• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of a predictive system of the sensitivity for L-asparaginase in tumor by monoclonal antibody

Research Project

Project/Area Number 24590713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionAichi Medical University

Principal Investigator

Kitoh Toshiyuki  愛知医科大学, 医学部, 准教授 (50243027)

Co-Investigator(Kenkyū-buntansha) YOKOI TOYOHARU  愛知医科大学, 医学部, 教授 (40200886)
TSURUSAWA MASAHITO  愛知医科大学, 医学部, 教授 (90172064)
KATO HIDEFUMI  愛知医科大学, 医学部, 教授 (40298584)
Co-Investigator(Renkei-kenkyūsha) HAMAKUBO TAKAO  東京大学, 先端科学技術研究センター, 教授 (90198797)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords分子標的療法 / アミノ酸要求性 / 選択毒性 / 抗がん剤 / 細胞死 / 酵素製剤 / 感受性予測 / アミノ酸代謝 / 国際情報交換 / 選択的毒性
Outline of Final Research Achievements

Due to the lack of rapid upregulation of asparagine synthetase (ASNS) in ALL cells, they are preferentially killed by ASNase-induced asparagine depletion. The purpose of this study was to examine the usefulness of a rapid flow cytometric assay that measure ASNS protein in whole cells to predict sensitivity and resistance to ASNase. ASNS expression evaluated by cytosolic flow cytometry with the Z5808 monoclonal antibody (McAb) (Hybridoma, 2012) significantly correlated with ASNS activity in leukaemia cell lines. The ASNS protein level was inversely correlated with sensitivity to ASNase in both leukaemia cell lines and primary leukaemia cells. We have shown that ASNS protein expression measured by flow cytometry assay strongly predicts ASNase activity in leukaemia cells and that lower levels of ASNS protein found in AML-M1, M5 and M7 subtypes. The utility of using flow cytometry to measure ASNS levels in clinical samples and the future potential of this methodology is promising.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (6 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and Down syndrome2015

    • Author(s)
      Goto, H. Kaneko, T. Shioda, Y. Kajiwara, M. Sakashita, K. Kitoh, T. Hayakawa, A. Miki, M. Kato, K. Ogawa, A. Hashii, Y. Inukai, T. Kato, C. Sakamaki, H. Yabe, H. Suzuki, R. Kato, K.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 62 Issue: 1 Pages: 148-152

    • DOI

      10.1002/pbc.25245

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism.2015

    • Author(s)
      Okuno Y, Hoshino A, Muramatsu H, Kawashima N, Wang X, Yoshida K, Wada T, Gunji M, Toma T, Kato T, Shiraishi Y, Iwata A, Hori T, Kitoh T, Chiba K, Tanaka H, Sanada M, Takahashi Y, Nonoyama S, Ito M, Miyano S, Ogawa S, Kojima S, Kanegane H.
    • Journal Title

      J Clin Immunol

      Volume: 35 Issue: 7 Pages: 610-614

    • DOI

      10.1007/s10875-015-0202-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Childhood-onset psoriatic arthritis in Down syndrome with psoriasis susceptibility variant CARD14 rs116520752015

    • Author(s)
      Sugiura K, Kitoh T, Watanabe D, Muto M, Akiyama M
    • Journal Title

      Rheumatology (Oxford)

      Volume: 54 Issue: 1 Pages: 197-199

    • DOI

      10.1093/rheumatology/keu419

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced intensity conditioning in allogeneic stem cell transplantation for AML with Down syndrome.2014

    • Author(s)
      Muramatsu H, Sakaguchi H, Taga T, Tabuchi K, Adachi S, Inoue M, Kitoh T, Suminoe A, Yabe H, Azuma E, Shioda Y, Ogawa A, Kinoshita A, Kigasawa H, Osugi Y, Koike K, Kawa K, Kato K, Atsuta Y, Kudo K.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 61 Issue: 5 Pages: 925-927

    • DOI

      10.1002/pbc.24883

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients.2014

    • Author(s)
      Minoia, F. Davi, S. Horne, A. Gao, Y. J. Huasong, Z. Kitoh, T. et. al
    • Journal Title

      Arthritis & rheumatology

      Volume: 66 Issue: 11 Pages: 3160-3169

    • DOI

      10.1002/art.38802

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] THE THERAPEUTIC VALUE OF ASPARAGINE SYNTHETASE DEFICIENCY IN LANGERHANS CELL HISTIOCYTOSIS.2013

    • Author(s)
      Kitoh Toshiyuki, Shimomura Yasuto, Hori Toshinari, Terashima Tsuyoshi, Yokoi Toyoharu, Tsurusawa Masahito.
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 60

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics and outcomes of Chédiak-Higashi syndrome: a nationwide survey of Japan.2013

    • Author(s)
      Nagai K, Yasukawa M, et al.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 60 Issue: 10 Pages: 1582-1586

    • DOI

      10.1002/pbc.24637

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease.2013

    • Author(s)
      Wada T
    • Journal Title

      J Clin Immunol.

