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がん重粒子線治療の高度化と治療個別化の為の基礎的・臨床的研究

Research Project

Project/Area Number 16H05388
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionGunma University

Principal Investigator

中野 隆史  群馬大学, その他部局等, 特別教授 (20211427)

Co-Investigator(Kenkyū-buntansha) 白井 克幸  自治医科大学, 医学部, 教授 (10400748)
岡本 雅彦  群馬大学, 医学部附属病院, 講師 (10451725)
田巻 倫明  福島県立医科大学, 医学部, 准教授 (20400749)
柴田 淳史  群馬大学, 大学院医学系研究科, 助教 (30707633)
若月 優  自治医科大学, 医学部, 教授 (40399449)
鈴木 義行  福島県立医科大学, 医学部, 教授 (60334116)
野田 真永  埼玉医科大学, 医学部, 教授 (60396645)
齋藤 淳一  富山大学, 大学院医学薬学研究部(医学), 教授 (70572816)
河村 英将  群馬大学, 大学院医学系研究科, 准教授 (80431716)
鳥飼 幸太  群馬大学, 医学部附属病院, 准教授 (90443077)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Granted (Fiscal Year 2019)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords重粒子線 / 放射線治療 / 放射線生物学 / 粒子線治療 / 放射線治療学
Outline of Annual Research Achievements

最先端のがん治療方法である重粒子線治療をさらに発展させるための研究をおこなった。
臨床的研究として、局所進行悪性骨および軟部組織腫瘍に対する炭素イオン放射線療法(CIRT)における重要なリスク臓器である、皮膚に与える影響を解析した。CIRT後の急性皮膚反応の重症度と皮膚線量パラメーターとの相関関係を評価したところ、皮膚炎グレードと最大線量(Dmax)、線源標的腫瘍間距離(STD)、および40Gy(RBE)が照射された面積(S40)が、急性期皮膚反応の予測因子であることを明らかにした。
また、免疫チェックポイント阻害剤との併用を目指した研究として、放射線照射により誘導される、腫瘍細胞のPD-L1発現メカニズムの解明を目指した研究をおこなった。X線照射により生じるDNA二本鎖切断から、DNA損傷シグナルを介してPD-L1が発現すること、また、DNA二本鎖切断修復において重要であるKu80およびBRCA2のノックダウン細胞では、放射線照射後のPD-L1発現誘導が亢進することを明らかにした。発現誘導には、DNA損傷シグナルであるChk1の活性化が重要であった。さらに、PD-L1発現経路として従来知られていたSTAT-IRF1シグナル経路も、放射線照射後に誘導されていることも明らかにした。DNA損傷を誘導する化学療法剤処理でも同様に、DNA損傷シグナルおよび DNA修復関連タンパクが、腫瘍細胞のPD-L1発現誘導に関与することを明らかにした。この成果は、Nature Communicationに発表した。
これらの研究結果は、放射線治療や化学療法といったDNA損傷を誘発することで抗腫瘍効果を得るがん治療法と、PD-1/PD-L1阻害治療の併用による増感効果の可能性を示唆し、さらに、併用治療が推奨されるべき患者を抽出するための先行指標研究にも貢献できると考える。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初予定していた研究実施計画のから、進行状況に応じて一部に変更を加えながら研究を遂行している。当初の計画から見て概ね順調に進展したと判断する。

Strategy for Future Research Activity

引き続き、重粒子線治療のさらなる発展を目指した研究を継続する。具体的には、化学療法剤、分子標的薬、抗腫瘍免疫治療等との併用による集学的重粒子線治療の研究、さらなる高精度治療方法の確立、Precision Medicineの時代における、重粒子線治療が推奨されるべき患者の個別化を目指した研究をおこなう予定である。

Report

(3 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report

Research Products

(41 results)

All 2019 2018 2017 2016

All Journal Article Presentation Book

  • [Journal Article] In vivo simultaneous imaging with 99mTc and 18F using a Compton camera2018

    • Author(s)
      Sakai Makoto、Yamaguchi Mitsutaka、Nagao Yuto、Kawachi Naoki、Kikuchi Mikiko、Torikai Kota、Kamiya Tomihiro、Takeda Shin’ichiro、Watanabe Shin、Takahashi Tadayuki、Arakawa Kazuo、Nakano Takashi
    • Journal Title

      Phys Med Biol

      Volume: 63 Pages: 205006-205006

    • DOI

      10.1088/1361-6560/aae1d1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis2018

    • Author(s)
      Okonogi N, Fukahori M, Wakatsuki M, Ohkubo Y, Kato S, Miyasaka Y, Tsuji H, Nakano T, Kamada T
    • Journal Title

