Cover Page


Glioblastoma (GBM) is the most common type of primary brain cancer that characterized by poor prognosis due to the rapid progression, active angiogenesis, enhanced tumor cell invasion and the emergence of resistance toward conventional therapy. In this connection, nowadays, new approaches for selective inhibition of crucial steps in tumor progression are actively developing. The key feature of tumor growth and development is angiogenesis. VEGF and its receptor VEGFR2 play the pivotal role in regulation of tumor vessel formation. Therefore, VEGFR2, as the main receptor of VEGF’s pro-angiogenic signal transducer, is a promising molecular target for anti-angiogenic therapy. There is evidence that inhibitors of VEGF and VEGFR2 reduce endothelial cell proliferation, migration and survival that lead to regression of vessel density and decrease vascular permeability, thereby slowing tumor growth. Currently, a number of VEGFR2 inhibitors are under clinical trials (ramucirumab, cediranib) and several were approved (sunitinib, sorafenib). Despite the promising results of preclinical studies, the efficacy of antiangiogenic drugs in the clinical practice is significantly lower, mainly, due to rapid adaptation of malignant cells that consists of alternative pro-angiogenic pathways activation, recruitment of endothelial progenitor cells from bone marrow and increasing of the invasive growth. Given the diversity of pro-angiogenic mechanisms, enhancement of the efficacy of tumor therapy could be achieved by specific inhibition of VEGFR2 functions that will be supplemented by other antiangiogenic drugs (anti-VEGF,-PlGF,-HIF1α). In addition, multitargeting therapy should focus on the combined inhibition of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells.


About the authors

A. A. Korchagina

Pirogov Russian National Research Medical University, Moscow, Russian Federation

Author for correspondence.

postgraduate of the Department of Medical nanobiotechnologies of N.I. Pirogov RRMU. Address: 1, Ostrovityanov Street, Moscow, RF, 117997, tel.: +7 (495) 434-13-01

Russian Federation

S. A. Shein

Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian Federation

MD, research scientist of the Laboratory of Neurochemistry of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62 Russian Federation

O. I. Gurina

Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian Federation

PhD, Head of the Laboratory of Neurochemistry of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62 Russian Federation

V. P. Chekhonin

Pirogov Russian National Research Medical University, Moscow, Russian Federation
Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian Federation

PhD, professor, academician of RAMS, Head of the Department of Fundamental and applied neurobiology of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”, Head of the Department of Medical nanobiotechnologies of N.I. Pirogov RRMU. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62 Russian Federation


