The cell-to-cell interaction for migration of brain tumor cells by carbon ion irradiation

• Project/Area Number: 15K09988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: Yoshida Yukari 群馬大学, 重粒子線医学推進機構, 助教 (90431717)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脳腫瘍 / 放射線 / 増殖能 / 正常神経細胞 / バイスタンダー効果 / 増殖 / 遊走 / 悪性脳腫瘍 / 神経細胞 / 脳正常細胞 / 重粒子線

Outline of Final Research Achievements

The aim is to clarify molecules target to restrain ability of proliferation and migration. To investigate the molecular mechanism of the bystander effect between normal brain cell/tissue and the brain tumor cells by irradiation, this study was mainly evaluated the ability of proliferation and migration of tumor cells in cell culture medium after irradiation. Normal neuronal cells were made by collecting from hippocampal of mouse and used the period of maturity. The brain tumor cells were used the glioma cell lines.
This study clarified that the glioma cells release factors to increase proliferation and migration of the glioma cells and to induce death of the neuronal cells by X-ray irradiation.

Academic Significance and Societal Importance of the Research Achievements

従来、放射線治療に反応せず照射野外に浸潤あるいは転移した腫瘍に関しては放射線抵抗性として片付けられてきた。しかし、これは現状での認識の限界を示しているにすぎない。放射線照射に伴う”遊走・浸潤”による機序や、これを抑止し阻害するための方策の手掛かりが解明されていないからである。また、放射線によるがん研究の多くが腫瘍細胞のみに着目しており、放射線治療に伴う腫瘍の生物学的効果は周囲の正常細胞／組織が密接にかかわっている可能性があることが考慮されていない。本研究から新たな知見を得ることは、脳腫瘍だけでなく、がんの治療戦略を考える上で非常に重要なものである。

