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Epigenomic analysis with reprogramming technology in lower grade glioma

Research Project

Project/Area Number 16K10754
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKyoto University

Principal Investigator

Arakawa Yoshiki  京都大学, 医学研究科, 特定講師 (20378649)

Co-Investigator(Kenkyū-buntansha) Thumkeo Dean  京都大学, 医学研究科, 特定准教授 (40372594)
平田 英周  金沢大学, がん進展制御研究所, 准教授 (40761937)
Co-Investigator(Renkei-kenkyūsha) Yamada Yasuhiro  京都大学, iPS細胞研究所, 教授 (70313872)
Research Collaborator Liu Bin  
Fukui Nobuyuki  
Terada Yukinori  
Matsui Yasuzumi  
Makino Yasuhide  
Sumiyoshi Sosuke  
Hattori Etsuko  
Yokogawa Ryuta  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords低悪性度グリオーマ / ダイレクトリプログラミング / エピゲノム異常 / 分化誘導 / 脳腫瘍 / グリオーマ / エピゲノム / iPS / リプログラミング
Outline of Final Research Achievements

Although cell lines and spheroid colony lines were established from glioma surgical specimens containing tumor stem cells, cell lines with IDH1R132H could not be established. Introduction of IDH1R132H into human induced pluripotent stem (iPS) cells and neural stem cells derived from iPS cells impaired those cell proliferation. These results suggest that the IDH1R132H impairs cell survival and proliferation, which is a kind of senescence. Although the culture of cells with IDH1R132H were carried out under conditions using various drugs, difficulty of cell growth was identified. Taken together, we confirmed that it was impossible to establish iPS-derived neural stem cells with IDH1R132H expression.

Academic Significance and Societal Importance of the Research Achievements

グリオーマは、未だ根治は困難な疾患である。低悪性度グリオーマの多くは、IDH1/2遺伝子変異が初期の遺伝子異常である。本研究では、IDH1遺伝子変異に伴う腫瘍発生の生物学的意義解明を目指した。その結果、IDH1遺伝子変異伴う細胞老化に似たような現象が神経幹細胞に生じることが、腫瘍発生に関わることを示唆した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (37 results)

All 2018 2017 2016 Other

All Journal Article (19 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 19 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.2018

    • Author(s)
      Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, Kobayashi H, Fujimaki T, Goto H, Takeshima H, Ueba T, Abe H, Tamiya T, Sonoda Y, Natsume A, Kakuma T, Sugita Y, Komatsu N, Yamada A, Sasada T, Matsueda S, Shichijo S, Itoh K, Terasaki M.
    • Journal Title

      Neuro Oncol.

      Volume: 21 Issue: 3 Pages: 348-359

    • DOI

      10.1093/neuonc/noy200

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-induced cystic brain necrosis developing 10 years after linac-based stereotactic radiosurgery for brain metastasis2018

    • Author(s)
      Aizawa Rihito、Uto Megumi、Takehana Keiichi、Arakawa Yoshiki、Miyamoto Susumu、Mizowaki Takashi
    • Journal Title

      Oxford Medical Case Reports

      Volume: 2018 Issue: 11 Pages: 387-390

    • DOI

      10.1093/omcr/omy090

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Diagnosis between Low-Grade and High-Grade Astrocytoma Using System A Amino Acid Transport PET Imaging with C-11-MeAIB: A Comparison Study with C-11-Methionine PET Imaging2018

    • Author(s)
      Nishii Ryuichi、Higashi Tatsuya、Kagawa Shinya、Arimoto Maya、Kishibe Yoshihiko、Takahashi Masaaki、Yamada Shigeki、Saiki Masaaki、Arakawa Yoshiki、Yamauchi Hiroshi、Okuyama Chio、Hojo Masato、Munemitsu Toshihiro、Sawada Masahiro、Kobayashi Masato、Kawai Keiichi、Nagamachi Shigeki、Hirai Toshinori、Miyamoto Susumu
    • Journal Title

      Contrast Media & Molecular Imaging

      Volume: 2018 Pages: 1-9

    • DOI

      10.1155/2018/1292746

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of surgery with salvage stereotactic radiosurgery versus surgery with whole-brain radiation therapy in patients with one to four brain metastases (JCOG0504): A Phase III, noninferiority, randomized controlled trial2018

    • Author(s)
      Kayama Takamasa、Sato Shinya、Sakurada Kaori、et al
    • Journal Title

