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Combination therapy with micro RNA and therapeutic stem cells expressing TRAIL overcomes resistant brain tumor

Research Project

Project/Area Number 25861260
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TAMURA Kaoru  東京医科歯科大学, 医学部附属病院, 助教 (70629146)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords悪性脳腫瘍 / 幹細胞 / microRNA
Outline of Final Research Achievements

Despite the development of new glioma therapies that allow for tumor-targeted in situ delivery of cytotoxic drugs, tumor resistance to apoptosis remains a key impediment to effective treatment. Recent evidence indicates that microRNAs, which have a central role in the regulation of gene expression, might play a fundamental role in tumorigenesis, controlling cell proliferation and apoptosis. We hypothesized that modulation of microRNA (miRX) might sensitize gliomas for cytotoxic tumor therapy. In this study, we show that the combination of miRX modulation and therapeutic stem cells expressing cytotoxic agent tumor necrosis factor-related apoptosis inducing ligand (TRAIL) leads to a synergistic increase in caspase activity and significantly decreased cell viability in resistant glioma in vitro and in vivo. Our findings provide the basis for developing combination therapies using microRNA modulation and therapeutic stem cells expressing cytotoxic agent.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Antiangiogenic variant of TSP-1 targets tumor cells in glioblastomas2015

    • Author(s)
      Choi SH, Tamura K, Khajuria RK, Bhere D, Nesterenko I, Lawler J, Shah K
    • Journal Title

      Molecular Therapy

      Volume: 23 Issue: 2 Pages: 235-43

    • DOI

      10.1038/mt.2014.214

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stem cells loaded with multimechanistic oncolytic herpes simplex virus variants for brain tumor therapy2014

    • Author(s)
      Duebgen M, Martinez-Quintanilla J, Tamura K, Hingtgen S, Redjal N, Wakimoto H, Shah K
    • Journal Title

      J Natl Cancer Inst

      Volume: 106 Issue: 6

    • DOI

      10.1093/jnci/dju090

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem cells and the origin of different glioma subtypes. Response.2014

    • Author(s)
      Tamura K, Aoyagi M
    • Journal Title

      J Neurosurgy

      Volume: 120 Pages: 1010-1

    • Related Report
      2014 Annual Research Report
  • [Journal Article] CD133-positive stem cells. Response.2014

    • Author(s)
      Tamura K, Aoyagi M
    • Journal Title

      J Neurosurgy

      Volume: 120 Pages: 1012-1012

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Expansion of CD133-positive glioma cells in recurrent de novo glioblastomas after radiation and chemotherapy2013

    • Author(s)
      Kaoru Tamura, Masaru Aoyagi, Noboru Ando, Takahiro Ogishima , Hiroaki Wakimoto , Masaaki Yamamoto, Kikuo Ohno:
    • Journal Title

      Journal of Neurosurgery

      Volume: 119 Issue: 5 Pages: 1145-1155

    • DOI

      10.3171/2013.7.jns122417

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multimchanistic tumor targeted oncolytic virus overcomes resistance in Brain tumors2013

    • Author(s)
      Kaoru Tamura, Hiroaki Wakimoto, Aayush S Agarwal, Samuel D Rabkin, Deepak Bhere, Robert L Martuza, Toshihiko Kuroda, Randa Kasmieh, Khalid Shah
    • Journal Title

      Molecular Therapy

      Volume: 21(1) Issue: 1 Pages: 6-77

    • DOI

      10.1038/mt.2012.175

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Monitoring of biological response to bevacizumab in malignant glioma patients based on L-[methyl-11C] methionine-positron emission tomography2014

    • Author(s)
      Tamura K., Inaji M., Nariai T., Tamaki M., Hirai S., Saigusa K., Tanaka Y., Maehara T.
    • Organizer
      19th Annual Scientific Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Florida, USA
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Malignant gliomaにおけるBevacizumabの抗腫瘍効果のMethionin-PETによる検討2014

    • Author(s)
      田村 郁、稲次基希、成相 直、玉置正史、平井作京、三枝邦康、田中洋次、前原健寿
    • Organizer
      第73回日本脳神経外科学会総会 東京
    • Place of Presentation
      東京
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tumor vascular damage and glioma stem-like cell expansion after radiotherapy in malignant gliomas2013

    • Author(s)
      Kaoru Tamura, Masaru Aoyagi, Noboru Ando, Takahiro Ogishima, Masaaki Yamamoto, Kikuo Ohno, Taketoshi Maehara
    • Organizer
      4th Quadrennial meeting of the World Federation of Neuro-Oncology Meeting and the 18th Annual Scientific Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 放射線治療後の悪性神経膠腫における腫瘍血管障害と腫瘍幹細胞の増殖2013

    • Author(s)
      田村 郁、青柳 傑、安藤登、荻島 隆浩、脇本浩明、山本昌昭、大野喜久郎、前原健寿
    • Organizer
      第31回日本脳腫瘍学会学術集会
    • Place of Presentation
      宮崎(フェニックス・シーガイア・リゾート)
    • Related Report
      2013 Research-status Report

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

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