低酸素状態における脳腫瘍細胞と血管内皮前駆細胞間のクロストーク解析と分子標的治療

2008 Fiscal Year Annual Research Report

• Project/Area Number: 19591690
• Research Institution: Oita University
• Principal Investigator: 阿部 竜也 Oita University, 医学部, 准教授 (40281216)
• Co-Investigator(Kenkyū-buntansha): 上田 徹 大分大学, 医学部, 講師 (90315333) ; 森重 真毅 大分大学, 医学部, 助教 (60381050)
• Keywords: 脳腫瘍 / 血管内皮細胞 / 幹細胞 / クロストーク / 分子標的治療

Research Abstract

神経膠芽腫に代表される脳腫瘍では著明な血管新生演見られるものの、腫瘍細胞は異常な増殖により孤立した状態で十分に酸素も栄養分も届かないにも関わらず生存している.固形腫瘍では低酸素状態を呈するために、抗癌剤や放射線の感受性那低く,治療成績の低下、予後の悪化、再発の原因の一つとなっている.我々はこれまでに低酸素状態で働く転写因子hypoxia-inducible factor1α(HIF1α)DNAの発現制御について着目し研究をすすめた。さらには同遺伝子を用いた遺伝子療法の研究を行った。近年、HIF1α遺伝子はstromal cell-derived factor-1(SDF-1)とそのレセプターであるCXCR4遺伝子の発現を誘導させることが報告され、SDF-1はCXCR4陽性のstem cellやprogenitor cellをリクルートし、虚血など組織障害の修復に働くことが分かってきた。このような反応は、虚血細胞とそれらを取り巻く間質系細胞が密接に関与していることを示すものと考えられる。またこのような低酸素下の微小環境は腫瘍自体が生存するために必要不可欠であると同時に、微小環境自体が腫瘍の性状を規定しているものと考えられる。そこで低酸素状態において腫瘍細胞と血管内皮細胞間のクロストークを解析すると同時に、それらに関与する幹細胞に関しても様々な段階で制御することによって、治療への応用を図ることを目的とし、研究をすすめ成果を挙げつつある。

