Skip to main content

Advertisement

Log in

Clinical biomarkers of angiogenesis inhibition

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Introduction

An expanding understanding of the importance of angiogenesis in oncology and the development of numerous angiogenesis inhibitors are driving the search for biomarkers of angiogenesis. We review currently available candidate biomarkers and surrogate markers of anti-angiogenic agent effect.

Discussion

A number of invasive, minimally invasive, and non-invasive tools are described with their potential benefits and limitations. Diverse markers can evaluate tumor tissue or biological fluids, or specialized imaging modalities.

Conclusions

The inclusion of these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, prediction of individual response to an agent, insight into the interaction of chemotherapy and radiation following exposure to these agents, and perhaps most importantly, a better understanding of the complex nature of angiogenesis in human tumors. While many markers have potential for clinical use, it is not yet clear which marker or combination of markers will prove most useful.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Folkman, J. (1971). Tumor angiogenesis: Therapeutic implications. The New England Journal of Medicine, 285(21), 1182–1186.

    PubMed  CAS  Google Scholar 

  2. Carmeliet, P. (2005). Angiogenesis in life, disease and medicine. Nature, 438(7070), 932–936.

    PubMed  CAS  Google Scholar 

  3. Carmeliet, P., & Jain, R. K. (2000). Angiogenesis in cancer and other diseases. Nature, 407(6801), 249–257.

    PubMed  CAS  Google Scholar 

  4. Ferrara, N., & Kerbel, R. S. (2005). Angiogenesis as a therapeutic target. Nature, 438(7070), 967–974.

    PubMed  CAS  Google Scholar 

  5. Nieder, C., et al. (2006). Current status of angiogenesis inhibitors combined with radiation therapy. Cancer Treatment Reviews, 32(5), 348–364.

    PubMed  CAS  Google Scholar 

  6. Quesada, A. R., Munoz-Chapuli, R., & Medina, M. A. (2006). Anti-angiogenic drugs: From bench to clinical trials. Medicinal Research Reviews, 26(4), 483–530.

    PubMed  CAS  Google Scholar 

  7. Walsh, D. A. (2007). Pathophysiological mechanisms of angiogenesis. Advances in Clinical Chemistry, 44, 187–221.

    PubMed  CAS  Google Scholar 

  8. Ferrara, N. (2004). Vascular endothelial growth factor: Basic science and clinical progress. Endocrine Reviews, 25(4), 581–611.

    PubMed  CAS  Google Scholar 

  9. Longo, R., & Gasparini, G. (2007). Challenges for patient selection with VEGF inhibitors. Cancer Chemotherapy and Pharmacology, 60(2), 151–170.

    PubMed  CAS  Google Scholar 

  10. Moreira, I. S., Fernandes, P. A., & Ramos, M. J. (2007). Vascular endothelial growth factor (VEGF) inhibition—A critical review. Anti-Cancer Agents in Medicinal Chemistry, 7(2), 223–245.

    PubMed  CAS  Google Scholar 

  11. Arora, N., et al. (1999). Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells. Cancer Research, 59(1), 183–188.

    PubMed  CAS  Google Scholar 

  12. Frankel, A. E. (2002). Increased sophistication of immunotoxins. Clinical Cancer Research, 8(4), 942–944.

    PubMed  CAS  Google Scholar 

  13. Hicklin, D. J., & Ellis, L. M. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of Clinical Oncology, 23(5), 1011–1027.

    PubMed  CAS  Google Scholar 

  14. Yang, J. C., et al. (2003). A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. The New England Journal of Medicine, 349(5), 427–434.

    PubMed  CAS  Google Scholar 

  15. Moffat, B. A., et al. (2006). Inhibition of vascular endothelial growth factor (VEGF)-A causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D. Clinical Cancer Research, 12(5), 1525–1532.

    PubMed  CAS  Google Scholar 

  16. Senan, S., & Smit, E. F. (2007). Design of clinical trials of radiation combined with antiangiogenic therapy. Oncologist, 12(4), 465–477.

    PubMed  CAS  Google Scholar 

  17. Folkman, J., & Camphausen, K. (2001). CANCER: Enhanced: What does radiotherapy do to endothelial cells? Science, 293(5528), 227–228.

    PubMed  CAS  Google Scholar 

  18. Wachsberger, P., Burd, R., & Dicker, A. P. (2003). Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: Exploring mechanisms of interaction. Clinical Cancer Research, 9(6), 1957–1971.

    PubMed  CAS  Google Scholar 

  19. Brizel, D. M., et al. (1999). Oxygenation of head and neck cancer: Changes during radiotherapy and impact on treatment outcome. Radiotherapy and Oncology, 53(2), 113–117.

    PubMed  CAS  Google Scholar 

  20. Brizel, D. M., et al. (1996). Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Research, 56(5), 941–943.

    PubMed  CAS  Google Scholar 

  21. Hall, E. (2000). Radiobiology for the radiologist (5th ed.). Philadelphia: Lippincott, Williams, & Wilkins.

    Google Scholar 

  22. Dewhirst, M. W., et al. (2007). Exploring the role of HIF-1 in early angiogenesis and response to radiotherapy. Radiotherapy and Oncology, 83(3), 249–255.

    PubMed  CAS  Google Scholar 

  23. Moeller, B. J., et al. (2004). Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules. Cancer Cell, 5(5), 429–441.

    PubMed  CAS  Google Scholar 

  24. Harada, H., et al. (2007). Significance of HIF-1-active cells in angiogenesis and radioresistance. Oncogene, 26, 7508–7516.

    PubMed  CAS  Google Scholar 

  25. Gaffney, D. K., et al. (2003). Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 56(4), 922–928.

    PubMed  CAS  Google Scholar 

  26. Gorski, D. H., et al. (1999). Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Research, 59(14), 3374–3378.

    PubMed  CAS  Google Scholar 

  27. Kermani, P., et al. (2001). Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: The role of VEGF(165). International Journal of Radiation Oncology, Biology, Physics, 50(1), 213–220.

    PubMed  CAS  Google Scholar 

  28. Sonveaux, P., et al. (2003). Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: Implications for tumor radiotherapy. Cancer Research, 63(5), 1012–1019.

    PubMed  CAS  Google Scholar 

  29. Teicher, B. A., Sotomayor, E. A., & Huang, Z. D. (1992). Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Research, 52(23), 6702–6704.

    PubMed  CAS  Google Scholar 

  30. Batchelor, T. T., et al. (2007). AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell, 11(1), 83–95.

    PubMed  CAS  Google Scholar 

  31. Dings, R. P., et al. (2007). Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clinical Cancer Research, 13(11), 3395–3402.

    PubMed  CAS  Google Scholar 

  32. Fukumura, D., & Jain, R. K. (2007). Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize. Journal of Cellular Biochemistry, 101(4), 937–949.

    PubMed  CAS  Google Scholar 

  33. Fukumura, D., & Jain, R. K. (2007). Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalization. Microvascular Research, 74, 72–84.

    PubMed  CAS  Google Scholar 

  34. Winkler, F., et al. (2004). Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell, 6(6), 553–563.

    PubMed  CAS  Google Scholar 

  35. Riesterer, O., et al. (2006). Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment. Clinical Cancer Research, 12(11 Pt 1), 3518–3524.

    PubMed  CAS  Google Scholar 

  36. Kummar, S., et al. (2007). Compressing drug development timelines in oncology using phase ‘0’ trials. Nature Reviews. Cancer, 7(2), 131–139.