      Radiat Oncol

      Volume: 13(1) Pages: 119-119

    • DOI

      10.1186/s13014-018-1061-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High linear energy transfer carbon-ion irradiation increases the release of the immune mediator high mobility group box 1 from human cancer cells2018

    • Author(s)
      Onishi Masahiro、Okonogi Noriyuki、Oike Takahiro、Yoshimoto Yuya、Sato Hiro、Suzuki Yoshiyuki、Kamada Tadashi、Nakano Takashi
    • Journal Title

      J Radiat Res

      Volume: 59 Pages: 1093-1093

    • DOI

      10.1093/jrr/rry049

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells.2017

    • Author(s)
      Sato Hiro、Niimi Atsuko、Yasuhara Takaaki、Permata Tiara Bunga Mayang、Hagiwara Yoshihiko、Isono Mayu、Nuryadi Endang、Sekine Ryota、Oike Takahiro、Kakoti Sangeeta、Yoshimoto Yuya、Held Kathryn D.、Suzuki Yoshiyuki、Kono Koji、Miyagawa Kiyoshi、Nakano Takashi、Shibata Atsushi
    • Journal Title

      Nat Commun

      Volume: 8 Pages: 1751-1751

    • DOI

      10.1038/s41467-017-01883-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Predictive factors of acute skin reactions to carbon ion radiotherapy for the treatment of malignant bone and soft tissue tumors2017

    • Author(s)
      Takakusagi Y, Saitoh JI, Kiyohara H, Oike T, Noda SE, Ohno T, Nakano T
    • Journal Title

      Radiat Oncol

      Volume: 12(1) Pages: 185-185

    • DOI

      10.1186/s13014-017-0927-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy2017

    • Author(s)
      Kobayashi D, Shibata A, Oike T, Nakano T
    • Journal Title

      J Vis Exp

      Volume: 23(128) Pages: 56338-56338

    • DOI

      10.3791/56338

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbon ion radiotherapy for 80 years or older patients with hepatocellular carcinoma2017

    • Author(s)
      Shiba S, Abe T, Shibuya K, Katoh H, Koyama Y, Shimada H, Kakizaki S, Shirabe K, Kuwano H, Ohno T, Nakano T
    • Journal Title

      BMC Cancer

      Volume: 17(1) Pages: 721-721

    • DOI

      10.1186/s12885-017-3724-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Thyroid Anaplastic Carcinoma Presenting Marked Neutrophilia and Eosinophilia due to Co-Production of GM-CSF, M-CSF and IL-62017

    • Author(s)
      Jun-ichi Saitoh, Katsuyukii Shirai, Atsushi Musha, Tatsuji Mizukami, Takanori Abe and Takashi Nakano
    • Journal Title

      Int J Radiol Radiat Ther

      Volume: 3(2) Pages: 00055-00055

    • DOI

      10.15406/ijrrt

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequential histological findings and clinical response after carbon ion radiotherapy for unresectable sarcoma2017

    • Author(s)
      Hayashi K, Yamamoto N, Shirai T, Takeuchi A, Kimura H, Miwa S, Higuchi T, Abe, K, Taniguchi Y, Aiba H, Kiyohara H, Imai R, Ikeda H, Tsuchiya H
    • Journal Title

      Clinical and Translational Radiation Oncology

      Volume: 2 Pages: 41-45

    • DOI

      10.1016/j.ctro.2017.01.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [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

      Sci Rep.

      Volume: 7 Pages: 40588-40588

    • DOI

      10.1038/srep40588

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Initial Results of Hypofractionated Carbon Ion Radiotherapy for Cholangiocarcinoma.2016

    • Author(s)
      Abe T, Shibuya K, Koyama Y, Okamoto M, Kiyohara H, Katoh H, Shimada H, Kuwano H, Ohno T, Nakano T
    • Journal Title

      Anticancer research

      Volume: 12(1) Pages: 2955-2960

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture after carbon ion radiotherapy for lung cancer.2016

    • Author(s)
      Abe T, Shirai K, Saitoh J, Ebara T, Shimada H, Tashiro M, Okano N, Ohno T, Nakano T
    • Journal Title

      ACTA ONCOLOGICA

      Volume: 55 Pages: 163-166

    • DOI

      10.3109/0284186x.2015.1088169

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Charged Particles on Human Tumor Cells2016

    • 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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Verification of Dose Distribution in Carbon Ion Radiation Therapy for Stage I Lung Cancer.2016

    • Author(s)
      Irie D, Saitoh JI, Shirai K, Abe T, Kubota Y, Sakai M, Noda SE, Ohno T, Nakano T
    • Journal Title

      International Journal of Radiation Oncology & Biology & Physics

      Volume: 96(5) Pages: 1117-1123

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in rectal dose due to alterations in beam angles for setup uncertainty and range uncertainty in carbon ion radiotherapy for prostate cancer2016

