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Development of new treatment for refractory malignant diseases and investigation of new cell death mechanisms

Research Project

Project/Area Number 20591254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKyoto University

Principal Investigator

ADACHI Souichi  Kyoto University, 大学院・医学研究科, 教授 (10273450)

Co-Investigator(Renkei-kenkyūsha) WATANABE Ken-Ichirou  京都大学, 大学院・医学研究科, 講師 (20324634)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords難治性血液腫瘍疾患 / 細胞死 / アポトーシス / オートファジー / 転移抑制 / 予後因子解析
Research Abstract

We reported autophagy in malignant rhabdoid cells induced by depsipeptide and found that AIF translocation from mitochondria to nuclei has been related with this autophagy. We also analysed resistant mechanism of depsipeptide from our depsipepside-resisitant cell lines and ERK pathway was activated in these resistant cells. We established mouse osteosarcoma cell line which is easily metastasize to lung and treated those mice by zoledronic acid and CPT11. CPT11 inhibited invasion of osteosarcoma cells and inhibited lung metastasis in vivo. We also reported that exon 5 of BAALC as a new poor prognostic factor and CEBPA mutations as good prognostic marker in child acute myelogenous leukemia (AML).

Report

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

    (46 results)

All 2011 2010 2009 2008 Other

All Journal Article (29 results) (of which Peer Reviewed: 28 results) Presentation (12 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype : a study by the Japanese Childhood AML Cooperative Study Group.2010

    • Author(s)
      Mizushima Y, Watanabe K, Adachi S
    • Journal Title

      Int J Hematol 91

      Pages: 831-837

    • NAID

      10026511260

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] N-acetyl cysteine scavenges singlet oxygen but cannot protect cells from it.2010

    • Author(s)
      Nishinaka Y, Arai T, Adachi S
    • Journal Title

      Life Sci 86

      Pages: 808-813

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of chronic idiopathic thrombocytopenic purpura in Japanese children ; a retrospective multi-center study.2010

    • Author(s)
      Kubota M, Adachi S, et al.
    • Journal Title

      Int J Hematol 91

      Pages: 252-257

    • NAID

      10026111433

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of refractory donor lymphocyte infusion-induced immune-mediated pancytopenia by rituximab.2010

    • Author(s)
      Kato I, Adachi S
    • Journal Title

      Ped Blood Cancer 54

      Pages: 329-331

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype : a study by the Japanese Childhood AML Cooperative Study Group.2010

    • Author(s)
      Mizushima Y, Adachi S, et.al.
    • Journal Title

      Int J Hematol

      Volume: 91 Pages: 831-837

    • NAID

      10026511260

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of refractory donor lymphocyte infusion-induced immune-mediated pancytopenia by rituximab.2010

    • Author(s)
      Kato I, Adachi S, et.al.
    • Journal Title

      Ped Blood Cancer

      Volume: 54 Pages: 329-331

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of chronic idiopathic thrombocytopenic purpura in Japanese children ; a retrospective multi-center study.2010

    • Author(s)
      Kubota M, Adachi S, et.al.
    • Journal Title

      Int J Hematol

      Volume: 91 Pages: 252-257

    • NAID

      10026111433

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-acetyl cysteine scavenges singlet oxygen but cannot protect cells from it.2010

    • Author(s)
      Nishinaka Y, Adachi S, et.al.
    • Journal Title

      Life Sci

      Pages: 808-813

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The antioxidant EUK-8 prevents murine dilated cardiomyopathy.2009

    • Author(s)
      Kawakami S, Adachi S, Shimizu T, et al.
    • Journal Title

      Circ J 73

      Pages: 2125-2134

    • NAID

      10025937556

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful cord blood transplantation using reduced-intensity conditioning regimen for advanced childhood-onset cerebral adrenoleukodystrophy.2009

    • Author(s)
      Awaya T, Adachi S, et al.
    • Journal Title

      Pediatr Transplant Epub ahead of print

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survival after HLA-haploidentical SCT from noninherited maternal antigen-mismatched family donors : impact of chronic GVHD.2009

    • Author(s)
      Kanda J, Adachi S., et al.
    • Journal Title

      Bone Marrow Transplant 44

      Pages: 327-329

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Catechin, green tea component, causes caspase-independent necrosis-like cell death in chronic myelogenous leukemia.2009

    • Author(s)
      Iwasaki R, Adachi S, et al.
    • Journal Title

      Cancer Sci 100

      Pages: 349-356

    • NAID

      10025142762

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury.2009

    • Author(s)
      Hiraumi Y, Watanabe K, Adachi S, et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 296

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of ERK activation in human osteosarcoma cell resistance to the HDAC inhibitor FK228.2009

    • Author(s)
      Matsubara H, Watanabe K, Adachi S, et al.
    • Journal Title

      J Pharmcol Exp Ther 328

      Pages: 839-848

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model.2009

    • Author(s)
      Koto K, Adachi S, Maekawa T, et al.
    • Journal Title

      Cancer Lett 274

      Pages: 271-278

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The key role of stemcell factor/KIT signaling in the proliferation of blast cells from Down syndrome-related leukemia.2009

    • Author(s)
      Toki T, Kanezaki R, Adachi S, et al.
    • Journal Title

      Leukemia 23

      Pages: 95-103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation.2009

    • Author(s)
      Watanabe M, Adachi S, Watanabe K, et al.
    • Journal Title

      Int J Cancer 124

      Pages: 55-67

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury.2009

    • Author(s)
      Hiraumi Y, Adachi S, et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 296

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survival after HLA-haploidentical SCT from noninherited maternal antigen-mismatched family donors : impact of chronic GVHD.2009

