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Molecular therapy for malignant brain tumors using microRNAs of drug-resistant genes

Research Project

Project/Area Number 26293324
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKagawa University

Principal Investigator

Tamiya Takashi  香川大学, 医学部, 教授 (50252953)

Co-Investigator(Kenkyū-buntansha) 三宅 啓介  香川大学, 医学部附属病院, 講師 (00398033)
岡田 真樹  香川大学, 医学部附属病院, 助教 (40457346)
小川 大輔  香川大学, 医学部附属病院, 助教 (70524057)
河井 信行  香川大学, 医学部, 准教授 (40294756)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords薬剤耐性遺伝子 / MGMT / MicroRNA / 脳腫瘍
Outline of Final Research Achievements

It is well known that O6-methylguanine-DNA methyltransferase (MGMT) is related to resistance of aggressive brain tumor glioblastoma (GBM) to DNA alkylating agent Temozolomide (TMZ) therapy. In this study, we searched for microRNA that modulate MGMT expression and give better sensitivity to TMZ. One out of 6 microRNAs (miR-655) down regulated more than 40% MGMT mRNA and protein level in both T98G glioma cell line and primary GBM cell line (GBM30). We will also show that microRNA expressing GBM30 transplanted in nude mice showed better survival with injection of TMZ in vivo. Thus, this endogenous mechanism of suppressing drug resistance gene MGMT will increase chemo-sensitivity to TMZ.This study will provide a new target to enhance efficacy of chemotherapy. In addition, The (pro) renin receptor ((P)RR) as a modular within Wnt receptor complex is essential for early CNS development by the activation of Wnt/β-catenin signaling pathway. Then we examined the role of (P)RR in gliomas.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (25 results)

All 2016 2015 2014

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] (Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway.2016

    • Author(s)
      Kochi m. Shibayama Y, Ogawa D, Miyake K, Nishiyama A, Tamiya T
    • Journal Title

      J Neurosurg

      Volume: epub Issue: 4 Pages: 1-10

    • DOI

      10.3171/2016.9.jns16431

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease2016

    • Author(s)
      Kishimoto Y, Shishido H, Sawanishi M, Toyota Y, Ueno M, Kubota T, Kirino Y, Tamiya T, Kawai N
    • Journal Title

      Data Brief.

      Volume: 9 Pages: 62

    • DOI

      10.1016/j.dib.2016.08.041

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease2016

    • Author(s)
      Shishido H, Kishimoto Y, Kawai N, Toyota Y, Ueno M, Kubota T, Kirino Y, Tamiya T.
    • Journal Title

      Neurosci Lett.

      Volume: 629 Pages: 62

    • DOI

      10.1016/j.neulet.2016.06.066

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] d-Allose Attenuates Overexpression of Inflammatory Cytokines after Cerebral Ischemia/Reperfusion Injury in Gerbil.2016

    • Author(s)
      Shinohara N, Nakamura T, Abe Y, Hifumi T, Kawakita K, Shinomiya A, Tamiya T, Tokuda M, Keep RF, Yamamoto T, Kuroda Y.
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 25 Issue: 9 Pages: 2184-2188

    • DOI

      10.1016/j.jstrokecerebrovasdis.2016.01.030

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of positron emission tomographic studies for gliomas2016

    • Author(s)
      Miyake K, Ogawa D, Okada M, Hatakeyama T, Tamiya T.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 56 Issue: 7 Pages: 396-408

    • DOI

      10.2176/nmc.ra.2015-0305

    • NAID

      130005165067

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological investigation of glioblastomas resected under bevacizumab treatment.2016

    • Author(s)
      Tamura R, Tanaka T, Miyake K, Tabei Y, Ohara K, Sampetrean O, Kono M, Mizutani K, Yamamoto Y, Murayama Y, Tamiya T, Yoshida K, Sasaki H.
    • Journal Title

      Oncotarget.

      Volume: 7 Issue: 32 Pages: 52423-52435

    • DOI

      10.18632/oncotarget.9387

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of 58-kD Microspherule Protein (MSP58) is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients.2016

    • Author(s)
      Lin W, Dai SH, Chen T, Kawai N, Miyake K, Okada M, Haba R, Yamamoto Y, Tamiya T, Fei Z.
    • Journal Title

      Cell Physiol Biochem.

      Volume: 38 Issue: 2 Pages: 635-645

    • DOI

      10.1159/000438656

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose-based regulation of miR-451/AMPK signaling depends on the OCT1 transcription factor.2015

    • Author(s)
      Ansari KI, Ogawa D, Rooj AK, Lawler SE, Krichevsky AM, Johnson MD, Chiocca EA, Bronisz A, Godlewski J.
    • Journal Title

      Cell Rep. 12;11(6):902-9. 2015

      Volume: 12 Issue: 6 Pages: 902-909

    • DOI

      10.1016/j.celrep.2015.04.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging2015

    • Author(s)
      Toyota, Y. Miyake, K. Kawai, N. Hatakeyama, T. Yamamoto, Y. Toyohara, J. Nishiyama, Y. Tamiya, T.
    • Journal Title

      EJNMMI Res

      Volume: 5 Issue: 1 Pages: 7-7

    • DOI

      10.1186/s13550-015-0085-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between ¹⁸F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas2014

    • Author(s)
      Kawai N, Lin W, Cao WD, Ogawa D, Miyake K, Haba R, Maeda Y, Yamamoto Y, Nishiyama Y, Tamiya T
    • Journal Title

      Eur J Nucl Med Mol Imaging.

      Volume: 41 Issue: 10 Pages: 1870-1878

    • DOI

      10.1007/s00259-014-2776-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] Response assessment of bevacizumab therapy for glioblastoma treatment by using 11C-methionine, 18F-fluorothymidine and 18F-fluoromisonidazole PET tracers2016

    • Author(s)
      Miyake K, Kochi M, Ogawa D, Okada M, Hatakeyama T, Shinomiya A, Tamiya T
    • Organizer
      2016 SNO Annual Meeting - Society for Neuro-Oncology
    • Place of Presentation
      San Antonio, Texas, USA
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膠芽腫に対するbevacizumab治療効果判定におけるPET検査の有用性2016

    • Author(s)
      三宅啓介、河内雅章、小川大輔、岡田真樹、畠山哲宗、四宮あや、岡内正信、新堂 敦、川西正彦、田宮 隆
    • Organizer
      社団法人日本脳神経外科学会第75回学術総会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経膠腫におけるWntβ-catenin を介した(pro) renin receptorの発現と役割2016

    • Author(s)
      河内雅章、柴山弓季、小川大輔、三宅啓介、西山 成、田宮 隆
    • Organizer
      社団法人日本脳神経外科学会第75回学術総会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PET studies findings correlate with multi-drug resistant genens in the human gliomas2016

    • Author(s)
      Tamiya T, Miyake K, Shinomiya A, Okada M, Ogawa D
    • Organizer
      13th Asian Society for Neuro-Oncology (ASNO) Meeting
    • Place of Presentation
      Sydney
    • Year and Date
      2016-09-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glioma cells adapt metabolic stress by regulating mir-451 expression2016

    • Author(s)
      Ogawa D, Matsumoto A, Kochi M, Okada M, Miyake K, Tamiya T, Chiocca EA, Godlewski J
    • Organizer
      13th Asian Society for Neuro-Oncology (ASNO) Meeting
    • Place of Presentation
      Sydney
    • Year and Date
      2016-09-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経膠腫におけるWntβ-catenin を介した(pro) renin receptorの発現と役割2016

    • Author(s)
      河内雅章、柴山弓季、小川大輔、三宅啓介、西山 成、田宮 隆
    • Organizer
      第17回日本分子脳神経外科学会
    • Place of Presentation
      東京
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of multidrug resistant genes in the human glioblastomas2016

    • Author(s)
      Tamiya T, Miyake K, Okada M, Ogawa D
    • Organizer
      21st International Conference on Brain Tumor and Research and Therapy (2016. 4. Okinawa)
    • Place of Presentation
      Okinawa
    • Year and Date
      2016-04-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neutrophil to lymphocyte count ratio in elderly patients with glioblastoma2016

    • Author(s)
      Okada M, Ogawa D, Hatakeyama T, Shinomiya A, Miyake K, Tamiya T.
    • Organizer
      2016 SNO Annual Meeting - Society for Neuro-Oncology
    • Place of Presentation
      San Antonio, Texas, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNAがグリオーマに与える影響のin vivoにおける検討2015

    • Author(s)
      小川大輔 岡田真樹 三宅啓介 田宮 隆
    • Organizer
      第33回日本脳腫瘍学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経膠腫におけるWntβ-catenin を介した(pro) renin receptorの発現と役割2015

    • Author(s)
      河内雅章、柴山弓季、小川大輔、三宅 啓介、西山 成、田宮 隆
    • Organizer
      第33回日本脳腫瘍学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] Response assessment of bevacizumab for malignant gliomas by using 11C-Methionine and 18F-Fluoromisonidazole PET tracers2015

    • Author(s)
      Miyake K, Kouchi M, Ogawa D, Okada M, Hatakeyama T, Shinomiya A, Tamiya T
    • Organizer
      20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      San Antonio, Texas, USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNA Targeting MGMT Prolongs Prognosis with GBM in vivo2015

    • Author(s)
      Ogawa D, Okada M, Miyake M, Tamiya,EA Chiocca, Jakub Godlewski
    • Organizer
      20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      San Antonio, Texas, USA
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNAがグリオーマの遊走能および糖代謝に与える病理学的な影響についての 検討2015

    • Author(s)
      小川大輔、三宅啓介、田宮 隆、EA Chiocca、 Jakub Godlewski
    • Organizer
      第33回日本脳腫瘍病理学会
    • Place of Presentation
      高松
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Usefulness of 11C-methionine positron emission tomography for detection of germinoma in central nervous system2015

    • Author(s)
      Miyake K, Kouchi M, Ogawa D, Okada M, Hatakeyama T, Kawai N, Tamiya T
    • Organizer
      The 4th International CNS Germ Cell Tumor Symposium,
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-04-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PET studies findings correlate with multi-drug resistant genes in the human gliomas2014

    • Author(s)
      Tamiya T, Miyake K, Ogawa D, Okada M, Kawai N
    • Organizer
      2014 CNS annual meeting
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2014-10-20
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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