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Cancer stem cell assay by a new immunodeficient mouse model Cancer stem cell assay by a new immunodeficient mouse model harboring with optimal bone marrow microenvironment

Research Project

Project/Area Number 15K15365
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKyushu University

Principal Investigator

Akashi Koichi  九州大学, 医学研究院, 教授 (80380385)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsがん幹細胞 / 異種移植アッセイ / 免疫不全マウス / マクロファージ / SIRPA / 骨髄ニッチ / ヒト疾患モデル / マクロファージ寛容 / 幹細胞アッセイシステム / 異種移植モデル
Outline of Final Research Achievements

To evaluate human cancer stem cells in xenotransplantation models, a variety of immunodeficient mouse lines have been developed. We found that in xenograft engraftment, inhibition of phagocytic reaction of mouse macrophages is essential in addition to lymphoid depletion. Here, we have established a new immunodeficient BRGhS mouse line, harbouring a complete macrophage tolerance. Furthermore, we introduced KITW/v mutation into BRGhS line to optimize mouse bone marrow microenvironment for human cell engraftment. This strain should be very useful for human cancer stem cell assay.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015

All Journal Article (21 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 21 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 11 results)

  • [Journal Article] Identification of unipotent megakaryocyte progenitors in human hematopoiesis.2017

    • Author(s)
      K. Miyawaki. Iwasaki, T. Jiromaru, H. Kusumoto, A. Yurino, T. Sugio, Y. Uehara, J. Odawara, S. Daitoku, Y. Kunisaki, Y. Mori, Y. Arinobu, H. Tsuzuki, Y. Kikushige, T. Iino, K. Kato, K. Takenaka, T. Miyamoto, T. Maeda, *K. Akashi
    • Journal Title

      Blood

      Volume: 印刷中 Issue: 25 Pages: 3332-3343

    • DOI

      10.1182/blood-2016-09-741611

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Notch1 expression is regulated at the post-transcriptional level by the 3′ untranslated region in hematopoietic stem cell development2017

    • Author(s)
      Mizuno Shinichi、Iino Tadafumi、Ozawa Hidetoshi、Arinobu Yojiro、Chong Yong、Akashi Koichi
    • Journal Title

      International Journal of Hematology

      Volume: 107 Issue: 3 Pages: 311-319

    • DOI

      10.1007/s12185-017-2358-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent detection of alternatively spliced BCR-ABL variant results in a failure to achieve deep molecular response2017

    • Author(s)
      Yuda Junichiro、Miyamoto Toshihiro、Odawara Jun、Ohkawa Yasuyuki、Semba Yuichiro、Hayashi Masayasu、Miyamura Koichi、Tanimoto Mitsune、Yamamoto Kazuhito、Taniwaki Masafumi、Akashi Koichi
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 11 Pages: 2204-2212

    • DOI

      10.1111/cas.13353

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a human clonogenic progenitor with strict monocyte differentiation potential: A counterpart of mouse cMoPs2017

    • Author(s)
      Kawamura S, Onai N, Miya F, Sato T, Tsunoda T, Kurabayashi K, Yotsumoto S, Kuroda S, Takenaka K, Akashi K, Ohteki T
    • Journal Title

      Immunity

      Volume: 46 Issue: 5 Pages: 835-848

    • DOI

      10.1016/j.immuni.2017.04.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinical features and outcomes of patients with primary myelofibrosis in Japan: report of a 17-year nationwide survey by the Idiopathic Disorders of Hematopoietic Organs Research Committee of Japan.2017

    • Author(s)
      Takenaka K, Shimoda K, Uchida N, Shimomura T, Nagafuji K, Kondo T, Shibayama H, Mori T, Usuki K, Azuma T, Tsutsumi Y, Tanaka J, Dairaku H, Matsuo K, Ozawa K, Kurokawa M, Arai S, Akashi K.
    • Journal Title

      Int J Henatol

      Volume: 105 Issue: 1 Pages: 59-69

    • DOI

      10.1007/s12185-016-2102-3

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes.2017

    • Author(s)
      Tsuzuki H, Arinobu Y, Miyawaki K, Takaki A, Ota SI, Ota Y, Mitoma H, Akahoshi M, Mori Y, Iwasaki H, Niiro H, Tsukamoto H, and Akashi K.
    • Journal Title

      Immunology

      Volume: 150 Issue: 1 Pages: 64-73

    • DOI

      10.1111/imm.12667

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calreticulin mutation does not contribute to disease progression in essential thrombocythemia by inhibiting phagocytosis.2016

