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

• Project/Area Number: 20591254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto 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: ¥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).

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Three hour drip infusion of cyclosporine A and C3 monitnring in nediatric cord blood transplantation (2008)
  • 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
• [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
• [Remarks] ホームページ等
  • URL: http://www.hs.med.kyoto-u.ac.jp/achieve-mt1.html
• [Remarks]
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• [Remarks]
  • URL: http://www.hs.med.kyoto-u.ac.jp/achieve-mtl.html.
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  • URL: http://www.hs.med.kyoto-u.ac.jp/achieve-mt1.html