      Journal of Clinical Oncology

      Volume: 36 Issue: 33 Pages: 3282

    • DOI

      10.1200/jco.2018.78.6186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes2018

    • Author(s)
      Liu Bin、Arakawa Yoshiki、Yokogawa Ryuta、Tokunaga Shinya、Terada Yukinori、Murata Daiki、Matsui Yasuzumi、Fujimoto Ko-ichi、Fukui Nobuyuki、Tanji Masahiro、Mineharu Yohei、Minamiguchi Sachiko、Miyamoto Susumu
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 4 Pages: 1-17

    • DOI

      10.1371/journal.pone.0194594

    • NAID

      120006463746

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-dose chemotherapy with autologous stem cell transplantation spares re-irradiation for recurrent intracranial germinoma2018

    • Author(s)
      Kubota Hirohito、Umeda Katsutsugu、Kagehiro Kouzuki、Tanaka Kuniaki、Daifu Tomoo、Hamabata Takayuki、Nodomi Seishiro、Kato Itaru、Hiramatsu Hidefumi、Arakawa Yoshiki、Mizowaki Takashi、Adachi Souichi
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 65 Issue: 8

    • DOI

      10.1002/pbc.27104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sudden spinal hemorrhage in a pediatric case with total body irradiation-induced cavernous hemangioma2018

    • Author(s)
      Mikami T, Kato I, Nozaki F, Umeda K, Kamitori T, Tasaka K, Ogata H, Hiramatsu H, Arakawa Y, Adachi S
    • Journal Title

      Pediatr Blood Cancer.

      Volume: 65 Issue: 10

    • DOI

      10.1002/pbc.27250

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation2018

    • Author(s)
      Chen Zhiping、Takehana Keiichi、Mizowaki Takashi、Uto Megumi、Ogura Kengo、Sakanaka Katsuyuki、Arakawa Yoshiki、Mineharu Yohei、Miyabe Yuki、Mukumoto Nobutaka、Miyamoto Susumu、Hiraoka Masahiro
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 23 Issue: 4 Pages: 608-614

    • DOI

      10.1007/s10147-018-1267-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>B</i><sub>1</sub> Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain2018

    • Author(s)
      7.Yuki Kanazawa, Yasutaka Fushimi, Naotaka Sakashita, Tomohisa Okada, Yoshiki Arakawa, Mitsue Miyazaki
    • Journal Title

      Magnetic Resonance in Medical Sciences

      Volume: 17 Issue: 1 Pages: 86-94

    • DOI

      10.2463/mrms.tn.2016-0069

    • NAID

      130006306801

    • ISSN
      1347-3182, 1880-2206
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack2017

    • Author(s)
      Yoshida Y, Wang H, Hiwasa T, Machida T, Takiguchi M, Iwadate Y, et al.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 3 Pages: 8836-8848

    • DOI

      10.1007/s11060-018-2831-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High PD-L1 expression associated with CD8+ T cell infiltration and poor prognosis in human medulloblastoma2017

    • Author(s)
      9.Daiki Murata, Yohei Mineharu, Yoshiki Arakawa, Bin Liu, Masahiro Tanji, Makoto Yamaguchi, Ko-ichi Fujimoto, Nobuyuki Fukui, Yukinori Terada, Ryuta Yokogawa, Maki Yamaguchi, Sachiko Minamiguchi, Susumu Miyamoto
    • Journal Title

      Journal of Neurosurgery

      Volume: 128 Issue: 3 Pages: 710-716

    • DOI

      10.3171/2016.11.jns16991

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK62017

    • Author(s)
      8.Charlotte H. Durkin1, Flavia Leite, Jo&atilde;o V. Cordeiro, Yutaka Handa, Yoshiki Arakawa, Ferran Valderrama, Michael Way
    • Journal Title

      Developmental Cell

      Volume: 41 Issue: 3 Pages: 315-329

    • DOI

      10.1016/j.devcel.2017.04.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway2017

    • Author(s)
      Yamao Y, Suzuki K, Kunieda T, Matsumoto R, Arakawa Y, Nakae T, Nishida S, Inano R, Shibata S, Shimotake A, Kikuchi, T, Sawamoto N, Mikuni N, Ikeda A, Fukuyama H, Miyamoto S
    • Journal Title

      Human Brain Mapping

      Volume: 38 (4) Issue: 4 Pages: 1977-1991

    • DOI

      10.1002/hbm.23498

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Diagnostic performance between contrast enhancement, proton MR spectroscopy, and amide proton transfer imaging in patients with brain tumors2017

