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Integrative genomic and proteomic analyses of low-dose ionizing radiation in EBV infected-B cells

Research Project

Project/Area Number 24501306
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Carcinogenesis
Research InstitutionJuntendo University

Principal Investigator

TABE Yoko  順天堂大学, 医学部, 准教授 (70306968)

Co-Investigator(Kenkyū-buntansha) IWABUCHI Kazuhisa  順天堂大学, 看護学部, 教授 (10184897)
SASAI Keisuke  順天堂大学, 医学部, 教授 (20225858)
金 林花  順天堂大学, 医学(系)研究科(研究院), 研究員 (90531955)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords低線量放射線 / 微小環境 / 前がん細胞 / microRNA / プロテオミクス / miRNA / 骨髄微小環境 / 間質細胞 / アポトーシス
Outline of Final Research Achievements

Exposure to low-dose ionizing radiation (LDIR) can alter mammalian cell gene expression. We compared the cellular response of irradiated immortalized, EB virus;infected, B-cells (EBV-B) cultured alone with that of EBV-B cells co-cultured with bone marrow derived stromal cells (MSCs). The miRNAs let7a, miR-15b, miR-16, miR-21 and a lipid metabolic miRNA hub miR-23b were upregulated after LDIR exposure in the mono-cultured EBV-B cells, but were downregulated in EBV-B cells co-irradiated with MSCs. A lipid biosynthesis enzyme GPAM, the common target of these miRNAs, was downregulated at the level of protein and mRNA expression in the LDIR exposed mono-cultured EBV-B cells and upregulated MSCs co-cultured EBV-B cells, suggesting a putative novel miRNA regulatory mechanism in the genetic control of the LDIR-induced stress response. These findings illustrate that LDIR exposure and the cell’s microenvironment can affect specific gene expression, resulting in altered protein expression.

Report

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

    (38 results)

All 2015 2014 2013 2012 Other

All Journal Article (16 results) (of which Peer Reviewed: 15 results) Presentation (20 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Role of microenvironment in resistance to therapy in AML.2015

    • Author(s)
      Tabe Y, Konopleva M.
    • Journal Title

      Current Hematologic Malignancy Reports

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of p53-mediated transcription and apoptosis by Exportin-1 (XPO1) inhibition in mantle cell lymphoma.2014

    • Author(s)
      4.Yoshimura M, Ishizawa J, Ruvolo V, Dilip A, Quintas-Cardama A, McDonnell TJ, Neelapu SS, Kwak LW, Shacham S, Kauffman M, Tabe Y, Yokoo M, Kimura S, Andreeff M, Kojima K
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 7 Pages: 795-801

    • DOI

      10.1111/cas.12430

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches2014

    • Author(s)
      Tabe Y
    • Journal Title

      Juntendo Medical Journal

      Volume: 60 Pages: 156-160

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Class IA PI3K inhibition inhibits cell growth and proliferation in mantle cell lymphoma.2014

    • Author(s)
      Tabe Y, Jin L, Konopleva M, Shikami M, Kimura S, Andreeff M, Raffeld M, Miida T.
    • Journal Title

      Acta Haematol.

      Volume: 131 Issue: 1 Pages: 59-69

    • DOI

      10.1159/000353164

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ICSH guidelines for the verification and performance of automated cell counters for body fluids.2014

    • Author(s)
      Bourner G, De la Salle B, George T, Tabe Y, Baum H, Culp N, Keng TB
    • Journal Title

      Int J Lab Hematol.

      Volume: in press Issue: 6 Pages: 598-612

    • DOI

      10.1111/ijlh.12196

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rivaroxaban attenuates leukocyte adhesion in the microvasculature and thrombus formation in an experimental mouse model of type 2 diabetes mellitus.2014

    • Author(s)
      Iba T, Aihara K, Yamada A, Nagayama M, Tabe Y, Ohsaka A.
    • Journal Title

      Thromb Res.

      Volume: 133 Issue: 2 Pages: 276-280

    • DOI

      10.1016/j.thromres.2013.11.013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advances in understanding the leukaemia microenvironment.2014

    • Author(s)
      Tabe Y, Konopleva M.
    • Journal Title

      Br J Haematol.

