Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 483040, 15 pages
http://dx.doi.org/10.1155/2012/483040
Review Article

Antiangiogenic Therapy for Glioma

1Department of Pharmacology, CNR Institute of Neuroscience, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
2Neuromuscular Diseases and Neuroimmunology, Neurological Institute Foundation Carlo Besta, Via Celoria 11, 20133 Milan, Italy

Received 9 January 2012; Revised 27 April 2012; Accepted 2 May 2012

Academic Editor: Laura Cerchia

Copyright © 2012 Valentina Cea et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Bello, C. Giussani, G. Carrabba, M. Pluderi, F. Costa, and A. Bikfalvi, “Angiogenesis and invasion in gliomas,” Cancer treatment and research, vol. 117, pp. 263–284, 2004. View at Google Scholar · View at Scopus
  2. K. H. Plate, G. Breier, H. A. Weich, H. D. Mennel, and W. Risau, “Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms,” International Journal of Cancer, vol. 59, no. 4, pp. 520–529, 1994. View at Publisher · View at Google Scholar · View at Scopus
  3. D. G. Duda, T. T. Batchelor, C. G. Willett, and R. K. Jain, “VEGF-targeted Cancer therapy strategies: current progress, hurdles and future prospects,” Trends in Molecular Medicine, vol. 13, no. 6, pp. 223–230, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. D. G. Duda, K. S. Cohen, D. T. Scadden, and R. K. Jain, “A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood,” Nature Protocols, vol. 2, no. 4, pp. 805–810, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. F. Bertolini, Y. Shaked, P. Mancuso, and R. S. Kerbel, “The multifaceted circulating endothelial cell in Cancer: towards marker and target identification,” Nature Reviews Cancer, vol. 6, no. 11, pp. 835–845, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. S. L. Holbeck, “Update on NCI in vitro drug screen utilities,” European Journal of Cancer, vol. 40, no. 6, pp. 785–793, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. K. D. Paull, R. H. Shoemaker, L. Hodes et al., “Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm,” Journal of the National Cancer Institute, vol. 81, no. 14, pp. 1088–1092, 1989. View at Google Scholar · View at Scopus
  8. B. Lambert, L. De Ridder, F. De Vos et al., “Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma,” Canadian journal of physiology and pharmacology, vol. 84, no. 10, pp. 1021–1028, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Hirschberg, C. H. Sun, T. Krasieva, and S. J. Madsen, “Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells,” Lasers in Surgery and Medicine, vol. 38, no. 10, pp. 939–945, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Kern, M. Steurer, G. Gastl, E. Gunsilius, and G. Untergasser, “Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo,” BMC Cancer, vol. 9, article 1471, p. 284, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. L. A. Kunz-Schughart, J. A. Schroeder, M. Wondrak et al., “Potential of fibroblasts to regulate the formation of three-dimensional vessel-like structures from endothelial cells in vitro,” American Journal of Physiology, vol. 290, no. 5, pp. C1385–C1398, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Ghosh, M. B. Joshi, D. Ivanov et al., “Use of multicellular tumor spheroids to dissect endothelial cell-tumor cell interactions: a role for T-cadherin in tumor angiogenesis,” FEBS Letters, vol. 581, no. 23, pp. 4523–4528, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. K. W. Kross, J. H. Heimdal, C. Olsnes, J. Olofsson, and H. J. Aarstad, “Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis,” Scandinavian Journal of Immunology, vol. 67, no. 4, pp. 392–399, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Durupt, D. Koppers-Lalic, B. Balme et al., “The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses,” Cancer Gene Therapy, vol. 19, no. 1, pp. 58–68, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Ko, A. Koestner, and W. Wechsler, “Morphological characterization of nitrosourea-induced glioma cell lines and clones,” Acta Neuropathologica, vol. 51, no. 1, pp. 23–31, 1980. View at Google Scholar · View at Scopus
  16. E. A. Sausville and A. M. Burger, “Contributions of human tumor xenografts to antiCancer drug development,” Cancer Research, vol. 66, no. 7, pp. 3351–3354, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. G. G. Steel, V. D. Courtenay, and M. J. Peckham, “The response to chemotherapy of a variety of human tumour xenografts,” British Journal of Cancer, vol. 47, no. 1, pp. 1–13, 1983. View at Google Scholar · View at Scopus
  18. T. H. Kuo, T. Kubota, M. Watanabe et al., “Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: the importance of orthotopic models to obtain relevant drug evaluation data,” AntiCancer Research, vol. 13, no. 3, pp. 627–630, 1993. View at Google Scholar · View at Scopus
  19. R. M. Hoffman, “Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic,” Investigational New Drugs, vol. 17, no. 4, pp. 343–359, 1999. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Candolfi, J. F. Curtin, W. S. Nichols et al., “Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression,” Journal of Neuro-Oncology, vol. 85, no. 2, pp. 133–148, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Inoue et al., “Novel animal glioma models that separately exhibit two different invasive and angiogenic phenotypes of human glioblastomas,” World Neurosurg. In press.