    • Author(s)
      Sakata Akihiko、Fushimi Yasutaka、Okada Tomohisa、Arakawa Yoshiki、Kunieda Takeharu、Minamiguchi Sachiko、Kido Aki、Sakashita Naotaka、Miyamoto Susumu、Togashi Kaori
    • Journal Title

      Journal of Magnetic Resonance Imaging

      Volume: 46 Issue: 3 Pages: 732-739

    • DOI

      10.1002/jmri.25597

    • NAID

      120006731149

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials.2017

    • Author(s)
      Edward K. Avila, Marc Chamberlain, David Schiff, Jaap C. Reijneveld, Terri S. Armstrong, Roberta Ruda, Patrick Y. Wen, Michael Weller, Johan A. F. Koekkoek, Sandeep Mittal, Yoshiki Arakawa
    • Journal Title

      Neuro Oncology

      Volume: 19 Issue: 1 Pages: 12-21

    • DOI

      10.1093/neuonc/now190

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group2017

    • Author(s)
      Tomokazu Aoki, Yoshiki Arakawa Tetsuya Ueba, Masashi Oda, Namiko Nishida, Yukinori Akiyama, Tetsuya Tsukahara Koichi Iwasaki, Nobuhiro Mikuni, Susumu Miyamoto.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 57 Issue: 1 Pages: 17-27

    • DOI

      10.2176/nmc.oa.2016-0162

    • NAID

      130005290679

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological, Radiological, and Genetic Analyses of Cerebellar Gangliogliomas with Long-Term Survival.2016

    • Author(s)
      7.Bin Liu, Yoshiki Arakawa, Daiki Murata, Yohei Mineharu, Ryuta Yokogawa, Masahiro Tanji, Ko-ichi Fujimoto, Nobuyuki Fukui, Yukinori Terada, Susumu Miyamoto.
    • Journal Title

      World Neurosurgery

      Volume: 94 Pages: 521-528

    • DOI

      10.1016/j.wneu.2016.07.051

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images2016

    • Author(s)
      Inano R, Oishi N, Kunieda T, Arakawa Y, Kikuchi T, Fukuyama H, Miyamoto S.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 30344-30344

    • DOI

      10.1038/srep30344

    • NAID

      120005825907

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feasibility evaluation of hypofractionated radiotherapy with concurrent temozolomide in elderly patients with glioblastoma.2016

    • Author(s)
      8.Megumi Uto, Takashi Mizowaki, Kengo Ogura, Yoshiki Arakawa, Yohei Mineharu, Susumu Miyamoto, Masahiro Hiraoka.
    • Journal Title

      International Journal of Clinical Oncology.

      Volume: 21 Issue: 6 Pages: 1023-1029

    • DOI

      10.1007/s10147-016-1014-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] HMGA2 is a prognostic factor to induce malignant phenotype in medulloblastoma2018

    • Author(s)
      Yoshiki Arakawa, Bin Liu, Yukinori Terada, Yasuzumi Matsui, Etsuko Hattori, Sosuke Sumiyoshi, Nobuyuki Fukui, Masahiro Tanji, Yohei Mineharu, Susumu Miyamoto.
    • Organizer
      2018 International Symposium on Pediatric Neuro-Oncology (ISPNO)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High mobility group AT-hook 2 (HMGA2) is a prognostic factor associated with malignant phenotype in medulloblastomas.2018

    • Author(s)
      Yoshiki Arakawa, Bin Liu, Masahiro Tanji, Yohei Mineharu, Susumu Miyamoto.
    • Organizer
      23th ANNUAL SCIENTIFIC MEETING AND EDUCATION DAY OF THE SOCIETY FOR NEURO-ONCOLOGY
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Coagulating suction technique for endoscopic surgery in brain tumors.2018

    • Author(s)
      Yoshiki Arakawa
    • Organizer
      The 11th Kyoto-Seoul-Taipei Neurosurgical meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳室内・脳室近傍腫瘍に対する内視鏡手術の治療成績と今後の課題2018

    • Author(s)
      荒川芳輝 姜裕 安田崇之 山尾幸広 丹治正大 峰晴陽平 菊池隆幸 片岡大治 吉田和道 宮本享
    • Organizer
      日本脳神経外科学会 第77回学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Future perspectives of endoscopic surgery for intraparenchymal brain tumors2018

