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Role of Notch in the pathophysiology of leukemia stem cells and drug sensitivity tests for Notch inhibitors

Research Project

Project/Area Number 20590557
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TOHDA Shuji  Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 准教授 (80251510)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords臨床血液学 / 白血病 / 幹細胞 / Notch / 分子標的治療 / ガンマセクレターゼ / 白血病幹細胞 / Notchリガンド
Research Abstract

In order to treat leukemia effectively, we have to understand the pathophysiology of leukemia stem cells. Notch signaling is important for the regulation of self-renewal of leukemia stem cells. We found the molecular mechanism how the Notch ligand stimulation activates the Notch signaling and how it leads to cell growth. Moreover, we found that gamma-secretase inhibitors, which inhibit Notch signaling, suppress the growth of leukemia cells. We developed the methods to predict its effects.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (35 results)

All 2011 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 9 results) Presentation (7 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Effects of Combination of Notch Inhibitor plus Hedgehog Inhibitor or Wnt Inhibitor on Growth of Leukemia Cells.2011

    • Author(s)
      Okuhashi Y, Itoh M, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 31

      Pages: 893-896

    • Related Report
      2010 Final Research Report
  • [Journal Article] Promotionof the Self-renewal Capacity of Human Leukemia Cells by Sonic Hedgehog Protein.2011

    • Author(s)
      Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Murohashi I, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 31

      Pages: 781-784

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effects of gamma-secretase inhibitors on the growth of leukemia cells.2010

    • Author(s)
      Okuhashi Y, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 30

      Pages: 495-498

    • Related Report
      2010 Final Research Report
  • [Journal Article] Amplification of IGH/CCND1 fusion gene in a primary plasma cell leukemia case.2010

    • Author(s)
      Ishigaki T, Sasaki K, Watanabe K, Nakamura N, Toyota S, Kobayashi H, Tohda S
    • Journal Title

      Cancer Genet Cytogenet. 201

      Pages: 62-65

    • Related Report
      2010 Final Research Report
  • [Journal Article] Gamma-secretase inhibitors induce erythroid differentiation in erythroid leukemia cell lines.2010

    • Author(s)
      Okuhashi Y, Itoh M, Arai A, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 30

      Pages: 4071-4074

    • Related Report
      2010 Final Research Report
  • [Journal Article] 白血病の分子標的治療のケミカルバイオロジー2010

    • Author(s)
      東田修二
    • Journal Title

      臨床化学 39

      Pages: 234-237

    • NAID

      10025632530

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effects of gamma-secretase inhibitors on the growth of leukemia cells2010

    • Author(s)
      Okuhashi Y, Nara N, Tohda S
    • Journal Title

      Anticancer Research

      Volume: 30 Pages: 495-498

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amplification of IGH/CCND1 fusion gene in a primary plasma cell leukemia-case2010

    • Author(s)
      Ishigaki T, Sasaki K, Kobayashi H, Tohda S
    • Journal Title

      Cancer Genetics and Cytogenetics

      Volume: 201 Pages: 62-65

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors induce erythroid differentiation in erythroid leukemia cell lines2010

    • Author(s)
      Okuhashi Y, Itoh M, Arai A, Nara N, Tohda S
    • Journal Title

      Anticancer Research

      Volume: 30 Pages: 4071-4074

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells.2009

    • Author(s)
      Kawahara T, Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 29

      Pages: 4629-4632

    • Related Report
      2010 Final Research Report
  • [Journal Article] Transition of cleaved Notch1 and gene expression changes in myeloblastic leukemia cells stimulated with notch ligands.2009

    • Author(s)
      Fu L, Katsube K, Tohda S
    • Journal Title

      Anticancer Res. 29

      Pages: 3967-3970

    • Related Report
      2010 Final Research Report
  • [Journal Article] NF-kappaB activation induced by Notch ligandstimulation in acute myeloid leukemia cells.2009

    • Author(s)
      Itoh M, Fu L, Tohda S
    • Journal Title

      Oncol Rep. 22

      Pages: 631-634

    • Related Report
      2010 Final Research Report
  • [Journal Article] 白血病の病態におけるNotchの機能解析2009

    • Author(s)
      東田修二
    • Journal Title

      臨床病理 57

      Pages: 351-356

    • NAID

      10025224703

    • Related Report
      2010 Final Research Report
  • [Journal Article] Transition of cleaved Notch1 and gene expression changes in myeloblastic leukemia cells stimulated with notch ligands2009