  22. M. A. Elmeliegy, A. M. Carcaboso, L. M. L. Chow et al., “Magnetic resonance imaging-guided microdialysis cannula implantation in a spontaneous high-grade glioma murine model,” Journal of Pharmaceutical Sciences, vol. 100, no. 10, pp. 4210–4214, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. L. Chow, R. Endersby, X. Zhu et al., “Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain,” Cancer Cell, vol. 19, no. 3, pp. 305–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. L. M. Shelton, P. Mukherjee, L. C. Huysentruyt, I. Urits, J. A. Rosenberg, and T. N. Seyfried, “A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion,” Journal of Neuro-Oncology, vol. 99, no. 2, pp. 165–176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. P. J. Dickinson, R. A. LeCouteur, R. J. Higgins et al., “Canine spontaneous glioma: a translational model system for convection-enhanced delivery,” Neuro-Oncology, vol. 12, no. 9, pp. 928–940, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. G. L. Heidner, J. N. Kornegay, R. L. Page, R. K. Dodge, and D. E. Thrall, “Analysis of survival in a retrospective study of 86 dogs with brain tumors,” Journal of Veterinary Internal Medicine, vol. 5, no. 4, pp. 219–226, 1991. View at Google Scholar · View at Scopus
  27. N. Kobayashi, N. Allen, and N. R. Clendenon, “An improved rat brain-tumor model,” Journal of Neurosurgery, vol. 53, no. 6, pp. 808–815, 1980. View at Google Scholar · View at Scopus
  28. J. Holash, P. C. Maisonpierre, D. Compton et al., “Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF,” Science, vol. 284, no. 5422, pp. 1994–1998, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Brem, R. Cotran, and J. Folkman, “Tumor angiogenesis: a quantitative method for histologic grading,” Journal of the National Cancer Institute, vol. 48, no. 2, pp. 347–356, 1972. View at Google Scholar · View at Scopus
  30. B. Birlik, S. Canda, and E. Ozer, “Tumour vascularity is of prognostic significance in adult, but not paediatric astrocytomas,” Neuropathology and Applied Neurobiology, vol. 32, no. 5, pp. 532–538, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. S. P. Leon, R. D. Folkerth, and P. McL. Black, “Microvessel density is a prognostic indicator for patients with astroglial brain tumors,” Cancer, vol. 77, no. 2, pp. 362–372, 1996. View at Publisher · View at Google Scholar · View at Scopus
  32. A. Tandle, D. G. Blazer, and S. K. Libutti, “Antiangiogenic gene therapy of Cancer: recent developments,” Journal of Translational Medicine, vol. 2, article 22, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. K. M. Dameron, O. V. Volpert, M. A. Tainsky, and N. Bouck, “Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1,” Science, vol. 265, no. 5178, pp. 1582–1584, 1994. View at Google Scholar · View at Scopus
  34. D. J. Good, P. J. Polverini, F. Rastinejad et al., “A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 17, pp. 6624–6628, 1990. View at Google Scholar · View at Scopus
  35. J. Fang, Y. Shing, D. Wiederschain et al., “Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 8, pp. 3884–3889, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. S. A. Raithatha, H. Muzik, N. B. Rewcastle, R. N. Johnston, D. R. Edwards, and P. A. Forsyth, “Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas,” Neuro-Oncology, vol. 2, no. 3, pp. 145–150, 2000. View at Google Scholar · View at Scopus
  37. T. Martens, Y. Laabs, H. S. Günther et al., “Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2,” Clinical Cancer Research, vol. 14, no. 17, pp. 5447–5458, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell, vol. 86, no. 3, pp. 353–364, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Zhang, N. Zhang, B. Dai et al., “FoxM1B transcriptionally regulates vascular endothelial growth factor expression and promotes the angiogenesis and growth of glioma cells,” Cancer Research, vol. 68, no. 21, pp. 8733–8742, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Ido, T. Nakagawa, T. Sakuma, H. Takeuchi, K. Sato, and T. Kubota, “Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors,” Neuropathology, vol. 28, no. 6, pp. 604–611, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. K. Nakamura, K. C. Martin, J. K. Jackson, K. Beppu, C. W. Woo, and C. J. Thiele, “Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1α in neuroblastoma cells,” Cancer Research, vol. 66, no. 8, pp. 4249–4255, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Tan, S. Cruet-Hennequart, A. Troussard et al., “Regulation of tumor angiogenesis by integrin-linked kinase (ILK),” Cancer Cell, vol. 5, no. 1, pp. 79–90, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. K. H. Plate, G. Breier, H. A. Weich, and W. Risau, “Vascular endothelial growth factor is a potential tumour angiogenssis factor in human gliomas in vivo,” Nature, vol. 359, no. 6398, pp. 845–848, 1992. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Kerber, Y. Reiss, A. Wickersheim et al., “Flt-1 signaling in macrophages promotes glioma growth in vivo,” Cancer Research, vol. 68, no. 18, pp. 7342–7351, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. E. Y. Lin and J. W. Pollard, “Tumor-associated macrophages press the angiogenic switch in breast Cancer,” Cancer Research, vol. 67, no. 11, pp. 5064–5066, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. M. K. Jones, R. M. Itani, H. Wang et al., “Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury,” American Journal of Physiology, vol. 276, part 1, no. 6, pp. G1345–G1355, 1999. View at Google Scholar · View at Scopus
