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Development of bio-marker for diagnosing prostate cancer and its application

Research Project

Project/Area Number 15390011
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKanazawa University

Principal Investigator

SHIMADA Kazutake  Kanazawa University, Graduate School of Natural Science and Technology, Professor, 自然科学研究科, 教授 (90004605)

Co-Investigator(Kenkyū-buntansha) HIGASHI Tatsuya  Kanazawa University, Graduate School of Natural Science and Technology, Associate professor, 自然科学研究科, 助教授 (90272963)
三田村 邦子  金沢大学, 自然科学研究科, 助手 (70242526)
本間 誠次郎  帝国臓器製薬メディカル, 受託研究部, 部長
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥13,500,000 (Direct Cost: ¥13,500,000)
Keywordsprostate cancer / benign prostatic hyperplasia / bio-marker / testosterone / dihydrotestosterone / deivatization-LC / MS / mass-screening / inhibitor / LC / 電子捕獲型 / エレクトロスプレーイオン化 / MSプローブ / 再燃 / 予後診断 / アンドロゲン / 誘導体化試薬
Research Abstract

During the last decade, prostate cancer has been a commonly diagnosed malignancy in males. The research focused on steroids [testosterone (T) and its active form dihydrotestosterone (DHT)] in human prostate or serum, which are the potential bio-markers for diagnosing prostate cancer (PC) or benign prostatic hyperplasia (BPH). We have developed a new derivatization reagent (2-hydrazino-1-methylpyridine) having a quarternary pyridinium moiety for the analysis of these androgens using LC/electrospray ionization-MS. The reagent quantitatively reacted with the above oxo-steroids (T and DHT) and the derivatives provided a 70-1600 fold higher sensitivity compared to intact steroids. The developed method allowed the reproducible quantification of nanogram/gram levels of T and DHT with a 10 mg tissue sample of the prostate. The method was applied to the determination of T and DHT in PC and BPH tissues. DHT was determined in BPH tissue, but not detected in PC tissue. T was not detected in both tissues. These data is useful for establishment of mass screening for these diseases.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (28 results)

All 2005 2004 2003 Other

All Journal Article (21 results) Book (3 results) Patent(Industrial Property Rights) (1 results) Publications (3 results)

  • [Journal Article] Determination of sulfates of androsterone and epiandrosterone in human serum using isotope diluted liquid chromatography-electrospray ionization-mass spectrometry2005

    • Author(s)
      Kuniko Mitamura
    • Journal Title

      Biomed.Chromatogr. 19(10)

      Pages: 796-801

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination of prostatic androgens in 10 mg of tissue using liquid chromatography-tandem mass spectrometry with charged derivatization2005

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      Anal.Bioanal.Chem. 382(4)

      Pages: 1035-1043

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination method for steroid 5α-reductase activity using liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry2005

    • Author(s)
      Kuniko Mitamura
    • Journal Title

      Anal.Sci. 21(10)

      Pages: 1241-1244

    • NAID

      80017765174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Enzymatic conversion of 3β-hydroxy-5-ene-steroids and their sulfates to 3-oxo-4-ene-steroids for increasing sensitivity in LC-APCI-MS2005

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      J.Pharm.Biomed.Anal. 39(3-4)

      Pages: 718-723

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination of sulfates of androsterone and epiandrosterone in human serum using isotope diluted liquid chromatography-electrospray ionization-mass spectrometry2005

    • Author(s)
      Kuniko Mitamura et al.
    • Journal Title

      Biomed.Chromatogr. 19(10)

      Pages: 796-801

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination of prostatic androgens in 10 mg of tissue using liquid chromatography-tandem mass spectrometry with charged derivatization2005

    • Author(s)
      Tatsuya Higashi et al.
    • Journal Title

      Anal.Bioanal.Chem. 382(4)

      Pages: 1035-1043

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination method for steroid 5α-reductase activity using liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry2005

    • Author(s)
      Kuniko Mitamura et al.
    • Journal Title

      Anal.Sci. 21(10)

      Pages: 1241-1244

    • NAID

      80017765174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enzymatic conversion of 3ss-hydroxy-5-ene-steroids and their sulfates to 3-oxo-4-ene-steroids for increasing sensitivity in LC-APCI-MS2005

    • Author(s)
      Tatsuya Higashi et al.
    • Journal Title

      J.Pharm.Biomed.Anal. 39(3-4)

      Pages: 718-723

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Determination of sulfates of androsterone and epiandrosterone in human serum using isotope diluted liquid chromatography/electrospray ionization mass spectrometry2005

    • Author(s)
      Kuniko Mitamura
    • Journal Title

      Biomed.Chromatogr. 19(10)