    • Author(s)
      Kanda J, Adachi S, et al.
    • Journal Title

      Bone Marrow Transplant 44

      Pages: 327-329

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The antioxidant EUK-8 prevents murine dilated cardiomyopathy.2009

    • Author(s)
      Kawakami S, Adachi S, et al.
    • Journal Title

      Circ J 73

      Pages: 2125-2134

    • NAID

      10025937556

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      足立壮一
    • Journal Title

      小児白血病の治療 血液診療エキスパート Vol 1. 白血病(中外医学社)

      Pages: 108-111

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation.2009

    • Author(s)
      Watanabe M, Adachi S, et al.
    • Journal Title

      Int J Cancer 124

      Pages: 55-67

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of ERK activation in human osteosarcoma cell resistance to the HDAC inhibitor FK228.2009

    • Author(s)
      Matsubara H, Adachi S, et al.
    • Journal Title

      J Pharmcol Exp Ther 328

      Pages: 839-848

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model.2009

    • Author(s)
      Koto K, Adachi S, et al.
    • Journal Title

      Cancer Lett 274

      Pages: 271-278

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of cell death execution in Bcr-Abl-positive leukemias.2008

    • Author(s)
      Kamitsuji Y, Adachi S, et al.
    • Journal Title

      Cell Death Differ 15

      Pages: 1712-1722

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal mode of migration participates in pulmonary metastasis of mouse osteosarcoma LM8.

    • Author(s)
      Yui Y, Watanabe K, Adachi S, et al.
    • Journal Title

      Clin Exp Metastasis in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil differentiation from human-induced pluripotent stem cells for disease investigation.

    • Author(s)
      Morishima T, Watanabe K, Adachi S, Heike T, et al.
    • Journal Title

      J Cell Physiol in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Down syndrome and GATA1 mutations in transient abnormal myeloproliferative disorder: mutation classes correlate with progression to myeloid leukemia.

    • Author(s)
      Kanezaki R, Adachi S, Ito E
    • Journal Title

      Blood in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ring/marker chromosome derived from chromosome 7 in childhood acute megakaryoblastic leukemia with monosomy 7.

    • Author(s)
      Fujino H, Watanabe K, Adachi S
    • Journal Title

      Int J Hematol in press

    • NAID

      10026712631

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 血液腫瘍疾患における細胞死-アポトーシスとオートファジー(特別講演)2011

    • Author(s)
      足立壮一
    • Organizer
      第17回Nagoyaアポトーシス研究会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-02-03
    • Related Report
      2010 Final Research Report
  • [Presentation] 血液腫瘍疾患における細胞死-アポトーシスとオートファジー2011

    • Author(s)
      足立壮一
    • Organizer
      第17回Nagoyaアポトーシス研究会
    • Place of Presentation
      名古屋(招待講演)
    • Year and Date
      2011-02-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 小児造血幹細胞移植におけるシクロスポリン3時間点滴静注法とC3モニタリングの有用性の検討2010

    • Author(s)
      足立壮一
    • Organizer
      第52回日本小児血液学会総会 第26回日本小児がん学会学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2010-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] 難治性血液疾患におけるアポトーシスとオートファジー(特別講演)2010

    • Author(s)
      足立壮一
    • Organizer
      第9回血液腫瘍フォーラム
    • Place of Presentation
      津市
    • Year and Date
      2010-02-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 難治性血液疾患におけるアポトーシスとオートファジー2010

    • Author(s)
      足立壮一
    • Organizer
      第9回血液腫瘍フォーラム
    • Place of Presentation
      三重県
    • Year and Date
      2010-02-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] 小児ALL、AMLに対する初回移植成績の解析-小児移植のドナーソース選択のトレンドは?Which Stem Cell Source is Best for Pediatric All and AML? Retrospective Analysis of Pediatric ALL and AML for 1^<st> SCT.2010

    • Author(s)
      足立壮一
    • Organizer
      第32回日本造血細胞移植学会総会
    • Place of Presentation
      浜松市
    • Year and Date
      2010-02-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 血液疾患におけるオートファジー2009

    • Author(s)
      足立壮一
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2009-10-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 思春期と悪性腫瘍2009

    • Author(s)
      足立壮一
    • Organizer
      第21回北海道思春期研究会(特別講演)
    • Place of Presentation
      札幌市
    • Year and Date
      2009-07-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 難治性白血病、癌治療におけるアポトーシスとオートファジー2009

    • Author(s)
      足立壮一
    • Organizer
      第82回日本薬理学会年会シンポジウム
    • Place of Presentation
      横浜市
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 難治性白血病、癌治療におけるアポトーシスとオートファジー2009

    • Author(s)
      足立壮一
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] AMLにおけるdysplasiaの意義2009

    • Author(s)
      足立壮一
    • Organizer
      第7回京滋血液腫瘍懇話会
    • Year and Date
      2009-02-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Three hour drip infusion of cyclosporine A and C3 monitnring in nediatric cord blood transplantation2008

    • Author(s)
      Matsubara H, Adachi S, et al.
    • Organizer
      The 6th Meeting of the EBMT Paediatric Diseases Working Party
    • Place of Presentation
      Ponzan, Poland
    • Year and Date
      2008-06-03
    • Related Report
      2008 Annual Research Report
  • [Book] 小児白血病の治療 血液診療エキスパート(Vol 1)(白血病)2009

    • Author(s)
      足立壮一
    • Total Pages
      229
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.hs.med.kyoto-u.ac.jp/achieve-mt1.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.hs.med.kyoto-u.ac.jp/achieve-mt1.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.hs.med.kyoto-u.ac.jp/achieve-mtl.html.

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.hs.med.kyoto-u.ac.jp/achieve-mt1.html

    • Related Report
      2008 Annual Research Report

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

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