  47. T. Takahashi and M. Shibuya, “The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-γ pathway and partially induces mitotic signals in NIH3T3 fibroblasts,” Oncogene, vol. 14, no. 17, pp. 2079–2089, 1997. View at Google Scholar · View at Scopus
  48. B. K. Lal, S. Varma, P. J. Pappas, R. W. Hobson, and W. N. Durán, “VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways,” Microvascular Research, vol. 62, no. 3, pp. 252–262, 2001. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Esser, K. Wolburg, H. Wolburg, G. Breier, T. Kurzchalia, and W. Risau, “Vascular endothelial growth factor induces endothelial fenestrations in vitro,” Journal of Cell Biology, vol. 140, no. 4, pp. 947–959, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. C. G. Kevil, N. Ohno, D. C. Gute et al., “Role of cadherin internalization in hydrogen peroxide-mediated endothelial permeability,” Free Radical Biology and Medicine, vol. 24, no. 6, pp. 1015–1022, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. B. Li, C. M. Chang, M. Yuan, W. G. McKenna, and H. K. G. Shu, “Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas,” Cancer Research, vol. 63, no. 21, pp. 7443–7450, 2003. View at Google Scholar · View at Scopus
  52. M. Takahashi, A. Matsui, M. Inao, S. Mochida, and K. Fujiwara, “ERK/MAPK-dependent PI3K/Akt phosphorylation through VEGFR-1 after VEGF stimulation in activated hepatic stellate cells,” Hepatology Research, vol. 26, no. 3, pp. 232–236, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. R. C. Castellino and D. L. Durden, “Mechanisms of disease: the PI3K-Akt-PTEN signaling node—an intercept point for the control of angiogenesis in brain tumors,” Nature Clinical Practice Neurology, vol. 3, no. 12, pp. 682–693, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. S. K. Hobbs, W. L. Monsky, F. Yuan et al., “Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4607–4612, 1998. View at Publisher · View at Google Scholar · View at Scopus
  55. W. L. Monsky, D. Fukumura, T. Gohongi et al., “Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor,” Cancer Research, vol. 59, no. 16, pp. 4129–4135, 1999. View at Google Scholar · View at Scopus
  56. E. Bullitt, D. Zeng, G. Gerig et al., “Vessel tortuosity and brain tumor malignancy: a blinded study,” Academic Radiology, vol. 12, no. 10, pp. 1232–1240, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Zagzag, A. Hooper, D. R. Friedlander et al., “In situ expression of angiopoietins in astrocytomas identifies angiopoietin-2 as an early marker of tumor angiogenesis,” Experimental Neurology, vol. 159, no. 2, pp. 391–400, 1999. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Ferrara, H. P. Gerber, and J. LeCouter, “The biology of VEGF and its receptors,” Nature Medicine, vol. 9, no. 6, pp. 669–676, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. K. J. Kim, B. Li, J. Winer et al., “Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo,” Nature, vol. 362, no. 6423, pp. 841–844, 1993. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Hurwitz, L. Fehrenbacher, W. Novotny et al., “Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal Cancer,” The New England Journal of Medicine, vol. 350, no. 23, pp. 2335–2342, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. M. C. Chamberlain, “Bevacizumab for the treatment of recurrent glioblastoma,” Clinical Medicine Insights, vol. 5, pp. 117–129, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. D. Shweiki, A. Itin, D. Soffer, and E. Keshet, “Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis,” Nature, vol. 359, no. 6398, pp. 843–845, 1992. View at Publisher · View at Google Scholar · View at Scopus
  63. E. J. Bernhard, “Interventions that induce modifications in the tumor microenvironment,” Cancer/Radiotherapie, vol. 15, no. 5, pp. 376–382, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Relf, S. Lejeune, P. A. E. Scott et al., “Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor β-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast Cancer and its relation to angiogenesis,” Cancer Research, vol. 57, no. 5, pp. 963–969, 1997. View at Google Scholar · View at Scopus