    PubMed  CAS  Google Scholar 

  37. Citrin, D., Menard, C., & Camphausen, K. (2006). Combining radiotherapy and angiogenesis inhibitors: Clinical trial design. International Journal of Radiation Oncology, Biology, Physics, 64(1), 15–25.

    PubMed  Google Scholar 

  38. Jubb, A. M., et al. (2006). Predicting benefit from anti-angiogenic agents in malignancy. Nature Reviews. Cancer, 6(8), 626–635.

    PubMed  CAS  Google Scholar 

  39. Korn, E. L., et al. (2001). Clinical trial designs for cytostatic agents: Are new approaches needed? Journal of Clinical Oncology, 19(1), 265–272.

    PubMed  CAS  Google Scholar 

  40. Bernsen, H. J., et al. (1995). Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse. British Journal of Cancer, 71(4), 721–726.

    PubMed  CAS  Google Scholar 

  41. Bussink, J., Kaanders, J. H., & van der Kogel, A. J. (2003). Tumor hypoxia at the micro-regional level: Clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers. Radiotherapy and Oncology, 67(1), 3–15.

    PubMed  Google Scholar 

  42. Macchiarini, P., et al. (1992). Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet, 340(8812), 145–146.

    PubMed  CAS  Google Scholar 

  43. Weidner, N., et al. (1991). Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. The New England Journal of Medicine, 324(1), 1–8.

    PubMed  CAS  Google Scholar 

  44. Zhong, H., et al. (1999). Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Research, 59(22), 5830–5835.

    PubMed  CAS  Google Scholar 

  45. Agulnik, M., et al. (2006). Impact and perceptions of mandatory tumor biopsies for correlative studies in clinical trials of novel anticancer agents. Journal of Clinical Oncology, 24(30), 4801–4807.

    PubMed  Google Scholar 

  46. Helft, P. R., & Daugherty, C. K. (2006). Are we taking without giving in return? The ethics of research-related biopsies and the benefits of clinical trial participation. Journal of Clinical Oncology, 24(30), 4793–4795.

    PubMed  Google Scholar 

  47. Willett, C. G., et al. (2004). Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nature Medicine, 10(2), 145–147.

    PubMed  CAS  Google Scholar 

  48. Willett, C. G., et al. (2005). Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a Phase I trial in rectal cancer patients. Journal of Clinical Oncology, 23(31), 8136–8139.

    PubMed  Google Scholar 

  49. Kolev, Y., et al. Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Annals of Surgical Oncology, 14, 2738–2747.

  50. Lentsch, E. J., et al. (2006). Microvessel density in head and neck squamous cell carcinoma primary tumors and its correlation with clinical staging parameters. Laryngoscope, 116(3), 397–400.

    PubMed  Google Scholar 

  51. Nieto, Y., et al. (2007). Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy. British Journal of Cancer, 97(3), 391–397.

    PubMed  CAS  Google Scholar 

  52. Uzzan, B., et al. (2004). Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Research, 64(9), 2941–2955.

    PubMed  CAS  Google Scholar 

  53. Hlatky, L., Hahnfeldt, P., & Folkman, J. (2002). Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. Journal of the National Cancer Institute, 94(12), 883–893.

    PubMed  Google Scholar 

  54. Tozer, G. M. (2003). Measuring tumour vascular response to antivascular and antiangiogenic drugs. British Journal of Radiology, 76(suppl_1), S23–S35.

    PubMed  CAS  Google Scholar 

  55. Beecken, W. D., et al. (2001). Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in mice. Journal of the National Cancer Institute, 93(5), 382–387.

    PubMed  CAS  Google Scholar 

  56. Bertolini, F., Martinelli, G., & Goldhirsch, A. (2001). Mosaic tumour blood vessels and high-dose chemotherapy for breast cancer. Lancet Oncology, 2(10), 595.

    PubMed  CAS  Google Scholar 

  57. Chhieng, D. C., et al. (2003). Microvessel density and vascular endothelial growth factor expression in infiltrating lobular mammary carcinoma. The Breast Journal, 9(3), 200–207.

    PubMed  CAS  Google Scholar 

  58. Dahut, W. L., et al. (2006). Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors. Cancer Biology & Therapy, 5(1), 22–27.

    CAS  Google Scholar 

  59. Dowlati, A., et al. (2005). Novel Phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416. Clinical Cancer Research, 11(21), 7938–7944.

    PubMed  CAS  Google Scholar 

  60. Singhal, S., et al. (1999). Antitumor activity of thalidomide in refractory multiple myeloma. The New England Journal of Medicine, 341(21), 1565–1571.

    PubMed  CAS  Google Scholar 

  61. Wedam, S. B., et al. (2006). Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. Journal of Clinical Oncology, 24(5), 769–777.

    PubMed  CAS  Google Scholar 

  62. Miller, J. C., et al. (2005). Imaging angiogenesis: applications and potential for drug development. Journal of the National Cancer Institute, 97(3), 172–187.

    PubMed  CAS  Google Scholar 

  63. Soo, R. A., et al. (2006). Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression. Annals of Oncology, 17(11), 1625–1630.

    PubMed  CAS  Google Scholar 

  64. Zhou, Y., et al. (2007). Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in gastric cancer. Cancer Biology & Therapy, 6(2), 269–275.

    Google Scholar 

  65. Ruegg, C., et al. (2003). The quest for surrogate markers of angiogenesis: A paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials. Current Molecular Medicine, 3(8), 673–691.

    PubMed  Google Scholar 

  66. Schor, A. M., et al. (1998). Heterogeneity in microvascular density in lung tumours: Comparison with normal bronchus. British Journal of Cancer, 77(6), 946–951.

    PubMed  CAS  Google Scholar 

  67. Dales, J. P., et al. (2004). Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: Correlation with long-term patient outcome. International Journal of Oncology, 24(5), 1197–1204.

    PubMed  Google Scholar 

  68. Duff, S. E., et al. (2003). CD105 is important for angiogenesis: Evidence and potential applications. The FASEB Journal, 17(9), 984–992.

    PubMed  CAS  Google Scholar 

  69. Kumar, S., et al. (1999). Breast carcinoma: Vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Research, 59(4), 856–861.

    PubMed  CAS  Google Scholar 

  70. Tanaka, F., et al. (2001). Evaluation of angiogenesis in non-small cell lung cancer: Comparison between anti-CD34 antibody and anti-CD105 antibody. Clinical Cancer Research, 7(11), 3410–3415.

    PubMed  CAS  Google Scholar 

  71. Sharma, S., Sharma, M. C., & Sarkar, C. (2005). Morphology of angiogenesis in human cancer: A conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology, 46(5), 481–489.

    PubMed  CAS  Google Scholar 

  72. Algire, G. H., Chalkley, H. W., Legallais, F. Y., & Park, H. D. (1945). Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. Journal of the National Cancer Institute, 6, 73–85.

    Google Scholar 

  73. Vogel, A. W. (1965). Intratumoral vascular changes with increased size of a mammary adenocarcinoma: New method and results. Journal of the National Cancer Institute, 34, 571–578.

    PubMed  CAS  Google Scholar 

  74. Hilmas, D. E., & Gillette, E. L. (1975). Tumor microvasculature following fractionated x irradiation. Radiology, 116(1), 165–169.

    PubMed  CAS  Google Scholar 

  75. Kadambi, A., et al. (2001). Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: Role of VEGF-receptor 2 and host VEGF-A. Cancer Research, 61(6), 2404–2408.

    PubMed  CAS  Google Scholar 

  76. Cho, W. C., & Cheng, C. H. (2007). Oncoproteomics: Current trends and future perspectives. Expert Review of Proteomics, 4(3), 401–410.

