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Establishment of a new laboratory test for radiation sensitivity targeting p53 signal transduction system

Research Project

Project/Area Number 20590580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionNagasaki University

Principal Investigator

YAMADA Yasuaki  Nagasaki University, 医歯薬学総合研究科, 准教授 (60145232)

Co-Investigator(Kenkyū-buntansha) KAMIHIRA Shimeru  長崎大学, 医歯薬学総合研究科, 教授 (80108290)
HASEGAWA Hiroo  長崎大学, 医歯薬学総合研究科, 助教 (00398166)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords臨床検査医学 / p53 / 放射線 / Hzf / ATM / アポトーシス
Research Abstract

Although radiation therapy is one of the effective therapies for cancers, there are some patients who are extraordinarily sensitive to radiation in whom radiation-induced skin ulcer and perforation of gastro-intestinal tracts sometimes occur. Since there is no way to identify such radiation hypersensitive patients before therapy, we tried to establish a laboratory test for this purpose in the present study. Objects are mamma cancer patients who are planned to receive radiation therapy. Peripheral blood mononuclear cells were obtained from these patients before and after radiation. Radiation-induced skin damage was evaluated in all patients, but there was no significant difference among patients, indicating that radiation hypersensitive patients were not included in the study. Absolute peripheral blood lymphocyte count decreased in all patients after radiation, but absolute neutrophil count showed no changes. Interestingly, radiation sensitivity was different among lymphocyte subsets, and T lymphocytes were more sensitive than B lymphocyte or NK lymphocytes. CD8+ T-cell subset was the most sensitive lymphocytes and decrease of the absolute count prolonged even after 12 weeks after radiation. Nevertheless, increase of apoptotic lymphocytes was not observed in the peripheral blood. We then quantified mRNAs of various molecules that are supposed to be influenced by radiation, such as p53, p14ARF、p16INK4A and Hzf. There was however no significant correlation between the changes of the mRNA levels of these molecules and the level of the decrease of absolute lymphocyte counts.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Overexpression of enhancer of zeste homolog 2 with trimethylation of lysine 27 on histone H3 in adult T-cell leukemia/lymphoma as a target for epigenetic therapy.2011

    • Author(s)
      Sasaki D, Imaizumi Y, Hasegawa H, Osaka A, Tsukasaki K, Choi YL, Mano H, Marquez V, Hayashi T, Yanagihara K, Moriwaki Y, Miyazaki Y, Kamihira S, Yamada Y.
    • Journal Title

      Hematologica in press.

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of enhancer of zeste homolog 2 with trimethylation of lysine 27 on histone H3 in adult T-cell leukemia/lymphoma as a target for epigenetic therapy.2011

    • Author(s)
      Sasaki D., et al.
    • Journal Title

      Hematologica

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High human T cell leukemia virus type-1 (HTLV-1) provirus load in patients with HTLV-1 carriers complicated with HTLV-1-unrelated disorders.2010

    • Author(s)
      Sasaki D, Doi Y, Hasegawa H, Yanagihara K, Tsukasaki K, Iwanaga M, Yamada Y, Watanabe T, Kamihira S.
    • Journal Title

      Virology Journal 28;7:81(電子ジャーナル)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High human T cell leukemia virus type-1(HTLV-1) provirus load in patients with HTLV-1 carriers complicated with HTLV-1-unrelated disorders.2010

    • Author(s)
      Sasaki D., et al.
    • Journal Title

      Virology Journal

      Volume: 28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCR7 is inducible by HTLV-1 Tax and promotes growth and survival of HTLV-1-infected T cells.2009

    • Author(s)
      Jin Z, Nagakubo D, Shirakawa AK, Nakayama T, Shigeta A, Hieshima K, Yamada Y, Yoshie O
    • Journal Title

      International Journal of Cancer 125巻

      Pages: 2229-2235

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant p53 protein expression and function in a panel of hematopoietic cell lines with different p53 mutations.2009

    • Author(s)
      Kamihira S, Terada C, Sasaki D, Yanagihara K, Tsukasaki K, Hasegawa H, Yamada Y
    • Journal Title

      European Journal of Haematology 82巻

      Pages: 301-307

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCR7 is inducible by HTLV-1 Tax and promotes growth and survival of HTLV-1-infected T cells.2009

    • Author(s)
      Jin Z, et al.
    • Journal Title

      International Journal of Cancer 125

      Pages: 2229-2235

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant p53 protein expression and function in a panel of hematonoietic cell lines with different p53 mutations.2009

    • Author(s)
      Kamihira S, et al.
    • Journal Title

      European Journal of Haematology 82

      Pages: 301-307

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunological aspects of adult T-cell leukemia/lymphoma (ATLL), a possible neoplasm of regulatory T-cells.2008

    • Author(s)
      Yamada Y, Kamihira S
    • Journal Title

      Current Immunology Reviews 4巻

      Pages: 242-250

    • NAID

      120006984074

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia.2008

    • Author(s)
      Nakayama T, Hieshima K, Arao T, Jin Z, Nagakubo D, Shirakawa AK, Yamada Y, Fujii M, Oiso N, Kawada A, Nishio K, Yoshie O
    • Journal Title

      Oncogenes 27巻

      Pages: 3221-3232

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunological aspects of adult T-cell leukemia/lymphoma(ATLL), a possible neoplasm of regulatory T-cells.2008

    • Author(s)
      Yamada Y, et al.
    • Journal Title

      Current Immunology Reviews 4

      Pages: 242-250

    • NAID

      120006984074

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia.2008

    • Author(s)
      Nakayama T, et al.
    • Journal Title

      Oncogene 27

      Pages: 3221-3232

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Membrane-associated mucin MUC1 is overexpressed in adult T-cell leukemia/lymphoma cells and contributes to anti-apoptotic properties.2010

    • Author(s)
      Hasegawa H, Yamada Y, Kamihira S, et al
    • Organizer
      15th Congress of European Hematology Association
    • Year and Date
      2010-06-12
    • Related Report
      2010 Final Research Report
  • [Presentation] Membrane-associated mucin MUC1 is overexpressed in adult T-cell leukemia/lymphoma cells and contributes to anti-apoptotic properties.2010

    • Author(s)
      Hasegawa H, et al.
    • Organizer
      15th Congress of European Hematology Association
    • Place of Presentation
      バルセロナ、スペイン
    • Year and Date
      2010-06-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 成人T細胞白血病(ATLL)におけるEZH2高発現の病的意義2009

    • Author(s)
      佐々木大介、山田恭暉、上平憲, 他
    • Organizer
      第71回日本血液学会学術集会
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 成人T細胞白血病(ATLL)におけるEZH2高発現の病的意義。2009

    • Author(s)
      佐々木大介, ほか
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 造血器細胞株におけるp53遺伝子変異とp53mRNA及び蛋白定量による発現の検討2008

    • Author(s)
      寺田千春、山田恭暉、上平憲, 他
    • Organizer
      第55回日本臨床検査医学会学術集会
    • Year and Date
      2008-11-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 造血器細胞株におけるp53遺伝子変異とp53mRNA及び蛋白定量による発現の検討2008

    • Author(s)
      寺田千春, 他
    • Organizer
      第55回日本臨床検査医学会学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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