Research Products

• [Journal Article] Space radiation biology for “Living in Space” (2020)
  • Author(s): Furukawa S, Nagamatsu A, Nenoi M, Fujimori A, Kakinuma S, Katsube T, Wang B, Tsuruoka C, Shirai T, Nakamura AJ, Sakaue-Sawano A, Miyawaki A, Harada H, Kobayashi M, Kobayashi J, Kunieda T, Funayama T, Suzuki M, Miyamoto T, Hidema J, Yoshida Y, Takahashi A.
  • Journal Title: BioMed Res Int. Volume: 2020 Issue: 1 Pages: 4703286-4703286
  • DOI: 10.1155/2020/4703286
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression Profile of Cell Cycle-Related Genes in Human Fibroblasts Exposed Simultaneously to Radiation and Simulated Microgravity (2019)
  • Author(s): Ikeda Hiroko、Muratani Masafumi、Hidema Jun、Hada Megumi、Fujiwara Keigi、Souda Hikaru、Yoshida Yukari、Takahashi Akihisa
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 19 Pages: 4791-4791
  • DOI: 10.3390/ijms20194791
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased Chromosome Aberrations in Cells Exposed Simultaneously to Simulated Microgravity and Radiation. (2018)
  • Author(s): Hada M, Ikeda H, Rhone JR, Beitman AJ, Plante I, Souda H, Yoshida Y, Held KD, Fujiwara K, Saganti PB, Takahashi A.
  • Journal Title: Int J Mol Sci. Volume: 20 Issue: 1 Pages: 43-43
  • DOI: 10.3390/ijms20010043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Temporary Loading Prevents Cancer Progression and Immune Organ Atrophy Induced by Hind-Limb Unloading in Mice. (2018)
  • Author(s): Takahashi A, Wakihata S, Ma L, Adachi T, Hirose H, Yoshida Y, Ohira Y.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 12 Pages: 3959-3959
  • DOI: 10.3390/ijms19123959
  • Peer Reviewed / Open Access
• [Journal Article] X-ray irradiation induces disruption of the blood-brain barrier with localized changes in claudin-5 and activation of microglia in the mouse brain. (2018)
  • Author(s): Yoshida Y, Sejimo Y, Kurachi M, Ishizaki Y, Nakano T, Takahashi A.
  • Journal Title: Neurochem Int. Volume: 印刷中 Pages: 199-206
  • DOI: 10.1016/j.neuint.2018.03.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Space radiobiology applicable to high-LET radiobiology for charged-particle therapy (2018)
  • Author(s): Akihisa Takahashi, Hiroko Ikeda, Yukari Yoshida
  • Journal Title: International Journal of Particle Therapy Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Development and performance evaluation of a three-dimensional clinostat synchronized heavy-ion irradiation system (2017)
  • Author(s): Ikeda H, Hidema J and Takahashi A et al.
  • Journal Title: Life Sci Space Res Volume: 12 Pages: 51-60
  • DOI: 10.1016/j.lssr.2017.01.003
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells. (2017)
  • Author(s): Park SJ, Heo K, Choi CW, Yang K, Adachi A, Okada H, Yoshida Y, Ohno T, Nakano T, Takahashi A
  • Journal Title: J Radiat Res. Volume: 印刷中 Issue: 6 Pages: 765-771
  • DOI: 10.1093/jrr/rrx022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin (2017)
  • Author(s): Kobayashi D, Oike T, Shibata A, Niimi A, Kubota Y, Sakai M, Amornwhichet N, Yoshimoto Y, Hagiwara Y, Kimura Y, Hirota Y, Sato H, Isono M, Yoshida Y, Kohno T, Ohno T, Nakano T
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 40588-40588
  • DOI: 10.1038/srep40588
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation (2017)
  • Author(s): Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano, Atsushi Shibata
  • Journal Title: Cell Reports Volume: 18 Issue: 2 Pages: 520-532