    • Author(s)
      Fu L, Katsube K, Tohda S
    • Journal Title

      Anticancer Research 29

      Pages: 3967-3970

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NF-kappaB activation induced by Notch ligand stimulation in acute myeloid leukemia cells2009

    • Author(s)
      Itoh M, Fu L, Tohda S
    • Journal Title

      Oncology Reports 22

      Pages: 631-634

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells2009

    • Author(s)
      Kawahara T, Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Nara N, Tohda S
    • Journal Title

      Anticancer Research 29

      Pages: 4629-4632

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Promotion of the self-renewal capacity of human acute leukemia cells by Wnt3A.2008

    • Author(s)
      Kawaguchi-Ihara N, Murohashi I, Nara N, Tohda S
    • Journal Title

      Anticancer Res. 28

      Pages: 2701-2704

    • Related Report
      2010 Final Research Report
  • [Journal Article] Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury.2008

    • Author(s)
      Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, Kuwahara M, Tohda S, Sakano S, Sasaki S.
    • Journal Title

      Kidney Int 73

      Pages: 1240-1250

    • Related Report
      2010 Final Research Report
  • [Journal Article] Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis.2008

    • Author(s)
      Nemoto Y, Kanai T, Tohda S, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Fukuda T, Miura O, Yagita H, Watanabe M.
    • Journal Title

      Inflamm Bowel Dis 14

      Pages: 1491-1503

    • Related Report
      2010 Final Research Report
  • [Journal Article] Promotion of the self-renewal capacity of human acute leukemia cells by Wnt3A2008

    • Author(s)
      Kawaguchi-Ihara N, Murohashi I, Nara N, Tohda S
    • Journal Title

      Anticancer Research 28

      Pages: 2701-2704

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury2008

    • Author(s)
      Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, KUwahara M, Tohda S, Sakano S, Sasaki S
    • Journal Title

      Kidney International 73

      Pages: 1240-1250

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Negative feedback regulation of colitogenie CD4+T cells byincreased granulopoiesis2008

    • Author(s)
      Nemoto Y, Kanai T, Tohda s, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Fukuda T, Miura O, Yagita H, Watanabe M
    • Journal Title

      Inflammatory Bowel Diseases 14

      Pages: 1491-1503

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 白血病細胞の増殖におけるNotchシグナルとWnt, Hedgehogシグナルとの相互作用2010

    • Author(s)
      奥橋佑基, 石垣知寛, 伊藤真以, 東田修二
    • Organizer
      第57回日本臨床検査医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2010-09-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 白血病細胞の増殖におけるNotchシグナルとWnt, Hedgehogシグナルとの相互作用2010

    • Author(s)
      奥橋佑基, 石垣知寛, 伊藤真以, 東田修二
    • Organizer
      第57回日本臨床検査医学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 白血病の分子標的治療のケミカルバイオロジー2009

    • Author(s)
      東田修二
    • Organizer
      第49回日本臨床化学会学術集会ワークショップ
    • Place of Presentation
      長崎
    • Year and Date
      2009-09-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 白血病の分子標的治療のケミカルバイオロジー2009

    • Author(s)
      東田修二
    • Organizer
      第49回日本臨床化学会学術集会
    • Place of Presentation
      長崎大学医学部
    • Year and Date
      2009-09-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Notchシグナル阻害剤による赤白血病細胞の赤芽球分化誘導効果2009

    • Author(s)
      奥橋佑基、河原達雄、井原寛子、星百合子、東田修二
    • Organizer
      第56回日本臨床検査医学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-08-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 日本臨床検査医学会学会賞生命科学賞受賞、受賞講演.白血病の病態におけるNotchの機能解析2008

    • Author(s)
      東田修二
    • Organizer
      第55回日本臨床検査医学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-11-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 白血病の病態におけるNotchの機能解析2008

    • Author(s)
      東田修二
    • Organizer
      第55回日本臨床検査医学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report
  • [Book] 急性白血病、血友病など17項目(福井次矢、奈良信雄 編)(内科診断学第2版)2008

    • Author(s)
      東田修二
    • Publisher
      医学書院
    • Related Report
      2010 Final Research Report
  • [Book] 可溶性IL-2レセプター、顆粒球コロニー刺激因子など15項目(櫻林郁之介、熊坂一成監修)(最新臨床検査項目辞典)2008

    • Author(s)
      東田修二
    • Publisher
      医歯薬出版
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.tmd.ac.jp/med/mlab/mlab_graduate-school.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/med/mlab/mlab_graduate-school.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/med/mlab/mlab_graduate-school.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://wv/w.tmd.ac.jp/med/ralab/inlab_graduate-school.html

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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