  1. Norden A.D., Drappatz J., Wen P.Y. Antiangiogenic therapies for high-grade glioma. Nat. Rev. Neurol. 2009; 5 (11): 610–620.
  2. Miletic H., Niclou S.P., Johansson M., Bjerkvig R. Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms. Expert. Opin. 2009; 13(4): 455–468.
  3. Jain R.K., di Tomaso E., Duda D.G., Loeffler J.S., Sorensen A.G., Batchelor T.T. Angiogenesis in brain tumours. Nat. Rev. Neurosci. 2007; 8 (8): 610–622.
  4. Lakka S.S., Rao J.S. Antiangiogenic therapy in brain tumors. Exp. Rev. Neurother. 2008; 8 (10): 1457–1473.
  5. Stewart L.A. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002; 359 (9311): 1011–1018.
  6. Zalutsky M.R. Current status of therapy of solid tumors: brain tumor therapy. J. Nucl. Med. 2005; 1: 151–156.
  7. Gerstner E.R., Batchelor T.T. Antiangiogenic therapy for glioblastoma. Cancer J. 2012; 18 (1): 45–50.
  8. Chekhonin V.P., Shein S.A., Korchagina A.A., Gurina O.I. VEGF in neoplastic angiogenesis. Vestn. Ross. Akad. Med. Nauk. 2012; (2): 23–33.
  9. Tong R.T., Boucher Y., Kozin S.V., Winkler F., Hicklin D.J., Jain R.K. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer. Res. 2004; 64: 3731–3736.
  10. Ferrara N., Gerber H.P., LeCouter J. The biology of VEGF and its receptors. Nat. Med. 2003; 9 (6): 669–676.
  11. Ferrara N., Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr. Rev. 1997; 18 (1): 4–25.
  12. Ferrara N. Molecular and biological properties of vascular endothelial growthfactor. J. Mol. Med. 1999; 77 (7): 527–543.
  13. Holmes K., Roberts O.L., Thomas A.M., Cross M.J. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell Signal. 2007; 19 (10): 2003–2012.
  14. Semenza G.L., Wang G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 1992; 12: 5447–5454.
  15. Goel S., Duda D.G., Xu L., Munn L.L., Boucher Y., Fukumura D. et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol. Rev. 2011; 91 (3): 1071–1121.
  16. Lee S.L., Rouhi P., Dahl Jensen L., Zhang D., Ji H., Hauptmann G. et al. Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model. Proc. Natl. Acad. Sci. U S A. 2009; 106 (46): 19485–19490.
  17. Liu W., Xu J., Wang M. et al. Tumor-derived vascular endothelial growth factor (VEGF)-a facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway. Int. J. Oncol. 2011; 39 (5): 1213–1220.
  18. Jain R.K. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat. Med. 2001; 7 (9): 987–989.
  19. Jain R.K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005; 307 (5706): 58–62.
  20. Stohrer M., Boucher Y., Stangassinger M., Jain R.K. et al. Oncotic pressure in solid tumors is elevated. Cancer. Res. 2000; 60: 4251–4255.
  21. Hubbard S.R. Autoinhibitory mechanisms in receptor tyrosine kinases. Front Biosci, 2002; 7: 330–340.
  22. Keyt B.A., Nguyen H.V., Berleau L.T., Duarte C.M., Park J., Chen H. et al. Identification of vascular ndothelial growth factor determinants for binding KDR and FLT-1 receptors. Generation of receptor-selective VEGF variants by site-directed mutagenesis. J. Biol. Chem. 1996; 271: 5638–5646.
  23. Shinkai A., Ito M., Anazawa H., Yamaguchi S. Shitara K., Shibuya M. et al. Mapping of the sites involved in ligand association and dissociation at the extracellular domain of the kinase insert domaincontaining receptor for vascular endothelial growth factor. J. Biol. Chem. 1998; 273: 31283–31288.
  24. Heldin C.H., Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 1999; 79 (4): 1283–1316.
  25. Ruch C., Skiniotis G., Steinmetz M.O., Walz T., Ballmer-Hofer K. et al. Structure of a VEGF-VEGF receptor complex determined by electron microscopy. Nat. Struct. Mol. Biol. 2007; 14 (3): 249–250.
  26. Kappert K., Peters K.G., Bohmer F.D., Ostman A. et al. Tyrosine phosphatases in vessel wall signaling. Cardiovasc. Res. 2005; 65(3): 587–598.
  27. Ewan L.C., Jopling H.M., Jia H., Mittar S., Bagherzadeh A., Howell G.J. et al. Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells. Traffic. 2006; 7 (9): 1270–1282.
