• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analyses of anti-tumor activities regarding pazopanib in soft tissue sarcoma

Research Project

Project/Area Number 17K10987
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionJuntendo University

Principal Investigator

Kaneko Kazuo  順天堂大学, 医学部, 教授 (50311981)

Co-Investigator(Kenkyū-buntansha) 末原 義之  順天堂大学, 医学部, 准教授 (70509405)
齋藤 剛  順天堂大学, 医学部, 准教授 (80439736)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords軟部肉腫 / pazopanib / GLI1 / 12q13 / 著効例 / Pazopanib / 骨軟部腫瘍 / キナーゼ阻害剤 / 遺伝子変異 / リン酸化
Outline of Final Research Achievements

In this study, we performed integrate analyses using tumor/normal samples of a advanced STS that achieved a CR to pazopanib to elucidate molecular pathological background of pazopanib response in STSs. The integrate analyses was consisting of a next-generation sequencer (DNA / RNA sequence) and phosphorylation kinase membrane antibody array. As validation study, we verified identified gene alterations and phosphorylated protein expression using the comparative verification cohorts. As the results, we found both characteristic elevated PDGFRB phosphorylation protein of PDGFRB which is the target of pazopanib and specific gene amplification (12q13-14 locus: GLI1, CDK4) in cases that had highly sensitive response to pazopanib. Furthermore, functional analysis also confirmed that characteristic gene amplifications induced the expression of PDGFRB. Based on subsequent validation studies, it was considered that it would contribute to the development of personalized medicine for STSs.

Academic Significance and Societal Importance of the Research Achievements

本研究は、難治性かつ「希少がん」である高悪性軟部肉腫における生命予後の改善に貢献する新規治療法の開発を目的とした。具体的には我々のグループが、Tyrosine kinase (TK)阻害剤であるpazopanib 著効例の高悪性軟部肉腫手術検体より新規発見したキナーゼ遺伝子変異、及びそれらに一致したリン酸化タンパク質の高発現に注目し、大規模コホートによる変異・発現検証及びin vitro, in vivoの機能解析を行った。それら成果は現在まで未知であった難治性軟部肉腫におけるpazopanibの治療奏効・抵抗因子の解明に寄与し、新規個別化治療法の開発に貢献した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (13 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results)

  • [Journal Article] Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.2019

    • Author(s)
      Suehara Y, Okubo T, Kurihara T, Hayashi T, Kohsaka S, Kazuno S, Sano K, Hasegawa N, Miura Y, Akaike K, Kim Y, Takamochi K, Takahashi F, Ueno T, Kaneko K, Saito T.
    • Journal Title

      Proteomics Clin Appl

      Volume: 13 Issue: 5 Pages: 1800147-1800147

    • DOI

      10.1002/prca.201800147

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of circulating sarcoma tumor cells using a microfluidic chip-type cell sorter.2019

    • Author(s)
      Hasegawa N, Takeda Nakamura I, Ueno T, Kojima S, Kawazu M, Akaike K, Okubo T, Takagi T, Suehara Y, Hayashi T, Saito T, Kaneko K, Mano H, Kohsaka S.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 20047-20047

    • DOI

      10.1038/s41598-019-56377-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Squamous cell carcinoma arising from chronic osteomyelitis massively expanding into the medullary cavity: A case report.2019

    • Author(s)
      Kurihara T, Suehara Y, Akaike K, Hayashi T, Okubo T, Kim Y, Takagi T, Kaneko K, Yao T, Saito T.
    • Journal Title

      Human Pathology Case reports

      Volume: 16 Pages: 100288-100288

    • DOI

      10.1016/j.ehpc.2019.01.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibrocartilaginous mesenchymoma of the tibia with predominant microcystic features: A case report and literature review2019

    • Author(s)
      Saito T, Motoi T, Suehara Y, Takagi T, Okubo T, Kurihara T, Hayashi T, Kudo T, Maruyama Y, Kaneko K, YaoT.
    • Journal Title

      Human Pathology Case reports

      Volume: 16 Pages: 100288-100288

    • DOI

      10.1016/j.ehpc.2019.01.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.2018

    • Author(s)
      Ishii M, Suehara Y, Sano K, Kohsaka S, Hayashi T, Kazuno S, Akaike K, Mukaihara K, Kim Y, Okubo T, Takamochi K, Takahashi F, Kaneko K, Saito T.
    • Journal Title

      Oncotarget

      Volume: 9(101) Issue: 101 Pages: 37509-37519

    • DOI

      10.18632/oncotarget.26493

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PPP2R1A regulated by PAX3/FOXO1 fusion contributes to the acquisition of aggressive behavior in PAX3/FOXO1-positive alveolar rhabdomyosarcoma.2018

    • Author(s)
      Akaike K, Suehara Y, Kohsaka S, Hayashi T, Tanabe Y, Kazuno S, Mukaihara K, Toda-Ishii M, Kurihara T, Kim Y, Okubo T, Hayashi Y, Takamochi K, Takahashi F, Kaneko K, Ladanyi M, Saito T.
    • Journal Title

      Oncotarget

      Volume: 9(38) Issue: 38 Pages: 25206-25215

    • DOI

      10.18632/oncotarget.25392

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors.2018

    • Author(s)
      Suehara Y, Akaike K, Mukaihara K, Kurisaki-Arakawa A, Kubota D, Okubo T, Mitomi H, Mitani K, Takahashi M, Toda-Ishii M1, Kim Y, Tanabe Y, Takagi T, Hayashi T, Mogushi K, Kaneko K, Yao T, Saito T.
    • Journal Title

      Oncotarget

      Volume: 9(43) Issue: 43 Pages: 27016-27026

    • DOI

      10.18632/oncotarget.25469

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IRE1α-XBP1 inhibitors exerted anti-tumor activities in Ewing's sarcoma.2018

    • Author(s)
      Tanabe Y, Suehara Y, Kohsaka S, Hayashi T, Akaike K, Mukaihara K, Kurihara T, Kim Y, Okubo T, Ishii M, Kazuno S, Kaneko K, Saito T.
    • Journal Title

      Oncotarget

      Volume: 9(18) Issue: 18 Pages: 14428-14443

    • DOI

      10.18632/oncotarget.24467

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma2017

    • Author(s)
      Mukaihara K, Tanabe Y, Kubota D, Akaike K, Hayashi T, Mogushi K, Hosoya M, Sato S,Kobayashi E, Okubo T, Kohsaka S, Saito T, Kaneko K, Suehara Y.
    • Journal Title

      PLoS One

      Volume: 12(9) Issue: 9 Pages: 0185321-0185321

    • DOI

      10.1371/journal.pone.0185321

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Integrative analysis including whole genome sequencing, transcriptome sequencing, and phospho-protein expression profiling of super responder to pazopanib in high-grade soft tissue sarcomas.2019

    • Author(s)
      Suehara Y, Kohsaka S, Yamaguchi S, Hayashi T, Kurihara T, Akaike K, Ueno T, Kojima S, Ikegami M, Mizuno S, Kaneko K , Kato S, Mano H, Saito T.
    • Organizer
      20th International Symposium on Limb Salvage
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟部肉腫pazopanib著効例の12q13-14遺伝子増幅変化.2019

    • Author(s)
      末原義之, 高阪真路, 山口茂夫, 林大久生, 栗原大聖, 赤池慶祐, 金子和夫, 齋藤 剛, 間野博行, 加藤俊介.
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 軟部肉腫pazopanib著効例の特徴的遺伝子増幅変化.2019

    • Author(s)
      末原義之, 高阪真路, 山口茂夫, 林大久生, 栗原大聖, 赤池慶祐, 金子和夫, 齋藤 剛, 間野博行, 加藤俊介.
    • Organizer
      第92回日本整形外科学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Metabolic fluctuations in adriamycin-resistant osteosarcomas using metabolomic approaches2019