    PubMed  CAS  Google Scholar 

  77. Mittal, V., & Nolan, D. J. (2007). Genomics and proteomics approaches in understanding tumor angiogenesis. Expert Review of Molecular Diagnostics, 7(2), 133–147.

    PubMed  CAS  Google Scholar 

  78. Petricoin, E. F., & Liotta, L. A. (2004). Proteomic approaches in cancer risk and response assessment. Trends in Molecular Medicine, 10(2), 59–64.

    PubMed  CAS  Google Scholar 

  79. Alexander, H., et al. (2004). Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clinical Cancer Research, 10(22), 7500–7510.

    PubMed  CAS  Google Scholar 

  80. Bhattacharyya, S., et al. (2004). Diagnosis of pancreatic cancer using serum proteomic profiling. Neoplasia, 6(5), 674–686.

    PubMed  CAS  Google Scholar 

  81. Petricoin, E. F., et al. (2002). Use of proteomic patterns in serum to identify ovarian cancer. Lancet, 359(9306), 572–577.

    PubMed  CAS  Google Scholar 

  82. Petricoin 3rd, E. F., et al. (2002). Serum proteomic patterns for detection of prostate cancer. Journal of the National Cancer Institute, 94(20), 1576–1578.

    PubMed  CAS  Google Scholar 

  83. Conrads, T. P., et al. (2004). Proteomic patterns as a diagnostic tool for early-stage cancer: A review of its progress to a clinically relevant tool. Molecular Diagnosis, 8(2), 77–85.

    PubMed  Google Scholar 

  84. Kuerer, H. M., et al. (2004). Association between ductal fluid proteomic expression profiles and the presence of lymph node metastases in women with breast cancer. Surgery, 136(5), 1061–1069.

    PubMed  Google Scholar 

  85. Pusztai, L., et al. (2004). Pharmacoproteomic analysis of prechemotherapy and postchemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast carcinoma. Cancer, 100(9), 1814–1822.

    PubMed  CAS  Google Scholar 

  86. Bouamrani, A., et al. (2006). Direct-tissue SELDI-TOF mass spectrometry analysis: A new application for clinical proteomics. Clinical Chemistry, 52(11), 2103–2106.

    PubMed  CAS  Google Scholar 

  87. Hwang, S. I., et al. (2007). Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues. Oncogene, 26(1), 65–76.

    PubMed  CAS  Google Scholar 

  88. Irish, J. M., Kotecha, N., & Nolan, G. P. (2006). Mapping normal and cancer cell signalling networks: Towards single-cell proteomics. Nature Reviews. Cancer, 6(2), 146–155.

    PubMed  CAS  Google Scholar 

  89. Tarnok, A., Bocsi, J., & Brockhoff, G. (2006). Cytomics—importance of multimodal analysis of cell function and proliferation in oncology. Cell Proliferation, 39(6), 495–505.

    PubMed  CAS  Google Scholar 

  90. Ornstein, D. K., & Petricoin 3rd, E. F. (2004). Proteomics to diagnose human tumors and provide prognostic information. Oncology (Williston Park), 18(4), 521–529 discussion 529–32.

    Google Scholar 

  91. Reid, J. D., Parker, C. E., & Borchers, C. H. (2007). Protein arrays for biomarker discovery. Current Opinion in Molecular Therapeutics, 9(3), 216–221.

    PubMed  CAS  Google Scholar 

  92. Adachi, J., et al. (2006). The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins. Genome Biology, 7(9), R80.

    PubMed  Google Scholar 

  93. Venable, J. D., et al. (2007). Relative quantification of stable isotope labeled peptides using a linear ion trap-Orbitrap hybrid mass spectrometer. Analytical Chemistry, 79(8), 3056–3064.

    PubMed  CAS  Google Scholar 

  94. Imami, K., et al. (2007). Simple on-line sample preconcentration technique for peptides based on dynamic pH junction in capillary electrophoresis-mass spectrometry. Journal of Chromatography A, 1148(2), 250–255.

    PubMed  CAS  Google Scholar 

  95. Bruneel, A., et al. (2005). Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis. Proteomics, 5(15), 3876–3884.

    PubMed  CAS  Google Scholar 

  96. Chen, R., et al. (2005). Pancreatic cancer proteome: The proteins that underlie invasion, metastasis, and immunologic escape. Gastroenterology, 129(4), 1187–1197.

    PubMed  CAS  Google Scholar 

  97. Shen, F., et al. (2006). Functional proteometrics for cell migration. Cytometry A, 69(7), 563–572.

    PubMed  Google Scholar 

  98. Shen, J., et al. (2006). Identification and validation of differences in protein levels in normal, premalignant, and malignant lung cells and tissues using high-throughput western array and immunohistochemistry. Cancer Research, 66(23), 11194–11206.

    PubMed  CAS  Google Scholar 

  99. Thompson, L. P., & Dong, Y. (2005). Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts. Journal of the Society for Gynecologic Investigation, 12(6), 388–395.

    PubMed  CAS  Google Scholar 

  100. Oh, P., et al. (2004). Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature, 429(6992), 629–635.

    PubMed  CAS  Google Scholar 

  101. Mustafa, D. A. N., et al. (2007). Identification of glioma neovascularization-related proteins by using MALDI-FTMS and Nano-LC fractionation to microdissected tumor vessels. Molecular & Cellular Proteomics, 6(7), 1147–1157.

    CAS  Google Scholar 

  102. Christian, S., et al. (2003). Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. The Journal of Cell Biology, 163(4), 871–878.

    PubMed  CAS  Google Scholar 

  103. Hu, J., et al. (2005). Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer. Oncogene, 24(7), 1212–1219.

    PubMed  CAS  Google Scholar 

  104. Croix, B. S., et al. (2000). Genes expressed in human tumor endothelium. Science, 289(5482), 1197–1202.

    Google Scholar 

  105. Seaman, S., et al. (2007). Genes that distinguish physiological and pathological angiogenesis. Cancer Cell, 11(6), 539–554.

    PubMed  CAS  Google Scholar 

  106. Li, J.-L., & Harris, A. L. (2007). The potential of new tumor endothelium-specific markers for the development of antivascular therapy. Cancer Cell, 11(6), 478–481.

    PubMed  CAS  Google Scholar 

  107. Nanda, A., & St Croix, B. (2004). Tumor endothelial markers: New targets for cancer therapy. Current Opinion in Oncology, 16(1), 44–49.

    PubMed  CAS  Google Scholar 

  108. Beaty, R., et al. (2007). PLXDC1 (TEM7) is identified in a genome-wide expression screen of glioblastoma endothelium. Journal of Neuro-Oncology, 81(3), 241–248.

    PubMed  CAS  Google Scholar 

  109. Madden, S. L., et al. (2004). Vascular gene expression in nonneoplastic and malignant brain. The American Journal of Pathology, 165(2), 601–608.

    PubMed  CAS  Google Scholar 

  110. Parker, B. S., et al. (2004). Alterations in vascular gene expression in invasive breast carcinoma. Cancer Research, 64(21), 7857–7866.

    PubMed  CAS  Google Scholar 

  111. Ho, M., et al. (2003). Identification of endothelial cell genes by combined database mining and microarray analysis. Physiological Genomics, 13(3), 249–262.

    PubMed  CAS  Google Scholar 

  112. Yang, X., & Sun, X. (2007). Meta-analysis of several gene lists for distinct types of cancer: A simple way to reveal common prognostic markers. BMC Bioinformatics, 8(1), 118.