  28. Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L. et al. Signal transduction by vascular endothelial growth receptors. Biochem. J. 2011; 437: 169–183.
  29. Jakobsson L., Kreuger J., Holmborn K., Lundin L., Eriksson I., Kjellén L. et al. Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis. Dev. Cell. 2006; 10 (5): 625–634.
  30. Grosskreutz C.L., Anand-Apte B., Duplaa C., Quinn T.P., Terman B.I., Zetter B. et al. Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro. Microvasc. Res. 1999; 58 (2): 128–136.
  31. Sawano A., Iwai S., Sakurai Y., Ito M., Shitara K., Nakahata T. et al. Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood. 2001; 97 (3): 785–791.
  32. Hiratsuka S., Minowa O., Kuno J., Noda T., Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc. Natl. Acad. Sci. USA. 1998; 95 (16): 9349–9354.
  33. Fong G. H., Rossant J., Gertsenstein M., Breitman M.L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly ofvascular endothelium. Nature. 1995; 376 (6535): 66–70.
  34. Wang F., Yamauchi M., Muramatsu M., Osawa T., Tsuchida R., Shibuya M. RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3-K/Akt pathway. J. Biol. Chem. 2011; 286 (11): 9097–9106.
  35. Cai J., Ahmad S., Jiang W.G., Huang J., Kontos C.D., Boulton M. Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. Diabetes.2003; 52 (12): 2959–2968.
  36. Taylor A. P., Leon E., Goldenberg D. Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement. Brit. J. Cancer. 2010; 103 (1): 82–89.
  37. Wey J.S., Fan F., Gray M.J., Bauer T.W., McCarty M.F., Somcio R. et al. Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer. 2005; 104: 427–438.
  38. Lyden D., Hattori K., Dias S. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Med. 2001; 7: 1194–1201.
  39. Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J. Biochem. Mol. Biol. 2006; 39 (5): 469–478.
  40. Meyer R.D., Mohammadi M., Rahimi N. A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1. J. Biol. Chem. 2006; 281: 867–875.
  41. Rahimi N., Dayanir V., Lashkari K. Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells. J. Biol. Chem. 2000; 275 (22): 16986–16992.
  42. Autiero M., Waltenberger J., Communi D., Kranz A., Moons L., Lambrechts D. et al. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat. Med. 2003; 9: 936–943.
  43. Cleaver O., Melton D.A. Endothelial signaling during development. Nat. Med. 2003; 9:661–668.
  44. Shalaby F., Rossant J., Yamaguchi T.P., Gertsenstein M., Wu X.F., Breitman M.L. et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995; 376: 62–66.
  45. Hicklin D.J., Ellis L.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 2005; 23: 1011–1027.
  46. Oelrichs R.B., Reid H.H., Bernard O., Ziemiecki A., Wilks A.F. NYK/FLK-1: a putative receptor protein tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo. Oncogene. 1993; 8: 11–18.
  47. Maharaj A.S., Saint-Geniez M., Maldonado A.E., D'Amore P.A. Vascular endothelial growth factor localization in the adult. Am. J. Pathol. 2006; 168: 639–648.
  48. Smith N.R., Baker D., James N.H., Ratcliffe K., Jenkins M., Ashton S.E. et al. Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin. Cancer Res. 2010; 16: 3548–3561.
  49. Zozulia U., Vasilyeva I., Slin’ko E., Chopick N. Comparative study of vascular endothelial growth factor receptor-2 expression in spinal tumors. Ukr. Neurosci. J. 2001; 3: 85–92.
  50. Plate K.H., Breier G., Millauer B., Ullrich A., Risau W. Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer. Res. 1993; 53 (23): 5822–5827.
  51. Podar K., Anderson K.C. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood. 2005; 105: 1383–1395.
  52. Dias S., Hattori K., Zhu Z., Heissig B., Choy M., Lane W. et al. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J. Clin. Invest. 2000; 106 (4): 511–521.
  53. Hicklin D.J., Ellis L.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 2005; 23: 1011–1027.
  54. Calvani M., Rapisarda A., Uranchimeg B., Shoemaker R.H., Melillo G. Hypoxic induction of an HIF-1alpha-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells. Blood. 2006; 107: 2705–2712.
