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Significance of evaluating RUNX3 expression in acute myeloid leukemia

Research Project

Project/Area Number 16K08976
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionNational Cancer Center Japan

Principal Investigator

Matsushita Hiromichi  国立研究開発法人国立がん研究センター, 中央病院, 医長 (50286481)

Co-Investigator(Kenkyū-buntansha) 安藤 潔  東海大学, 医学部, 教授 (70176014)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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)
KeywordsRUNX3 / 急性骨髄性白血病 / 遺伝子変異 / 予後不良因子 / 抗がん剤耐性 / 予後
Outline of Final Research Achievements

We previously elucidated that FLT3-ITD, a poor prognostic factor in acute myeloid leukemia (AML), induces Ara-C resistance through the upregulation of RUNX3. The current study aimed to investigate whether the RUNX3 expression is an excellent biomarker that predicts the prognosis of AML. In 71 AML cases with various genetic mutations, the cases with lower RUNX3 expression tended to have better overall survival (OS) than higher expression without statistical significances. Forty AML cases with normal karyotype also showed no difference in OS, when the cases with higher and lower RUNX3 expression were compared. Additionally, the mutations in epigenetic associated-genes such as TET2, DNMT3A, IDH2 and ASXL1 as well as the FLT3-ITD mutation did not affect the RUNX3 expression. Although there have been no apparent evidences that showed the RUNX3 expression is a useful biomarker for AML thus far, we will continue to examine in detail the significance of RUNX3 expression in AML.

Academic Significance and Societal Importance of the Research Achievements

急性骨髄性白血病(AML)の悪性度は症例によって様々であり、染色体・遺伝子異常などの指標(=バイオマーカー)を参考にしながら治療方法を決定することが多い。今回の研究では、私達が抗がん剤耐性に関係すると報告してきたRUNX3遺伝子についてバイオマーカーとしての可能性を検討した。検討したAML71症例全体ではRUNX3遺伝子の量の低い方が生存率が高い傾向であったが、まだ十分な結果は得られていない。今後さらなる解析を続けて、RUNX3遺伝子の量を検索することの有用性を明らかにしていきたい。

Report

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

    (46 results)

All 2019 2018 2017 2016

All Journal Article (25 results) (of which Int'l Joint Research: 13 results,  Peer Reviewed: 20 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Feasibility and utility of a panel testing for 114 cancer‐associated genes in a clinical setting: A hospital‐based study2019

    • Author(s)
      Sunami Kuniko、Ichikawa Hitoshi、Kubo Takashi、Kato Mamoru、Fujiwara Yutaka、Shimomura Akihiko、Koyama Takafumi、Kakishima Hiroki、Kitami Mayuko、Matsushita Hiromichi、Furukawa Eisaku、Narushima Daichi、Nagai Momoko、Taniguchi Hirokazu、Motoi Noriko、、Kohno Takashi et al.
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1480-1490

    • DOI

      10.1111/cas.13969

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Composite Lymphoma with Extranodal NK/T-cell Lymphoma, Nasal-type and Diffuse Large B-cell Lymphoma2019

    • Author(s)
      Kawai H, Matsushita H, Kawakami S, Furuya D, Shiraiwa-Hara S, Ichiki A, Hara R, Aoyama Y, Ogiya D, Suzuki R, Machida S, Onizuka M, Shirasugi Y, Ogawa Y, Kawada H, Nakamura N, Ando K
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 59 Issue: 1 Pages: 34-39

    • DOI

      10.3960/jslrt.18038

    • NAID

      130007626105

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A simple screening method for the diagnosis of chronic myeloid leukemia using the parameters of a complete blood count and differentials2019

    • Author(s)
      Ogasawara A, Matsushita H, Tanaka Y, Shirasugi Y, Ando K, Asai S, Miyachi H
    • Journal Title

      Clinica Chimica Acta

      Volume: 489 Pages: 249-253

    • DOI

      10.1016/j.cca.2018.08.038

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 第65 回学術集会シンポジウム8:血液形態診断のためのケースカンファレンス 司会のことば.2019

    • Author(s)
      田村孝子、松下弘道
    • Journal Title

      臨床病理

      Volume: 67 Pages: 74-76

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Eprobe mediated RT-qPCR for the detection of leukemia-associated fusion genes2018

    • Author(s)
      Tsuchiya K, Tabe Y, Ai T, Ohkawa T, Usui K, Yuri M, Misawa S, Morishita S, Takaku T, Kakimoto A, Yang H, Matsushita H, Hanami T, Yamanaka Y, Okuzawa A, Horii T, Hayashizaki Y, Ohsaka A
    • Journal Title