  • DOI: 10.1016/j.celrep.2016.12.042
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of charged particles on human tumor cells (2016)
  • Author(s): Kathryn D. Held, Kawamura H, Kaminuma T, Athena Evalour S. Paz, Yoshida Y, Willers H, Takahashi A
  • Journal Title: Frontiers in Oncology Volume: 23 Pages: 1-19
  • DOI: 10.3389/fonc.2016.00023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775. (2015)
  • Author(s): Ma H, Takahashi A, Sejimo Y, Adachi A, Kubo N, Isono M, Yoshida Y, Kanai T, Ohno T, Nakano T.
  • Journal Title: Radiat Res Volume: 184 Issue: 6 Pages: 660-669
  • DOI: 10.1667/rr14171.1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells. (2015)
  • Author(s): Ma H, Takahashi A, Yoshida Y, Adachi A, Kanai T, Ohno T, Nakano T.
  • Journal Title: Radiat Oncol Volume: 10 Issue: 1 Pages: 225-225
  • DOI: 10.1186/s13014-015-0536-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using the tumor growth delay and crypt survival assays. (2015)
  • Author(s): Yoshida Y, Ando K, Ando K, Murata K, Yoshimoto Y, Musha A, Kubo N, Kawamura H, Koike S, Uzawa A, Takahashi T, Ohno T, Nakano T.
  • Journal Title: Radiother Oncol. Volume: 117 Issue: 2 Pages: 315-317
  • DOI: 10.1016/j.radonc.2015.09.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Oxygen-glucose deprivation increases firing of unipolar brush cells and enhances spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum. (2015)
  • Author(s): Takayasu Y, Shino M, Nikkuni O, Yoshida Y, Furuya N, Chikamatsu K.
  • Journal Title: Neurosci Res Volume: 106 Pages: 1-11
  • DOI: 10.1016/j.neures.2015.10.009
  • Peer Reviewed
• [Journal Article] Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells. (2015)
  • Author(s): Isono M, Yoshida Y, Takahashi A, Oike T, Shibata A, Kubota Y, Kanai T, Ohno T, Nakano T.
  • Journal Title: J Radiat Res. Volume: 56 Issue: 5 Pages: 856-861
  • DOI: 10.1093/jrr/rrv033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells. (2015)
  • Author(s): Amornwichet N, Oike T, Shibata A, Nirodi CS, Ogiwara H, Makino H, Kimura Y, Hirota Y, Isono M, Yoshida Y, Ohno T, Kohno T, Nakano T.
  • Journal Title: Sci Rep. Volume: 11 Issue: 1 Pages: 11305-11305
  • DOI: 10.1038/srep11305
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] マウス悪性黒色腫移植モデルを用いたX線および炭素イオン線照射の局所制御効果とサイトカイン発現量との関連 (2020)
  • Author(s): 吉田由香里、脇畑庄人、石川仁、高橋昭久、櫻井英幸
  • Organizer: 第22回癌治療増感シンポジウム
  • Int'l Joint Research
• [Presentation] 低酸素環境下における温熱感受性とDNA二本鎖切断生成 (2019)
  • Author(s): 吉田由香里、富永信太朗、髙橋昭久
  • Organizer: 日本ハイパーサーミア学会第36回大会
• [Presentation] 放射線による脳障害の機序に関する研究 (2019)
  • Author(s): 吉田由香里
  • Organizer: 日本放射線影響学会第62回大会
  • Invited
• [Presentation] 宇宙環境を模擬した放射線と無重力による脳障害およびその回復機構の解析 (2019)
  • Author(s): 吉田由香里, Espinosa-Jeffrey Araceli, Fernandez-Quezada David, Luquin de Anda Sonia, 髙橋昭久
  • Organizer: 日本宇宙生物科学会第33回大会
• [Presentation] 低酸素環境下における温熱誘導DNA二本鎖切断の生成 (2018)
  • Author(s): 吉田由香里, 富永信太朗, 高橋昭久
  • Organizer: 第22回関東ハイパーサーミア研究会・全身ハイパーサーミア研究会合同学術研究会
• [Presentation] 重粒子線による正常皮膚障害の予測計算法の評価 (2018)
  • Author(s): 吉田由香里, 山口舞花, 安藤興一, 高橋昭久, 金井達明
  • Organizer: 第56回生物部会学術大会
• [Presentation] X-ray irradiation induces disruption of the blood brain barrier with localized changes in claudin-5 and activation of microglia in the mouse brain (2018)
  • Author(s): Yukari Yoshida, Yukihiko Sejimo, Masashi Kurachi, Yasuki Ishizaki, Takashi Nakano, Akihisa Takahashi