      Volume: 164 Issue: 6 Pages: 767-778

    • DOI

      10.1111/bjh.12725

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] TGF-β-neutralizing antibody 1D11 enhances cytarabine-induced apoptosis in AML cells in the bone marrow microenvironment.2013

    • Author(s)
      Tabe Y, Shi YX, Zeng Z, Jin L, Shikami M, Hatanaka Y, Miida T, Hsu FJ, Andreeff M, Konopleva M.
    • Journal Title

      PLoS One

      Volume: 8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML cells in the hypoxic bone marrow microenvironment.2013

    • Author(s)
      Jin L, Tabe Y, Kojima K, Shikami M, Benito J, Ruvolo V, Wang RY, McQueen T, Ciurea SO, Miida T,
    • Journal Title

      Mol Med (Berl)

      Volume: 91 Issue: 12 Pages: 1383-1397

    • DOI

      10.1007/s00109-013-1076-3

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Performance evaluation of the automated morphological analysis of erythrocytes by CellaVision DM96.2013

    • Author(s)
      Maenou I, Tabe Y, Bengtsson HI, Ishii K, Miyake K, Horiuchi Y, Idei M, Horii T, Satoh N, Miida T,
    • Journal Title

      Clin Lab.

      Volume: 59 Pages: 1413-1417

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Meropenem as predictive risk factor for isolation of multidrug-resistant Pseudomonas aeruginosa.2013

    • Author(s)
      Nakamura A, Miyake K, Misawa S, Kuno Y, Horii T, Kondo S, Tabe Y, Ohsaka A
    • Journal Title

      J Hosp Infect

      Volume: 83 Issue: 2 Pages: 153-155

    • DOI

      10.1016/j.jhin.2012.10.005

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutrophil extracellular traps, damage-associated molecular2013

    • Author(s)
      Iba T, Murai M, Nagaoka I, Tabe Y.
    • Journal Title

      Acute Medicine & Surgery

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] TGF-β-neutralizing antibody 1D11 enhances cytarabine-induced apoptosis in AML cells in the bone marrow microenvironment.2013

    • Author(s)
      Yoko Tabe, Yue Xi Shi, Zhihong Zeng, Linhua Jin, Masato Shikami,Yasuhito Hatanaka, Takashi Miida, Frank J. Hsu, Michael Andreeff, Marina Konopleva
    • Journal Title

      PLOS ONE

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.2012

    • Author(s)
      Jin L, Tabe Y, Lu H, Borthakur G, Miida T, Kantarjian H, Andreeff M, Konopleva M.
    • Journal Title

      Cancer Lett

      Volume: 329 Issue: 1 Pages: 45-58

    • DOI

      10.1016/j.canlet.2012.09.020

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts.2012

    • Author(s)
      Tabe Y, Jin L, Iwabuchi K, Wang RY, Ichikawa N, Miida T, Cortes J, Andreeff M, Konopleva M.
    • Journal Title

      Leukemia

      Volume: 26 Issue: 5 Pages: 883-892

    • DOI

      10.1038/leu.2011.291

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of PPARγ Ligands on Leukemia.2012

    • Author(s)
      Tabe Y, Konopleva M, Andreeff M, Ohsaka A.
    • Journal Title

      PPAR Res.

      Volume: なし Pages: 1-8

    • DOI

      10.1155/2012/483656

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] The mTOR kinase inhibitor AZD-2014 effectively reverses XPO1/CRM1 antagonist KPT-185–induced glycolysis / gluconeogenesis, enhancing antitumor effects in mantle cell lymphoma.2014

    • Author(s)
      Yoko Tabe, Masako Harada, Yuka Miyamae, Hiromichi Matsushita, Kensuke Kojima, Tsutomu Fujimura, Saiko Kazuno, Takashi Ueno, Takashi Miida, Marina Konopleva, Michael Andreeff
    • Organizer
      56th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Metabolic re-programming in Notch-activated T-ALL by mTOR inhibitor AZD2014 combined with L-Asparaginase.2014

    • Author(s)
      Yoko Tabe, Masako Harada, Yuka Miyamae, Tsutomu Fujimura, Saiko Kazuno, Takashi Ueno, Takashi Miida, Michael Andreeff, Marina Konopleva.
    • Organizer
      56th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pro-survival effects of TGF-β1 are associated with molecular signaling changes of ERK, FLI-1, and CD44 in AML cells.2014

    • Author(s)
      Yoko Tabe, Yasuhito Hatanaka, Peter Ruvolo, Takashi Miida, Steve Kornblau, Michael Andreeff, Marina Konopleva.
    • Organizer
      56th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Bone marrow adipocyte-derived free fatty acids induce gene signature linking transcription with metabolic changes that contribute to survival of acute monocytic leukemia cells2014

    • Author(s)
      Yoko Tabe, Masako Harada, Yuka Miyamae, Kaoru Mogushi, Saiko Kazuno, Tsutomu Fujimura, Hiromichi Matsushita, Takashi Ueno, Takehiko Yokomizo, Takashi Miida, Ismael Samudio, Michael Andreeff, Marina Konopleva.
    • Organizer
      56th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Selective inhibitor of nuclear export selinexor (KPT-330) and BCL2 inhibitor ABT-199 enhance the anti-lymphoma effect of BTK inhibitor ibrutinib in mantle cell lymphoma.2014

    • Author(s)
      Yoko Tabe, Masako Harada, Yuka Miyamae, Saiko Kazuno, Tsutomu Fujimura, Takashi Ueno, Takashi Miida, Marina Konopleva, Michael Andreeff
    • Organizer
      56th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanisms of inhibition of ribosomal biogenesis and translational flux by the Selective Inhibitor of Nuclear Export (SINE) XPO1/CRM1 antagonist KPT-185 in mantle cell lymphoma2014

    • Author(s)
      Yoko Tabe, Kensuke Kojima, Linhua Jin, Hiroko Iwanami, Hiromichi Matsushita, Saiko Kazuno, Michael Kauffman, Sharon Shacham, Tsutomu Fujimura, Takashi Ueno, Takashi Miida, Michael Andreeff
    • Organizer
      Global Academic Programs 2014 Annual Conference
    • Place of Presentation
      Soule, Korea
    • Year and Date
      2014-05-01 – 2014-05-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanisms of inhibition of ribosomal biogenesis and translational flux by the Selective Inhibitor of Nuclear Export (SINE) XPO1/CRM1 antagonist KPT-185 in mantle cell lymphoma.2013

    • Author(s)
      Tabe Y, Kojima K, Jin L, Iwanami H, Matsushita H, Kazuno S, Kauffman M, Shacham S, Fujimura T,
    • Organizer
      55th American Society of Hematology Annual Meeting
    • Place of Presentation
      New Orleans,USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Integrative genomic and proteomic analysis of low-dose ionizing irradiation effects on bone marrow stromal microenvironment and on survival of pre-leukemic cells.2013

    • Author(s)
      Tabe Y, Jin L, Hatanaka Y, Matsushita H, Kazuno S, Fujimura T, Ueno T, Sasai K, Iwabuchi K, Andreeff M, Konopleva M, Miida T
    • Organizer
      55th American Society of Hematology Annual Meeting
    • Place of Presentation
      New Orleans,USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Efficacy and mechanisms of the mTOR inhibitor AZD2014 combined with L-Asparaginase or JAK2 inhibitor TG101348 in ALL.2013

    • Author(s)
      Tabe Y, Jin L, Iwanami H, Matsushita H, Kazuno S, Fujimura T, Ueno T, Miida T, Weinstock D, Thomas DA, Andreeff M, Konopleva M.
    • Organizer
      55th American Society of Hematology Annual Meeting
    • Place of Presentation
      New Orleans,USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Metabolic shift in hypoxia-adapted CML cells and mechanisms of acquired dasatinib resistance uncovered by proteomic iTRAQ profiling.2013

    • Author(s)
      Tabe Y, Jin L, Iwanami H, Matsushita H, Kazuno S, Fujimura T, Ueno T, Miida T, Andreeff M, Konopleva M, Kimura S.
    • Organizer
      55th American Society of Hematology Annual Meeting
    • Place of Presentation
      New Orleans,USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Molecular mechanisms of adipocyte-leukemia interactions revealed by the quantitative proteomics technology: pro-survival function of adipocyte-derived free fatty acids on acute monoblastic leukemia mitochondrial biogenesis.2013

    • Author(s)
      Tabe Y, Jin L, Kazuno S, Fujimura T, Matsushita H, Ueno T, Miida T, Andreeff M, Konopleva M.
    • Organizer
      55th American Society of Hematology Annual Meeting
    • Place of Presentation
      New Orleans,USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Efficacy of the internet-based e-leaning system using the CellaVision Competency Software for continuing professional development.2013

