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Chromosomal translocation and the involvement of DNA repair system in sarcoma.

Research Project

Project/Area Number 18K09110
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOita University

Principal Investigator

Tanaka Kazuhiro  大分大学, 医学部, 准教授 (10274458)

Co-Investigator(Kenkyū-buntansha) 織田 信弥  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 腫瘍遺伝学研究室長 (40333372)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords肉腫 / 染色体転座 / 融合遺伝子 / DNA二本鎖切断修復
Outline of Final Research Achievements

Disease-specific chromosomal translocation and the resulting fusion genes are thought to contribute to the carcinogenesis of sarcomas. Abnormalities in the DNA double-strand break repair system (homologous recombination, HR; non-homologous end-joining, NHEJ) are thought to be involved in the development of chromosomal translocations, but the details of the molecular mechanism are still unclear. In this study, we analyzed the expression and dysfunction of the factors responsible for HR and NHEJ in detail at the gene and protein expression levels and confirmed the activation of the HR pathway in various translocation-positive sarcoma cells.
Based on these achievements, we worked on the construction of a model system that can verify the in vitro chromosomal translocation in sarcoma cells.

Academic Significance and Societal Importance of the Research Achievements

腫瘍における染色体転座はこれまでNHEJにより生起しているものと考えられてきたが、我々はむしろHR径路を介して生起しているのではないかと仮定し研究を進めて来た。その結果は、転座陽性肉腫細胞におけるHR径路の活性化を示唆している。HR径路を介した染色体転座は複数のDNA修復過程の異常を背景にしている可能性があるが、このようなDNA修復異常を正確にとらえ、転座の基礎となるDNA修復過程の全貌を明らかにするためには、各種DNA修復異常の意義を検証可能なモデル系を構築する必要がある。HRによる肉腫型染色体転座を再構成するin vitroモデル系を構築しようとする本研究は世界初の試みといえる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 17 results,  Open Access: 15 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (3 results)

  • [Journal Article] The benzylisoquinoline alkaloids, berberine and coptisine, act against camptothecin-resistant topoisomerase I mutants2021

    • Author(s)
      Inoue Naomi、Terabayashi Takeshi、Takiguchi-Kawashima Yuri、Fujinami Daisuke、Matsuoka Shigeru、Kawano Masanori、Tanaka Kazuhiro、Tsumura Hiroshi、Ishizaki Toshimasa、Narahara Hisashi、Kohda Daisuke、Nishida Yoshihiro、Hanada Katsuhiro
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 7718-7718

    • DOI

      10.1038/s41598-021-87344-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma2020

    • Author(s)
      Tanaka Kazuhiro、Kawano Masanori、Iwasaki Tatsuya、Itonaga Ichiro、Tsumura Hiroshi
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 379-379

    • DOI

      10.1186/s12885-020-06871-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surrogate endpoints for overall survival in randomised controlled trials of localised osteosarcoma: A meta-analytic evaluation2020

    • Author(s)
      Tanaka Kazuhiro、Kawano Masanori、Iwasaki Tatsuya、Matsuda Shogo、Itonaga Ichiro、Tsumura Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8573-8573

    • DOI

      10.1038/s41598-020-65591-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a High-Throughput Quantification Method for Pazopanib Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Clinical Application in Patients with Soft Tissue Tumors2020

    • Author(s)
      Shiraiwa Ken、Suzuki Yosuke、Tanaka Kazuhiro、Kawano Masanori、Iwasaki Tatsuya、Matsumoto Asami、Tanaka Ryota、Tatsuta Ryosuke、Tsumura Hiroshi、Itoh Hiroki
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: Publish Ahead of Print Issue: 3 Pages: 416-421

    • DOI

      10.1097/ftd.0000000000000821

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group2020

    • Author(s)
      Tanaka Kazuhiro、Ozaki Toshifumi
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 51 Issue: 2 Pages: 180-184

    • DOI

      10.1093/jjco/hyaa231

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients2020

    • Author(s)
      Nagano Akihito、Tanaka Kazuhiro、et al.
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 25 Issue: 2 Pages: 319-323

    • DOI

      10.1016/j.jos.2019.04.008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term disease control by trabectedin in a patient with dedifferentiated liposarcoma2020

    • Author(s)
      Matsuda Shogo、Tanaka Kazuhiro、Kawano Masanori、Iwasaki Tatsuya、Itonaga Ichiro、Tsumura Hiroshi
    • Journal Title

      Medicine

      Volume: 99 Issue: 2 Pages: 1-6

    • DOI

      10.1097/md.0000000000018689

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surrogacy of intermediate endpoints for overall survival in randomized controlled trials of first-line treatment for advanced soft tissue sarcoma in the pre- and post-pazopanib era: a meta-analytic evaluation.2019

    • Author(s)
      Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
    • Journal Title

      BMC Cancer.