    • Author(s)
      Yoshiki Kubota, Hidemasa Kawamura, Makoto Sakai, Ryou Tsumuraya, Mutsumi Tashiro, Ken Yusa, Nobuteru Kubo, Hiro Sato, Masahiro Kawahara, Hiroyuki Katoh, Tatsuaki Kanai, Tatsuya Ohno, Takashi Nakano
    • Journal Title

      PLoS One

      Volume: April Pages: 1-11

    • DOI

      10.1371/journal.pone.0153894

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oral mucosal melanoma treated with carbon ion radiotherapy: a case report.2016

    • Author(s)
      Musha A, Saitoh JI, Shirai K, Yokoo S, Ohno T, Nakano T
    • Journal Title

      Journal of Medical Case Reports

      Volume: 10(1) Pages: 284-284

    • DOI

      10.1186/s13256-016-1071-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of DNA double strand breaks at chromosome boundaries along the track of particle irradiation.2016

    • Author(s)
      Atsuko Niimi, Motohiro Yamauchi, Siripan Limsirichaikul, Ryota Sekine, Takahiro Oike, Hiro Sato, Keiji Suzuki, Kathryn D. Held, Takashi Nakano, Atsushi Shibata
    • Journal Title

      Genes, Chromosomes and Cancer

      Volume: 55 Pages: 650-60

    • DOI

      10.1002/gcc.22367

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy2016

    • Author(s)
      Takahiro Oike, Atsuko Niimi, Noriyuki Okonogi, Kazutoshi Murata, Akihiko Matsumura, Shin-Ei Noda, Daijiro Kobayashi, Mototaro Iwanaga, Keisuke Tsuchida, Tatsuaki Kanai, Tatsuya Ohno, Atsushi Shibata, Takashi Nakano
    • Journal Title

      Sci Rep

      Volume: 6 Pages: 22275-22275

    • DOI

      10.1038/srep22275

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Carbon-ion radiotherapy for locally advanced cervical cancer with bladder invasion2016

    • Author(s)
      Shiba S, Wakatsuki M, Kato S, Ohno T, Okonogi N, Karasawa K, Kiyohara H, Tsujii H, Nakano T, Kamada T, Shozu M; The Working Group of the Gynecological Tumor.
    • Journal Title

      J Radiat Res.

      Volume: 57(6) Pages: 684-690

    • DOI

      10.1093/jrr/rrw070

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 放射線治療に魅せられた温故知新2019

    • Author(s)
      中野隆史
    • Organizer
      放射線治療談話会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 子宮がんの小線源治療に導かれて2018

    • Author(s)
      中野隆史
    • Organizer
      第20回小線源治療部会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Radiotherapy Collaboration Research in Asia2018

    • Author(s)
      中野隆史
    • Organizer
      The 3rd Annual meeting of Federation of Asian Organization of Radiation Oncology, Bali, Indonesia
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Outcomes and Prognostic Factors after Carbon-ion Radiotherapy for Hepatocellular Carcinoma2018

    • Author(s)
      Hiroyuki Katoh、Yoshinori Koyama, Shintaro Shiba, Masahiko Okamoto, Kenichiro Araki, Akira Kakizaki, Tatsuya Ohno, Ken Shirabe, Takashi Nakano
    • Organizer
      APPLE2018 :The 9th Asia-Pacific Primary Liver Cancer Expert Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リンパ節転移を有する子宮頸部腺癌に対しCyberknifeによる追加照射が奏効した1例2018

    • Author(s)
      小林大二郎、村田和俊、吉本由哉、松井利晃、野田真永、中島温、大野達也、清水庸夫、中野隆史
    • Organizer
      日本放射線腫瘍学会第31回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膀胱浸潤前立腺癌に対する重粒子線治療の検討2018

    • Author(s)
      河村英将、久保亘輝、佐藤浩央、水上達治、大野達也、松井博、伊藤一人、鈴木和浩、中野隆史
    • Organizer
      日本放射線腫瘍学会第31回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Brainstem necrosis of head and neck tumors treated with Carbon-ion radiotherapy2017

    • Author(s)
      Katsuyuki Shirai, Kyohei Fukata, Akiko Adachi, Jun-ichi Saitoh, Atsushi Musha, Takanori Abe, Daijiro Kobayashi, Yuka Shigeta, Satoshi Yokoo, Kazuaki Chikamatsu, Tatsuya Ohno, Takashi Nakano.
    • Organizer
      第7回国際放射線神経生物学会
    • Place of Presentation
      ホテル双葉
    • Year and Date
      2017-02-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] [特別企画1] がんの重粒子線治療の現状と展望2017

