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Diagnostic value of peptidome analyses for protease activated pathological conditions beyond cancer diagnosis

Research Project

Project/Area Number 19390156
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HASHIGUCHI Teruto  Kagoshima University, 大学院・医歯学総合研究科, 准教授 (70250917)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Ikuro  鹿児島大学, 大学院・医歯学総合研究科, 教授 (20082282)
KAWAHARA Koichi  鹿児島大学, 大学院・医歯学総合研究科, 助教 (10381170)
INUI Akio  鹿児島大学, 大学院・医歯学総合研究科, 教授 (80168418)
NATSUGOE Shoji  鹿児島大学, 大学院・医歯学総合研究科, 教授 (70237577)
内村 友則  鹿児島大学, 医学部・歯学部附属病院, 助教 (20363616)
Research Collaborator TANAKA Kenji  , (株)プロトセラ・膜タンパク質&リガンド解析センター
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsプロテオーム / ペプチドーム / ペプチド / バイオマーカー / 質量分析 / 癌 / DIC / 検査 / 酵素 / 生体分子 / 蛋白質 / peptidome / proteome / peptide / biomarker / inflammation / cancer / diagnosis / degradome / MOF
Research Abstract

Human serum contains thousands of proteolytically derived low-molecular-weight peptide fragments (serum peptidome). The concept of utilizing the serum peptidome for cancer diagnosis has been developed. A pathological serum peptidome appears when the homeostatic balance between proteases and protease inhibitors is disrupted. We hypothesize if analyses of the serum peptidome are of diagnostic value as information on which molecules are disrupted, and the pathological course it will take in unknown pathological conditions and disseminated intravascular coagulation (DIC). We analyzed the serum peptidome in 3 stages (early stage, pre-DIC and DIC stages) in one patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, an intractable disease with unknown pathology, using a 1-dimensional gel electrophoresis/ matrix-assisted laser desorption/ionization-mass spectrometry (1-DE/MS)-based rapid quantitative approach. A very large number of peptide fragments appeared in the DIC stage, compared to pre-DIC. In addition, we identified fragments of transthyretin (ALGISPFHEHAEVVFTANDSGPR, m/z 2,451.18) and α1-antitrypsin (EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2,691.02) that significantly increased in the DIC stage, compared to those in the pre-DIC stage. Rapid analyses of the serum peptidome may lead to a diagnostic method that can predict on-going protease activated pathological conditions and help to decide on multilateral strategies including nutritional support and drug therapy.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (40 results)

All 2010 2009 2008 2007 Other

All Journal Article (23 results) (of which Peer Reviewed: 23 results) Presentation (10 results) Patent(Industrial Property Rights) (7 results)

  • [Journal Article] B cell-derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes.2010

    • Author(s)
      Hashiguchi T*, Shrestha B*, Ito T*, Miura N* (*Equal contribution), Takenouchi K, Oyama Y, Kawahara K, Tancharoen S, Ki-i Y, Arimura N, Yoshinaga N, Noma S, Shrestha C, Nitanda T, Kitajima S, Arimura K, Sato M, Sakamoto T, Maruyama I
    • Journal Title

      J Immunol 184

      Pages: 4819-4826

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The diagnostic value of endothelial function as a potential sensor of fatigue in health.2010

    • Author(s)
      Ohno Y, Hashiguchi T, Maenosono R, Yamashita H, Taira Y, Minowa K, Yamashita Y, Kato Y, Kawahara K, Maruyama I
    • Journal Title

      Vasc Health Risk Manag 6

      Pages: 135-144

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy2010

    • Author(s)
      Oyama Y, Hashiguchi T, et al.
    • Journal Title

      Lab Invest (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between reduced ADAMTS13 and diabetic nephropathy2010

    • Author(s)
      Taniguchi S, Hashiguchi T, et al.
    • Journal Title

      Thromb Res (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] B cell-derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes2010

    • Author(s)
      Hashiguchi T, Shrestha B, Ito T, Miura N, et al.
    • Journal Title

      J Immunol 184

      Pages: 4819-4826

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of serum peptidome analyses for protease activated pathological conditions beyond cancer diagnosis.2009

    • Author(s)
      Hashiguchi T, Tanaka K, Lee LJ, Sasaki K, Natsugoe S, Kawahara K, Arimura K, Maruyama I
    • Journal Title

      Med Hypotheses 73

      Pages: 760-763

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy.2009

    • Author(s)
      Arimura N, Otsuka H, Yamakiri K, Sonoda Y, Nakao S, Noda Y, Hashiguchi T, Maruyama I, Sakamoto T
    • Journal Title

      Ophthalmology 116

      Pages: 921-926

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.2009

    • Author(s)
      Arimura N, Ki-i Y, Hashiguchi T, Kawahara K, Biswas KK, Nakamura M, Sonoda Y, Yamakiri K, Okubo A, Sakamoto T, Maruyama I
    • Journal Title

      Lab Invest 89

      Pages: 278-289

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage.2009

    • Author(s)
      Deguchi T, Hashiguchi T, Horinouchi S, Uto T, Oku H, Kimura K, Makisumi K, Arimura K
    • Journal Title

      Diabet Med 26

      Pages: 247-252

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage2009

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

      Diabet Med 26

      Pages: 247-252

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraocular expression and release of high-mobility group box 1 protein in retinal detachment2009

    • Author(s)
      Arimura N, Ki-I Y, Hashiguchi T, et al.
    • Journal Title

      Lab Invest 89

      Pages: 278-289

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of serum peptidome analyses for protease activated pathological conditions beyond cancer diagnosis2009

    • Author(s)
      Hashiguchi T, Tanaka K, et al.
    • Journal Title

      Med Hypotheses 73

      Pages: 760-763

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The diagnostic value of endothelial function as a potential sensor of fatigue in health2009

    • Author(s)
      Ohno Y, Hashiguchi T, et al.
    • Journal Title

      Vasc Health Risk Manag 6

      Pages: 135-144

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.2009

    • Author(s)
      Arimura N, Ki-I Y, Hashiguchi T, et al.
    • Journal Title

      Lab Invest 89(3)

      Pages: 278-89

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage.2009

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

      Diabet Med 26(3)

      Pages: 247-52

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box 1 protein in endophthalmitis.2008

    • Author(s)
      Arimura N, Ki-I Y, Hashiguchi T, Sakamoto T, Maruyama I
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol 24

      Pages: 1053-1058

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box 1 protein in endophthalmitis.2008

    • Author(s)
      Arimuta N, Ki-I Y, Hashiguchi T, et al.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol 246(7)

      Pages: 1053-8

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stromal-derived factor-1 and inflammatory cytokines in retinal vein occlusion.2007

    • Author(s)
      Ki-I Y, Arimura N, Noda Y, Yamakiri K, Doi N, Hashiguchi T, Maruyama I, Shimura M, Sakamoto T
    • Journal Title

      Curr Eye Res 32

      Pages: 1065-1072

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum VEGF-as a prognostic factor of atherosclerosis.2007

    • Author(s)
      Kimura K, Hashiguchi T, Deguchi T, Horinouchi S, Uto T, Oku H, Setoyama S, Maruyama I, Osame M, Arimura K
    • Journal Title

      Atherosclerosis 194

      Pages: 182-188

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum VEGF-as a prognostic factor of atherosclerosis.2007

    • Author(s)
      Kimura K, Hashiguchi T, et. al.
    • Journal Title

      Atherosclerosis 194(1)

      Pages: 182-188

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High mobility group box 1 and refeeding-resistance in anorexia nervosa.2007

    • Author(s)
      Yasuhara D, Hashiguchi T, et. al.
    • Journal Title

      Mol Psychiatry 12(11)

      Pages: 976-977

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between reduced ADAMTS13 and diabetic nephropathy

    • Author(s)
      Taniguchi S, Hashiguchi T, Ono T, Takenouchi K, Nakayama K, Kawano T, Kato K, Matsushita R, Nagatomo M, Nakamura S, Nakashima T, Maruyama I
    • Journal Title

      Thromb Res (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy.

    • Author(s)
      Oyama Y, Hashiguchi T, Taniguchi N, Tancharoen S, Uchimura T, Biswas KK, Kawahara K, Nitanda T, Umekita Y, Lotz M, Maruyama I
    • Journal Title

      Lab Invest (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Presentation] Endothelial function as an objective assessment tool of fatigue in healthy individuals2010

    • Author(s)
      Ohno Y, Hashiguchi T, Maenosono R, Yamashita H, Taira Y, Minowa K, Yamashita Y, Kato Y, Kawahara K, Maruyama I
    • Organizer
      ICOHN&ACOHN Joint Conference2010
    • Place of Presentation
      Yokohama
    • Related Report
      2009 Final Research Report
  • [Presentation] 生体蛋白質のnon-homeostatic degradation解析による病態予知診断次世代検査医学への応用を目指して.2009