  65. R. Kerbel and J. Folkman, “Clinical translation of angiogenesis inhibitors,” Nature Reviews Cancer, vol. 2, no. 10, pp. 727–739, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Abdollahi, K. E. Lipson, A. Sckell et al., “Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects,” Cancer Research, vol. 63, no. 24, pp. 8890–8898, 2003. View at Google Scholar · View at Scopus
  67. J. Wang, Y. Sun, Y. Liu et al., “Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients,” Chinese Journal of Lung Cancer, vol. 8, no. 4, pp. 283–290, 2005. View at Google Scholar · View at Scopus
  68. M. R. Gilbert, J. Kuhn, K. R. Lamborn et al., “Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery,” Journal of Neuro-Oncology, pp. 1–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Stupp, M. E. Hegi, B. Neyns et al., “Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma,” Journal of Clinical Oncology, vol. 28, no. 16, pp. 2712–2718, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Delbaldo, E. Raymond, K. Vera et al., “Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors,” Investigational New Drugs, vol. 26, no. 1, pp. 35–43, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Hersey, J. Sosman, S. O'Day et al., “A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma,” Cancer, vol. 116, no. 6, pp. 1526–1534, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. K. M. Bell-Mcguinn, C. M. Matthews, S. N. Ho et al., “A phase II, single-arm study of the anti-α5β1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal Cancer,” Gynecologic Oncology, vol. 121, no. 2, pp. 273–279, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. V. A. Levin, S. Phuphanich, W. K. A. Yung et al., “Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation,” Journal of Neuro-Oncology, vol. 78, no. 3, pp. 295–302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. F. A. Shepherd, G. Giaccone, L. Seymour et al., “Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung Cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer,” Journal of Clinical Oncology, vol. 20, no. 22, pp. 4434–4439, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. D. A. Reardon, J. J. Vredenburgh, A. Coan et al., “Phase i study of sunitinib and irinotecan for patients with recurrent malignant glioma,” Journal of Neuro-Oncology, vol. 105, no. 3, pp. 621–627, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. L. B. Nabors, J. G. Supko, M. Rosenfeld et al., “Phase I trial of sorafenib in patients with recurrent or progressive malignant glioma,” Neuro-Oncology, vol. 13, no. 12, pp. 1324–1330, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. L. L. Garland, K. Chansky, A. J. Wozniak et al., “Phase II study of cediranib in patients with Malignant pleural mesothelioma: SWOG S0509,” Journal of Thoracic Oncology, vol. 6, no. 11, pp. 1938–1945, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. S. R. Alberts, T. R. Fitch, G. P. Kim et al., “Cediranib (AZD2171) in patients with advanced hepatocellular carcinoma: a phase II north central Cancer treatment group clinical trial,” American Journal of Clinical Oncology, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. T. T. Batchelor, D. G. Duda, E. Di Tomaso et al., “Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma,” Journal of Clinical Oncology, vol. 28, no. 17, pp. 2817–2823, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. B. Neyns, J. Sadones, C. Chaskis et al., “Phase II study of sunitinib malate in patients with recurrent high-grade glioma,” Journal of Neuro-Oncology, vol. 103, no. 3, pp. 491–501, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. D. A. Reardon, G. Dresemann, S. Taillibert et al., “Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma,” British Journal of Cancer, vol. 101, no. 12, pp. 1995–2004, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. E. Razis, P. Selviaridis, S. Labropoulos et al., “Phase II study of neoadjuvant imatinib in glioblastoma: evaluation of clinical and molecular effects of the treatment,” Clinical Cancer Research, vol. 15, no. 19, pp. 6258–6266, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. G. Dresemann, M. Weller, M. A. Rosenthal et al., “Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide,” Journal of Neuro-Oncology, vol. 96, no. 3, pp. 393–402, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. J. J. Vredenburgh, A. Desjardins, J. E. Herndon et al., “Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma,” Clinical Cancer Research, vol. 13, no. 4, pp. 1253–1259, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. A. D. Norden, J. Drappatz, A. Muzikansky et al., “An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma,” Journal of Neuro-Oncology, vol. 92, no. 2, pp. 149–155, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. T. Xu, J. Chen, Y. Lu, and