    PubMed  Google Scholar 

  113. Costouros, N. G., et al. (2002). Microarray gene expression analysis of murine tumor heterogeneity defined by dynamic contrast-enhanced MRI. Molecular Imaging, 1(3), 301–308.

    PubMed  CAS  Google Scholar 

  114. Jackson, A., et al. (2007). Imaging tumor vascular heterogeneity and angiogenesis using dynamic contrast-enhanced magnetic resonance imaging. Clinical Cancer Research, 13(12), 3449–3459.

    PubMed  Google Scholar 

  115. Menard, C., et al. (2005). An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement. Molecular Imaging, 4(1), 63–66.

    PubMed  Google Scholar 

  116. Jaeger, J., et al. (2007). Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Clinical Cancer Research, 13(3), 806–815.

    PubMed  CAS  Google Scholar 

  117. Pen, A., et al. (2007). Molecular markers of extracellular matrix remodeling in glioblastoma vessels: Microarray study of laser-captured glioblastoma vessels. Glia, 55(6), 559–572.

    PubMed  Google Scholar 

  118. Schuetz, C. S., et al. (2006). Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. Cancer Research, 66(10), 5278–5286.

    PubMed  CAS  Google Scholar 

  119. Yang, F., et al. (2006). Laser microdissection and microarray analysis of breast tumors reveal ER-alpha related genes and pathways. Oncogene, 25(9), 1413–1419.

    PubMed  CAS  Google Scholar 

  120. Scappaticci, F. A., et al. (2005). Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. Journal of Surgical Oncology, 91(3), 173–180.

    PubMed  CAS  Google Scholar 

  121. Drevs, J., & Schneider, V. (2006). The use of vascular biomarkers and imaging studies in the early clinical development of anti-tumour agents targeting angiogenesis. Journal of Internal Medicine, 260(6), 517–529.

    PubMed  CAS  Google Scholar 

  122. Zhang, D., et al. (2007). Effects of a monoclonal anti-avb3 integrin antibody on blood vessels—A pharmacodynamic study. Investigational New Drugs, 25(1), 49–55.

    PubMed  CAS  Google Scholar 

  123. Mundhenke, C., et al. (2001). Tissue examination to monitor antiangiogenic therapy: A phase I clinical trial with endostatin. Clinical Cancer Research, 7(11), 3366–3374.

    PubMed  CAS  Google Scholar 

  124. Lockhart, A. C., et al. (2003). Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clinical Cancer Research, 9(2), 586–593.

    PubMed  CAS  Google Scholar 

  125. Alvarez Secord, A., et al. (2004). The relationship between serum vascular endothelial growth factor, persistent disease, and survival at second-look laparotomy in ovarian cancer. Gynecologic Oncology, 94(1), 74–79.

    PubMed  CAS  Google Scholar 

  126. Braybrooke, J. P., et al. (2000). A phase II study of razoxane, an antiangiogenic topoisomerase II inhibitor, in renal cell cancer with assessment of potential surrogate markers of angiogenesis. Clinical Cancer Research, 6(12), 4697–4704.

    PubMed  CAS  Google Scholar 

  127. Chan, L. W., et al. (2004). Urinary VEGF and MMP levels as predictive markers of 1-year progression-free survival in cancer patients treated with radiation therapy: A longitudinal study of protein kinetics throughout tumor progression and therapy. Journal of Clinical Oncology, 22(3), 499–506.

    PubMed  CAS  Google Scholar 

  128. Coskun, U., et al. (2003). Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients. Breast, 12(2), 104–110.

    PubMed  Google Scholar 

  129. Duque, J. L., et al. (2006). Measurement of plasma levels of vascular endothelial growth factor in prostate cancer patients: Relationship with clinical stage, Gleason score, prostate volume, and serum prostate-specific antigen. Clinics, 61(5), 401–408.

    PubMed  Google Scholar 

  130. Fine, H. A., et al. (2000). Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. Journal of Clinical Oncology, 18(4), 708–715.

    PubMed  CAS  Google Scholar 

  131. Kaya, A., et al. (2004). The prognostic significance of vascular endothelial growth factor levels in sera of non-small cell lung cancer patients. Respiratory Medicine, 98(7), 632–636.

    PubMed  Google Scholar 

  132. Krzystek-Korpacka, M., et al. (2007). Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Cancer Letters, 249(2), 171–177.

    PubMed  CAS  Google Scholar 

  133. Li, L., et al. (2004). Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Research, 24(3b), 1973–1979.

    PubMed  CAS  Google Scholar 

  134. Poon, R. T., et al. (2004). Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. The British Journal of Surgery, 91(10), 1354–1360.

    PubMed  CAS  Google Scholar 

  135. Poon, R. T.-P., et al. (2003). Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Research, 63(12), 3121–3126.

    PubMed  CAS  Google Scholar 

  136. Shariat, S. F., et al. (2004). Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule-1 with lymph node status and biochemical progression after radical prostatectomy. Journal of Clinical Oncology, 22(9), 1655–1663.

    PubMed  CAS  Google Scholar 

  137. Shariat, S. F., et al. (2004). Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression. Clinical Cancer Research, 10(6), 1992–1999.

    PubMed  CAS  Google Scholar 

  138. Sliutz, G., et al. (1995). Serum evaluation of basic FGF in breast cancer patients. Anticancer Research, 15(6B), 2675–2677.

    PubMed  CAS  Google Scholar 

  139. Tamura, M., et al. (2004). Chest CT and serum vascular endothelial growth factor-C level to diagnose lymph node metastasis in patients with primary non-small cell lung cancer. Chest, 126(2), 342–346.

    PubMed  CAS  Google Scholar 

  140. Gonzalez, F. J., et al. (2007). Prognostic value of serum angiogenic activity in colorectal cancer patients. Journal of Cellular and Molecular Medicine, 11(1), 120–128.

    PubMed  CAS  Google Scholar 

  141. Negrier, S., et al. (2004). Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: Prognostic value of interleukin-6-from the Groupe Francais d’Immunotherapie. Journal of Clinical Oncology, 22(12), 2371–2378.

    PubMed  CAS  Google Scholar 

  142. Tas, F., et al. (2006). Serum vascular endothelial growth factor (VEGF) and bcl-2 levels in advanced stage non-small cell lung cancer. Cancer Investigation, 24(6), 576–580.

    PubMed  CAS  Google Scholar 

  143. Brostjan, C., et al. (2003). Monitoring of circulating angiogenic factors in dendritic cell-based cancer immunotherapy. Cancer, 98(10), 2291–2301.

    PubMed  CAS  Google Scholar 

  144. Norden-Zfoni, A., et al. (2007). Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clinical Cancer Research, 13(9), 2643–2650.

    PubMed  CAS  Google Scholar 

  145. Drevs, J., et al. (2007). Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. Journal of Clinical Oncology, 25(21), 3045–3054.

    PubMed  CAS  Google Scholar 

  146. Drevs, J. (2003). Soluble markers for the detection of hypoxia under antiangiogenic treatment. Anticancer Research, 23(2A), 1159–1161.

    PubMed  CAS  Google Scholar 

  147. Vincenzi, B., et al. (2007). Circulating VEGF reduction, response and outcome in advanced colorectal cancer patients treated with cetuximab plus irinotecan. Pharmacogenomics, 8(4), 319–327.

    PubMed  CAS  Google Scholar 

  148. Ria, R., et al. (2004). Serum levels of angiogenic cytokines decrease after antineoplastic radiotherapy. Cancer Letters, 216(1), 103–107.

    PubMed  CAS  Google Scholar 

  149. Shimada, H., et al. (2002). Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma. British Journal of Cancer, 86(4), 552–557.