      PLoS One

      Volume: 13(10) Issue: 10 Pages: e0202429-e0202429

    • DOI

      10.1371/journal.pone.0202429

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 第19回 日本検査血液学会学術集会 テクニカルセミナー2 フローサイトメトリー検査を用いた造血器腫瘍診断の進歩 2. マルチカラー解析の基礎.2018

    • Author(s)
      松下弘道、有賀祐、池田千秋
    • Journal Title

      日本検査血液学会雑誌 2018

      Volume: 19 Pages: 422-429

    • Related Report
      2018 Annual Research Report
  • [Journal Article] FFRE検体を用いたHER2 FISH検査の市販精度管理用ブロックの基礎的検討2018

    • Author(s)
      山口佳織、若井進、澁木 康雄、川村公彦、角南久仁子、松下弘道
    • Journal Title

      日本染色体遺伝子検査学会雑誌

      Volume: 36 Pages: 82-88

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Dysplastic features seen in a patient with acute myeloid leukemia harboring the KTM2A-TET1 fusion gene2018

    • Author(s)
      Kawai H, Matsushita H, Aoyama Y, Matsui K, Onizuka M, Ando K
    • Journal Title

      Int J Hematol

      Volume: in press Issue: 1 Pages: 1-2

    • DOI

      10.1007/s12185-018-2469-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Marked erythroblastosis in myelodysplastic syndrome induced by gastric hemorrhaging.2018

    • Author(s)
      Yoshimura S, Munakata W, Ikeda C, Matsushita H.
    • Journal Title

      Int J Hematol

      Volume: 107 Issue: 4 Pages: 387-389

    • DOI

      10.1007/s12185-017-2374-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pseudo-Chediak-Higashi granules and Auer rods in mixed phenotype acute leukaemia, T/myeloid, not otherwise specified.2018

    • Author(s)
      Aruga Y, Arakawa A, Ono K, Ogawa C, Matsushita H.
    • Journal Title

      Br J Haematol

      Volume: 180 Issue: 2 Pages: 175-175

    • DOI

      10.1111/bjh.14924

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The infiltration of classical Hodgkin lymphoma cells into pleural effusion.2018

    • Author(s)
      Kito M, Munakata W, Ono K, Maeshima AM, Matsushita H.
    • Journal Title

      Int J Hematol

      Volume: 107 Issue: 1 Pages: 1-2

    • DOI

      10.1007/s12185-017-2329-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib.2017

    • Author(s)
      Hara R, Onizuka M, Matsusita E, Kikkawa E, Nakamura Y, Matsushita H, Ohgiya D, Murayama H, Machida S, Ohmachi K, Shirasugi Y, Ogawa Y, Kawada H, Ando K.
    • Journal Title

      Int J Hematol

      Volume: 106 Issue: 5 Pages: 666-674

    • DOI

      10.1007/s12185-017-2294-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Successful Prevention of Thromboembolism Using Rivaroxaban in a Patient with Antithrombin Deficiency during the Perioperative Period2017

    • Author(s)
      Kawai H, Matsushita H, Kawada H, Ogawa Y, Ando K.
    • Journal Title

      Internal Medicine

      Volume: 56 Issue: 17 Pages: 2339-2342

    • DOI

      10.2169/internalmedicine.8487-16

    • NAID

      130006039397

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells between Humans and a Humanized Xenograft Model.2017

    • Author(s)
      Matsuzawa H, Matsushita H, Yahata T, Tanaka M, Ando K
    • Journal Title

      Tokai J Exp Clin Med

      Volume: 42 Pages: 41-51

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 悪性リンパ腫(CLL, ATL, GLPD/LGLを除く)2017

    • Author(s)
      松下 弘道
    • Journal Title

      臨床検査

      Volume: 61 Pages: 984-991

    • Related Report
      2017 Research-status Report
  • [Journal Article] Comparison of the gene expression profiles of human hematopoietic stem cells between humans and a humanized xenograft model.2017

    • Author(s)
      Matsuzawa H, Matsushita H, Yahata T, Tanaka M, Ando K.
    • Journal Title

      Tokai J Exp Clin Med

      Volume: 42 Pages: 41-51

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells.2017

    • Author(s)
      Tabe Y, Yamamoto S, Saitoh K, Sekihara K, Monma N, Ikeo K, Mogushi K, Shikami M, Ruvolo V, Ishizawa J, Hail N Jr, Kazuno S, Igarashi M, Matsushita H, Yamanaka Y, Arai H, Nagaoka I, Miida T, Hayashizaki Y, Konopleva M, Andreeff M.
    • Journal Title

      Cancer Res.