    • Author(s)
      中野隆史
    • Organizer
      第46回日本IVR学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Advance Technologies in Radiation Oncology in Asia Today2017

    • Author(s)
      中野隆史
    • Organizer
      2017 FNCA Workshop, Philippines
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Current status of carbon ion therapy for cancers2017

    • Author(s)
      中野隆史
    • Organizer
      IAEA Scientific Forum, Vienna, Austria
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Education and training activities of JASTRO2017

    • Author(s)
      中野隆史
    • Organizer
      International Conference on Advances in Radiation Oncology(ICRO2) VIENNA, Austria
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 重粒子線治療における子宮頸癌骨盤内リンパ節転移に対するブースト照射の解析2017

    • Author(s)
      柴慎太郎、若月優、加藤真吾、小此木範之、大野達也、中野隆史、鎌田正
    • Organizer
      第8回日本放射線外科学会
    • Place of Presentation
      ANAクラウンプラザホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] The impact of duration of androgen deprivation therapy on sexual function for prostate cancer patients receiving carbon ion radiation therapy2016

    • Author(s)
      Hidemasa Kawamura1, Nobuteru Kubo1, Hiro Sato1, Tatsuji Mizukami1, Akiko Adachi1, Hiroyuki Katoh1, Tatsuya Ohno1, Hiroshi Matsui2, Kazuhiro Suzuki2, and Takashi Nakano1
    • Organizer
      日本放射線腫瘍学会第29回学術大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 放射線治療時に免疫チェックポイント阻害剤の抗腫瘍効果増強を導くDNA修復機構の解明2016

    • Author(s)
      佐藤 浩央, 新見 敦子, 磯野 真由, 中野 隆史, 柴田 淳史
    • Organizer
      54回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 婦人科腫瘍における放射線治療後の照射野内リンパ節再発に対する炭素イオン線治療2016

    • Author(s)
      柴慎太郎1,2、若月 優3、小此木範之 2、加藤真吾4、大野達也1、唐澤久美子5、中野隆史1、鎌田 正2
    • Organizer
      54回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 手術不能原発性尿管癌に対する重粒子線治療の初期経験2016

    • Author(s)
      河村英将、久保亘輝、佐藤浩央、川原正寛、安達彰子、関根芳岳、小池秀和、松井博、柴田康博、伊藤一人、鈴木和浩、大野達也、中野隆史
    • Organizer
      54回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 外陰部悪性黒色腫に対する炭素イオン線治療の成績2016

    • Author(s)
      柴慎太郎、若月優、小此木範之、加藤真吾、唐澤久美子、清原浩樹、大野達也、中野隆史、鎌田正
    • Organizer
      第58回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      米子コンベンションセンター
    • Year and Date
      2016-07-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胆管癌に対する炭素線治療の初期成績2016

    • Author(s)
      渋谷圭、小山佳成、岡本雅彦、清原浩樹、大野達也、中野隆史
    • Organizer
      第52回日本肝癌研究研究会
    • Place of Presentation
      虎ノ門ヒルズフォーラム
    • Year and Date
      2016-07-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] 早期肺癌に対する重粒子線治療成績2016

    • Author(s)
      白井 克幸、齋藤 淳一、阿部 孝憲、小林 大二郎、入江 大介、大野 達也、中野 隆史
    • Organizer
      第25回 日本癌病態治療研究会
    • Place of Presentation
      三井ガーデンホテル千葉
    • Year and Date
      2016-06-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Dosimetric analysis on rib fracture after carbon ion radiotherapy for peripheral stage I lung cancer.2016

    • Author(s)
      Abe Takanori, Shirai Katsuyuki, Saitoh Jun-ichi, Kawashima Motohiro,Shimada Hirofumi, Ohno Tatsuya, Nakano Takashi
    • Organizer
      PTCOG55
    • Place of Presentation
      Prague Congress Centre
    • Year and Date
      2016-05-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of cluster DNA double strand break formation using high-resolution microscopy2016

    • Author(s)
      Atsuko Niimi, Nakajima Izumi Nakako, Motohiro Yamauchi, Siripan Limsirichaikul, Takahiro Oike, Hiro Sato, Penny A. Jeggo, Kathryn D. Held, Takashi Nakano and Atsushi Shibata
    • Organizer
      10th Quinquennial Conference: “Responses to DNA damage: from molecule to disease”
    • Place of Presentation
      Netherland
    • Year and Date
      2016-04-07
    • Related Report
      2016 Annual Research Report
  • [Book] Brachytherapy: Techniques and Evidences2018

    • Author(s)
      Yasuo Yoshioka,Jun Itami,Masahiko Oguchi,Takashi Nakano
    • Total Pages
      304
    • Publisher
      Springer
    • ISBN
      9789811304897
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2019-12-27  

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