J. E. A. Wolff, “Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis,” BMC Cancer, vol. 10, article 252, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. O. Keunen, M. Johansson, A. Oudin et al., “Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 9, pp. 3749–3754, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. A. K. Lucio-Eterovic, Y. Piao, and J. F. De Groot, “Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy,” Clinical Cancer Research, vol. 15, no. 14, pp. 4589–4599, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. V. Lorgis et al., “Relation between bevacizumab dose intensity and high-grade glioma survival: a retrospective study in two large cohorts,” Journal of Neurooncol, vol. 107, no. 2, pp. 351–358, 2012. View at Google Scholar
  90. S. M. Sweeney, G. DiLullo, S. J. Slater et al., “Angiogenesis in collagen I requires α2β1 ligation of a GFP*GER sequence and possibly p38 MAPK activation and focal adhesion disassembly,” The Journal of Biological Chemistry, vol. 278, no. 33, pp. 30516–30524, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. D. R. Senger, C. A. Perruzzi, M. Streit, V. E. Koteliansky, A. R. De Fougerolles, and M. Detmar, “The α1β1 and α2β1 integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis,” American Journal of Pathology, vol. 160, no. 1, pp. 195–204, 2002. View at Google Scholar · View at Scopus
  92. P. C. Brooks, R. A. F. Clark, and D. A. Cheresh, “Requirement of vascular integrin α(v)β3 for angiogenesis,” Science, vol. 264, no. 5158, pp. 569–571, 1994. View at Google Scholar · View at Scopus
  93. M. Friedlander, P. C. Brooks, R. W. Shaffer, C. M. Kincaid, J. A. Varner, and D. A. Cheresh, “Definition of two angiogenic pathways by distinct αv integrins,” Science, vol. 270, no. 5241, pp. 1500–1502, 1995. View at Google Scholar · View at Scopus
  94. C. J. Drake, D. A. Cheresh, and C. D. Little, “An antagonist of integrin α(v)β3 prevents maturation of blood vessels during embryonic neovascularization,” Journal of Cell Science, vol. 108, no. 7, pp. 2655–2661, 1995. View at Google Scholar · View at Scopus
  95. Y. Fu, M. L. Ponce, M. Thill, P. Yuan, S. W. Nam, and K. G. Csaky, “Angiogenesis inhibition and choroidal neovascularization suppression by sustained delivery of an integrin antagonist, EMD478761,” Investigative Ophthalmology and Visual Science, vol. 48, no. 11, pp. 5184–5190, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. D. A. Reardon, K. L. Fink, T. Mikkelsen et al., “Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme,” Journal of Clinical Oncology, vol. 26, no. 34, pp. 5610–5617, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. J. B. Vermorken, J. Guigay, R. Mesia et al., “Phase I/II trial of cilengitide with cetuximab, cisplatin and 5-fluorouracil in recurrent and/or metastatic squamous cell Cancer of the head and neck: findings of the phase i part,” British Journal of Cancer, vol. 104, no. 11, pp. 1691–1696, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. D. A. Reardon, B. Neyns, M. Weller, J. C. Tonn, L. B. Nabors, and R. Stupp, “Cilengitide: an RGD pentapeptide ανβ3 and ανβ5 integrin inhibitor in development for glioblastoma and other malignancies,” Future Oncology, vol. 7, no. 3, pp. 339–354, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. W. Cai, Y. Wu, K. Chen, Q. Cao, D. A. Tice, and X. Chen, “In vitro and in vivo characterization of 64Cu-labeled Abegrin, a humanized monoclonal antibody against integrin αvβ3,” Cancer Research, vol. 66, no. 19, pp. 9673–9681, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. A. D. Ricart, A. W. Tolcher, G. Liu et al., “Volociximab, a chimeric monoclonal antibody that specifically binds α5β1 integrin: a phase l, pharmacokinetic, and biological correlative study,” Clinical Cancer Research, vol. 14, no. 23, pp. 7924–7929, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. M. D. Groves, V. K. Puduvalli, K. R. Hess et al., “Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme,” Journal of Clinical Oncology, vol. 20, no. 5, pp. 1383–1388, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. M. L. H. Wong, A. Prawira, A. H. Kaye, and C. M. Hovens, “Tumour angiogenesis: its mechanism and therapeutic implications in malignant gliomas,” Journal of Clinical Neuroscience, vol. 16, no. 9, pp. 1119–1130, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. M. L. Maitland, K. E. Kasza, T. Karrison et al., “Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment,” Clinical Cancer Research, vol. 15, no. 19, pp. 6250–6257, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. W. Fiedler, R. Mesters, M. Heuser et al., “An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid Leukemia,” Leukemia Research, vol. 34, no. 2, pp. 196–202, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. R. J. Motzer, T. E. Hutson, P. Tomczak et al., “Sunitinib versus interferon alfa in metastatic renal-cell carcinoma,” The New England Journal of Medicine, vol. 356, no. 2, pp. 115–124, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. E. Raymond, L. Dahan, J.-L. Raoul et al., “Sunitinib malate for the treatment of pancreatic neuroendocrine tumors,” The New England Journal of Medicine, vol. 364, no. 6, pp. 501–513, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. G. D. Demetri, A. T. van Oosterom, C. R. Garrett et al., “Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial,” The Lancet, vol. 368, no. 9544, pp. 1329–1338, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Matsumoto, S. Batra, K. Saito et al., “Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia,” Cancer Research, vol. 71, no. 20, pp. 6350–6359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. E. Ranza, G. Mazzini, A. Facoetti, and R. Nano, “In-vitro effects of the tyrosine kinase inhibitor imatinib on glioblastoma cell proliferation,” Journal of Neuro-Oncology, vol. 96, no. 3, pp. 349–357, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. P. Y. Wen, W. K. A. Yung, K. R. Lamborn et al., “Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American brain tumor consortium study 99-08,” Clinical Cancer Research, vol. 12, no. 16, pp. 4899–4907, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. Y. Jin, J.-P. Li, L.-Y. Tang et al., “Protein expression and significance of VEGF, EGFR and MMP-9 in non-small cell lung carcinomas,” Asian Pacific Journal of Cancer Prevention, vol. 12, no. 6, pp. 1473–1476, 2011. View at Google Scholar · View at Scopus
  112. A. Kamat, S. Rajoria, A. George et al., “Estrogen-mediated angiogenesis in thyroid tumor microenvironment is mediated through VEGF signaling pathways,” Archives of Otolaryngology, vol. 137, no. 11, pp. 1146–1153, 2011. View at Google Scholar · View at Scopus
  113. L. B. Saltz, H. J. Lenz, H. L. Kindler et al., “Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal Cancer: the BOND-2 study,” Journal of Clinical Oncology, vol. 25, no. 29, pp. 4557–4561, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. H. L. Kindler, D. Niedzwiecki, D. Hollis et al., “Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic Cancer: phase III trial of the Cancer and Leukemia group B (CALGB 80303),” Journal of Clinical Oncology, vol. 28, no. 22, pp. 3617–3622, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. O. Casanovas, D. J. Hicklin, G. Bergers, and D. Hanahan, “Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors,” Cancer Cell, vol. 8, no. 4, pp. 299–309, 2005. View at Publisher · View at Google Scholar · View at Scopus
  116. T. Kamba and D. M. McDonald, “Mechanisms of adverse effects of anti-VEGF therapy for Cancer,” British Journal of Cancer, vol. 96, no. 12, pp. 1788–1795, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Kourembanas, R. L. Hannan, and D. V. Faller, “Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells,” Journal of Clinical Investigation, vol. 86, no. 2, pp. 670–674, 1990. View at Google Scholar · View at Scopus
  118. D. V. Faller, “Endothelial cell responses to hypoxic stress,” Clinical and Experimental Pharmacology and Physiology, vol. 26, no. 1, pp. 74–84, 1999. View at Publisher · View at Google Scholar · View at Scopus
  119. J. Huang, S. Z. Softer, E. S. Kim et al., “Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis,” Molecular Cancer Research, vol. 2, no. 1, pp. 36–42, 2004. View at Google Scholar · View at Scopus
  120. J. L. Rubenstein, J. Kim, T. Ozawa et al., “Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption,” Neoplasia, vol. 2, no. 4, pp. 306–314, 2000. View at Google Scholar · View at Scopus
  121. J. Glade Bender, E. M. Cooney, J. J. Kandel, and D. J. Yamashiro, “Vascular remodeling and clinical resistance to antiangiogenic Cancer therapy,” Drug Resistance Updates, vol. 7, no. 4-5, pp. 289–300, 2004. View at Publisher · View at Google Scholar · View at Scopus
  122. L. Hiatky, C. Tsionou, P. Hahnfeldt, and C. N. Coleman, “Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia—induced vascular endothelial growth factor up—regulation and protein expression,” Cancer Research, vol. 54, no. 23, pp. 6083–6086, 1994. View at Google Scholar · View at Scopus
  123. M. B. Ruzinova, R. A. Schoer, W. Gerald et al., “Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors,” Cancer Cell, vol. 4, no. 4, pp. 277–289, 2003. View at Publisher · View at Google Scholar · View at Scopus
  124. A. S. Bailey, H. Willenbring, S. Jiang et al., “Myeloid lineage progenitors give rise to vascular endothelium,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13156–13161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  125. F. Shojaei, X. Wu, A. K. Malik et al., “Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells,” Nature Biotechnology, vol. 25, no. 8, pp. 911–920, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. R. D. Leek, C. E. Lewis, R. Whitehouse, M. Greenall, J. Clarke, and A. L. Harris, “Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma,” Cancer Research, vol. 56, no. 20, pp. 4625–4629, 1996. View at Google Scholar · View at Scopus