  55. Waldner M.J., Wirtz S., Jefremow A., Warntjen M., Neufert C., Atreya R. et al. VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer. J. Exp. Med. 2010; 207: 2855–2868.
  56. Motzer R.J., Michaelson M.D., Redman B.G., Hudes G.R., Wilding G., Figlin R.A. et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2006; 24: 16–24.
  57. de Bouard S., Herlin P., Christensen J.G., Lemoisson E., Gauduchon P., Raymond E. et al. Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro Oncol. 2007; 9: 412–423.
  58. Tvorogov D, Anisimov A., Zheng W., Leppänen V.M., Tammela T., Laurinavicius S. et al. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell. 2010; 18: 630–640.
  59. Spratlin J. Ramucirumab (IMC-1121B): Monoclonal antibody inhibition of vascular endothelial growth factor receptor-2. Curr. Oncol .Rep. 2011; 13 (2): 97–102.
  60. Spratlin J.L., Mulder K.E., Mackey J.R. Ramucirumab (IMC-1121B): a novel attack on angiogenesis. Future Oncol. 2010; 6 (7): 1085–1094.
  61. Krupitskaya Y., Wakelee H.A. Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer. Curr. Opin. Investig. Drugs. 2009; 10(6): 597–605.
  62. Ton N.C., Parker G.J., Jackson A., Mullamitha S., Buonaccorsi G.A., Roberts C. et al. Phase I evaluation of CDP791, a PEGylated di-Fab' conjugate that binds vascular endothelial growth factor receptor 2. Clin. Cancer Res. 2007; 13 (23): 7113–7118.
  63. Hansen-Algenstaedt N., Stoll B.R., Padera T.P., Dolmans D.E., Hicklin D.J., Fukumura D. et al. Tumor oxygenation in hormone-dependent tumors during vascular endothelial growth factor receptor-2 blockade, hormone ablation, and chemotherapy. Cancer Res. 2000; 60: 4556–4560.
  64. Juan T.Y., Roffler S.R., Hou H.S., Huang S.M., Chen K.C., Leu Y.L. et al. Antiangiogenesis targeting tumor microenvironment synergizes glucuronide prodrug antitumor activity. Clin Cancer Res. 2009; 15: 4600–4611.
  65. Kozin S.V., Boucher Y., Hicklin D.J., Bohlen P., Jain R.K., Suit H.D. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. 2001; 61: 39–44.
  66. Winkler F., Kozin S.V., Tong R.T., Chae S.S., Booth M.F., Garkavtsev I. et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004; 6: 553–563.
  67. Sullivan L.A., Brekken R.A. The VEGF family in cancer and antibody-based strategies for their inhibition. MAbs. 2010; 2 (2): 165–175.
  68. Kim K.J., Li B., Winer J., Armanini M., Gillett N., Phillips H.S. et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993; 362: 841–844.
  69. Carmeliet P., Jain R.K. Angiogenesis in cancer and other diseases. Nature. 2000; 407: 249–257.
  70. Keunen O., Johansson M., Oudin A., Sanzey M., Rahim S.A., Fack F. et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc. Natl. Acad. Sci. U S A. 2011; 108 (9): 3749–3754.
  71. Roodink I., Leenders W.P. Targeted therapies of cancer: angiogenesis inhibition seems not enough. Cancer Lett. 2010; 299(1): 1–10.
  72. Bergers G., Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer. 2008; 8 (8): 592–603.
  73. di Tomaso E., London N., Fuja D., Logie J., Tyrrell J.A., Kamoun W. et al. PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment. PLoS One. 2009; 4 (4): е5123.
  74. Batchelor T.T. Sorensen A.G., di Tomaso E., Ryg P.A., Loeffler J.S., Sorensen A.G. et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007; 11 (1): 83–95.
  75. Mizukami Y, Jo W.S., Duerr E.M., Gala M., Li J., Zhang X. et al. Induction of interleukin-8 preserves the angiogenic response in HIF-1 α-deficient colon cancer cells. Nature Med. 2005; 11: 992–997.
  76. Ali M.M., Janic B., Babajani-Feremi A., Varma N.R., Iskander A.S., Anagli J. et al. Changes in vascular permeability and expression of different angiogenic factors following anti-angiogenic treatment in rat glioma. PLoS One. 2010; 5 (1): 8727.
  77. Fan F., Samuel S., Gaur P., Lu J., Dallas N.A., Xia L. et al. Chronic exposure of colorectal cancer cells to bevacizumab promotes compensatory pathways that mediate tumour cell migration. Brit. J. Cancer. 2011; 104 (8): 1270–1277.