      Volume: 77 Issue: 6 Pages: 1453-1464

    • DOI

      10.1158/0008-5472.can-16-1645

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 認定試験筆記問題の作成要領 ― 第17回日本検査血液学会学術集会 特別ワークショップの概要 ―.2017

    • Author(s)
      稲葉亨、東田修二、金子誠、河野誠司、松下弘道、今井重良、梅村茂人、中村恒仁、吉村慎一、佐藤尚武.
    • Journal Title

      日本検査血液学会雑誌

      Volume: 18 Pages: 10-8

    • Related Report
      2016 Research-status Report
  • [Journal Article] CD34/HLA-DR陰性の急性骨髄性白血病の解析 当院における38例の検討.2017

    • Author(s)
      日下拓、松下弘道、二見恭子、星かおり 、坂入和豊、浅井さとみ、矢部みはる、安藤潔、田中由美子、宮地勇人.
    • Journal Title

      日本検査血液学会雑誌

      Volume: 18 Pages: 45-53

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 炎症指標としての血算・血液像検査の利用状況(臨床医の意識調査結果)と桿状核好中球分類の有用性.2017

    • Author(s)
      山本剛正、田部陽子、石井清、三宅一徳、岩崎陽介、増田亜希子、松下弘道、堀井隆、佐藤尚武、大坂顯通.
    • Journal Title

      日本検査血液学会雑誌

      Volume: 18 Pages: 71-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone marrow involvement of primary cutaneous γ/δ T-cell lymphoma.2016

    • Author(s)
      Matsushita H, Maruyama D.
    • Journal Title

      Blood

      Volume: 128 Issue: 18 Pages: 2274-2274

    • DOI

      10.1182/blood-2016-07-730002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chediak-Higashi-like granules and waxy Auer bodies in a case of acute promyelocytic leukemia.2016

    • Author(s)
      Ogiya D, Matsushita H, Murayama H, Ando K.
    • Journal Title

      Int J Hematol

      Volume: 104 Issue: 6 Pages: 637-8

    • DOI

      10.1007/s12185-016-2078-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinicopathologic analysis of angioimmunoblastic T-cell lymphoma with or without RHOA G17V mutation using formalin-fixed paraffin-embedded sections.2016

    • Author(s)
      Nagao R, Kikuti YY, Carreras J, Kikuchi T, Miyaoka M, Matsushita H, Kojima M, Ando K, Sakata-Yanagimoto M, Chiba S, Nakamura N.
    • Journal Title

      Am J Surg Pathol

      Volume: 40 Issue: 8 Pages: 1041-50

    • DOI

      10.1097/pas.0000000000000651

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.2016

    • Author(s)
      Takahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito AM, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi S.
    • Journal Title

      Br J Haematol.

      Volume: 印刷中 Issue: 3 Pages: 437-443

    • DOI

      10.1111/bjh.14068

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The formation of an aberrant PAX5 transcript in a patient with mixed phenotype acute leukemia harboring der(9)t(7;9)(q11.2;p13).2016

    • Author(s)
      Amaki J, Matsushita H, Kitamura Y, Nagao R, Murayama H, Kojima M, Ando K.
    • Journal Title

      Leuk Res Rep

      Volume: 5 Pages: 14-7

    • DOI

      10.1016/j.lrr.2016.04.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] フローサイトメトリー検査実践講座 初級・中級者向け 「ケーススタディ(リンパ系腫瘍)」2018

    • Author(s)
      松下弘道
    • Organizer
      第65回 日本臨床検査医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リンパ腫における病理組織標本からのMYCおよびIGH-BCL2遺伝子FISH検査の判定基準に関する一考察2018

    • Author(s)
      若井進、野本順子、山野環、柿島裕樹、千木良浩志、川村公彦、角南久仁子、福原傑、松下弘道
    • Organizer
      第65回 日本臨床検査医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] テクニカルセミナ-2 マルチカラー解析の基礎2018

    • Author(s)
      松下弘道
    • Organizer
      第19回 日本検査血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ランチョンセミナー9 骨髄検査の結果報告 -1つ上の報告を目指してー2018

    • Author(s)
      松下弘道
    • Organizer
      第19回 日本検査血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 慢性リンパ性白血病における微笑残存病変検出法の検討2018

    • Author(s)
      有賀祐、池田千秋、小野剛司、吉村咲子、鬼頭桃子、宮木聡恵、川村公彦、松下弘道
    • Organizer
      第19回 日本検査血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フローサイトメトリーが疾患推定に有用であったALK陽性未分化大細胞型リンパ腫の一例2018

