Brain Tumor Angiogenesis
The growth of malignant tumors of the central nervous system requires adequate supplies of oxygen and nutrients obtained by the formation of new capilliaries from existing blood vessels. This process is called angiogenesis. Accordingly, anti-angiogenic th
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Brain Tumor Angiogenesis
S. Lakka . J. S. Rao
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2 Molecular Regulation of Glioma Angiogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3 Genetic Alterations in Glioma Angiogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4 Angiogenesis Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
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2009 Springer ScienceþBusiness Media, LLC.
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Brain tumor angiogenesis
Abstract: The growth of malignant tumors of the central nervous system requires adequate supplies of oxygen and nutrients obtained by the formation of new capilliaries from existing blood vessels. This process is called angiogenesis. Accordingly, anti-angiogenic therapy represents a promising modality for the treatment of brain tumors. This review describes the main biological events, molecular factors and critical signaling cascades implicated in brain tumor angiogenesis. We also summarized the key attributes of the emerging synthetic small molecular inhibitors and molecular targets with anti-angiogenic activities that make them potent anti-tumor agents. The studies reviewed here suggest that there is an urgent need for a new comprehensive treatment strategy combining anti-angiogenic agents with conventional cytoreductive treatments in the control of brain cancer. List of Abbreviations: bFGF, basic fibroblast growth factor; EGF, epidermal growth factor; EGFR, Epidermal growth factor receptor; FGF, Fibroblast growth factors; FKBP, FK506‐binding protein; FTS, farnesylthiosalicylic acid; HGA, High‐grade astrocytoma; HIF, hypoxia‐inducible transcription factor; HIF‐1, Hypoxia‐inducible factor 1; HIF‐1alpha, Hypoxia‐inducible factor 1alpha; IM, intramuscular; MMPs, matrix metalloproteinases; NABTC, North American Brain Tumor Consortium; PDGF, platelet derived growth factor; PDGF‐R, Platelet derived growth factor receptor; PDGFR‐beta, platelet‐derived growth factor receptor‐beta; PI3K, phosphatidyl inositol‐3 kinase; PIGF, placental growth factor; PIP2, Phosphatidyl inositol bi phosphate; PIP3, phosphatidyl inositol tri phosphate; TNF‐alpha, tumor necrosis factor alpha; TSP, Thrombospondin; PTEN, Phosphatese and tensin hemalog; VEGF, vascular endothelial growth factor; vHL, von Hippel–Lindau
1 Introduction A tumor’s ability to grow is linked to its ability to recruit a supply of new blood vessels. A tumor remains in a dormant state, the cellular proliferation rate balanced by the apoptotic rate, unable to grow
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