  78. Song S., Ewald A.J., Stallcup W. Werb Z., Bergers G. PDGFRβ + perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nature Cell. Biol. 2005; 7: 870–879.
  79. Du R., Lu K.V., Petritsch C., Liu P., Ganss R., Passegué E. et al. HIF1α induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008; 13 (3): 206–220.
  80. Wang R., Chadalavada K., Wilshire J., Kowalik U., Hovinga K.E., Geber A. et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 2010; 468 (7325): 829–833.
  81. Ricci-Vitiani L., Pallini R., Biffoni M., Todaro M., Invernici G., Cenci T. et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010; 468 (7325): 824–828.
  82. Hendriksen E.M., Span P.N., Schuuring J., Peters J.P., Sweep F.C., van der Kogel A.J. et al. Angiogenesis, hypoxia and VEGF expression during tumour growth in a human xenograft tumour model. Microvasc. Res. 2009; 77 (2): 96–103.
  83. Robey R.B., Hay N. Is Akt the «Warburg kinase»?-Akt-energy metabolism interactions and oncogenesis. Semin. Cancer Biol. 2009; 19 (1): 25–31.
  84. Yu J.L., Rak J.W., Coomber B.L., Hicklin D.J., Kerbel R.S. Effect of p53 status on tumor response to antiangiogenic therapy. Science. 2002; 295 (5559): 1526–1528.
  85. Calabrese C., Poppleton H., Kocak M., Hogg T.L., Fuller C., Hamner B. et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007; 11 (1): 69–82.
  86. Paez-Ribes M., Allen E., Hudock J., Takeda T., Okuyama H., Viñals F. et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009; 15 (3): 220–231.
  87. Ebos J.M., Lee C.R., Cruz-Munoz W., Bjarnason G.A., Christensen J.G., Kerbel R.S. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009; 15 (3): 232–239.
  88. Bikfalvi A., Moenner M., Javerzat S., North S., Hagedorn M. Inhibition of angiogenesis and the angiogenesis/invasion shift. Biochem. Soc. Trans. 2011; 39 (6): 1560–1564.
  89. Lucio-Eterovic A.K., Piao Y., de Groot J.F. Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin. Cancer Res. 2009; 15 (14): 4589–4599.
  90. Wu X., Northcott P.A., Dubuc A., Dupuy A.J., Shih D.J., Witt H. et al. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature. 2012; 482 (7386): 529–533.
  91. Lyden D., Hattori K., Dias S., Costa C., Blaikie P., Butros L. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat. Med. 2001; 7 (11): 1194–1201.
  92. Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J. Biochem. Mol. Biol. 2006; 39 (5): 469–478.
  93. Salhia B., Angelov L., Roncari L., Wu X., Shannon P., Guha A. Expression of vascular endothelial growth factor by reactive astrocytes and associated neoangiogenesis. Brain. Res. 2000; 883 (1): 87–97.
  94. Wuestefeld R., Chen J., Meller K., Brand-Saberi B., Theiss C. Impact of vegf on astrocytes: analysis of gap junctional intercellular communication, proliferation, and motility. Glia. 2012; 60 (6): 936–947.
  95. Ma Y., Shurin G.V., Gutkin, D. W., Shurin M.R. Tumor associated regulatory dendritic cells. Semin. Cancer Biol. 2012; 22 (4): 298–306.
  96. Gabrilovich D., Ishida T., Oyama T., Ran S., Kravtsov V., Nadaf S. et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood. 1998; 92: 4150–4166.
  97. Chaux P., Moutet M., Faivre J., Martin F., Martin M. Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T-cell activation. Lab. Invest. 1996; 74 (5): 975–983.
  98. Caraglia M., De Rosa G., Salzano G., Santini D., Lamberti M., Sperlongano P. et al. Nanotech revolution for the anti-cancer drug delivery through blood-brain-barrier. Curr. Cancer Drug. Targets. 2012; 12 (3): 186–196.
  99. Zhan C., Lu W. The blood-brain/tumor barriers: challenges and chances for malig-nant gliomas targeted drug delivery. Curr. Pharm. Biotechnol. 2012; 13 (12): 2380–2387.
  100. Chekhonin V.P., Baklaushev V.P., Iusubalieva G.M., Volgina N.E., Gurina O.I. Fundamental and applied aspects of the hematoencephalic barrier research. Vestn. Ross. Akad. Med. Nauk. 2012; (8): 66–78.
  101. Zhou J., Atsina K.B., Himes B.T., Strohbehn G.W., Saltzman W.M. Novel delivery strategies for glioblastoma. Cancer J. 2012; 18 (1): 89–99.
