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Characterization of cellular phenotypes specific for the ATL development in HTLV-1 infected humanized mouse

Research Project

Project/Area Number 24590562
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionKansai Medical University

Principal Investigator

FUJISAWA Jun-ichi  関西医科大学, 医学部, 教授 (40181341)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsウイルス / ATL / 動物モデル / HTLV-1 / ヒト化マウス / CD25 / マウスモデル
Outline of Final Research Achievements

Tumorigenesity of CD25-negative and -positive CD4 T cells isolated from HTLV-1-infected humanized mice that exhibit ATL-like symptoms was examined by transplanting cells to the spleen of NOG mouse and only CD25-positive HTLV-1-infected CD4 T cells was found to form tumor. cDNA microarray analysis demonstrated that several genes related to the regulatory T-cells and a cellular mutator gene, APOBEC3B, were activated upon HTLV-1 infection. Genes for BATF3 and SYK were upregulated in parallel with the expression of CD25. Since no sign of mutation in the level of host genome was detected, the epigenetic modifications are suggested to be mainly involved in the leukemogenesis of HTLV-1 infected humanized mouse.

Report

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

    (22 results)

All 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 2 results) Presentation (13 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] ATLマウスモデルの樹立とその新知見2014

    • Author(s)
      藤澤順一
    • Journal Title

      血液内科

      Volume: 69 Pages: 394-399

    • Related Report
      2014 Annual Research Report
  • [Journal Article] HTLV-1感染の動物モデル2014

    • Author(s)
      藤澤順一
    • Journal Title

      細胞

      Volume: 26 Pages: 12-19

    • Related Report
      2014 Annual Research Report
  • [Journal Article] An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity2014

    • Author(s)
      Tezuka K, Xun R, Tei M, Ueno T, Tanaka M, Takenouchi N, Fujisawa J
    • Journal Title

      Blood

      Volume: 123 Issue: 3 Pages: 346-355

    • DOI

      10.1182/blood-2013-06-508861

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Carrier model of HTLV-1 infection in humanized NOG mice2014

    • Author(s)
      Tezuka K, Tei M, Ueno T, Xun R, Fujisawa J
    • Journal Title

      Retrovirology

      Volume: 11(Suppl1) Issue: S1 Pages: 42-42

    • DOI

      10.1186/1742-4690-11-s1-p42

    • Related Report
      2013 Research-status Report
  • [Journal Article] Inhibition of ATL development in humanized mouse model by AZT/INF treatment2014

    • Author(s)
      Tezuka K, Tei M, Ueno T, Xun R, Iha H, Fujisawa J
    • Journal Title

      Retrovirology

      Volume: 11(Suppl1) Issue: S1 Pages: 43-43

    • DOI

      10.1186/1742-4690-11-s1-p43

    • Related Report
      2013 Research-status Report
  • [Journal Article] A novel HSP90 inhibitor, 17-DMAG, induces Tax down-regulation and its oral administration to ATL-model mice intervenes against the infiltration property of the ATL-like lymphocytes and provides extended survival period2014

    • Author(s)
      Ikebe E, Kawaguchi A, Tezuka K, Taguchi S, Hirose S, Matsumoto T, Mitsui T, Senba K, Nishizono A, Hori M, Hasegawa H, Yamada Y, Ueno T, Tanaka Y, Sawa H, Hall W, Minami Y, Jeang K-T, Ogata M, Morishita K, Hasegawa H, Fujisawa J, Iha H
    • Journal Title

      Retrovirology

      Volume: 11(Suppl1) Issue: S1 Pages: 44-44

    • DOI

      10.1186/1742-4690-11-s1-p44

    • Related Report
      2013 Research-status Report
  • [Journal Article] Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice.2013

    • Author(s)
      Ikebe E, Kawaguchi A, Tezuka K, et al
    • Journal Title

      Blood Cancer Journal

      Volume: 3 Issue: 8 Pages: e132-e132

    • DOI

      10.1038/bcj.2013.30

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Tax ペプチドワクチンのヒト化マウス鼻腔投与によるHTLV-1感染抑制2014