      Volume: 19 Issue: 1 Pages: 56-56

    • DOI

      10.1186/s12885-019-5268-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A meta-analysis of randomized controlled trials that compare standard doxorubicin with other first-line chemotherapies for advanced/metastatic soft tissue sarcomas.2019

    • Author(s)
      Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 1 Pages: 1-18

    • DOI

      10.1371/journal.pone.0210671

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG03042019

    • Author(s)
      Tanaka Kazuhiro、Mizusawa Junki、Naka Norifumi、Kawai Akira、et al.
    • Journal Title

      BMC Cancer

      Volume: 19 Issue: 1 Pages: 1-7

    • DOI

      10.1186/s12885-019-6114-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A randomized phase III trial of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group Study JCOG16102019

    • Author(s)
      Urakawa Hiroshi、Mizusawa Junki、Tanaka Kazuhiro、Eba Junko、Hiraga Hiroaki、Kawai Akira、Nishida Yoshihiro、Hosaka Masami、Iwamoto Yukihide、Fukuda Haruhiko、Ozaki Toshifumi
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 49 Issue: 4 Pages: 379-382

    • DOI

      10.1093/jjco/hyz004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eighth edition of the American Joint Committee on Cancer staging system for soft tissue sarcoma of the trunk and extremity: in search of a better staging system2019

    • Author(s)
      Tanaka Kazuhiro、Tsumura Hiroshi
    • Journal Title

      Annals of Translational Medicine

      Volume: 7 Issue: S1 Pages: 1-3

    • DOI

      10.21037/atm.2019.01.31

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells.2018

    • Author(s)
      Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
    • Journal Title

      Cancer Cell Int.

      Volume: 18 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s12935-018-0536-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG03042018

    • Author(s)
      Tanaka K, Ogawa G, Mizusawa J, Naka N, Kawai A, Takahashi M, Hiruma T, Matsumoto Y, Tsuchiya H, Nakayama R, Hatano H, Emori M, Hosaka M, Yoshida Y, Toguchida J, Abe S, Asanuma K, Yokoyama R, Hiraga H, Yonemoto T, Morii T, Matsumoto S, Nagano A, Yoshikawa H, Fukuda H, Ozaki T, Iwamoto Y.
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 16 Issue: 1 Pages: 160-160

    • DOI

      10.1186/s12957-018-1462-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment.2018

    • Author(s)
      Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
    • Journal Title

      Cell Commun Signal.

      Volume: 16(1) Issue: 1 Pages: 13-13

    • DOI

      10.1186/s12964-018-0225-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study2018

    • Author(s)
      Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T.
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 16 Issue: 1 Pages: 162-162

    • DOI

      10.1186/s12957-018-1459-6

    • NAID

      120006502536

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of the Novel Tooth-Specific Transcription Factor AmeloD2018

    • Author(s)
      He B.、Chiba Y.、Li H.、de Vega S.、Tanaka K.、Yoshizaki K.、Ishijima M.、Yuasa K.、Ishikawa M.、Rhodes C.、Sakai K.、Zhang P.、Fukumoto S.、Zhou X.、Yamada Y.
    • Journal Title

      Journal of Dental Research

      Volume: 98 Issue: 2 Pages: 234-241

    • DOI

      10.1177/0022034518808254

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.2020

    • Author(s)
      Tanaka K, Machida R, Kawai A, Nakayama R, Tsukushi S, Asanuma K, Matsumoto Y, Hiraga H, Hiraoka K, Watanuki M, Yonemoto T, Abe S, Katagiri H, Nishida Y, Nagano A, Suehara Y, Kataoka T, Fukuda H, Ozaki T, Iwamoto Y
    • Organizer
      2020 Annual Meeting of American Society of Clinical Oncology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A meta-analytic evaluation of the correlation between surrogate endpoints and overall survival in randomized controlled trials of newly diagnosed osteosarcoma.2020

    • Author(s)
      Tanaka K, Kawano M, Iwasaki T, Kubota Y, Itonaga I, Tsumura H
    • Organizer
      2020 Annual Meeting of Connective Tissue Oncology Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨軟部肉腫に対する標準治療と臨床試験2020

    • Author(s)
      田仲和宏
    • Organizer
      第53回西日本腫瘍懇話会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 成人、AYA世代における骨・軟部肉腫の臨床試験2020

    • Author(s)
      田仲和宏
    • Organizer
      第18回日本臨床腫瘍学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 10-year follow-up results of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG0304.2019

    • Author(s)
      Tanaka K, Mizusawa J, et al.
    • Organizer
      2019 Annual Meeting of American Society of Clinical Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ewing肉腫細胞におけるmiR-20bによるTGFBR2発現抑制と腫瘍増殖能の解析2019

    • Author(s)
      岩崎達也、田仲和宏、他
    • Organizer
      第52回日本整形外科学会骨・軟部腫瘍学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 最新主要文献とガイドラインでみる 整形外科学レビュー 2021-’222021

    • Author(s)
      田仲和宏
    • Total Pages
      296
    • Publisher
      総合医学社
    • ISBN
      9784883787340
    • Related Report
      2020 Annual Research Report
  • [Book] 軟部腫瘍診療ガイドライン2020(改訂第3版)2020

    • Author(s)
      田仲和宏
    • Total Pages
      96
    • Publisher
      南江堂
    • ISBN
      9784524228119
    • Related Report
      2020 Annual Research Report
  • [Book] 肉腫 : 基礎・臨床の最新知見2020

    • Author(s)
      田仲和宏
    • Total Pages
      692
    • Publisher
      日本臨床社
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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