  127. C. E. Lewis and J. W. Pollard, “Distinct role of macrophages in different tumor microenvironments,” Cancer Research, vol. 66, no. 2, pp. 605–612, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. E. Y. Lin, A. V. Nguyen, R. G. Russell, and J. W. Pollard, “Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy,” Journal of Experimental Medicine, vol. 193, no. 6, pp. 727–739, 2001. View at Publisher · View at Google Scholar · View at Scopus
  129. L. Bingle, N. J. Brown, and C. E. Lewis, “The role of tumour-associated macrophages in tumour progression: implications for new antiCancer therapies,” Journal of Pathology, vol. 196, no. 3, pp. 254–265, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Platten, A. Kretz, U. Naumann et al., “Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas,” Annals of Neurology, vol. 54, no. 3, pp. 388–392, 2003. View at Publisher · View at Google Scholar · View at Scopus
  131. M. M. Mueller and N. E. Fusenig, “Constitutive expression of G-CSF and GM-CSF in human skin carcinoma cells with functional consequence for tumor progression,” International Journal of Cancer, vol. 83, no. 6, pp. 780–789, 1999. View at Publisher · View at Google Scholar · View at Scopus
  132. T. W. Briers, C. Desmaretz, and E. Vanmechelen, “Generation and characterization of mouse microglial cell lines,” Journal of Neuroimmunology, vol. 52, no. 2, pp. 153–164, 1994. View at Publisher · View at Google Scholar · View at Scopus
  133. J. V. Lafuente, B. Adán, K. Alkiza, J. M. Garibi, M. Rossi, and F. F. Cruz-Sánchez, “Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-β (PDGFR-β) in human gliomas,” Journal of Molecular Neuroscience, vol. 13, no. 1-2, pp. 177–185, 1999. View at Google Scholar · View at Scopus
  134. L. Zhang, T. Himi, and S. Murota, “Induction of hepatocyte growth factor (HGF) in rat microglial cells by prostaglandin E(2),” Journal of Neuroscience Research, vol. 62, no. 3, pp. 389–395, 2000. View at Google Scholar
  135. P. Kunkel, S. Müller, P. Schirmacher et al., “Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas,” Neuro-Oncology, vol. 3, no. 2, pp. 82–88, 2001. View at Publisher · View at Google Scholar · View at Scopus
  136. C. Hao, I. F. Parney, W. H. Roa, J. Turner, K. C. Petruk, and D. A. Ramsay, “Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation,” Acta Neuropathologica, vol. 103, no. 2, pp. 171–178, 2002. View at Publisher · View at Google Scholar · View at Scopus
  137. H. Galarneau, J. Villeneuve, G. Gowing, J. P. Julien, and L. Vallières, “Increased glioma growth in mice depleted of macrophages,” Cancer Research, vol. 67, no. 18, pp. 8874–8881, 2007. View at Publisher · View at Google Scholar · View at Scopus
  138. A. Ghosh and S. Chaudhuri, “Microglial action in glioma: a boon turns bane,” Immunology Letters, vol. 131, no. 1, pp. 3–9, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. A. Persson and E. Englund, “The glioma cell edge—winning by engulfing the enemy?” Medical Hypotheses, vol. 73, no. 3, pp. 336–337, 2009. View at Publisher · View at Google Scholar · View at Scopus
  140. T. N. Seyfried, M. A. Kiebish, J. Marsh, L. M. Shelton, L. C. Huysentruyt, and P. Mukherjee, “Metabolic management of brain Cancer,” Biochimica et Biophysica Acta, vol. 1807, no. 6, pp. 577–594, 2011. View at Publisher · View at Google Scholar · View at Scopus
  141. M. Rachkovsky, S. Sodi, A. Chakraborty et al., “Melanoma x macrophage hybrids with enhanced metastatic potential,” Clinical and Experimental Metastasis, vol. 16, no. 4, pp. 299–312, 1998. View at Publisher · View at Google Scholar · View at Scopus
  142. J. M. Pawelek and A. K. Chakraborty, “Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis,” Nature Reviews Cancer, vol. 8, no. 5, pp. 377–386, 2008. View at Publisher · View at Google Scholar · View at Scopus
  143. T. Strojnik, R. Kavalar, and T. T. Lah, “Experimental model and immunohistochemical analyses of U87 human glioblastoma cell xenografts in immunosuppressed rat brains,” AntiCancer Research, vol. 26, no. 4 B, pp. 2887–2900, 2006. View at Google Scholar · View at Scopus
  144. I. Shabo, H. Olsson, X. F. Sun, and J. Svanvik, “Expression of the macrophage antigen CD163 in rectal Cancer cells is associated with early local recurrence and reduced survival time,” International Journal of Cancer, vol. 125, no. 8, pp. 1826–1831, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. T. Browder, C. E. Butterfield, B. M. Kräling et al., “Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant Cancer,” Cancer Research, vol. 60, no. 7, pp. 1878–1886, 2000. View at Google Scholar · View at Scopus