  102. Chekhonin V.P., Baklaushev V.P., Yusubalieva G.M., Belorusova A.E., Gulyaev M.V., Tsitrin E.B. et al. Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43. Nanomedicine. 2012; 8 (1): 83–70.
  103. Chekhonin V.P., Baklaushev V.P., Yusubalieva G.M., Gurina O.I., Dmitrieva T.B. A targeted transport of 125I-labeled monoclonal antibodies to target proteins in experimental glioma focus. Doklady Biochem. i Biophys. 2008; 418 (5): 1–4.
  104. Сhekhonin V.P., Baklaushev V.P., Yusubalieva G.M., Gurina O.I. Targeted Transport of 125I-Labeled Antibody to GFAP and AMVB1 in an Experimental Rat Model of C6 Glioma. J. Neur.Pharmacol. 2009; 4 (1): 28–34.
  105. Сhekhonin V.P., Dmitrieva T.B., Zhirkov U.A., Kabanov A.V., Gendel'man Kh. E. Nanosystems and targeted transport of medicinal preparations to the brain. Vestn. Ross. Akad. Med. Nauk = Annual of Academy of Medical sciences. 2009; 2: 32–40.
  106. Lebedev S.V., Petrov S.V., Volkov A.I., Chekhonin V.P. The translocation of macromolecules via the hematoencephalic barrier. Vestn. Ross. Akad. Med. Nauk = Annual of Academy of Medical sciences. 2007; 6: 37–49.
  107. Ogunshola O.O., Stewart W.B., Mihalcik V., Solli T., Madri J.A., Ment L.R. Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain. Brain. Res. 2000; 119 (1): 139–153.
  108. Argaw A.T., Asp L., Zhang J., Navrazhina K., Pham T., Mariani J.N. et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J. Clin. Invest. 2012; 122 (7): 2454–2468.
  109. Dejana E., Tournier-Lasserve E., Weinstein B.M. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev. Cell. 2009; 16: 09–221.
  110. Srikanth M., Kessler J.A. Nanotechnology-novel therapeutics for CNS disorders. Nat. Rev. Neurol. 2012; 8 (6): 307–318.
  111. Duggan S.T.; Keating G.M. Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma. Drugs. 2011; 71 (18): 2531–2558.
  112. Chang H.I., Yeh M.K. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int. J. Nanomed. 2012; 7: 49–60.
  113. Lingappa M., Song H., Thompson S., Bruchertseifer F., Morgenstern A., Sgouros G. Immunoliposomal delivery of 213Bi for alpha-emitter targeting of metastatic breast cancer. Cancer Res. 2010; 70 (17): 6815–6823.
  114. Feng B., Tomizawa K., Michiue H., Han X.J., Miyatake S., Matsui H. Development of a bifunctional immunoliposome system for combined drug delivery and imaging in vivo. Biomaterials. 2010; 31 (14): 4139–4145.
  115. Abakumov M.A., Shein S.A., Vishvasrao H., Nukolova N.V., Sokol'ski-Papkov M., Sandalova T.O. et al. Visualization of experimental glioma C6 by MRI with magnetic nanoparticles conjugated with monoclonal antibodies to vascular endothelial growth factor. Bull. Exp. Biol .Med. 2012; 154 (8): 242–246.
  116. Wicki A., Rochlitz C., Orleth A., Ritschard R., Albrecht I., Herrmann R. et al. Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth. Clin. Cancer Res. 2012; 18 (2): 454–464.
  117. Ebos J.M., Bocci G., Man S., Thorpe P.E., Hicklin D.J., Zhou D. et al. A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol. Cancer Res. 2004; 2 (6): 315–326.
  118. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell. 2011; 144 (5): 646–674.
  119. Erber R., Thurnher A., Katsen A.D., Groth G., Kerger H., Hammes H.P. et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 2004; 18 (2): 338–340.
  120. Hiratsuka S., Duda D.G., Huang Y., Goel S., Sugiyama T., Nagasawa T. et al. C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells. Proc. Natl. Acad. Sci. U S A. 2011; 108 (1): 302–307.
  121. Rapisarda A., Hollingshead M., Uranchimeg B. et al. Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition. Mol. Cancer Ther. 2009; 8 (7): 1867–1877.
  122. Chekhonin V.P., Shein S.A., Korchagina A.A., Gurina O.I. et al. VEGF in tumor progression and targeted therapy. Curr. Cancer Drug .Targets. 2013; 13 (4): 423–443.



Abstract: 976

PDF (Russian): 925

Article Metrics

Metrics Loading ...



Copyright (c) 1970 Russian academy of sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies