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Diagnostic approach of diseases using non-invasive biosamples (saliva, hair and nail)

Research Project

Project/Area Number 15K07895
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

Toyo'oka Toshimasa  静岡県立大学, 薬学部, 特任教授 (40183496)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords疾病診断 / 光学活性誘導体化試薬 / 非侵襲的試料 / バイオマーカー探索 / 液体クロマトグラフィー / 質量分析 / 非侵襲的試料解析 / 疾病バイオマーカー / 光学活性代謝物 / バイオマーカー
Outline of Final Research Achievements

Diagnostic approach of several diseases using non-invasive biological samples (saliva, hair and nail) was performed in this study. The determination of biomarker(s) related to diseases was based on targeted and non-targeted metabolomics by UPLC-MS. The chiral derivatization reagents, DMT-3(S)-Apy and DMT-L-Pro-OSu, were first synthesized for the determination of carboxylic acids and amines, respectively. The opposite enantiomer reagents and the isotopic variants were also synthesized.
The ratio of D/L-lactic acids in the saliva of diabetic patients was higher than that of healthy persons. The ratio of polyamines in saliva was also different between breast cancer patients and healthy persons. Several N-acethyl amino acids in hairs of diabetes were significantly different from healthy subjects. Furthermore, the concentration of uric acid was obviously higher in gout patients. The efficiency of saliva, hair and nail as diagnostic sample was shown in this study.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 Other

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 8 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (4 results)

  • [Journal Article] The great importance of normalization of LC-MS data for highly-accurate non-targeted metabolomics.2017

    • Author(s)
      Mizuno H, Ueda K, Kobayashi Y, Tsuyama N, Todoroki K, Min JZ, Toyo'oka T.
    • Journal Title

      Biomed Chromatogr.

      Volume: 31 Issue: 1 Pages: 1-7

    • DOI

      10.1002/bmc.3864

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Derivatization-based High-throughput Bioanalysis by LC-MS2017

    • Author(s)
      Toyo'oka Toshimasa
    • Journal Title

      Analytical Sciences

      Volume: 33 Issue: 5 Pages: 555-564

    • DOI

      10.2116/analsci.33.555

    • NAID

      130006777385

    • ISSN
      0910-6340, 1348-2246
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic Approach to Disease Using Non-invasive Samples Based on Derivatization and LC-ESI-MS/MS2016

    • Author(s)
      Toshimasa Toyo'oka
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 9 Pages: 1397-1411

    • DOI

      10.1248/bpb.b16-00453

    • NAID

      130005262298

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dried saliva spot (DSS) as a convenient and reliable sampling for bioanalysis: An application for the diagnosis of diabetes mellitus2016

    • Author(s)
      Masahiro Numako, Takahiro Takayama, Ichiro Noge, Yutaka Kitagawa, Kenichiro Todoroki, Hajime Mizuno, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytical Chemistry

      Volume: 88 Issue: 1 Pages: 635-639

    • DOI

      10.1021/acs.analchem.5b04059

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Determination of creatinine-related molecules in saliva by reversed-phase liquid chromatography with tandem mass spectrometry and the evaluation of hemodialysis in chronic kidney disease patients2016

    • Author(s)
      Mayu Suzuki, Mitsuyoshi Furuhashi, Shogo Sesoko, Kazuhiro Kosuge, Toshio Maeda, Kenichiro Todoroki, Koichi Inoue, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytica Chimica Acta

      Volume: 911 Pages: 92-99

    • DOI

      10.1016/j.aca.2016.01.032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry.2016

    • Author(s)
      Takayama T, Tsutsui H, Shimizu I, Toyama T, Yoshimoto N, Endo Y, Inoue K, Todoroki K, Min JZ, Mizuno H, Toyo'oka T.
    • Journal Title

      Clin Chim Acta.

      Volume: 452 Pages: 18-26

    • DOI

      10.1016/j.cca.2015.10.032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Towards the chiral metabolomics: Liquid chromatography-mass spectrometry based DL-amino acid analysis after labeling with a new chiral reagent, (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidine-2-carboxylate, and the application to saliva of healthy volunteers2015

    • Author(s)
      Toshiki Mochizuki, Takahiro Takayama, Kenichiro Todoroki, Koichi Inoue, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytica Chimica Acta

      Volume: 875 Pages: 73-82

    • DOI

      10.1016/j.aca.2015.02.054

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel approach for LC-MS/MS-based chiral metabolomics fingerprinting and chiral metabolomics extraction using a pair of enantiomers of chiral derivatization reagents2015

    • Author(s)
      Takahiro Takayama, Toshiki Mochizuki, Kenichiro Todoroki, Jun Zhe Min,Hajime Mizuno, Koichi Inoue, Hiroyasu Akatsu, Ichiro Noge, Toshimasa Toyo'oka
    • Journal Title

      Analytica Chimica Acta

      Volume: 898 Pages: 73-84

    • DOI

      10.1016/j.aca.2015.10.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] First observation of N-acetyl leucine and N-acetyl isoleucine in diabetic patient hair and quantitative analysis by UPLC-ESI-MS/MS2015

    • Author(s)
      Jun Zhe Min, Yuki Tomiyasu, Takashi Morotomi, Ying-Zi Jiang, Gao Li, Qing Shi, Hai-fu Yu, Koichi Inoue, Kenichiro Todoroki, Toshimasa Toyo'oka
    • Journal Title