    PubMed  CAS  Google Scholar 

  150. Shimada, H., et al. (2001). Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma. Cancer, 92(3), 663–669.

    PubMed  CAS  Google Scholar 

  151. Bewick, M., et al. (2004). Evaluation of sICAM-1, sVCAM-1, and sE-selectin levels in patients with metastatic breast cancer receiving high-dose chemotherapy. Stem Cells and Development, 13(3), 281–294.

    PubMed  CAS  Google Scholar 

  152. Ding, Y. B., et al. (2003). Association of VCAM-1 overexpression with oncogenesis, tumor angiogenesis and metastasis of gastric carcinoma. World Journal of Gastroenterology, 9(7), 1409–1414.

    PubMed  CAS  Google Scholar 

  153. Kumar, H., et al. (2002). Soluble FLT-1 is detectable in the sera of colorectal and breast cancer patients. Anticancer Research, 22(3), 1877–1880.

    PubMed  CAS  Google Scholar 

  154. Opala, T., et al. (2003). Evaluation of soluble intracellular adhesion molecule-1 (sICAM-1) in benign and malignant ovarian masses. European Journal of Gynaecological Oncology, 24(3–4), 255–257.

    PubMed  CAS  Google Scholar 

  155. Pasieka, Z., et al. (2004). Soluble intracellular adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood of patients with thyroid cancer. Neoplasma, 51(1), 34–37.

    PubMed  CAS  Google Scholar 

  156. Pasieka, Z., et al. (2003). Evaluation of the levels of bFGF, VEGF, sICAM-1, and sVCAM-1 in serum of patients with thyroid cancer. Recent Results in Cancer Research, 162, 189–194.

    PubMed  CAS  Google Scholar 

  157. Ishii, Y., & Kitamura, S. (1999). Soluble intercellular adhesion molecule-1 as an early detection marker for radiation pneumonitis. The European Respiratory Journal, 13(4), 733–738.

    PubMed  CAS  Google Scholar 

  158. Nordal, R. A., & Wong, C. S. (2004). Intercellular adhesion molecule-1 and blood-spinal cord barrier disruption in central nervous system radiation injury. Journal of Neuropathology and Experimental Neurology, 63(5), 474–483.

    PubMed  CAS  Google Scholar 

  159. Religa, P., et al. (2005). Presence of bone marrow-derived circulating progenitor endothelial cells in the newly formed lymphatic vessels. Blood, 106(13), 4184–4190.

    PubMed  CAS  Google Scholar 

  160. Jansen, M., et al. (2004). Current perspectives on antiangiogenesis strategies in the treatment of malignant gliomas. Brain Research. Brain Research Reviews, 45(3), 143–163.

    PubMed  CAS  Google Scholar 

  161. Lyden, D., et al. (2001). Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine, 7(11), 1194–1201.

    PubMed  CAS  Google Scholar 

  162. Capillo, M., et al. (2003). Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. Clinical Cancer Research, 9(1), 377–382.

    PubMed  CAS  Google Scholar 

  163. Shaked, Y., et al. (2005). Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis: Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell, 7(1), 101–111.

    PubMed  CAS  Google Scholar 

  164. Gill, M., et al. (2001). Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circulation Research, 88(2), 167–174.

    PubMed  CAS  Google Scholar 

  165. Shintani, S., et al. (2001). Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation, 103(23), 2776–2779.

    PubMed  CAS  Google Scholar 

  166. Rabascio, C., et al. (2004). Assessing tumor angiogenesis: increased circulating VE-cadherin RNA in patients with cancer indicates viability of circulating endothelial cells. Cancer Research, 64(12), 4373–4377.

    PubMed  CAS  Google Scholar 

  167. Furstenberger, G., et al. (2006). Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. British Journal of Cancer, 94(4), 524–531.

    PubMed  CAS  Google Scholar 

  168. Ocak, I., et al. (2007). The biologic basis of in vivo angiogenesis imaging. Frontiers in Bioscience, 12, 3601–3616.

    PubMed  CAS  Google Scholar 

  169. Provenzale, J. M. (2007). Imaging of angiogenesis: Clinical techniques and novel imaging methods. AJR. American Journal of Roentgenology, 188(1), 11–23.

    PubMed  Google Scholar 

  170. Schirner, M., et al. (2004). Molecular imaging of tumor angiogenesis. Annals of the New York Academy of Sciences, 1014(1), 67–75.

    PubMed  CAS  Google Scholar 

  171. Herbst, R. S., et al. (2002). Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. Journal of Clinical Oncology, 20(18), 3804–3814.

    PubMed  CAS  Google Scholar 

  172. Jennens, R., et al. (2004). Complete radiological and metabolic response of metastatic renal cell carcinoma to SU5416 (semaxanib) in a patient with probable von Hippel–Lindau syndrome. Urologic Oncology, 22(3), 193–196.

    PubMed  Google Scholar 

  173. Mullamitha, S. A., et al. (2007). Phase I evaluation of a fully human anti-{alpha}v integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clinical Cancer Research, 13(7), 2128–2135.

    PubMed  CAS  Google Scholar 

  174. Turner, C. D., et al. (2007). Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme. Journal of Neurooncology, 82(1), 95–101.

    CAS  Google Scholar 

  175. Willett, C. G., et al. (2007). Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer. Nature Clinical Practice. Oncology, 4(5), 316–321.

    PubMed  CAS  Google Scholar 

  176. Clavo, A., Brown, R., & Wahl, R. (1995). Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. Journal of Nuclear Medicine, 36(9), 1625–1632.

    PubMed  CAS  Google Scholar 

  177. Sivitz, W. I., et al. (1992). Pretranslational regulation of two cardiac glucose transporters in rats exposed to hypobaric hypoxia. American Journal of Physiology: Endocrinology and Metabolism, 263(3), E562–E569.

    CAS  Google Scholar 

  178. McDonald, D. M., & Choyke, P. L. (2003). Imaging of angiogenesis: From microscope to clinic. Nature Medicine, 9(6), 713–725.

    PubMed  CAS  Google Scholar 

  179. Eschmann, S. M., et al. (2005). Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. Journal of Nuclear Medicine, 46(2), 253–260.

    PubMed  Google Scholar 

  180. Gagel, B., et al. (2006). [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study. BMC Cancer, 6, 51.

    PubMed  Google Scholar 

  181. Laking, G. R., & Price, P. M. (2003). Positron emission tomographic imaging of angiogenesis and vascular function. British Journal of Radiology, 76(suppl_1), S50–S59.

    PubMed  Google Scholar 

  182. Thorwarth, D., et al. (2005). A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia. Physics in Medicine & Biology, 50(10), 2209–2224.

    Google Scholar 

  183. Thorwarth, D., et al. (2005). Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer, 5, 152.

    PubMed  Google Scholar 

  184. Cher, L. M., et al. (2006). Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and Immunohistochemical Studies. Journal of Nuclear Medicine, 47(3), 410–418.

    PubMed  CAS  Google Scholar 

  185. Hicks, R. J., et al. (2005). Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. European Journal of Nuclear Medicine and Molecular Imaging, 32(12), 1384–1391.

    PubMed  Google Scholar 

  186. Rischin, D., et al. (2006). Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: A substudy of Trans-Tasman Radiation Oncology Group Study 98.02. Journal of Clinical Oncology, 24(13), 2098–2104.

    PubMed  Google Scholar 

  187. Rischin, D., et al. (2001). Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. Journal of Clinical Oncology, 19(2), 535–542.

    PubMed  CAS  Google Scholar 

  188. Pal, A., et al. (2006). Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography. Molecular Imaging and Biology, 8(5), 262–277.

    PubMed  CAS  Google Scholar 

  189. Schmidt, K., et al. (2006). Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization. Journal of Nuclear Medicine, 47(3), 543–551.

    PubMed  CAS  Google Scholar 

  190. Anderson, H., et al. (2003). Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane. British Journal of Cancer, 89(2), 262–267.

    PubMed  CAS  Google Scholar 

  191. Lehtio, K., et al. (2004). Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics, 59(4), 971–982.

    PubMed  Google Scholar 

  192. Mullani, N., et al. (2000). First pass FDG measured blood flow in tumors: A comparison with O-15 labeled water measured blood flow. Clinical Positron Imaging, 3(4), 153.

    PubMed  Google Scholar 

  193. Tseng, J., et al. (2004). 18F-FDG kinetics in locally advanced breast cancer: Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. Journal of Nuclear Medicine, 45(11), 1829–1837.

    PubMed  CAS  Google Scholar 

  194. Wells, P., et al. (2002). Assessment of proliferation in vivo using 2-[11C]thymidine positron emission tomography in advanced intra-abdominal malignancies. Cancer Research, 62(20), 5698–5702.

    PubMed  CAS  Google Scholar 

  195. Chen, X., et al. (2004). Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor {alpha}v{beta}3-integrin expression. Journal of Nuclear Medicine, 45(10), 1776–1783.

    PubMed  CAS  Google Scholar 

  196. Chen, X., et al. (2004). MicroPET imaging of breast cancer alphav-integrin expression with 64Cu-labeled dimeric RGD peptides. Molecular Imaging and Biology, 6(5), 350–359.

    PubMed  Google Scholar 

  197. Chen, X., et al. (2004). MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide. European Journal of Nuclear Medicine and Molecular Imaging, 31(8), 1081–1089.

    PubMed  CAS  Google Scholar 

  198. Collingridge, D. R., et al. (2002). The Development of [124I]Iodinated-VG76e: A novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Research, 62(20), 5912–5919.

    PubMed  CAS  Google Scholar 

  199. Furumoto, S., et al. (2003). Tumor detection using 18F-labeled matrix metalloproteinase-2 inhibitor. Nuclear Medicine and Biology, 30(2), 119–125.

    PubMed  CAS  Google Scholar 

  200. Haubner, R., et al. (2001). Glycosylated RGD-containing peptides: Tracer for tumor targeting and angiogenesis imaging with improved biokinetics. Journal of Nuclear Medicine, 42(2), 326–336.

    PubMed  CAS  Google Scholar 

  201. Kobayashi, H., et al. (2004). Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. Clinical Cancer Research, 10(22), 7712–7720.

    PubMed  CAS  Google Scholar 

  202. Zheng, Q., et al. (2003). Synthesis, biodistribution and micro-PET imaging of a potential cancer biomarker carbon-11 labeled MMP inhibitor (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid [11C]methyl ester. Nuclear Medicine and Biology, 30(7), 753–760.

    PubMed  CAS  Google Scholar 

  203. Zinn, K., et al. (2000). Imaging Tc-99m-labeled FGF-1 targeting in rats. Nuclear Medicine and Biology, 27(4), 407–414.

    PubMed  CAS  Google Scholar 

  204. Cai, W., et al. (2006). PET of vascular endothelial growth factor receptor expression. Journal of Nuclear Medicine, 47(12), 2048–2056.

    PubMed  CAS  Google Scholar 

  205. Wang, H., et al. (2007). A new PET tracer specific for vascular endothelial growth factor receptor 2. European Journal of Nuclear Medicine and Molecular Imaging, 34(12), 2001–2010.

    PubMed  CAS  Google Scholar 

  206. Beer, A. J., et al. (2005). Biodistribution and pharmacokinetics of the {alpha}v{beta}3-selective tracer 18F-Galacto-RGD in cancer patients. Journal of Nuclear Medicine, 46(8), 1333–1341.

    PubMed  CAS  Google Scholar 

  207. Wu, Z., et al. (2007). MicroPET of tumor integrin {alpha}v{beta}3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4). Journal of Nuclear Medicine, 48(9), 1536–1544.

    PubMed  CAS  Google Scholar 

  208. Kamel, E., et al. (2002). CT vs 68Ge attenuation correction in a combined PET/CT system: evaluation of the effect of lowering the CT tube current. European Journal of Nuclear Medicine and Molecular Imaging, 29(3), 346–350.

    PubMed  CAS  Google Scholar 

  209. Antoch, G., et al. (2004). Accuracy of whole-body dual-modality fluorine-18–2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for tumor staging in solid tumors: Comparison with CT and PET. Journal of Clinical Oncology, 22(21), 4357–4368.

    PubMed  Google Scholar 

  210. Gorres, G., Steinert, H., & Schulthess, G. v. (2004). PET and functional anatomic fusion imaging in lung and breast cancers. The Cancer Journal, 10(4), 251–261.

    PubMed  Google Scholar 

  211. Barrett, T., et al. (2007). MRI of tumor angiogenesis. Journal of Magnetic Resonance Imaging, 26(2), 235–249.

    PubMed  Google Scholar 

  212. Hylton, N. (2006). Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. Journal of Clinical Oncology, 24(20), 3293–3298.

    PubMed  CAS  Google Scholar 

  213. Choyke, P., Dwyer, A., & Knopp, M. (2003). Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging. Journal of Magnetic Resonance Imaging, 17(5), 509–520.

    PubMed  Google Scholar 

  214. Padhani, A., & Dzik-Jurasz, A. (2004). Perfusion MR imaging of extracranial tumor angiogenesis. Topics in Magnetic Resonance Imaging, 15(1), 41–57.

    PubMed  Google Scholar 

  215. Kiessling, F., Morgenstern, B., & Zhang, C. (2007). Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging. Current Medicinal Chemistry, 14(1), 77–91.

    PubMed  CAS  Google Scholar 

  216. Daldrup, H. E., et al. (1998). Quantification of the extraction fraction for gadopentetate across breast cancer capillaries. Magnetic Resonance in Medicine, 40(4), 537–543.

    PubMed  CAS  Google Scholar 

  217. Padhani, A. (2002). Dynamic contrast-enhanced MRI in clinical oncology: Current status and future directions. Journal of Magnetic Resonance Imaging, 16(4), 407–422.

    PubMed  Google Scholar 

  218. Wikstrom, M., et al. (1989). Contrast-enhanced MRI of tumors. Comparison of Gd-DTPA and a macromolecular agent. Investigative Radiology, 24(8), 609–615.

    PubMed  CAS  Google Scholar 

  219. Kang, H., et al. (2002). Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjugate Chemistry, 13(1), 122–127.

    PubMed  CAS  Google Scholar 

  220. McCarthy, J. R., et al. (2007). Targeted delivery of multifunctional magnetic nanoparticles. Nanomed, 2(2), 153–167.

    PubMed  CAS  Google Scholar 

  221. Sancey, L., et al. (2007). In vivo imaging of tumour angiogenesis in mice with the alpha(v)beta (3) integrin-targeted tracer (99m)Tc-RAFT-RGD. European Journal of Nuclear Medicine and Molecular Imaging, 34, 2037–2047.

    PubMed  CAS  Google Scholar 

  222. Sipkins, D., et al. (1998). Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nature Medicine, 4(5), 623–626.

    PubMed  CAS  Google Scholar 

  223. Winter, P. M., et al. (2003). Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel {alpha}{nu}{beta}3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Research, 63(18), 5838–5843.