    • Author(s)
      田中正和、李 成一、荀 潤澤、姚 錦春、藤澤順一
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mouse model of ATL2014

    • Author(s)
      Fujisawa J-i, Tanaka M, Ueno T, Xun R, Yao J, Lee S-il
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Long peptides vaccine to Tax suppressed the overgrowth of HTLV-1-infected lymphocytes in humanized mouse model2014

    • Author(s)
      Tanaka M, Lee S-il, Xun R, Yao J, Fujisawa J-i
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト化マウスを用いたHTLV-1感染防御ワクチンの開発2014

    • Author(s)
      田中正和、李 成一、荀 潤澤、姚 錦春、藤澤順一
    • Organizer
      第1回日本HTLV-1学会学術集会
    • Place of Presentation
      東京大学医科学研究所講堂(東京)
    • Year and Date
      2014-08-23 – 2014-08-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Carrier model of HTLV-1 infection in humanized NOG mice2013

    • Author(s)
      Kenta Tezuka, Mami Tei, Takaharu Ueno, Runze Xun, Jun-ichi Fujisawa
    • Organizer
      16th International Conference on Human Retroviruses: HTLV and Related Viruses
    • Place of Presentation
      Montreal, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Inhibition of ATL development in humanized mouse model by AZT/INF treatment2013

    • Author(s)
      Kenta Tezuka, Mami Tei, Takaharu Ueno, Runze Xun, Hidekatu Iha, Jun-ichi Fujisawa
    • Organizer
      16th International Conference on Human Retroviruses: HTLV and Related Viruses
    • Place of Presentation
      Montreal, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Inhibition of ATL development by HSP90 inhibitor 17-DMAG in humanized mouse model2013

    • Author(s)
      Kenta Tezuka, Emi Ikebe, Hidekatu Iha,Takaharu Ueno, Runze Xun, Jun-ichi Fujisawa
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice2013

    • Author(s)
      伊波英克、池辺詠美、川口 晶、手塚健太、田口慎也、廣瀬仁志,、西園 晃、堀 光雄、 長谷川寛雄、山田恭暉、上野孝治、 田中勇悦、澤 洋文、 Hall Wiliam W、 南 康文、Jeang Kuan-The、 緒方正男、森下和広、長谷川秀樹、藤澤順一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場、神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] ATL-like phenotype in HTLV-1 infected humanized mouse model

    • Author(s)
      藤澤順一
    • Organizer
      25th International Conference on Antiviral Research
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] IBMI-ヒト化マウスを用いたHTLV-1感染マウスモデル

    • Author(s)
      手塚健太、上野孝治、鄭真美、荀潤澤、田中正和、竹之内徳博、藤澤順一
    • Organizer
      第1回 ATLシンポジウム
    • Place of Presentation
      東京大学医科学研究所講堂(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Carrier model of HTLV-1 infection in humanized NOG-mouse

    • Author(s)
      手塚健太、鄭真美、上野孝治、荀潤澤、藤澤順一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(札幌)
    • Related Report
      2012 Research-status Report
  • [Presentation] Altered pattern in viral mRNA expression of Iranian type HTLV-1 leading to enhanced viral production

    • Author(s)
      荀潤澤、上野孝治、齊藤峰輝、手塚健太、田中勇悦、藤澤順一
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2012 Research-status Report
  • [Presentation] HTLV-1感染ヒト化マウスを用いた抗ATL治療法の評価

    • Author(s)
      手塚健太、上野孝治、鄭真美、荀潤澤、竹之内徳博、藤澤順一
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2012 Research-status Report
  • [Remarks] 関西医科大学 医学部 医学部医学科(基礎社会系講座) 微生物学

    • URL

      http://www.kmu.ac.jp/medical/2671t8000000407o.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 関西医科大学微生物学講座ホームページ

    • URL

      http://www3.kmu.ac.jp/microbiol/KMU_Microbiology/Top.html

    • Related Report
      2013 Research-status Report

URL: 

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

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