    • Author(s)
      S. Daitoku, K. Takenaka, T. Yamauchi, A. Yurino, F. Jinnouchi, T. Nunomura, T. Eto, T. Kamimura, M. Higuchi, N. Harada, N. Saito, T. Miyamoto, H. Iwasaki, *K. Akashi
    • Journal Title

      Exp Hematol

      Volume: 44 Issue: 9 Pages: 817-825

    • DOI

      10.1016/j.exphem.2016.05.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.2016

    • Author(s)
      A. Yurino, K. Takenaka, T. Yamauchi, T. Nunomura, Y. Uehara, F. Jinnouchi, K. Miyawaki, Y. Kikushige, K. Kato, T. Miyamoto, H. Iwasaki, Y. Kunisaki, *K. Akashi
    • Journal Title

      Stem Cell Reports

      Volume: 7 Issue: 3 Pages: 425-438

    • DOI

      10.1016/j.stemcr.2016.07.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.2016

    • Author(s)
      Nio K, Higashi D, Kumagai H, Arita S, Shirakawa T, Nakashima K, Shibata Y, Esaki M, Manabe T, Nagai S, Ueki T, Nakano M, Ariyama H, Kusaba H, Hirahashi M, Oda Y, Esaki T, Mitsugi K, Futami K, Akashi K, Baba E.
    • Journal Title

      Anticancer Drugs

      Volume: 27 Issue: 5 Pages: 457-463

    • DOI

      10.1097/cad.0000000000000338

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced Dose of Salvage-line Regorafenib Monotherapy for Metastatic Colorectal Cancer in Japan.2015

    • Author(s)
      Hirano G, Makiyama A, Makiyama C, Esaki T, Oda H, Uchino K, Komoda M, Tanaka R, Matsushita Y, Mitsugi K, Shibata Y, Kumagai H, Arita S, Ariyama H, Kusaba H, Akashi K, Baba E.
    • Journal Title

      Anticancer Res

      Volume: 35 Pages: 371-377

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T-cell leukemia/lymphoma in a pilot study.2015

    • Author(s)
      Suehiro Y, Atsuhiko Hasegawa A, Tadafumi Iino T, Amane Sasada A, Nobukazu Watanabe N, Masao Matsuoka M, Ayako Takamori A, Ryuji Tanosaki R, Atae Utsunomiya A, Ilseung Choi I, Tetsuya Fukuda T, Osamu Miura O, Shigeo Takaishi S, Takanori Teshima T, Koichi Akashi K, Mari Kannagi M, Naokuni Uike N, Jun Okamura J
    • Journal Title

      Br J Haematol

      Volume: 169 Issue: 3 Pages: 356-367

    • DOI

      10.1111/bjh.13302

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.2015

    • Author(s)
      Oritani K, Okamoto S, Tauchi T, Saito S, Ohishi K, Handa H, Takenaka K, Gopalakrishna P, Amagasaki T, Ito K, Akashi K.
    • Journal Title

      Int J Hematol

      Volume: 101 Issue: 3 Pages: 295-304

    • DOI

      10.1007/s12185-015-1746-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Factors prognostic of eligibility for allogeneic HCT among older patients with AML-CR1 and adverse- or intermediate-risk cytogenetics.2015

    • Author(s)
      Yamasaki S, Yoshimoto G, Ogawa R, Aoki K, Higuchi M, Harada N, Arima F, Kondo S, Matubara F, Takahashi T, Uike N, Miyamoto T, Okamura S, Akashi K.
    • Journal Title

      Ann Hematol

      Volume: 94 Issue: 7 Pages: 1159-1165

    • DOI

      10.1007/s00277-015-2338-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.2015

    • Author(s)
      Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T.:
    • Journal Title

      Blood

      Volume: 125 Issue: 19 Pages: 3014-23

    • DOI

      10.1182/blood-2014-12-615781

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes.2015

    • Author(s)
      Izumi K, Mine K, Inoue Y, Teshima M, Ogawa S, Kai Y, Kurafuji T, Hirakawa K, Miyakawa D, Ikeda H, Inada A, Hara M, Yamada H, Akashi K, Niho Y, Ina K, Kobayashi T, Yoshikai Y, Anzai K, Yamashita T, Minagawa H, Fujimoto S, Kurisaki H, Shimoda K, Katsuta H, Nagafuchi S.
    • Journal Title

      Nat Commun.