    • Author(s)
      Sasa K, Suehara Y, Akaike K, Hayashi T, Taka H, Youngji K, Okubo T, Kaneko K, Saito T.
    • Organizer
      the 65th Annual Meeting of the Orthopaedic Research Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] IRE1α-XBP1 Inhibitor exerts antiyumor activity in osteosarcoma.2019

    • Author(s)
      Kurihara T, Suehara Y, Hayashi T, Akaike K, Okubo T, Kim Y, Kaneko K, Saito T.
    • Organizer
      the 65th Annual Meeting of the Orthopaedic Research Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive mRNA-based screen for tyrosine kinase fusions and a de novo alternative transcription initiation site in soft tissue sarcomas.2018

    • Author(s)
      Suehara Y, Kohsaka S, Kurisaki A, Akaike K, Hayashi T, Mogushi K, Okubo T, Kim Y, Sato S, Kobayashi E, Kaneko K, Mano H, Saito T.
    • Organizer
      European Society For Medical Oncology ASIA,
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] IRE1α-XBP1 Inhibitor exerts antiyumor activity in osteosarcoma.2018

    • Author(s)
      Kurihara T, Suehara Y, Hayashi T, Akaike K, Okubo T, Kim Y, Kaneko K, Saito T.
    • Organizer
      Connective Tissue Oncology Society, 23th Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Anti-tumor activity of tyrosine kinase inhibitors and gene expression profiles in alveolar soft part sarcoma.2018

    • Author(s)
      Suehara Y, Tanabe Y, Mukaihara K, Kurihara K, Akaike K, Hayashi T, Mogushi K, Kaneko K, Saito T.
    • Organizer
      the 64th Annual Meeting of the Orthopaedic Research Society March 10-13 2018, New Orleans, USA
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Anti-tumor activity of tyrosine kinase inhibitors in alveolar soft part sarcoma.2017

    • Author(s)
      Suehara Y, Tanabe Y, Akaike K, Mogushi K, Hayashi T, Kurihara T, Kaneko K, Saito T.
    • Organizer
      European Society For Medical Oncology ASIA, Nov 17-19th 2017, Singapore, Singapore
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A complete responder to pazopanib in high-grade soft tissue sarcomas.2017

    • Author(s)
      Suehara Y, Kohsaka S, Yamaguchi S, Akaike K, Hayashi T, Tanabe Y, Ueno T, Kojima S, Takeda I, Hayashi R, Saito T, Mano H, Kato S.
    • Organizer
      Connective Tissue Oncology Society, 22th Annual Meeting, November 8 - 11, 2017 , Hawaii, USA
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diagnostic strategy for skeletal metastasis of unknown primary origin at the initial visit/ Up-to-date treatment of skeletal metastasis2017

    • Author(s)
      Kim Y, Suehara Y, Kaneko K.
    • Organizer
      27th Korean-Japanese Combined Orthopedic Symposium May 25-26 2017, Incheon, Korea
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 軟部肉腫Pazopanib著効例における分子病理学的探索2017

    • Author(s)
      末原義之、高阪真路、赤池慶祐、加藤俊介、林大久生、山口茂夫、田邊雄、窪田大介、高木辰哉、金子和夫、間野博行、齋藤剛
    • Organizer
      第32回日本整形外科学会基礎学術集会 2017年10月26-27日 沖縄コンベンションセンター 那覇市 沖縄県
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 軟部肉腫Pazopanib著効例 “super-responder”に基づいた分子病理学的探索2017

    • Author(s)
      末原義之、高阪真路、赤池慶祐、加藤俊介、林大久生、山口茂夫、田邊雄、窪田大介、高木辰哉、金子和夫、間野博行、齋藤剛
    • Organizer
      第50回日本整形外科学会骨軟部腫瘍学術集会 2017年7月13-14日 京王プラザホテル 新宿 東京
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi