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Establishment of order-made therapy by mediating cholesterol metabolism pathways in castration-resistant prostate cancer dells

Research Project

Project/Area Number 26462432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionAichi Medical University

Principal Investigator

Sumitomo Makoto  愛知医科大学, 医学部, 教授 (50255535)

Research Collaborator MURAMATSU HIROYUKI  愛知医科大学, 医学部, 助教 (60714847)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords去勢抵抗性前立腺癌 / 嫌気性解糖系 / 乳酸脱水素酵素 / アポトーシス / タキサン / アミノ酸トランスポーター / オートファジー / 前立腺癌 / docetaxel
Outline of Final Research Achievements

We investigated the role of LDH-A in mediating castration resistance of human prostate cancer (PC) cells by analyzing PC cell lines. LDH expression is strongly associated with docetaxel (DOC) sensitivity in PC cells. A specific LDH-A inhibitor sodium oxamate (SO) inhibited cell growth in PC cells, which was presumably caused by the inhibition of LDH-A protein expression. Synergistic cytotoxicity was observed after the combination therapy with DOC and SO in castration resistant LN-CSS cells, but not in parental LNCaP cells. The combination with DOC and SO caused cell cycle arrest in G2-M and SO promotes DOC-induced apoptosis in LN-CSS cells, which was partially caused by inhibition of DOC-induced increases in LDH-A expression. Our study may provide valuable information for the future development of targeted therapies for CRPC.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016 2015

All Presentation (13 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 前立腺癌細胞株に対するdocetaxelとLDH阻害薬による抗腫瘍効果の検討2018

    • Author(s)
      村松洋行, 住友 誠, 杉江美穂, 森永慎吾, 小林郁生, 梶川圭史, 西川源也, 加藤義晴, 渡邊將人, 全並賢二, 金尾健人, 中村小源太, 吉川和宏
    • Organizer
      第27回泌尿器科分子・細胞研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetacel-induced cytotoxicity in prostate cancer cells2018

    • Author(s)
      Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Miho Sugie, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Masahito Watanabe, Kenji Zennami, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
    • Organizer
      Annual meeting of European Association of Urology 2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前立腺癌細胞株に対するLDH阻害薬とdocetaxelによる抗腫瘍効果の検討2017

    • Author(s)
      村松洋行, 住友 誠, 斎藤政信, 杉江美穂, 森永慎吾, 小林郁生, 梶川圭史, 西川源也, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetacel-induced cytotoxicity in prostate cancer cells.2017

    • Author(s)
      Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Masanobu Saito, Miho Sugie, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Masahito Watanabe, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
    • Organizer
      AACR annual meeting 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害薬の併用投与による抗腫瘍効果の検討2017

    • Author(s)
      村松洋行;住友誠;森永慎吾;梶川圭史;小林郁生;西川源也;加藤義晴;渡邊將人;金尾健人;中村小源太; 吉川和宏
    • Organizer
      第26回泌尿器科分子・
    • Place of Presentation
      大分
    • Related Report
      2016 Research-status Report
  • [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes  docetacel-induced cytotoxicity in prostate cancer cells.2017

    • Author(s)
      Hiroyuki Muramatsu,Makoto Sumitomo, Shingo Morinaga,Keishi Kajikawa,Ikuo Kobayashi,Genya Nishikawa,
    • Organizer
      AACR Annual Meeting 2017
    • Place of Presentation
      Washington DC
    • Related Report
      2016 Research-status Report
  • [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害の併用投与による抗腫瘍効果の検討2016

    • Author(s)
      村松洋行、住友 誠、渡邊將人、森永慎吾、梶川圭史、小林郁生、西川源也、吉澤孝彦、加藤義晴、渡邊將人、金尾健人、中村小源太、吉川 和宏
    • Organizer
      第104回日本泌尿器科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes  docetaxel-induced cytotoxicity in prostate cancer cells.2016

    • Author(s)
      Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Takahiko Yoshizawa, Yoshiharu Kto, Masahito Watanabe, Kenji Zennami, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa.
    • Organizer
      European urological association 30th Annual Congress
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2016-03-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害の併用投与による抗腫瘍効果の検討2016

    • Author(s)
      村松洋行、住友 誠、渡邊將人、森永慎吾、梶川圭史、小林郁生、西川源也、吉澤孝彦、加藤義晴、渡邊將人、金尾健人、中村小源太、吉川 和宏
    • Organizer
      第25回泌尿器科分子・細胞研究会
    • Place of Presentation
      大阪
    • Year and Date
      2016-02-06
    • Related Report
      2015 Research-status Report
  • [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害薬の併用投与による抗腫瘍効果の検討2016

    • Author(s)
      村松洋行;住友誠;森永慎吾;梶川圭史;小林郁生;西川源也;吉澤孝彦;加藤義晴;渡邊將人;金尾健人;中村小源太; 吉川和宏
    • Organizer
      第104回日本泌尿器科学会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
  • [Presentation] 前立腺癌の嫌気性解糖系に対するLDH阻害薬の細胞増殖抑制効果の検討2015

    • Author(s)
      村松洋行, 住友誠, 全並賢二, 森永慎吾, 梶川圭史, 小林郁生, 西川源也, 吉澤孝彦, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
    • Organizer
      第103回日本泌尿器科学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2015-04-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetaxel-induced cytotoxicity in prostate cancer cells.2015

    • Author(s)
      Hiroyuki Muramatsu, Makoto Sumitomo, Kenji Zennami, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Takahiko Yoshizawa, Yoshiharu Kato, Masahito Watanabe, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
    • Organizer
      30th European Association Urology annual meeting
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 前立腺癌の嫌気性解糖系に対するLDH阻害薬の細胞増殖抑制効果の検討2015

    • Author(s)
      村松洋行, 住友誠, 全並賢二, 森永慎吾, 梶川圭史, 小林郁生, 西川源也, 吉澤孝彦, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
    • Organizer
      第24回泌尿器分子・細胞研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-28
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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