    • Author(s)
      橋口照人
    • Organizer
      「臨床化学の若い力で発信しつつある新たな検査、病態解析法」第49回日本臨床化学会年次学術集会
    • Place of Presentation
      長崎
    • Related Report
      2009 Final Research Report
  • [Presentation] 生体蛋白質の non-homeostatic degradation 解析による病態予知診断次世代検医学への応用を目指して.「臨床化学の若い力で発信しつつある新たな検査、病態解析法」2009

    • Author(s)
      橋口照人, 他
    • Organizer
      第49回日本臨床化学会年次学術集会
    • Place of Presentation
      長崎大学医学部医学科医学部記念講堂・良順会館・ボンペ会館
    • Related Report
      2009 Annual Research Report
  • [Presentation] 重症病態における低分子量フラグメント(ペプチドーム/プロテオーム)解析(優秀演題賞)2008

    • Author(s)
      橋口照人, 他
    • Organizer
      第55回日本臨床検査医学会学術集会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2008-11-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] Degradation of non-hemostatic molecules in the state of DIC/MOF2008

    • Author(s)
      橋口照人, 川原幸一, 丸山征郎, 李良子, 田中憲次
    • Organizer
      第12回エンドトキシン血症救命治療研究会
    • Place of Presentation
      福岡
    • Related Report
      2009 Final Research Report
  • [Presentation] DIC/MOFにおける非止血関連分子の崩壊2008

    • Author(s)
      橋口照人, 李良子, 田中憲次, 丸山征郎
    • Organizer
      日本血栓止血学会学術標準化委員会(SSC)シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] Degradation of non-hemostatic molecules in DIC/MOF2008

    • Author(s)
      Hashiguchi T
    • Organizer
      7th International Bio Forum
    • Place of Presentation
      Tokyo
    • Related Report
      2009 Final Research Report
  • [Presentation] 重症病態における低分子量フラグメント(ペプチドーム/プロテオーム)解析2008

    • Author(s)
      橋口照人, 他
    • Organizer
      第7回国際バイオフォーラム
    • Place of Presentation
      東京ビッグサイト(東京都)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Degradation of homeostatic molecules in the state of DIC/MOF2007

    • Author(s)
      橋口照人、李 良子、田中憲次、丸山征郎
    • Organizer
      第30回日本血栓止血学会学術集会
    • Place of Presentation
      三重県
    • Year and Date
      2007-11-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] DIC/MOFにおける生体内蛋白分解の網羅的解析2007

    • Author(s)
      橋口照人, 川原幸一, 丸山征郎, 李良子, 田中憲次
    • Organizer
      第13回日本エンドトキシン研究会
    • Place of Presentation
      鹿児島
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 歯周病特異的ペプチド、並びにそれを用いた歯周病の治療および診断2010

    • Inventor(s)
      丸山征郎、橋口照人, タンジャルーン サランヤー, 川原幸一, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Number
      2010-061673
    • Filing Date
      2010-03-17
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 歯周病特異的ペプチド、並びにそれを用いた歯周病の治療および診断2010

    • Inventor(s)
      丸山征郎, 橋口照人, タンジャルーンサランヤー, 川原幸一, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Number
      2010-061673
    • Filing Date
      2010-03-17
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規癌マーカーおよびそれを用いた診断2009

    • Inventor(s)
      橋口照人, 夏越祥次, 丸山征郎, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Filing Date
      2009-01-07
    • Acquisition Date
      2009-07-16
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規癌マーカーおよびそれを用いた診断2008

    • Inventor(s)
      橋口照人, 夏越祥次, 丸山征郎, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Number
      2008-000776
    • Filing Date
      2008-01-07
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規癌マーカーおよびそれを用いた診断2008

    • Inventor(s)
      丸山征郎、橋口照人、夏越祥次、田中憲次、李 良子
    • Industrial Property Rights Holder
      鹿児島大学(株)プロトセラ
    • Industrial Property Number
      2008-000776
    • Filing Date
      2008-01-07
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規疾患マーカーおよびそれを用いた診断2007

    • Inventor(s)
      橋口照人, 夏越祥次, 丸山征郎, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Filing Date
      2007-12-12
    • Acquisition Date
      2008-06-19
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規癌マーカーおよびそれを用いた診断2007

    • Inventor(s)
      橋口照人, 夏越祥次, 丸山征郎, 田中憲次, 李良子
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Number
      2008-549347
    • Filing Date
      2007-12-12
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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