title: Recent advance in molecular angiogenesis in glioblastoma: the challenge and hope for anti-angiogenic therapy.
abstract: Glioblastoma (GBM) is the most highly malignant brain tumor in the human central nerve system. In this paper, we review new and significant molecular findings on angiogenesis and possible resistance mechanisms. Expression of a number of genes and regulators has been shown to be upregulated in GBM microvessel cells, such as interleukin-8, signal transducer and activator of transcription 3, Tax-interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2. The regulator factors that may strongly promote angiogenesis by promoting endothelial cell metastasis, changing the microenvironment, enhancing the ability of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are reviewed. Based on the current knowledge, several potential targets and strategies are proposed for better therapeutic outcomes, such as its mRNA interference of DII4-Notch signaling pathway and depletion of b1 integrin expression. We also discuss possible mechanisms underlying the resistance to anti-angiogenesis and future directions and challenges in developing new targeted therapy for GBM.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Gengfan
authors.initials: G
authors.lastname: Ye
authors.affiliation: Department of Pathology and Laboratory Medicine, North Shore-Long Island Jewish Health System, Lake Success, NY, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, 250012, People's Republic of China. wangyunyan0618@yeah.net.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000628:therapy; D015870:Gene Expression; D005909:Glioblastoma / Q000098:blood supply* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D019012:Integrin beta1; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009088:Mucoproteins; D009389:Neovascularization, Pathologic / Q000235:genetics*; D015513:Oncogene Proteins; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation
chemical_list: C502296:AGR2 protein, human; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D019012:Integrin beta1; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D050796:STAT3 Transcription Factor; C421249:TAX1BP3 protein, human
keywords: Anti-angiogenesis; Genomics; Glioblastoma; Microvascular proliferation; Vascular endothelial growth factor