    PubMed  CAS  Google Scholar 

  224. Nunn, A., Linder, K., & Tweedle, M. (1997). Can receptors be imaged with MRI agents? The Quarterly Journal of Nuclear Medicine, 41(2), 155–162.

    PubMed  CAS  Google Scholar 

  225. O'Donnell, A., et al. (2005). A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. British Journal of Cancer, 93(8), 876–883.

    PubMed  Google Scholar 

  226. Kothari, M., et al. (2003). Imaging in antiangiogenesis trial: a clinical trials radiology perspective. British Journal of Radiology, 76(suppl_1), S92–96.

    PubMed  Google Scholar 

  227. Jain, R. K. (2001). Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nature Medicine, 7(9), 987–989.

    PubMed  CAS  Google Scholar 

  228. Tatum, J. L., & Hoffman, J. M. (2000). Role of imaging in clinical trials of antiangiogenesis therapy in oncology. Academic Radiology, 7(10), 798–799.

    PubMed  CAS  Google Scholar 

  229. Medved, M., et al. (2004). Semiquantitative analysis of dynamic contrast enhanced MRI in cancer patients: Variability and changes in tumor tissue over time. Journal of Magnetic Resonance Imaging, 20(1), 122–128.

    PubMed  Google Scholar 

  230. Morgan, B., et al. (2003). Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two Phase I studies. Journal of Clinical Oncology, 21(21), 3955–3964.

    PubMed  CAS  Google Scholar 

  231. Xiong, H. Q., et al. (2004). A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Investigational New Drugs, 22(4), 459–466.

    PubMed  CAS  Google Scholar 

  232. Robinson, S. P., et al. (2007). Susceptibility contrast magnetic resonance imaging determination of fractional tumor blood volume: A noninvasive imaging biomarker of response to the vascular disrupting agent ZD6126. International Journal of Radiation Oncology, Biology, Physics, 69(3), 872–879.

    PubMed  Google Scholar 

  233. Liu, G., et al. (2005). Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: Results from a Phase I study. Journal of Clinical Oncology, 23(24), 5464–5473.

    PubMed  CAS  Google Scholar 

  234. Akella, N. S., et al. (2004). Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic resonance imaging: Quality and analysis results of a phase I trial. Journal of Magnetic Resonance Imaging, 20(6), 913–922.

    PubMed  Google Scholar 

  235. Nabors, L. B., et al. (2007). Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. Journal of Clinical Oncology, 25(13), 1651–1657.

    PubMed  CAS  Google Scholar 

  236. Thomas, A. L., et al. (2005). Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. Journal of Clinical Oncology, 23(18), 4162–4171.

    PubMed  CAS  Google Scholar 

  237. Cuenod, C. A., et al. (2006). Tumor angiogenesis: Pathophysiology and implications for contrast-enhanced MRI and CT assessment. Abdominal Imaging, 31(2), 188–193.

    PubMed  CAS  Google Scholar 

  238. Lee, T. Y., Purdie, T. G., & Stewart, E. (2003). CT imaging of angiogenesis. The Quarterly Journal of Nuclear Medicine, 47(3), 171–187.

    PubMed  Google Scholar 

  239. Miles, K. A. (2003). Functional CT imaging in oncology. European Radiology, 13(Suppl 5), M134–M138.

    PubMed  Google Scholar 

  240. Tateishi, U., et al. (2002). Contrast-enhanced dynamic computed tomography for the evaluation of tumor angiogenesis in patients with lung carcinoma. Cancer, 95(4), 835–842.

    PubMed  Google Scholar 

  241. Tateishi, U., et al. (2001). Tumor angiogenesis and dynamic CT in lung adenocarcinoma: radiologic–pathologic correlation. Journal of Computer Assisted Tomography, 25(1), 23–27.

    PubMed  CAS  Google Scholar 

  242. Yi, C. A., et al. (2004). Solitary pulmonary nodules: Dynamic enhanced multi-detector row CT study and comparison with vascular endothelial growth factor and microvessel density. Radiology, 233(1), 191–199.

    PubMed  Google Scholar 

  243. Ma, S.-H., et al. (2007). Peripheral lung cancer: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and cyclin D1 expression. Clinical Imaging, 31(3), 165–177.

    PubMed  Google Scholar 

  244. Faria, S. C., et al. (2007). CT quantification of effects of thalidomide in patients with metastatic renal cell carcinoma. American Journal of Roentgenology, 189(2), 378–385.

    PubMed  Google Scholar 

  245. McNeel, D. G., et al. (2005). Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. Clinical Cancer Research, 11(21), 7851–7860.

    PubMed  CAS  Google Scholar 

  246. Ng, Q.-S., et al. (2007). Effect of nitric-oxide synthesis on tumour blood volume and vascular activity: A phase I study. The Lancet Oncology, 8(2), 111–118.

    PubMed  CAS  Google Scholar 

  247. Xiong, H. Q., et al. (2004). A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Investigational New Drugs, 22(4), 459–466.

    PubMed  CAS  Google Scholar 

  248. Kim, J., et al. (2004). Solitary pulmonary nodules: A comparative study evaluated with contrast-enhanced dynamic MR imaging and CT. Journal of Computer Assisted Tomography, 28(6), 766–775.

    PubMed  Google Scholar 

  249. Korst, R., & Altorki, N. (2004). Imaging for esophageal tumors. Thoracic Surgery Clinics, 14(1), 61–69.

    PubMed  Google Scholar 

  250. Kramer, H., et al. (2004). Oesophageal endoscopic ultrasound with fine needle aspiration improves and simplifies the staging of lung cancer. Thorax, 59(7), 596–601.

    PubMed  CAS  Google Scholar 

  251. Massari, M., et al. (1998). Value and limits of endorectal ultrasonography for preoperative staging of rectal carcinoma. Surgical Laparoscopy & Endoscopy, 8(6), 438–444.

    CAS  Google Scholar 

  252. Saga, Y., et al. (2004). Comparative study of novel endoluminal ultrasonography and conventional transurethral ultrasonography in staging of bladder cancer. International Journal of Urology, 11(8), 597–601.

    PubMed  Google Scholar 

  253. Tarantino, D., & Bernstein, M. (2002). Endoanal ultrasound in the staging and management of squamous-cell carcinoma of the anal canal: Potential implications of a new ultrasound staging system. Diseases of the Colon & Rectum, 45(1), 16–22.

    Google Scholar 

  254. Yanai, H., et al. (2003). Prognostic value and interobserver agreement of endoscopic ultrasonography for superficial squamous cell carcinoma of the esophagus: A prospective study. International Journal of Gastrointestinal Cancer, 34(1), 1–8.

    PubMed  Google Scholar 

  255. Cosgrove, D. (2003). Angiogenesis imaging—ultrasound. British Journal of Radiology, 76(suppl_1), S43–S49.

    PubMed  Google Scholar 

  256. Huber, S., et al. (1994). Breast tumors: computer-assisted quantitative assessment with color Doppler US. Radiology, 192(3), 797–801.

    PubMed  CAS  Google Scholar 

  257. Fanelli, M., et al. (1999). Assessment of tumor vascularization: Immunohistochemical and non-invasive methods. The International Journal of Biological Markers, 14(4), 218–231.

    PubMed  CAS  Google Scholar 

  258. Dayton, P., et al. (2004). Ultrasonic analysis of peptide- and antibody-targeted microbubble contrast agents for molecular imaging of alphavbeta3-expressing cells. Molecular Imaging and Biology, 3(2), 125–134.