Research Products

• [Journal Article] Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus. (2009)
  • Author(s): Kamida T, Fujiki M, Ooba H, Anan M, Abe T, Kobayashi H.
  • Journal Title: Seizure 18 Pages: 71-75
  • Peer Reviewed
• [Journal Article] Intracranial infiltrating features of recurrent scalp dermatofibrosarcoma protuberans. (2009)
  • Author(s): Abe T, Kamida T, Goda M, Inoue R, Fujiki M, Kobayashi H, Hatano Y Shibuya H, Fujiwara S, Terashi H, Mori T.
  • Journal Title: Journal of Clinical Neuroscience (In press)
  • Peer Reviewed
• [Journal Article] The induction of collateral circulation by hypoxia-inducible factor-ladecreased cerebral infarction in the rat. (2009)
  • Author(s): Anan M, Abe T, Shimotaka K, Kamida T, Kubo T, Fujiki M, Kobayashi H.
  • Journal Title: Neurological Research (In press)
  • Peer Reviewed
• [Journal Article] A glioblastorma mimicking a thrombotic aneurysm of the middle cerebral artery. (2009)
  • Author(s): Abe T, Morishige M, Kamida T, Ishii K, Hikawa T, Fujiki M, Kobayashi H, Yamashita M, Hori Y, Nagatomi H
  • Journal Title: Neurosurgery Quarterly (In press)
  • Peer Reviewed
• [Journal Article] A rosette-forming glioneuronal tumor of the spinal cord : The first case of arosette-forming glioneuronal tumororiginating from the spinal cord. (2009)
  • Author(s): Anan M, Inoue R, Ishii K, Abe T, Fujiki M, Kobayashi H, Goya T, Nakazato Y.
  • Journal Title: Human Pathology (In press)
  • Peer Reviewed
• [Journal Article] Malignant fibrous histiocytosis (MFH)after high-dose proton radiationtherapy for anaplastic astrocytoma (2009)
  • Author(s): Ooba H, Abe T, Kamida T, Anan M, Momii Y, Tokuuye K, Fujiki M.
  • Journal Title: Journal of Clinical Neuroscience (In press)
  • Peer Reviewed
• [Journal Article] urgical technique for anterior skull base reconstruction using hydroxya patite cement and titanium mesh. (2009)
  • Author(s): Abe T, Anan M, Kamida T, Fujiki M.
  • Journal Title: Acta Neurochirgica (In press)
  • Peer Reviewed
• [Journal Article] The association between high VEGF levels and multiple probable punctuate cavernous malformations. (2009)
  • Author(s): Abe T, Morishige M, Ooba H, Kamida T, Fujiki M, Kobayashi H, Sakoda T, Kimba Y.
  • Journal Title: Acta Neurochirgica (In press)
  • Peer Reviewed
• [Journal Article] A hemispherotomy for intractable startle epilepsy characterized byinfantile hemiplegia and drop attacks. (2009)
  • Author(s): Anan M, Kamida T, Abe E, Kubo T, Abe T, Hikawa T, Fujiki M, Kobayashi H, Baba H
  • Journal Title: Journal of Clinical Neuroscience (In press)
  • Peer Reviewed
• [Journal Article] A rare case of a traumatic aneurysm of the occipital artery (2008)
  • Author(s): Anan M, Kamida T, Abe T, Fujiki M.
  • Journal Title: Neurosurgery Quarterly 18 Pages: 64-65
  • Peer Reviewed
• [Journal Article] Juvenile cerebral infarction owing to cervicocephalic fibromusculardysplasia. (2008)
  • Author(s): Wakabayashi Y, Ishii K, Murata, K, Ohba H, Kamida T, Hikawa T, Abe T, Kobayashi H.
  • Journal Title: Neurosurgery Quarterly 18 Pages: 57-59
  • Peer Reviewed
• [Journal Article] Neuroprotective and antiamnesic effect of donepezil, a nicotinic acetylcholine-receptor activator, on rats with concussive mild traumatic brain injury (2008)
  • Author(s): Fujiki M, Kubo T, Kamida T, Sugita K, Hikawa T, Abe T, Ishii K, Kobayashi H.
  • Journal Title: Journal of Clinical Neuroscience 15 Pages: 791-796
  • Peer Reviewed
• [Journal Article] Possible involvement of interferon βin postoperative vasculitis restrictedto the tumour bed (2008)
  • Author(s): Abe T, Sugita K, Morishige M, Ohnishi K, Ishii K, Kamida T, Hikawa T, Fujiki M, Kobayashi H, Kashima K, Yokoyamas.
  • Journal Title: Neurosurgical Review 31 Pages: 447-450
  • Peer Reviewed
• [Journal Article] Repeated skin-diving as a possible cause of aneurymal growth and rupture. (2008)
  • Author(s): Wakabayashi Y, Ishii K, Abe T, Kamida T, Kobayashi H.
  • Journal Title: Neurosurgery Quarterly. 18 Pages: 283-285
  • Peer Reviewed
• [Journal Article] Pilomyxoid astrocytoma : An immunohistologic study and review. (2007)
  • Author(s): Abe T, Inoue R, Goda M, Anaa M, Momii Y, Kamida T, Fujiki M, Kobayashi H, Kashima K, Yokoyama S, Nakazato Y.
  • Journal Title: Neurosurgery Quarterly 18 Pages: 60-63
  • Peer Reviewed
• [Presentation] 悪性リンパ腫に対するRituximab併用化学療法の検討 (2008)
  • Author(s): 阿部竜也, 森重真毅, 杉田憲司, 阿部英治, 下高一徳, 籾井泰朋, 上田徹, 肥川誉慎, 藤木稔, 古林秀則
  • Organizer: 第67回日本脳神経外科学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 20081001-20081003