    • Author(s)
      Tabe Y, Ishii K, Kasuga K, Maenoh I, Horii T, Miida T, Ohsaka A.
    • Organizer
      26th International Symposium on Technological Innovations in Laboratory Hematology.
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Performance evaluation of a novel high-risk Human Papilloma Virus Genotyping test (Clinichip HPV™).2013

    • Author(s)
      Yamada H, Tabe Y, Ishii K, Terao Y, Takeda S, Horii T, Ohsaka A.
    • Organizer
      American Association for Clinical Chemistry Annual Meeting.
    • Place of Presentation
      Houston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Detection of tumor cells in body fluids by the automated morphological analysis system CellaVision DM96 following the automated cell counting by the Sysmex XE5000.2013

    • Author(s)
      Takemura H, Tabe Y, Yamaguchi K, Ishii K, Kasuga K, Horii T, Miida T, Ohsaka A.
    • Organizer
      American Association for Clinical Chemistry Annual Meeting
    • Place of Presentation
      Houston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] The clinical significance of mesothelial cell in peritoneal dialysis effluent detected by Cellavision DM96.2013

    • Author(s)
      Idei M, Tabe Y, Miyake K, Hamada C, Takemura H, Io H, Ishii K, Horii T, Tomino Y, Ohsaka A, Miida T.
    • Organizer
      American Association for Clinical Chemistry Annual Meeting
    • Place of Presentation
      Houston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] TGF-beta1 Supports Leukemia Cell Survival Via Negative Regulation of FLI-1 Transcription Factor, ERK Inactivation and MMP-1 Secretion.2012

    • Author(s)
      Yoko Tabe, Linhua Jin, Yasuhito Hatanaka, Takashi Miida, Steven Kornblau, Michaell Andreeff, Marina Konopleva.
    • Organizer
      American Society of Hematology Annual Meeting
    • Place of Presentation
      Atlanta,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular Mechanisms of Antitumor Activity of the Selective Inhibitor of Nuclear Export (SINE) CRM1 Antagonist KPT-185 in Mantle Cell Lymphoma.2012

    • Author(s)
      Yoko Tabe, Kensuke Kojima, Linhua Jin, Takashi Miida, Shacham S, Kauffman M, Michaell Andreeff.
    • Organizer
      American Society of Hematology Annual Meeting
    • Place of Presentation
      Atlanta,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Analysis of Dasatinib-Induced Molecular Mechanisms of Apoptosis in Hypoxia-Adopted CML Cells Utilizing Quantitative Proteomics Technology.2012

    • Author(s)
      Yoko Tabe, Linhua Jin, Hiroko Iwanami, Kazuno S, Fujimura T, Hiromichi Matsushita, Takashi Ueno, Takashi Miida, Michaell Andreeff, Marina Konopleva, Shinya Kimura.
    • Organizer
      American Society of Hematology Annual Meeting
    • Place of Presentation
      Atlanta,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular Mechanisms of Pro-Survival and Differentiating Function of Bone Marrow-Derived Adipocytes On Acute Monoblastic Leukemia Cells.2012

    • Author(s)
      Linhua Jin, Marina Konopleva, Masato Shikami, Takako Ikegami, Kensuke Kojima , MichaellAndreeff, Takashi Miida, Yoko Tabe
    • Organizer
      American Society of Hematology Annual Meeting
    • Place of Presentation
      Atlanta,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] 低線量放射線被爆による生体微小環境内の発がん誘導機序.2012

    • Author(s)
      田部 陽子, 金 林花, 畑中 康人, 松下 弘道, 笹井 啓資, 三井田 孝
    • Organizer
      放射線影響学会
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
  • [Book] WBC differentiation Procedures2012

    • Author(s)
      Yoko Tabe, Naotake Satoh, Chiaki Tanaka
    • Total Pages
      69
    • Publisher
      Sysmex corporation scientic affairs
    • Related Report
      2012 Research-status Report
  • [Remarks] 順天堂大学医学部 臨床検査医学講座 【業績】

    • URL

      http://www.juntendo.ac.jp/med/labo/rinsyo_byori3.html

    • Related Report
      2013 Research-status Report

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

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