Epigenomic analysis with reprogramming technology in lower grade glioma

• Project/Area Number: 16K10754
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyoto 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: ¥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。

Research Products

• [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
  • Peer Reviewed / Open Access
• [Journal Article] Radiation-induced cystic brain necrosis developing 10 years after linac-based stereotactic radiosurgery for brain metastasis (2018)
  • 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
  • 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 Imaging (2018)
  • 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
  • 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 Trial (2018)
  • Author(s): Kayama Takamasa、Sato Shinya、Sakurada Kaori、et al
  • Journal Title: Journal of Clinical Oncology Volume: 36 Issue: 33 Pages: 3282-3289
  • DOI: 10.1200/jco.2018.78.6186
  • 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 lymphocytes (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] High-dose chemotherapy with autologous stem cell transplantation spares re-irradiation for recurrent intracranial germinoma (2018)
  • 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
  • Peer Reviewed
• [Journal Article] Sudden spinal hemorrhage in a pediatric case with total body irradiation-induced cavernous hemangioma (2018)
  • 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
  • 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 preservation (2018)
  • 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
  • Peer Reviewed
• [Journal Article] <i>B</i>₁ Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain (2018)
  • 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
  • Peer Reviewed
• [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack (2017)
  • 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
  • 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 medulloblastoma (2017)
  • 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
  • Peer Reviewed
• [Journal Article] RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6 (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway (2017)
  • 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
  • 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 tumors (2017)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group (2017)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images (2016)
  • 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
  • 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
  • Peer Reviewed
• [Presentation] HMGA2 is a prognostic factor to induce malignant phenotype in medulloblastoma (2018)
  • 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)
  • 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
  • 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
  • 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
• [Presentation] Future perspectives of endoscopic surgery for intraparenchymal brain tumors (2018)
  • 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
• [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
• [Presentation] Indication of endoscopic surgery with advanced technology for intraparenchymal and ventricular tumors (2017)
  • 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
• [Presentation] Analysis of immune checkpoint regulation in intracranial germinoma (2017)
  • 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
• [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
• [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
• [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 technique (2017)
  • 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
• [Presentation] Hypofractionated stereotactic radiotherapy plus concomitant and adjuvant temozolomide for elderly glioblastoma (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Analysis of pediatric cerebellar ganglioglioma (2016)
  • 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
• [Presentation] Clinical Significance of PD-L1 and CD8 Expression in Human Medulloblastoma (2016)
  • 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
  • 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
  • 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
  • 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
• [Remarks] 京都大学脳神経外科
  • URL: http://neurosur.kuhp.kyoto-u.ac.jp/