A new therapeutic strategy using adenovirus vector REIC gene in a new glioblastoma (GBM) mice model

• Project/Area Number: 23592128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: KAGEJI Teruyoshi 徳島大学, 大学病院, 特任教授 (70294684)
• Co-Investigator(Kenkyū-buntansha): MIZOBUCHI Yoshifumi 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助教 (80547993) ; NAGAHIRO Shinji 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (60145315) ; MURE Hideo 徳島大学, 病院, 助教 (00624355) ; KURASHIKI Yoshitaka 徳島大学, 病院, 特任助教 (10597503)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脳腫瘍 / REIC / Wntシグナル / 薬物排出ポンプ / REIC/Dkk-3 / アポトーシス / glioblastoma / Wnt シグナル

Research Abstract

Glioblastoma multiform (GBM) remains incurable despite the use of aggressive and multimodal therapies involving tumor resection, chemotherapy and radiation therapy. The cancer stem cell theory postulates that tumors are sustained by a select cell population with self-renewal ability and the capacity to give rise to a heterogeneous mass of tumor cells. Based on the existence of glioma stem cells for glioblastoma, Saya et al. established the new GBM model. Elsewhere we demonstrated that Dickkopf family3 (DKK3) was down-regulated in GBM cells and that its over-expression drastically inhibited their growth via caspase-dependent apoptosis. The aim of our study was 1) to establish this model in our institute and 2) to assess the efficacy of Ad-DKK3 in the GBM mice model and 3) to verify the mechanisms underlying the efficacy of DKK3. We partly verified the mechanisms underlying the efficacy by DKK3 in GBM and submitted our paper to Cancer Letter.

Research Products

• [Journal Article] Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma (2014)
  • Author(s): Okazaki T, Kageji T, Mizobuchi Y, Miyamoto T, Nagahiro S
  • Journal Title: A case report. Appl Radiat Isot Volume: 88 Pages: 28-31
  • Peer Reviewed
• [Journal Article] Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT) (2014)
  • Author(s): Kageji T, Mizobuchi Y, Nagahiro S, Nakagawa Y, Kumada H
  • Journal Title: Appl Radiat Isot Volume: 88 Pages: 20-22
  • Peer Reviewed
• [Journal Article] Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: A case report (2014)
  • Author(s): Toshiyuki Okazaki, Teruyoshi Kageji, Yoshifumi Mizobuchi, Takeshi Miyamoto, Shinji Nagahiro
  • Journal Title: Appl Radiat Isot Volume: S0969-8043(13) Pages: 629-5
  • Peer Reviewed
• [Journal Article] Differential diagnosis of and therapy for anaplastic astroblastoma : case report and review of the literature] (2013)
  • Author(s): Kurashiki Y, Kageji T, Mizobuchi Y, Satomi J, Satoh K, Hirose T, Nagahiro S
  • Journal Title: No Shinkei Geka Volume: 41 Pages: 891-899
  • Peer Reviewed
• [Journal Article] Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT) (2013)
  • Author(s): Kageji T, T. Kageji, Y. Mizobuchi, S. Nagahiro, Y. Nakagawa, H. Kumada
  • Journal Title: Appl Radiat Isot Volume: S0969-8043(13) Pages: 610-6
  • Peer Reviewed
• [Journal Article] Anaplastic astroblastomaの鑑別診断と治療 ー症例報告と文献的考察ー (2013)
  • Author(s): 倉敷佳孝、影治照喜、溝渕佳史、里見淳一郎、佐藤浩一、廣瀬隆則、永廣信治
  • Journal Title: 脳神経外科 Volume: 41 Pages: 891-899
  • Peer Reviewed
• [Presentation] Dkk-3, one of Dickkopf (Dkk) family members (2013)
  • Author(s): Hara K, Kageji T, Mizobuchi Y, Kitazato KT, Okazaki T, Fujihara T, Nakajima K, Mure H, Kuwayama K, Hara K, Nagahiro S
  • Organizer: contributes to the anti-tumor effects in glioblastoma through regulation of both Wnt signal pathways SNO 2013
  • Place of Presentation: Moscone West Convention Center (San Francisco, USA)
• [Presentation] Down- regulation of MDR by Ad-Dkk3 contri- butes to augment the chemotherapy by temozolomide (2013)
  • Author(s): Nakajima K, Hara K, Kageji T, Mizobuchi Y, Kitazato KT, Fujihara T, Kuwayama K, Otsuka R, Kung DK, Nagahiro S
  • Organizer: SNO 2013
  • Place of Presentation: Moscone West Convention Center (San Francisco, USA)
• [Presentation] A combination of interferon-b and temozolomide augments anti-tumor effects through p73/YAP-mediated apoptosis by PML in glioblastoma (2013)
  • Author(s): Mizobuchi Y, Okazaki T, Kageji T, Kuwayama K, Kitazato KT, Mure H, Hara K, Morigaki R, Matsuzaki K, Nakajima K, Fujihara T, Nagahiro S
  • Organizer: SNO 2013
  • Place of Presentation: Moscone West Convention Center (San Francisco, USA)
• [Presentation] Dkk-3, one of Dickkopf (Dkk) family members, contributes to the anti-tumor effects in glioblastoma through regulation of both Wnt signal pathways (2013)
  • Author(s): K.Hara, T.Kageji, Y.Mizobuchi, K.T.Kitazato, T.Okazaki, T.Fujihara, K.Nakajima, H.Mure, K.Kuwayama, T.Hara, S.Nagahiro
  • Organizer: SNO 2013
  • Place of Presentation: Marriott Maquis Hotel (San Francisco, USA)
• [Presentation] Down-regulation of MDR by Ad-Dkk3 contributes to augment the chemotherapy by temozolomide (2013)
  • Author(s): K.Nakajima, K.Hara, T.Kageji, Y.Mizobuchi, K.T.Kitazato, T.Fujihara, K.Kuwayama, R.Otsuka, D K.Kung, S.Nagahiro
  • Organizer: SNO 2013
  • Place of Presentation: Marriott Maquis Hotel (San Francisco, USA)
• [Presentation] A combination of interferon-b and temozolomide augments anti-tumor effects through p73/YAP-mediated apoptosis by PML in glioblastoma (2013)
  • Author(s): Y.Mizobuchi, T.Okazaki, T.Kageji, K.Kuwayama, K.T.Kitazato, H.Mure, K.Hara, R.Morigaki, K.Matsuzaki, K.Nakajima, T.Fujihara, S.Nagahiro
  • Organizer: SNO 2013
  • Place of Presentation: Marriott Maquis Hotel (San Francisco, USA)
• [Presentation] 悪性神経膠腫におけるREIC/Dkk-3遺伝子導入によるWnt蛋白制御の意義 (2012)
  • Author(s): 原慶次郎、溝渕佳史、北里慶子、岡﨑敏之、影治照喜、永廣信治、公文裕巳
  • Organizer: 第13回日本分子脳神経外科学会
  • Place of Presentation: 熊本市国際交流会館(熊本県熊本市)
• [Presentation] 悪性神経膠腫におけるREIC/Dkk-3遺伝子導入によるWnt蛋白制御の意義 (2012)
  • Author(s): 原慶次郎他
  • Organizer: 第13回日本分子脳神経外科学会
  • Place of Presentation: 熊本市国際交流会館（熊本県）