      Volume: 33 Issue: 4 Pages: 857-864

    • DOI

      10.1007/s10875-012-9859-9

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PBSCT is associated with poorer survival and increased chronic GvHD than BMT in Japanese paediatric patients with acute leukaemia and an HLA-matched sibling donor.2013

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

      Pediatric Blood and Cancer

      Volume: in press Issue: 9 Pages: 1513-1519

    • DOI

      10.1002/pbc.24524

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the asparagine synthetase level in leukemia cells by monoclonal antibodies.2012

    • Author(s)
      Kusano-Arai O
    • Journal Title

      ybridoma (Larchmt)

      Volume: Oct;31(5) Issue: 5 Pages: 325-332

    • DOI

      10.1089/hyb.2012.0014

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute myeloid leukemia with mediastinal myeloid sarcoma refractory to acute myeloid leukemia therapy but responsive to L-asparaginase2012

    • Author(s)
      Takahashi, Hiroyoshi Koh, Katsuyoshi Kato, Motohiro Kishimoto, Hiroshi Oguma, Eiji Hanada, Ryoji
    • Journal Title

      International Journal of Hematology

      Volume: 96 Issue: 1 Pages: 136-140

    • DOI

      10.1007/s12185-012-1111-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Flow Cytometric Detection of Asparagine Synthetase Protein in Leukemia Cells; Indication for L- Asparaginase Therapy2014

    • Author(s)
      Toshiyuki Kitoh, Kou Suchan Gao Siqiang, Hidefumi Kato, Kenji Miyata, Yasuto Shimomura, Toshinori Hori, Kimiyoshi Sakaguchi, Yasuo Horikoshi, Kentarou Ohki, Katsuyoshi Koh, and Takao Hamakubo.
    • Organizer
      56th ASH Annual Meeting and Exposition
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] DEVELOPMENT OF NEW CLASSIFICATION CRITERIA FOR MACROPHAGE ACTIVATION SYNDROME COMPLICATING SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS2014

    • Author(s)
      Minoia F, Davi S, Bovis F, Pistorio A, Arico M, Avcin T, Behrens E, FD, Filipovich L, Grom A,Henter JI, Horne A, Ilowite N,Jordan M, Khubchandani R,Kitoh T, et.al
    • Organizer
      the 21st European Pediatric Rheumatology Congress
    • Place of Presentation
      Belgrade, Serbia
    • Year and Date
      2014-09-17 – 2014-09-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Hematopoietic Cell Transplantation for Patients with Acute Lymphoblastic Leukemia and Down Syndrome.2014

    • Author(s)
      Hiroaki Goto, Takashi Kaneko, Yoko Shioda, Michiko Kajiwara, Kazuo Sakashita, Toshiyuki Kitoh, Akira Hayakawa, Mizuka Miki, Hisashi Sakamaki, Hiromasa Yabe, Ritsuro Suzuki, Kohji Kato
    • Organizer
      8th SIOP-Asia Congress
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2014-04-15 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Flow Cytometric Detection of Asparagine Synthetase Protein in Leukemia Cells; Indication for LAsparaginase Therapy2013

    • Author(s)
      Toshiyuki Kitoh, Kou Suchan Gao Siqiang, Hidefumi Kato, Yasuto Shimomura, Toshinori Hori, Kimiyoshi Sakaguchi, Hiroshi Miwa, Masahito Tsurusawa, Takao Hamakubo
    • Organizer
      EAP 2013-European Academy of Paediatrics Educational Congress & MasterCourse
    • Place of Presentation
      Lyon, France
    • Related Report
      2013 Research-status Report
  • [Presentation] AGGRESSIVE LANGERHANS CELL HISTIOCYTOSIS FOLLOWING T-ALL: CLONALLY RELATED NEOPLASMS WITHOUT BRAF V600E MUTATION AND SUFFICIENT EXPRESSION OF ASPARAGINE SYNTHETASE2013

    • Author(s)
      Kitoh Toshiyuki, Akiyama Masaharu, Taki Tomohiko, Shimomura Yasuto, Hori Toshinari, Terashima Tsuyoshi, Yokoi Toyoharu, Tsurusawa Masahito.
    • Organizer
      29th Histiocyte Society Annual Meeting
    • Place of Presentation
      Washington, DC. USA
    • Related Report
      2013 Research-status Report
  • [Presentation] THE THERAPEUTIC VALUE OF ASPARAGINE SYNTHETASE DEFICIENCY IN LANGERHANS CELL HISTIOCYTOSIS2012

    • Author(s)
      Kitoh T, Shimomura Y, Hori T, Terashima T, Yokoi T, Tsurusawa M
    • Organizer
      the 28th Annual Meeting of the Histiocyte Society
    • Place of Presentation
      London, UK
    • Related Report
      2012 Research-status Report
  • [Book] 「小児血液・腫瘍学テキスト」 「化学療法薬(ステロイド等)アスパラギナーゼ」2015

    • Author(s)
      鬼頭敏幸
    • Total Pages
      300
    • Publisher
      診断と治療社
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] アスパラギン合成酵素を特異的に認識するモノクローナル抗体2013

    • Inventor(s)
      浜窪隆雄、望月康弘、岩成宏子、新井 修、鬼頭敏幸、鶴澤正仁
    • Industrial Property Rights Holder
      浜窪隆雄、望月康弘、岩成宏子、新井 修、鬼頭敏幸、鶴澤正仁
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2011-218966
    • Filing Date
      2013-04-09
    • Related Report
      2012 Research-status Report
    • Overseas

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi