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Anti-tumor effects and Regulation of Wnt signaling pathway of adenovirus-mediated DKK3 in glioblastoma

Research Project

Project/Area Number 25462264
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionThe University of Tokushima

Principal Investigator

MIZOBUCHI Yoshifumi  徳島大学, 大学病院, 講師 (80547993)

Co-Investigator(Kenkyū-buntansha) MURE Hideo  徳島大学, 大学院医歯薬学研究部, 助教 (00624355)
NAGAHIRO Shinji  徳島大学, 大学院医歯薬学研究部, 教授 (60145315)
KAGEJI Teruyoshi  徳島大学, 病院, 特任教授 (70294684)
KUWAYAMA Kazuyuki  四国こどもとおとなの医療センター, 臨床研究部, 脳神経外科医長 (50614236)
NAKAJIMA Kohei  徳島大学, 病院, 助教 (40710554)
HARA Keijirou  徳島大学, 病院, 助教 (60710340)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords脳腫瘍 / グリオブラストーマ / Wnt / DKK3 / 遺伝子治療 / グリオブラストーマ / 悪性脳腫瘍 / Ad-REIC / Wntシグナル
Outline of Final Research Achievements

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2015 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma2015

    • Author(s)
      Hara K, Kageji T, Mizobuchi Y, Kitazato KT, Okazaki T, Fujihara T, Nakajima K, Mure H, Kuwayama K, Hara T, Nagahiro S
    • Journal Title

      Cancer Lett

      Volume: 356 Issue: 2 Pages: 496-505

    • DOI

      10.1016/j.canlet.2014.09.045

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnosis of brain tumors using dynamic contrast-enhanced perfusion imaging with a short acquisition time2015

    • Author(s)
      Abe T, Mizobuchi Y, Nakajima K, Otomi Y, Irahara S, Obama Y, Majigsuren M, Khashbat D, Kageji T, Nagahiro S, Harada M
    • Journal Title

      Springerplus

      Volume: 4 Issue: 1 Pages: 88-88

    • DOI

      10.1186/s40064-015-0861-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Significance of temozolomide re-challenge after progression of malignant gliomas in maintaining performance status of the patients-multicenter cooperative study2015

    • Author(s)
      S.Kohno, T.Ohnishi, T.Ichikawa, I. Date, K.Miyake, T.Tomiya, T. Kageji, S,Nagahiro, M.Ideguchi, M.Suzuki, A.Kanbe, T.Watanabe, K.Miyazaki, Y.Akiyama, N.Matushita, M.Uno
    • Organizer
      20th Annual Socientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      Texas, USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sonodynamic 5-ALA plus ultrasound therapy augments anti-tumor effects in the oncogene knock-in glioma stemcells2015

    • Author(s)
      K.Shono, T.Kageji, Y.Mizobuchi, T.Fujihara, K.Kitazato, K.Nakajima, H.Mure, K.Kuwayama, S.Nagahiro
    • Organizer
      20th Annual Socientific Meeting and Education Day of the Society for Neuro-Oncology,
    • Place of Presentation
      Texas,USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Down-regulation of MDR1 by DKK3 attenuates chemoresistance to temozolomide, and potentiates its anti-tumor effects2015

    • Author(s)
      T.Fujihara, T.Kageji, Y.Mizobuchi, R.Otsuka K.Kitazato, K.Hara, K.Shono, K.Nakajima H.Mure, K.Kuwayama, S.Nagahiro
    • Organizer
      20th Annual Socientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      Texas, USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intensive chemotherapy followed by reduced radiation dose for intracranial non-germinomatous germ cell tumors2015

    • Author(s)
      T.Kageji, Y.Mizobuchi, K.Nakajima, S.Nagahiro, H.Watanabe, N.Inoue, K.Okamura, S.Kagami
    • Organizer
      20th Annual Socientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      Texas, USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intensive chemotherapy followed by reduced radiation dose for intracranial non-germinomatous germ cell tumors2015

    • Author(s)
      T. Kageji, Y. Mizobuchi, K. Nakajima, S. Nagahiro, H. Watanabe, N. Inoue, K. Okamura, S. Kagami
    • Organizer
      13th Congress of the World Federatoin of Interventional and Therapeutic Neuroradiology
    • Place of Presentation
      Gold Coast, Australia
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Strategy and Clinical Results for Intracranial Non-germinomatous Germ Cell Tumors Induced Intensive Chemotherapy2015

    • Author(s)
      T.Kageji, Y.Mizobuchi, K.Nakajima, S.Nagahiro H.Watanabe, N.Inoue, K.Okamura, S.Kagami
    • Organizer
      The 4th International CNS Germ Cell Tumor Symposium
    • Place of Presentation
      HAPPO-EN,Tokyo, minato-ku
    • Year and Date
      2015-04-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Intensive Chemotherapy Followed by Reduced Dose Radiation for Intracranial Non-germinomatous Germ Cell Tumors2015

    • Author(s)
      H.Watanabe, N.Inoue, K.Okamura, S.Nagahiro, Y.Mizobuchi, K.Nakajima,T.Kageji, S.Kagami
    • Organizer
      The 4th International CNS Germ Cell Tumor Symposium
    • Place of Presentation
      HAPPO-EN,Tokyo, minato-ku
    • Year and Date
      2015-04-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dkk-3, one of Dickkopf (Dkk) family members, contributes to the anti-tumor effects in glioblastoma through regulation of both Wnt signal pathways2013

    • 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 Marquis Hotel (San Francisco, USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Down-regulation of MDR by Ad-Dkk3 contributes to augment the chemotherapy by temozolomide2013

    • 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 Marquis Hotel (San Francisco, USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] A combination of interferon-b and temozolomide augments anti-tumor effects through p73/YAP-mediated apoptosis by PML in glioblastoma2013

    • 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 Marquis Hotel (San Francisco, USA)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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