      Volume: 6 Issue: 1 Pages: 1-10

    • DOI

      10.1038/ncomms7748

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning.2015

    • Author(s)
      Sugita J, Kawashima N, Fujisaki T, Kakihana K, Ota S, Matsuo K, Miyamoto T, Akashi K, Taniguchi S, Harada M, Teshima T.
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 21 Issue: 9 Pages: 1646-1652

    • DOI

      10.1016/j.bbmt.2015.06.008

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis.2015

    • Author(s)
      Ayano M, Tsukamoto H, Kohno K, et al.
    • Journal Title

      J Immunol

      Volume: 195 Issue: 3 Pages: 892-900

    • DOI

      10.4049/jimmunol.1403046

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma.2015

    • Author(s)
      Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K.
    • Journal Title

      Blood

      Volume: 126 Issue: 19 Pages: 2193-2201

    • DOI

      10.1182/blood-2015-02-629600

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression.2015

    • Author(s)
      Kikushige Y, Miyamoto T, Yuda J, Jabbarzadeh-Tabrizi S, Shima T, Takayanagi S, Niiro H, Yurino A, Miyawaki K, Takenaka K, Iwasaki H, Akashi K
    • Journal Title

      Cell Stem Cell.

      Volume: 17 Issue: 3 Pages: 341-352

    • DOI

      10.1016/j.stem.2015.07.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chd5 Regulates MuERV-L/MERVL Expression in Mouse Embryonic Stem Cells Via H3K27me3 Modification and Histone H3.1/H3.2.2015

    • Author(s)
      Hayashi M, Maehara K, Harada A, Semba Y, Kudo K, Takahashi H, Oki S, Meno C, Ichiyanagi K, Akashi K, Ohkawa Y.
    • Journal Title

      J Cell Biochem

      Volume: 117 Issue: 3 Pages: 780-792

    • DOI

      10.1002/jcb.25368

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splenic irradiation provides transient palliation for symptomatic splenomegaly associated with primary myelofibrosis: a report on 14 patients.2015

    • Author(s)
      Kitanaka A, Takenaka K, Shide K, Miyamoto T, Kondo T, Ozawa K, Kurokawa M, Akashi K, Shimoda K.
    • Journal Title

      Int J Hematol

      Volume: 103 Issue: 4 Pages: 423-428

    • DOI

      10.1007/s12185-016-1940-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] がん幹細胞研究の進歩と治療開発2017

    • Author(s)
      赤司浩一
    • Organizer
      第114回日本内科学会総会・講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨髄性白血病幹細胞成立におけるTIM-3/Gal-9オートクラインシグナルの役割2017

    • Author(s)
      赤司浩一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ヒト白血病幹細胞研究の進歩2017

    • Author(s)
      赤司浩一
    • Organizer
      第54回日本臨床分子医学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ヒト骨髄性白血病に共通する悪性幹細胞の自己再生メカニズム2016

    • Author(s)
      赤司 浩一
    • Organizer
      The 47th International Symposium of the Princess Takamatsu Cancer Research Fund
    • Place of Presentation
      東京
    • Year and Date
      2016-11-08
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TIM-3/Galectin-9 axis is a potential therapeutic target for human myeloid leukemia stem cells2016

    • Author(s)
      赤司 浩一
    • Organizer
      第14回日本臨床腫瘍学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-07-29
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TIM-3 and Its Ligand, Galectin-9, Constitute an Autocrine Loop Universally Critical for Development of Human Myeloid Leukemia Stem Cells2016

    • Author(s)
      Koichi Akashi
    • Organizer
      JCA-AACR Special Joint Conference
    • Place of Presentation
      東京
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A TIM-3/Gal-9 autocrine stimulatory loop drives self-renewal of hu- man myeloid leukemia stem cells and leukemic progression2016

    • Author(s)
      Koichi Akashi
    • Organizer
      THE 41st 1NAITO CONFERENCE
    • Place of Presentation
      札幌
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] ヒト白血病幹細胞研究の進歩2016

    • Author(s)
      赤司 浩一
    • Organizer
      第20回日本がん分子標的治療学会学術集会
    • Place of Presentation
      別府
    • Year and Date
      2016-05-31
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] ヒト白血病幹細胞研究の進歩2016

    • Author(s)
      赤司 浩一
    • Organizer
      第51回日本血液学会春季北海道地方会
    • Place of Presentation
      札幌
    • Year and Date
      2016-04-09
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TIM-3 and its ligand, galectin-9, constitute an autocrine loop critical for development of human myeloid leukemia stem cells.2016

    • Author(s)
      Koichi Akashi
    • Organizer
      JSPS-NUS Joint Symposium“New Horizons in Normal and Cancer Stem Cell Research”
    • Place of Presentation
      Singapore
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 『TIM-3 and its ligand, galectin-9 constitute an autocrine loop to maintain stem cells in most human myeloid malignancies.2015

    • Author(s)
      Koichi Akashi
    • Organizer
      2015 ISEH Annual Meeting
    • Place of Presentation
      Kyoto Japan
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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