  146. M. Kioi, H. Vogel, G. Schultz, R. M. Hoffman, G. R. Harsh, and J. M. Brown, “Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice,” Journal of Clinical Investigation, vol. 120, no. 3, pp. 694–705, 2010. View at Publisher · View at Google Scholar · View at Scopus
  147. M. Frontczak-Baniewicz, D. Czajkowska, J. Andrychowski, and M. Walski, “The immature endothelial cell in human glioma. Ultrastructural features of blood capillary vessels,” Folia Neuropathologica, vol. 46, no. 1, pp. 49–56, 2008. View at Google Scholar · View at Scopus
  148. M. W. Kieran, C. D. Turner, J. B. Rubin et al., “A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive Cancer,” Journal of Pediatric Hematology/Oncology, vol. 27, no. 11, pp. 573–581, 2005. View at Publisher · View at Google Scholar · View at Scopus
  149. Y. Soda, T. Marumoto, D. Friedmann-Morvinski et al., “Transdifferentiation of glioblastoma cells into vascular endothelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 11, pp. 4274–4280, 2011. View at Publisher · View at Google Scholar · View at Scopus
  150. N. T. Fernando, M. Koch, C. Rothrock et al., “Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors,” Clinical Cancer Research, vol. 14, no. 5, pp. 1529–1539, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. T. T. Batchelor, A. G. Sorensen, E. di Tomaso et al., “AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients,” Cancer Cell, vol. 11, no. 1, pp. 83–95, 2007. View at Publisher · View at Google Scholar · View at Scopus
  152. M. Hagedorn, L. Zilberberg, J. Wilting et al., “Domain swapping in a COOH-terminal fragment of platelet factor 4 generates potent angiogenesis inhibitors,” Cancer Research, vol. 62, no. 23, pp. 6884–6890, 2002. View at Google Scholar · View at Scopus
  153. L. Bello, V. Lucini, F. Costa et al., “Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma,” Clinical Cancer Research, vol. 10, no. 13, pp. 4527–4537, 2004. View at Publisher · View at Google Scholar · View at Scopus
  154. D. L. Dai, N. Makretsov, E. I. Campos et al., “Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival,” Clinical Cancer Research, vol. 9, no. 12, pp. 4409–4414, 2003. View at Google Scholar · View at Scopus
  155. A. A. Troussard, P. Costello, T. N. Yoganathan, S. Kumagai, C. D. Roskelley, and S. Dedhar, “The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9),” Oncogene, vol. 19, no. 48, pp. 5444–5452, 2000. View at Publisher · View at Google Scholar · View at Scopus
  156. L. A. Edwards, J. Woo, L. A. Huxham et al., “Suppression of VEGF secretion and changes in glioblastoma multiforme microenvironment by inhibition of Integrin-linked kinase (ILK),” Molecular Cancer Therapeutics, vol. 7, no. 1, pp. 59–70, 2008. View at Publisher · View at Google Scholar · View at Scopus
  157. C. Verpelli, G. Bertani, V. Cea et al., “Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma,” PLoS ONE, vol. 5, no. 10, Article ID e13710, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. A. Saidi, M. Hagedorn, N. Allain et al., “Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness,” International Journal of Cancer, vol. 125, no. 5, pp. 1054–1064, 2009. View at Publisher · View at Google Scholar · View at Scopus
  159. A. Quintas-Cardama, H. Kantarjian, D. Jones et al., “Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous Leukemia after imatinib and nilotinib (AMN107) therapy failure,” Blood, vol. 109, no. 2, pp. 497–499, 2007. View at Publisher · View at Google Scholar · View at Scopus
  160. H. Kantarjian, F. Giles, L. Wunderle et al., “Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL,” The New England Journal of Medicine, vol. 354, no. 24, pp. 2542–2551, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. J. C. Reubi and B. Waser, “Unexpected high incidence of cholecystokinin-B/gastrin receptors in human medullary thyroid carcinomas,” International Journal of Cancer, vol. 67, no. 5, pp. 644–647, 1996. View at Google Scholar
  162. T. A. Slastnikova, A. A. Rosenkranz, P. V. Gulak et al., “Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery,” International Journal of Nanomedicine, vol. 7, pp. 467–482, 2012. View at Publisher · View at Google Scholar · View at Scopus
  163. J. R. Kanwar, G. Mahidhara, and R. K. Kanwar, “Antiangiogenic therapy using nanotechnological-based delivery system,” Drug Discovery Today, vol. 16, no. 5-6, pp. 188–202, 2011. View at Publisher · View at Google Scholar · View at Scopus
  164. E. W. M. Ng, D. T. Shima, P. Calias, E. T. Cunningham, D. R. Guyer, and A. P. Adamis, “Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease,” Nature Reviews Drug Discovery, vol. 5, no. 2, pp. 123–132, 2006. View at Publisher · View at Google Scholar · View at Scopus