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Development of immunotherapy against the bone destructive tumor

Research Project

Project/Area Number 23659946
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

HIASA Masahiro  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (90511337)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords破骨細胞 / 樹状細胞 / TACE / TIMP3 / TIMP-3
Research Abstract

Multiple myeloma (MM) generates devastating bone destruction. We recently reported that TNFα converting enzyme (TACE) expression in monocytes cleaved their surface M-CSF receptor (M-CSFR), which drastically disrupts osteoclastogenesis(Blood, 2009). Because TACE activity is inhibited by TIMP3, we explored the role of BMSC-derived TIMP3 in monocytic differentiation into DC or OC in MM. This study clarified that TIMP3 over-produced in MM bone marrow microenvironment restores surface M-CSFR on monocytes to facilitate their downstream signaling, which causes extensive bone destruction and impaired DC differentiation in MM. TIMP3 may therefore become a novel target in the treatment of MM bone disease.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (21 results)

All 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (14 results)

  • [Journal Article] Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors2012

    • Author(s)
      Ikegame A, Ozaki S, Tsuji D, Harada T, Fujii S, Nakamura S, Miki H, Nakano A, Kagawa K, Takeuchi K, Abe M, Watanabe K, Hiasa M, Kimura N, Kikuchi Y, Sakamoto A, Habu K, Endo M, Itoh K, Yamada-Okabe H, MatsumotoT
    • Journal Title

      Leukemia

      Volume: 26 Issue: 9 Pages: 2124-2134

    • DOI

      10.1038/leu.2012.78

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] KRN5500, a spicamycin derivative, exerts anti-myeloma effects through impairing both myeloma cells and osteoclasts2011

    • Author(s)
      Miki H, Ozaki S, Nakamura S, Oda A, Amou H, Ikegame A, Watanabe K, Hiasa M, Cui Q, Harada T, Fujii S, Nakano A, Kagawa K, Takeuchi K, Yata K, Sakai A, Abe M, Matsumoto T
    • Journal Title

      Br J Haematol

      Volume: 155 Issue: 3 Pages: 328-339

    • DOI

      10.1111/j.1365-2141.2011.08844.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Delayed treatment with vitamin C and N-acetyl-cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib2011

    • Author(s)
      Nakano A, Abe M, Oda A, Amou A, Hiasa M, Nakamura S, Miki H, Harada T, Fujii S, Kagawa K, Takeuchi K, Watanabe T, Ozaki S, Matsumoto T
    • Journal Title

      Int J Hematol

      Volume: 93 Issue: 6 Pages: 727-735

    • DOI

      10.1007/s12185-011-0850-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting myeloma-osteoclast interaction with V γ 9V 6 2 T cells2011

    • Author(s)
      Cui Q, Shibata H, Oda A, Amou H, Nakano A, Yata K, Hiasa M, Watanabe K, Nakamura S, Miki H, Harada T, Fujii S, Kagawa K, Takeuchi K, Ozaki S, Matsumoto T, Abe M
    • Journal Title

      Int J Hematol

      Volume: 94 Issue: 1 Pages: 63-70

    • DOI

      10.1007/s12185-011-0885-9

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells2011

    • Author(s)
      Asano J, Nakano A, Oda A, Amou H, Hiasa M, Takeuchi K, Miki H, Nakamura S, Harada T, Fujii S, Kagawa K, Endo I, Yata K, Sakai A, Ozaki S, Matsumoto T, Abe M
    • Journal Title

      Leukemia

      Volume: 25 Issue: 7 Pages: 1182-1188

    • DOI

      10.1038/leu.2011.60

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting myeloma-osteoclast interaction with Vγ9Vδ2 T cells.2011

    • Author(s)
      Cui Qu
    • Journal Title

      Int J Hematol.

      Volume: 94(1) Pages: 63-70

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Delayed treatment with vitamin C and N-acetyl-L-cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib.2011

    • Author(s)
      Ayako Nakano
    • Journal Title

      Int J Hematol.

      Volume: 93(6) Pages: 727-35

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Pim-2 acts as a common downstream mediator to suppress bone formation in myeloma2012

    • Author(s)
      日浅雅博
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2012-10-20
    • Related Report
      2012 Final Research Report
  • [Presentation] RelB attenuates the activation of the classical NF-κB pathway to facilitate osteoblastogenesis2012

    • Author(s)
      Masahiro Hiasa
    • Organizer
      ANZBMS 22nd Annual Scientific Meeting
    • Place of Presentation
      Pan Pacific Hotel (Australia)
    • Year and Date
      2012-09-05
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel role of NF-κB relB in bone remodeling2011

    • Author(s)
      日浅雅博
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2011-11-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Prevention of tumor growth and bone destruction in myeloma by Pim kinase inhibition2011

    • Author(s)
      Masahiro Hiasa
    • Organizer
      ASBMR 2011 Annual Meeting
    • Place of Presentation
      San Diego Convention Center (USA)
    • Year and Date
      2011-09-19
    • Related Report
      2012 Final Research Report
  • [Presentation] Pimキナーゼ阻害による腫瘍進展と骨破壊の抑制2011

    • Author(s)
      日浅雅博
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-09-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Dual effects of Pim inhibition on myeloma: induction of bone formation and tumor suppression2011

    • Author(s)
      Masahiro Hiasa
    • Organizer
      IOF-ANZBMS 2011 Annual Meeting
    • Place of Presentation
      Gold Coast Convention Centre (Australia)
    • Year and Date
      2011-09-06
    • Related Report
      2012 Final Research Report
  • [Presentation] Pimキナーゼの阻4害は骨芽細胞分化を促進し、骨髄腫骨病変の形成と腫瘍進展を抑制する2011

    • Author(s)
      日浅雅博
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2011-07-28
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel role of NF-κB relB in bone remodeling2011

    • Author(s)
      日浅雅博
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Research-status Report
  • [Presentation] Pimキナーゼ阻害による腫瘍進展と骨破壊の抑制2011

    • Author(s)
      日浅雅博
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2011 Research-status Report
  • [Presentation] Prevention of tumor growth and bone destruction in myeloma by Pim kinase inhibition.2011

    • Author(s)
      Masahiro Hiasa
    • Organizer
      ASBMR 2011 Annual Meeting
    • Place of Presentation
      San Diego Convention Center (San Diego)
    • Related Report
      2011 Research-status Report
  • [Presentation] Dual effects of Pim inhibition on myeloma: induction of bone formation and tumor suppression2011

    • Author(s)
      Masahiro Hiasa
    • Organizer
      IOF-ANZBMS 2011 Annual Meeting
    • Place of Presentation
      Gold Coast Convention Centre(Queensland)
    • Related Report
      2011 Research-status Report
  • [Presentation] Pimキナーゼの阻害は骨芽細胞分化を促進し、骨髄腫骨病変の形成と腫瘍進展を抑制する2011

    • Author(s)
      日浅雅博
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Related Report
      2011 Research-status Report
  • [Presentation] Pim-2 acts as a common downstream mediator to suppress bone formation in myeloma

    • Author(s)
      日浅雅博
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] RelB attenuates the activation of the classical NF-κB pathway to facilitate osteoblastogenesis

    • Author(s)
      Hiasa M
    • Organizer
      ANZBMS 22nd Annual Scientific Meeting
    • Place of Presentation
      Pan Pacific Hotel (Australia)
    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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