New antiangiogenic therapy for glioblastoma: photodynamic and synthetic peptide therapy

• Project/Area Number: 24659645
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: University of Tsukuba
• Principal Investigator: TAKANO Shingo 筑波大学, 学内共同利用施設等, 病院講師 (50292553)
• Co-Investigator(Kenkyū-buntansha): UEBA Tetsuya 高知大学, 医学部, 教授 (00314203)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血管新生 / 膠芽腫 / 合成ペプチド / FGF2 / FGF2受容体 / 脳梗塞 / アンチセンスホモロジーボックス / 血管内皮細胞 / グリオーマ / 血管新生抑制 / 内皮細胞 / 光線力学療法 / ペプチド療法 / アンチセンス・ホモロジーボックス / クラニアルウィンドウ / 管腔形成 / ホモロジーボックス / 組織因子 / endoglin / jagged-1 / VEGF

Outline of Final Research Achievements

As a specific inhibitor for angiogenic factor FGF2, we are interested in antisence homology box (AHB) in FGF2 receptor. Based on the computer analysis of FGF2 receptor, 13 synthetic peptides for AHB were designed. Human endothelial cell proliferation assay was determined with these peptides. Unexpectedly, some peptides demonstrated strong endothelial proliferation activity with elevated FGF2 signal transduction. Finally the angiogenic activity of the peptide was confirmed by other several assays. We propose AHB derived FGF2 receptor peptide is a candidate of angiogenic therapy for ischemic disease such as cerebral infarction.

Research Products

• [Journal Article] Interferon-β inhibits glioma angiogenesis through downregulation of vascular endothelial growth factor and upregulation of interferon inducible protein 10 (2014)
  • Author(s): 1.Takano S, Ishikawa E, Matsuda M, Yamamoto T, Matsumura A
  • Journal Title: Int J Oncol Volume: 45 Issue: 5 Pages: 1837-1846
  • DOI: 10.3892/ijo.2014.2620
  • NAID: 120007136594
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CXCL12 secreted from glioma stem cells regulates their proliferation. (2014)
  • Author(s): Uemae Y, Ishikawa E, Osuka S, Matsuda M, Sakamoto N, Takano S, Nakai K, Yamamoto T, Matsumura A
  • Journal Title: J Neurooncol. Volume: 117 Pages: 43-51
  • Peer Reviewed
• [Journal Article] Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation (2013)
  • Author(s): Akimoto K, Kimura K, Nagano M, Takano S, To'a Salazar G, Yamashita T, Ohneda O.
  • Journal Title: Stem Cells Dev Volume: 22 Issue: 9 Pages: 1370-1386
  • DOI: 10.1089/scd.2012.0486
  • Peer Reviewed
• [Journal Article] Establishment of novel monoclonal antibodies KMab-1 and MMab-1 specific for IDH2 mutations (2013)
  • Author(s): Kaneko MK, Morita S, Tsujimoto Y, Yanagiya R, Nasu K, Sasaki H, Hozumi Y, Goto K, Natsume A, Watanabe M, Kumabe T, Takano S, Kato Y.
  • Journal Title: Biol Biophys Res Commun Volume: 432 Pages: 40-45
  • Peer Reviewed
• [Journal Article] IGF1 receptor signaling regulates adaptive radioprotection in glioma stemcells (2013)
  • Author(s): Osuka S. Sampetrean O, Shimizu T, Saga l, Onishi N, Sugihara E, Okubo J, Fujita S, Takano S, Matsumura A, Saya H
  • Journal Title: Stem Cells Volume: 31 Issue: 4 Pages: 627-640
  • DOI: 10.1002/stem.1328
  • Peer Reviewed
• [Journal Article] Decrease in the apparent diffusion coefficient in peritumoral edema for the assessment of recurrent glioblastoma treated by bevacizumab (2013)
  • Author(s): Takano S, Kimu H, Tsuda K, Osuka S, Nakai K, Yamamoto T, Ishikawa E, Akutsu H, Matsuda M, Matsumura A
  • Journal Title: Acta Neurochir Suppl Volume: 118 Pages: 185-189
  • DOI: 10.1007/978-3-7091-1434-6_34
  • ISBN: 9783709114339, 9783709114346
  • Peer Reviewed
• [Journal Article] Establishment of novel monoclonal antibodies KMab-1 and MMab-1 specific for IDH2 mutations (2013)
  • Author(s): Kato MK, Takano S et al.
  • Journal Title: Biol Biophys Res Commun Volume: 1 Pages: 1-10
• [Journal Article] Decrease in the Apparent Diffusion Coefficient in Peritumoral Edemafor the Assessm ent of Recurrent Glioblastoma Treated by Bevacizumab , (2013)
  • Author(s): Takano S et al.
  • Journal Title: Acta Neurochirurgica Supplement Volume: 1 Pages: 1-10
• [Journal Article] Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote glioblastoma multiforme proliferation. (2012)
  • Author(s): Akimoto K, Takano S et al.
  • Journal Title: Stem Cells Dev Volume: 1 Pages: 1-10
• [Journal Article] Topics for antiangiogenic therapy for glioblastoma (2012)
  • Author(s): Takano S, Matsumura A
  • Journal Title: No Shinkei Geka Volume: 40 Pages: 481-502
• [Journal Article] Genome-wide identification of endothelial cell-enriched genes in the mouse embryo. (2012)
  • Author(s): Takase H, Takano S et al.
  • Journal Title: Blood Volume: 120 Pages: 914-923
• [Journal Article] Valproic acid inhibits angiogenesis in vitro and glioma angiogenesis in vivo in the brain. (2012)
  • Author(s): Osuka S, Takano S et al,
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 52 Pages: 186-193
  • NAID: 10030127723
• [Journal Article] Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors. (2012)
  • Author(s): Takano S et al.
  • Journal Title: J Neurooncol Volume: 108 Pages: 361-373
• [Journal Article] Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation (2012)
  • Author(s): Takano S
  • Journal Title: Brain Tumor Pathol Volume: 29 Pages: 73-86