    CAS  Google Scholar 

  259. Harrer, J., et al. (2004). Perfusion imaging of high-grade gliomas: A comparison between contrast harmonic and magnetic resonance imaging. Technical note. Journal of Neurosurgery, 101(4), 700–703.

    PubMed  Google Scholar 

  260. Kiessling, F., et al. (2003). Comparing dynamic parameters of tumor vascularization in nude mice revealed by magnetic resonance imaging and contrast-enhanced intermittent power Doppler sonography. Investigative Radiology, 38(8), 516–524.

    PubMed  Google Scholar 

  261. Abdollahi, A., et al. (2003). Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects. Cancer Research, 63(24), 8890–8898.

    PubMed  CAS  Google Scholar 

  262. Forsberg, F., et al. (2004). Assessment of angiogenesis: Implications for ultrasound imaging. Ultrasonics, 42(1–9), 325–330.

    PubMed  CAS  Google Scholar 

  263. Fury, M., et al. (2007). A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers. Investigational New Drugs, 25(2), 165–172.

    PubMed  CAS  Google Scholar 

  264. Mross, K., et al. (2005). Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. European Journal of Cancer, 41(9), 1291–1299.

    PubMed  CAS  Google Scholar 

  265. Mross, K., Fuxius, S., & Drevs, J. (2002). Serial measurements of pharmacokinetics, DCE-MRI, blood flow, PET and biomarkers in serum/plasma—what is a useful tool in clinical studies of anti-angiogenic drugs? International Journal of Clinical Pharmacology and Therapeutics, 40(12), 573–574.

    PubMed  CAS  Google Scholar 

  266. Gibson, A. P., Hebden, J. C., & Arridge, S. R. (2005). Recent advances in diffuse optical imaging. Physics in Medicine & Biology, 50(4), R1–R43.

    CAS  Google Scholar 

  267. Cai, W., & Chen, X. (2007). Multimodality imaging of vascular endothelial growth factor and vascular endothelial growth factor receptor expression. Frontiers in Bioscience, 12, 4267–4279.

    PubMed  CAS  Google Scholar 

  268. Chance, B., et al. (2005). Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: A six-year, two-site Study1. Academic Radiology, 12(8), 925–933.

    PubMed  Google Scholar 

  269. Zhu, Q., et al. (2005). Benign versus malignant breast masses: Optical differentiation with US-guided optical imaging reconstruction. Radiology, 237(1), 57–66.

    PubMed  Google Scholar 

  270. Ntziachristos, V., & Chance, B. (2001). Probing physiology and molecular function using optical imaging: applications to breast cancer. Breast Cancer Research, 3(1), 41–46.

    PubMed  CAS  Google Scholar 

  271. Escudier, B., et al. (2007). Sorafenib in advanced clear-cell renal-cell carcinoma. The New England Journal of Medicine, 356(2), 125–134.

    PubMed  CAS  Google Scholar 

  272. Giantonio, B. J., et al. (2007). Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200. Journal of Clinical Oncology, 25(12), 1539–1544.

    PubMed  CAS  Google Scholar 

  273. Hurwitz, H., et al. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. The New England Journal of Medicine, 350(23), 2335–2342.

    PubMed  CAS  Google Scholar 

  274. Sandler, A., et al. (2006). Paclitaxel–carboplatin alone or with bevacizumab for non-small-cell lung cancer. The New England Journal of Medicine, 355(24), 2542–2550.

    PubMed  CAS  Google Scholar 

  275. Bonner, J. A., et al. (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. The New England Journal of Medicine, 354(6), 567–578.

    PubMed  CAS  Google Scholar 

  276. Cunningham, D., et al. (2004). Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. The New England Journal of Medicine, 351(4), 337–345.

    PubMed  CAS  Google Scholar 

  277. Gibson, T. B., Ranganathan, A., & Grothey, A. (2006). Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clinical Colorectal Cancer, 6(1), 29–31.

    PubMed  Google Scholar 

  278. Van Cutsem, E., et al. (2007). Open-label Phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. Journal of Clinical Oncology, 25(13), 1658–1664.

    PubMed  Google Scholar 

  279. Piccart-Gebhart, M. J., et al. (2005). Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. The New England Journal of Medicine, 353(16), 1659–1672.

    PubMed  CAS  Google Scholar 

  280. Moore, M. J., et al. (2007). Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology, 25(15), 1960–1966.

    PubMed  CAS  Google Scholar 

  281. Shepherd, F. A., et al. (2005). Erlotinib in previously treated non-small-cell lung cancer. The New England Journal of Medicine, 353(2), 123–132.

    PubMed  CAS  Google Scholar 

  282. Thatcher, N., et al. (2005). Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet, 366(9496), 1527–1537.

    PubMed  CAS  Google Scholar 

  283. Dagher, R., et al. (2002). Approval summary: Imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clinical Cancer Research, 8(10), 3034–3038.

    PubMed  CAS  Google Scholar 

  284. Druker, B. J., et al. (2006). Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. The New England Journal of Medicine, 355(23), 2408–2417.

    PubMed  CAS  Google Scholar 

  285. Geyer, C. E., et al. (2006). Lapatinib plus capecitabine for HER2-positive advanced breast cancer. The New England Journal of Medicine, 355(26), 2733–2743.

    PubMed  CAS  Google Scholar 

  286. Casali, P. G., et al. (2006). Updated results from a phase III trial of sunitinib in GIST patients (pts) for whom imatinib (IM) therapy has failed due to resistance or intolerance. Journal of Clinical Oncology (Meeting Abstracts), 24(18_suppl), 9513.

    Google Scholar 

  287. Motzer, R. J., et al. (2007). Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. The New England Journal of Medicine, 356(2), 115–124.

    PubMed  CAS  Google Scholar 

  288. Orlowski, R. Z., et al. (2007). Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: Combination therapy improves time to progression. Journal of Clinical Oncology, 25(25), 3892–901.

    PubMed  CAS  Google Scholar 

  289. Richardson, P. G., et al. (2005). Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. The New England Journal of Medicine, 352(24), 2487–2498.

    PubMed  CAS  Google Scholar 

  290. Guilhot, F., et al. (1997). Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. The New England Journal of Medicine, 337(4), 223–229.

    PubMed  CAS  Google Scholar 

  291. Hauschild, A., et al. (2003). Prospective randomized trial of interferon Alfa-2b and Interleukin-2 as adjuvant treatment for resected intermediate- and high-risk primary melanoma without clinically detectable node metastasis. Journal of Clinical Oncology, 21(15), 2883–2888.

    PubMed  CAS  Google Scholar 

  292. Hudes, G., et al. (2007). Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. The New England Journal of Medicine, 356(22), 2271–2281.

    PubMed  CAS  Google Scholar 

  293. Barlogie, B., et al. (2006). Thalidomide and hematopoietic-cell transplantation for multiple myeloma. The New England Journal of Medicine, 354(10), 1021–1030.

    PubMed  CAS  Google Scholar 

  294. Weber, D. M., et al. (2006). Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009). Journal of Clinical Oncology (Meeting Abstracts), 24(18_suppl), 7521.

    Google Scholar 

Download references

Acknowledgements

AB: This research was supported by the Intramural Research Program of the NIH, NCI. This research year was made possible through the Clinical Research Training Program, a public–private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). DC, KC: This research was supported by the Intramural Research Program of the NIH, NCI.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deborah E. Citrin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, A.P., Citrin, D.E. & Camphausen, K.A. Clinical biomarkers of angiogenesis inhibition. Cancer Metastasis Rev 27, 415–434 (2008). https://doi.org/10.1007/s10555-008-9143-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9143-x

Keywords

Navigation