    • Author(s)
      Yoshiki Arakawa, Takayuki Yasuda, Yuhikiro Yamao, Masaharu Tanji, Yohei Mineharu, Hiroharu Kataoka, Kazumichi Yoshida, Susumu Miyamoto
    • Organizer
      The 36th Annual Meeting of the Japan Society for Neuro-Oncology
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膠芽腫に対する治療の現状から今後の展望を考える2018

    • Author(s)
      荒川芳輝 安田崇之 山尾幸広 丹治正大 峰晴陽平 菊池隆幸 片岡大治 吉田和道 宮本享
    • Organizer
      第23回日本脳腫瘍の外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Indication of endoscopic surgery with advanced technology for intraparenchymal and ventricular tumors2017

    • Author(s)
      Yoshiki Arakawa, Yoo Kang, Masaharu Tanji, Yohei Mineharu, Kazumichi Yoshida, Yasuhi Takagi, Susumu Miyamoto
    • Organizer
      The 76th Annual Meeting of the Japan Neurosurgical Society
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of immune checkpoint regulation in intracranial germinoma2017

    • Author(s)
      Yoshiki Arakawa, Bin Liu, Yohei Mineharu, Masahiro Tanji, Ryuta Yokogawa, Daiki Murata, Ko-ichi Fujimoto, Nobuyuki Fukui, Yukinori Terada, Susumu Miyamoto
    • Organizer
      第35回日本脳腫瘍病理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頭蓋内胚細胞腫におけるPD-1発現とFoxp3+ 、CD8+陽性リンパ球浸潤の解析2017

    • Author(s)
      荒川芳輝、劉濱、峰晴陽平、丹治正大、寺田行範、服部悦子、松井恭澄、福井伸行、南口早智子、宮本享
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Super high vision system の時代は脳腫瘍手術戦略を変えるのか?2017

    • Author(s)
      荒川芳輝 坂井かをり 川島鉄司 増田裕康 丹治正大 峰晴陽平 菊地隆幸 吉田和道
    • Organizer
      第22回日本脳腫瘍の外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 内視鏡下脳腫瘍摘出に適した凝固吸引管の開発とcoagulating suction technique2017

    • Author(s)
      荒川芳輝 姜裕 丹治正大 峰晴陽平 吉田和道 高木康志 宮本享
    • Organizer
      第24回日本神経内視鏡学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Hypofractionated stereotactic radiotherapy plus concomitant and adjuvant temozolomide for elderly glioblastoma2016

    • Author(s)
      Yoshiki Arakawa, Takashi Mizowaki, Yohei Mineharu, Masaharu Tanji, Megumi Uto, Yasushi Takagi, Susumu Miyamoto
    • Organizer
      13th Asian Society for Neuro-Oncology (ASNO) Meeting / 9th COGNO Annual Scientific Meeting
    • Place of Presentation
      Sydney Australia
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of pediatric cerebellar ganglioglioma2016

    • Author(s)
      Yoshiki Arakawa, Bin Liu, Daiki Murata, Yohei Mineharu, Ryuta Yokogawa, Masahiro Tanji, Ko-ichi Fujimoto, Bin Liu, Nobuyuki Fukui, Yukinori Terada, Susumu Miyamoto
    • Organizer
      The 17th International Symposium on Pediatric Neuro-Oncology
    • Place of Presentation
      Liverpool, UK
    • Year and Date
      2016-06-12
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinical Significance of PD-L1 and CD8 Expression in Human Medulloblastoma2016

    • Author(s)
      Yoshiki Arakawa, Daiki Murata, Yohei Mineharu, Masahiro Tanji, Ko-ichi Fujimoto, Bin Liu, Nobuyuki Fukui, Yukinori Terada, Susumu Miyamoto
    • Organizer
      21st International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Okinawa, Japan
    • Year and Date
      2016-04-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] グリオーマに対する外科治療から化学療法2016

    • Author(s)
      荒川芳輝
    • Organizer
      JCRミッドサマーセミナー2016
    • Place of Presentation
      神戸
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] グリオーマ手術の基本と注意点2016

    • Author(s)
      荒川芳輝
    • Organizer
      第36回日本脳神経外科コングレス総会
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 京都大学 教育研究活動データベース

    • URL

      https://kyouindb.iimc.kyoto-u.ac.jp/j/eI4qW

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学脳神経外科

    • URL

      http://neurosur.kuhp.kyoto-u.ac.jp/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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