      Pages: 796-801

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Determination of prostatic androgens in 10 mg tissue using liquid chromatography-tandem mass spectrometry with charged derivatization2005

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      Anal.Bioanal.Chem. 382(4)

      Pages: 1035-1043

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enzymatic conversion of 3ss-hydroxy-5-ene-steroids and their sulfates to 3-oxo-4-ene-steroids for increasing sensitivity in LC-APCI-MS2005

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      J.Pharm.Biomed.Anal. 39(3-4)

      Pages: 718-723

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Derivatization of neutral steroids to enhance their detection characteristics in liquid chromatography-mass spectrometry2004

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      Anal.Bioanal.Chem. 378(4)

      Pages: 875-882

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 前立腺癌とアンドロゲンの代謝分析2004

    • Author(s)
      東 達也
    • Journal Title

      臨床化学 33(4)

      Pages: 177-182

    • NAID

      10014070714

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 2-Hydrazino-1-methylpyridine : a highly sensitive derivatization reagent for oxosteroids in liquid chromatography-electrospray ionization-mass spectrometry2004

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      J.Chromatogr.B 825(2)

      Pages: 214-222

    • NAID

      10016977958

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Derivatization of neutral steroids to enhance their detection characteristics in liquid chromatography-mass spectrometry2004

    • Author(s)
      Tatsuya Higashi, Kazutake Shimdada
    • Journal Title

      Anal.Bioanal.Chem. 378(4)

      Pages: 875-882

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 2-Hydrazino-1-methyl-pyridine : a highly sensitive derivatization reagent for oxosteroids in liquid chromatography-electrospray ionization-mass spectrometry2004

    • Author(s)
      Tatsuya Higashi et al.
    • Journal Title

      J.Chromtaogr.B 825(2)

      Pages: 214-222

    • NAID

      10016977958

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prostate cancer and metabolic analysis of androgens2004

    • Author(s)
      Tatsuya Higashi et al.
    • Journal Title

      Rinshoukagaku 33(4)

      Pages: 177-182

    • NAID

      10014070714

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Derivatization of neutral steroids to enhance their detection charact-eristics in liquid chromatography/mass spectrometry2004

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      Anal.Bioanal.Chem. 378(4)

      Pages: 875-882

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 2-Hydrazino-I-methylpyridine : a highly sensitive derivatization reagent for oxostreoids in liquid chromatography-electrospray ionization-mass spectrometry.2004

    • Author(s)
      Tatsuya Higashi
    • Journal Title

      J.Chromatogr.B (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Simultaneous determination of androsterone 3-sulfate and dehydroepiandrosterone sulfate in human serum using isotope diluted liquid chromatography-electrospray ionization-mass spectrometry2003

    • Author(s)
      Kuniko Mitamura
    • Journal Title

      J.Chromatogr.B 796(1)

      Pages: 121-130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Simultaneous determination of androsterone 3-sulfate and dehydroepiandrosterone sulfate in human serum using isotopediluted liquid chromatography-electrospray ionization-mass spectrometry2003

    • Author(s)
      Kuniko Mitamura et al.
    • Journal Title

      J.Chromtaogr.B 796(1)

      Pages: 121-130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 先端の分析法-理工学からナノ・バイオまで-2004

    • Author(s)
      島田 和武(梅澤, 澤田, 寺部監修)
    • Publisher
      エヌ・テイ・エス社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Hyphenated Technique (in Japanese)2004

    • Author(s)
      Kazutake Shimada et al.
    • Publisher
      Sentan no Bunsekihou, NTS Co.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 先端の分析法-理工学からナノ・バイオまで-(梅澤, 澤田, 寺部監修)2004

    • Author(s)
      島田 和武
    • Publisher
      エヌ・ティ・エス社
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] ステロイド性生体内微量物質の測定方法2003

    • Inventor(s)
      東 達也
    • Industrial Property Rights Holder
      帝国臓器製薬
    • Filing Date
      2003-02-27
    • Acquisition Date
      2005-06-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Tatsuya Higashi: "Detection and characterization of 20-oxosteroids in rat brains using LC-electroncapture APCI-MS after derivatization with 2-nitro-4-trifluoromethylpnenylhydrazine"Analyst. 128(2). 130-133 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuniko Mitamura: "Simultaneous determination of androsterone 3-sulfate and dehydroepiandrosterone sulfate in human serum using isotope diluted liquid chromatography-elcetrospray ionization-mass spectrometry"J.Chromatogr.B. 796(1). 121-130 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tatsuya Higashi: "Derivatization of neutral steroids to enhance their detection characteristics in liquid chromatography/mass spectrometry"Anal.Bioanal.Chem.. (In press).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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