  • Organizer: 第8回国際放射線神経生物科学会
  • Int'l Joint Research
• [Presentation] Relation between LET dependency and NHEJ repair in cell survival parameter (2017)
  • Author(s): Yoshida Y, Takahashi A, Ando K, Yakoh T, Nakano T
  • Organizer: The 7th International Society of Radiation Neurobiology Conference
  • Place of Presentation: 湯沢
  • Year and Date: 2017-02-09
  • Int'l Joint Research
• [Presentation] マウス悪性黒色腫に対するＸ線照射の局所制御効果とサイトカイン発現量との関連 (2017)
  • Author(s): 吉田由香里、石川仁、高橋昭久、櫻井英幸、中野隆史
  • Organizer: 第19回癌治療増感シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2017-02-03
• [Presentation] 放射線が正常脳に及ぼす影響についての研究 (2017)
  • Author(s): 吉田 由香里, Anggraeni Puspitasari, 池田 裕子, 中野 隆史, 高橋 昭久
  • Organizer: 日本宇宙生物科学会第31回大会
• [Presentation] 吉田由香里，瀬下幸彦，倉知正，石崎泰樹，中野隆史，高橋昭久 (2017)
  • Author(s): 正常脳組織における放射線急性障害の解析
  • Organizer: 第55回日本放射線腫瘍学会生物部会学術大会
• [Presentation] Evaluation of survival curve for solid tumor cells after large doses of Carbon ion beams (2017)
  • Author(s): Yukari Yoshida, Koichi Ando, Sachiko Koike, Tomoko Yako, Hiroko Ikeda, Akiko Uzawa, Akihisa Takahashi, Tatsuaki Kanai, Takashi Nakano
  • Organizer: PTCOG56
  • Int'l Joint Research
• [Presentation] 正常組織における重粒子線の影響 (2017)
  • Author(s): 吉田由香里、山口舞花、安藤興一、八高知子、金井達明、中野隆史、高橋昭久
  • Organizer: 日本放射線影響学会第60回大会
• [Presentation] Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using a mouse model (2017)
  • Author(s): Yukari Yoshida, Koichi Ando, Sachiko Koike, Akiko Uzawa, Akihisa Takahashi, Tatsuya Ohno, Takashi Nakano
  • Organizer: ISSRPRT2017 meeting
  • Int'l Joint Research
• [Presentation] 炭素線分割照射治療におけるマウスモデルを用いた治療効果比の評価 (2016)
  • Author(s): 吉田由香里
  • Organizer: JASTRO第29会学術大会
  • Place of Presentation: 京都
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] 小脳培養切片を用いた正常脳の発達に及ぼす重粒子線の影響解析について (2016)
  • Author(s): 吉田由香里、舟山知夫、中野隆史、高橋昭久
  • Organizer: 日本宇宙生物科学会第30回大会
  • Place of Presentation: 愛知
  • Year and Date: 2016-10-13
• [Presentation] 炭素イオン線がん治療の分割照射における治療効果比の基礎的検討 (2016)
  • Author(s): 吉田由香里、安藤興一、小池幸子、鵜澤玲子、池田裕子、八高知子、高橋昭久、金井達明、中野隆史
  • Organizer: 第54会生物部会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-16
• [Presentation] 細胞生存パラメータのＬＥＴ依存性とNHEJ修復との関係 (2016)
  • Author(s): 吉田由香里、高橋昭久、安藤興一、八高知子、舟山知夫、中野隆史
  • Organizer: 第22回がん治療増感研究会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-07-02
• [Presentation] 放射線が正常脳に及ぼす影響についての研究動向 (2016)
  • Author(s): 吉田由香里
  • Organizer: 新学術領域研究「宇宙に生きる」２０１６ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2016-03-09
• [Presentation] 放射線脳壊死の生物学的研究の現状 (2015)
  • Author(s): 吉田由香里
  • Organizer: 伊香保BSの会 第4回多分野交流会～今再びの伊香保～
  • Place of Presentation: 群馬
  • Year and Date: 2015-07-14
• [Presentation] Evaluation of survival curves for solid tumor cells after large doses of carbon ion beams and X-rays (2015)
  • Author(s): Yukari Yoshida, Koichi Ando, Sachiko Koike, Tomoko Yako, Hiroko Ikeda, Akiko Uzawa, Tomoki Matsumoto, Mayu Isono, Tatsuaki Kanai, Takashi Nakano
  • Organizer: ICRR2015
  • Place of Presentation: 京都
  • Year and Date: 2015-05-28
  • Int'l Joint Research
• [Book] 生体の科学 (2018)
  • Author(s): 高橋昭久, 池田裕子, 吉田由香里
  • Total Pages: 5
  • Publisher: 公益財団法人金原一郎医学医療振興財団
• [Book] やさしくわかる放射線治療学 (2018)
  • Author(s): 筆頭著者 公益社団法人日本放射線腫瘍学会 (監修)
  • Total Pages: 4
  • Publisher: 学研メディカル秀潤社
  • ISBN: 9784059172239
• [Remarks] 群馬大学重粒子線医学研究センター
  • URL: http://heavy-ion.showa.gunma-u.ac.jp/
• [Remarks] 群馬大学重粒子線医学研究センター大学院重粒子線医学物理・生物学コース
  • URL: http://heavy-ion.showa.gunma-u.ac.jp/lab/