      Clinica Chimica Acta

      Volume: 444 Pages: 143-148

    • DOI

      10.1016/j.cca.2015.02.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Human nails metabolite analysis: A rapid and simple method for quantification of uric acid in human fingernail by high-performanceliquid chromatography with UV-detection2015

    • Author(s)
      Xi-Ling Li, Gao Li, Ying-Zi Jiang, Dongzhou Kang, Cheng Hua Jin, Qing Shi,Toufeng Jin, Koichi Inoue, Kenichiro Todoroki, Toshimasa Toyo'oka, Jun Zhe Min
    • Journal Title

      Journal of Chromatography B

      Volume: 1002 Pages: 394-398

    • DOI

      10.1016/j.jchromb.2015.08.044

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] アミノ酸キラル分析を指向した新規キラル誘導体化試薬の開発とその分離挙動解析2017

    • Author(s)
      柳澤拓摩、高山卓大、轟木 堅一郎、水野 初、閔 俊哲、豊岡利正
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 12C/13Cキラル誘導体化試薬を併用した高精度キラルメタボロミクスの開発2017

    • Author(s)
      高山卓大、轟木 堅一郎、水野 初、閔 俊哲、豊岡利正
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 簡易糖尿病診断を目的とした蛍光検出法による唾液中DL-乳酸の測定2017

    • Author(s)
      沼子将大、高山卓大、轟木堅一郎、水野 初、閔 俊哲、豊岡利正
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 唾液中ポリアミン安定化法の開発と乳がん診断法への応用2017

    • Author(s)
      鈴木安希子、高山卓大、清水逸平、轟木 堅一郎、水野 初、閔 俊哲、豊岡利正
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 誘導体化法によるアミノ酸の光学異性体一斉分離法の開発2017

    • Author(s)
      高山卓大、柳澤拓摩、水野 初、豊岡利正、轟木堅一郎
    • Organizer
      第24回クロマトグラフィーシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 3種同位体標識誘導体化試薬を組み合わせた迅速かつ高精度なキラルメタボロミクスの開発2017

    • Author(s)
      福井芹菜、高野大貴、高山卓大、水野 初、豊岡利正、轟木堅一郎
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Determination of chiral metabolites in fingernails from colorectal cancer patients2016

    • Author(s)
      Yuta Nishio, Jun Zhe Min, Kenichiro Todoroki, Hajime Mizuno, Toshimasa Toyo’oka
    • Organizer
      27th International Symposium on Pharmaceutical and Biomedical Analysis (PBA 2016)
    • Place of Presentation
      Guangzhou, China
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 誘導体化法を基盤とするバイオアナリシス研究 ―アミノ酸の光学異性体分析を中心に―2016

    • Author(s)
      豊岡利正
    • Organizer
      新アミノ酸分析研究会第6回学術講演会
    • Place of Presentation
      東京大学
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 生体機能性分子の高感度・特異的分析法の開発とバイオアナリシスへの展開2016

    • Author(s)
      豊岡利正
    • Organizer
      日本分析化学会第65年会
    • Place of Presentation
      北海道大学
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Diagnostic approach for diabetes mellitus using Dried Saliva Spot (DSS) by UPLC-MS/MS2016

    • Author(s)
      Toshimasa Toyo'oka, Masahiro Numako, Takahiro Takayama, Kenichiro Todoroki, Hajime Mizuno, Jun Zhe Min
    • Organizer
      31st Internal Symposium on Chromatography (ISC 2016)
    • Place of Presentation
      University College Cork, Ireland
    • Year and Date
      2016-08-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 非侵襲的試料を用いた疾病診断2016

    • Author(s)
      豊岡利正
    • Organizer
      第76回分析化学討論会
    • Place of Presentation
      岐阜薬科大学
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 唾液を用いた簡便な乳がん診断法の開発2015

    • Author(s)
      高山卓大、遠山竜也、吉本信保、遠藤友美、水野初、井之上浩-、轟木堅一郎、閔俊哲、豊岡利正
    • Organizer
      第26回クロマトグラフィー科学会議
    • Place of Presentation
      九州大学
    • Year and Date
      2015-11-11
    • Related Report
      2015 Research-status Report
  • [Presentation] カルボン酸分離分析用の安定同位体含有光学活性誘導体化試薬の合成と評価2015

    • Author(s)
      宇野馨、高山卓大、轟木堅一郎、水野初、閔俊哲、豊岡利正
    • Organizer
      第26回クロマトグラフィー科学会議
    • Place of Presentation
      九州大学
    • Year and Date
      2015-11-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 誘導体化LC―MS/MS測定法による光学活性代謝物の網羅的エナンチオマー分別分析法の開発と応用2015

    • Author(s)
      高山卓大、井之上浩一、轟木堅―郎、水野初、閔俊哲、豊岡利正
    • Organizer
      第28回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      長崎大学
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] LC-MS/MS用光学活性誘導体化試薬の創製とキラルメタボロミクスへの適用2015

    • Author(s)
      豊岡利正
    • Organizer
      第22回クロマトグラフィーシンポジウム
    • Place of Presentation
      近畿大学
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 静岡県立大学薬学部生体機能分子分析学分野

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 静岡県立大学薬学部生体機能分子分析学分野 研究業績

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/achievement.html

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 静岡県立大学薬学部生体機能分子分析学教室

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/

    • Related Report
      2015 Research-status Report
  • [Remarks] 研究業績

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/achievement.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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