    • Author(s)
      有賀祐、池田千秋、小野剛司、吉村咲子、鬼頭桃子、笠根萌美、阿出川裕子、高橋典子、川村公彦、前島亜希子、福原傑、松下弘道
    • Organizer
      第28回 日本サイトメトリー学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] チロシンキナーゼ阻害薬耐性である SEPT9 -ABL1 に対する CRM1 阻害薬 の効果2018

    • Author(s)
      川井英嗣、松下弘道、安藤潔
    • Organizer
      第22回 造血器腫瘍研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 急性骨髄性白血病と遺伝子異常2017

    • Author(s)
      松下 弘道
    • Organizer
      第32回 慶應血液検査研究会
    • Place of Presentation
      慶應義塾大学 信濃町キャンパス(東京都・新宿区)
    • Year and Date
      2017-02-18
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Overcoming Tyrosine Kinase Inhibitor Resistance to SEPT9-ABL1 Chimeric Fusion Protein Using CRM1 Inhibitors.2017

    • Author(s)
      Kawai H, Matsushita H, Kitamura Y, Ogawa Y, Kawada H, Ando K.
    • Organizer
      59th ASH Annual Meeting & Exposition
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] HER2 FISH検査精度管理用FFPEブロックの基礎的検討とその有用性2017

    • Author(s)
      山口佳織、若井進、柿島裕樹、澁木康雄、川村公彦、角南久仁子、松下弘道
    • Organizer
      第35回日本染色体遺伝子検査学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] FISH検査後のスライド標本からの再染色 (Reprobing) に関する検討2017

    • Author(s)
      若井進、柿島裕樹、山口佳織、角南久仁子、古田耕、吉田朗彦、松下弘道
    • Organizer
      第64回 日本臨床検査医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] sIL-2R測定試薬「ナノピアIL-2R」の基礎的検討2017

    • Author(s)
      松林 秀弥、山川 博史、上柿 涼子、宮越 基、内川 正弘、川村 公彦、松下 弘道、平岡 伸介松林 秀弥、山川 博史、上柿 涼子、宮越 基、内川 正弘、川村 公彦、松下 弘道、平岡 伸介
    • Organizer
      第71回 国立病院総合医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Targeted resequencing of acute myeloid leukemia using next generation sequencer.2017

    • Author(s)
      Matsushita H, Kawai H, Tanaka M, Harada H, Harada Y, Amaki J, Sheng Y, Shiina T, Onizuka M, Ando K.
    • Organizer
      第79回 日本血液学会学術集会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 治療経過中に胸水への浸潤を認めた古典的ホジキンリンパ腫の一例2017

    • Author(s)
      鬼頭桃子、小野剛司、吉村咲子、有賀祐、渋木康雄、中島哲、棟方理、前島亜希子、松下弘道
    • Organizer
      第18回 日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨髄および末梢血中に腫瘍細胞を認めた皮膚原発γδ型T細胞リンパ腫の1例2017

    • Author(s)
      吉村咲子、小野剛司、有賀祐、鬼頭桃子、佐々木春貴、内川正弘、中島哲、前島亜希子、油田さや子、丸山大、松下弘道
    • Organizer
      第18回 日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 著明なアズール顆粒の形成を認めた混合表現型急性白血病 MPAL, T/myeloidの一例2017

    • Author(s)
      有賀 祐、小野 剛司、吉村 咲子、鬼頭 桃子、荒川 歩、小川 千登世、中島 哲、松下 弘道
    • Organizer
      第18回 日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 造血器腫瘍における遺伝子異常の意義2017

    • Author(s)
      松下 弘道
    • Organizer
      第25回 染色体遺伝子検査 基礎技術セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Mechanism of tyrosine kinase inhibitors-resistance by SEPT9-ABL12016

    • Author(s)
      KawaiHH, Matsushita H, Kitamura Y, Ogawa Y, Kawada H. Ando K
    • Organizer
      第78回 日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Generation of the leukemic cell line models with common KIT mutations2016

    • Author(s)
      アナラ ダムディンスレン、松下弘道、浅井さとみ、宮地勇人
    • Organizer
      第63回 日本臨床検査医学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 慢性骨髄性白血病CMLの早期診断を目的としたカットオフ値の設定2016

    • Author(s)
      小笠原篤、田中由美子、白杉由香理、安藤潔、 浅井さとみ、松下弘道、 宮地勇人
    • Organizer
      第63回 日本臨床検査医学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] A simple method based on peripheral blood parameters for early diagnosis of chronic myelogenous leukemia2016

    • Author(s)
      Ogasawara A, Tanaka Y, Shirasugi Y, Ando K, Asai S, Matsushita H, Miyachi H
    • Organizer
      The 32nd World Congress of Biomedical Laboratory Science (IFBLS2016)
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2016-08-31
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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

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