;133(2):419-23 PMID: 3189515
  115. Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue.
    Otolaryngol Head Neck Surg. 1994 Oct;111(4):417-22 PMID: 7524005
  116. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705-9 PMID: 8248162
  117. Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro.
    J Cell Biol. 1990 Aug;111(2):743-55 PMID: 1696269
  118. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells.
    Biochem Biophys Res Commun. 1991 Dec 16;181(2):902-6 PMID: 1755866
  119. Determination of epidermal growth factor receptor provides additional prognostic information to measuring tumor angiogenesis in breast carcinoma patients.
    Breast Cancer Res Treat. 1994 Jan;29(1):97-107 PMID: 7517222
  120. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients.
    Biochim Biophys Acta. 1994 Mar 31;1221(2):211-4 PMID: 8148401
  121. The molecular detection of circulating tumour cells.
    Br J Cancer. 1995 Aug;72(2):268-76 PMID: 7640205
  122. Microvascularity in benign prostatic hyperplasia.
    Prostate. 1995 Mar;26(3):111-5 PMID: 7534916
  123. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.
    J Clin Oncol. 1994 Mar;12(3):454-66 PMID: 7509851
  124. Interstitial collagenase is required for angiogenesis in vitro.
    Dev Biol. 1994 Apr;162(2):499-510 PMID: 7512058
  125. Comparative expression of fibroblast growth factor mRNAs in benign and malignant breast disease.
    Br J Cancer. 1994 Apr;69(4):772-6 PMID: 7511406
  126. Plasminogen activator system in human breast cancer.
    Int J Cancer. 1992 Feb 1;50(3):345-8 PMID: 1735602
  127. Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients.
    Cancer Res. 1992 Nov 1;52(21):6101-5 PMID: 1394237
  128. A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues.
    Int J Cancer. 1986 Oct 15;38(4):481-8 PMID: 3531031
  129. Morphological aspects of angiogenesis in experimental liver metastases.
    Am J Pathol. 1993 Sep;143(3):926-36 PMID: 7689793
  130. Angiogenic activity and neovascularization in adenocarcinoma of endometrium.
    Int J Gynaecol Obstet. 1989 Aug;29(4):343-57 PMID: 2477290
  131. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets.
    Nature. 1992 Oct 29;359(6398):848-51 PMID: 1279433
  132. Demonstration and characterization of the angiogenic properties of cervical dysplasia.
    Cancer Res. 1994 Feb 1;54(3):800-4 PMID: 7508337
  133. A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues.
    Int J Cancer. 1993 May 28;54(3):363-70 PMID: 8509210
  134. Lymphocyte-endothelial cell adhesion molecules at the primary tumor site in human lung and renal cell carcinomas.
    J Natl Cancer Inst. 1993 Feb 3;85(3):246-7 PMID: 7678655
  135. Prostatic intra-epithelial neoplasia. Qualitative and quantitative analyses of the blood capillary architecture on thin tissue sections.
    Pathol Res Pract. 1993 Jun;189(5):542-8 PMID: 7690954
  136. Relation of neovascularisation to metastasis of non-small-cell lung cancer.
    Lancet. 1992 Jul 18;340(8812):145-6 PMID: 1378165
  137. Measurement of the grade of vascularisation in histological tumour tissue sections.
    Br J Cancer. 1985 Dec;52(6):945-8 PMID: 3907688
  138. Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma.
    Int J Cancer. 1993 Nov 11;55(5):739-44 PMID: 8244569
  139. Incremental angiogenesis assessed by color Doppler ultrasound in the tumorigenesis of ovarian neoplasms.
    Cancer. 1994 Feb 15;73(4):1251-6 PMID: 7508817
  140. Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer.
    Breast Cancer Res Treat. 1993;24(3):195-208 PMID: 8435475
  141. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.
    Int J Cancer. 1993 Sep 30;55(3):371-4 PMID: 7690738
  142. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin.
    J Clin Invest. 1995 Oct;96(4):1815-22 PMID: 7560073
  143. Microvessel density and distribution in ductal carcinoma in situ of the breast.
    J Natl Cancer Inst. 1994 Apr 20;86(8):614-9 PMID: 7511693
  144. Novel growth regulatory factors and tumour angiogenesis.
    Eur J Cancer. 1991;27(6):781-5 PMID: 1712608
  145. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro.
    Biochem Biophys Res Commun. 1992 Dec 15;189(2):824-31 PMID: 1281999
  146. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer.
    Hum Pathol. 1995 Jan;26(1):86-91 PMID: 7821921
  147. Different angiogenic pathways characterize superficial and invasive bladder cancer.
    Cancer Res. 1995 Feb 1;55(3):510-3 PMID: 7530595
  148. Tumor vascularity and basement membrane structure as prognostic factors in T1-2MO prostatic adenocarcinoma.
    Anticancer Res. 1994 Mar-Apr;14(2B):709-14 PMID: 8010731
  149. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
    N Engl J Med. 1991 Jan 3;324(1):1-8 PMID: 1701519
  150. Tumor angiogenesis: a quantitative method for histologic grading.
    J Natl Cancer Inst. 1972 Feb;48(2):347-56 PMID: 4347034
  151. Midkine and pleiotrophin expression in normal and malignant breast tissue.
    Cancer. 1994 Sep 1;74(5):1584-90 PMID: 7520350
  152. Predictors of pathologic stage in prostatic carcinoma. The role of neovascularity.
    Cancer. 1994 Feb 1;73(3):678-87 PMID: 7507798
  153. Clinical importance of the determination of tumor angiogenesis in breast carcinoma: much more than a new prognostic tool.
    J Clin Oncol. 1995 Mar;13(3):765-82 PMID: 7533829
  154. Vascular architecture of melanocytic skin tumors. A quantitative immunohistochemical study using automated image analysis.
    Pathol Res Pract. 1989 Nov;185(5):740-5 PMID: 2696951
  155. Cellular components of microvascular proliferation in human glial and metastatic brain neoplasms. A light microscopic and immunohistochemical study of formalin-fixed, routinely processed material.
    Acta Neuropathol. 1993;85(5):508-14 PMID: 7684179
  156. High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis.
    Cancer Res. 1993 Jun 1;53(11):2513-21 PMID: 8388317
  157. Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis.
    Thromb Haemost. 1994 Jul;72(1):151-4 PMID: 7526483
  158. Heterogeneity of the endothelial cell and its role in organ preference of tumour metastasis.
    Trends Pharmacol Sci. 1991 Dec;12(12):462-7 PMID: 1792690
Article Info
Journal
Investigational new drugs
Abbr.
Invest New Drugs
ISSN
0167-6997
DOI
10.1023/a:1005714527315
Published
1997-00-00
Pages
15-28
Language
English
Region
United States
NLM ID
8309330
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1005714527315 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2