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Development of anticancer therapy with the GGCT inhibitor for urothelial carcinoma

Research Project

Project/Area Number 18K09192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionShiga University of Medical Science

Principal Investigator

Kageyama Susumu  滋賀医科大学, 医学部, 講師 (50378452)

Co-Investigator(Kenkyū-buntansha) 河内 明宏  滋賀医科大学, 医学部, 教授 (90240952)
吉貴 達寛  滋賀医科大学, 医学部, 客員教授 (80230704)
茶野 徳宏  滋賀医科大学, 医学部, 准教授 (40346028)
吉田 哲也  滋賀医科大学, 医学部, 助教 (60510310)
富田 圭司  滋賀医科大学, 医学部, 助教 (30640148)
村井 亮介  滋賀医科大学, 医学部, 非常勤講師 (80748583)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsγ-グルタミルシクロトランスフェラーゼ / 尿路上皮癌 / 分子標的治療 / 抗がん剤 / RNA干渉 / 低分子阻害薬
Outline of Final Research Achievements

We performed an immunohistochemical analysis using anti-GGCT antibody in surgical specimens of bladder cancer obtained from transurethral resection (n=130). High expression of GGCT was observed in 59% (77 patients). High GGCT group showed lower recurrence-free survival than low group although there was no statistical significance. In cellular experiments in urothelial cancer cells, both GGCT-knockdown and administration of GGCT-inhibitor (Pro-GA) revealed significant inhibition of cell growth. The growth inhibitory effect of Pro-GA in the presence of mitomycin C was assessed in RT112 bladder cancer cell. Pro-GA increased the anti-tumor effect of mitomycin C. We concluded that GGCT is a novel promising therapeutic target for the treatment of urothelial cancers.

Academic Significance and Societal Importance of the Research Achievements

進行期尿路上皮癌はきわめて致死率の高い癌の一つである。また、早期診断癌であっても治療後の尿路内再発を頻繁に繰り返すという特徴がある。近年は種々の癌において新薬の登場が目覚ましいが、尿路上皮癌のその進歩は遅々としている。
本研究では尿路上皮癌細胞株に対するはGGCTノックダウンやGGCT阻害剤による著しい増殖抑制が明らかとなった。さらには既存の化学療法剤との併用で増殖抑制効果の増強を認めた。これらの結果から尿路上皮癌においてGGCTは新規抗癌標的として有用と考えられ、尿路上皮癌における新薬創製における重要な新知見と思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (32 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 8 results) Presentation (18 results)

  • [Journal Article] Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems2021

    • Author(s)
      Ryo Ikari, Ken-Ichi Mukaisho, Susumu Kageyama, Masayuki Nagasawa, Shigehisa Kubota, Takahisa Nakayama, Shoko Murakami, Naoko Taniura, Hiroyuki Tanaka, Ryoji P Kushima, Akihiro Kawauchi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 4 Pages: 1805-1805

    • DOI

      10.3390/ijms22041805

    • NAID

      120006974979

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single short retention instillation of pirarubicin prevents intravesical recurrence of low-risk non muscle invasive bladder cancer2021

    • Author(s)
      Susumu Kageyama, koki Maeda, Shigehisa Kubota, Tetsuya Yoshida, Takashi Osafune, Yutaka Arai, Hiroki Soga, Zenkai Nishikawa, Yuji Sano, Keita Takimoto, Chul Jang Kim, Tokuhiro Chano, Akihiro Kawauchi
    • Journal Title

      in vivo

      Volume: 35 Issue: 2 Pages: 1141-1145

    • DOI

      10.21873/invivo.12360

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma2020

    • Author(s)
      Kubota Shigehisa、Yoshida Tetsuya、Kageyama Susumu、Isono Takahiro、Yuasa Takeshi、Yonese Junji、Kushima Ryoji、Kawauchi Akihiro、Chano Tokuhiro
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 18 Issue: 1 Pages: 270-270

    • DOI

      10.1186/s12957-020-02046-9

    • NAID

      120006901558

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabotropic Glutamate Receptor Subtype 7 Is Essential for Ejaculation2020

    • Author(s)
      Masugi-Tokita Miwako、Tomita Keiji、Kobayashi Kenichi、Yoshida Tetsuya、Kageyama Susumu、Sakamoto Hirotaka、Kawauchi Akihiro
    • Journal Title

      Molecular Neurobiology

      Volume: 57 Issue: 12 Pages: 5208-5218

    • DOI

      10.1007/s12035-020-02090-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer.2020

    • Author(s)
      Nagasawa M, Tomimatsu K, Terada K, Kondo K, Miyazaki K, Miyazaki M, Motooka D, Okuzaki D, Yoshida T, Kageyama S, Kawamoto H, Kawauchi A, Agata Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 526 Issue: 1 Pages: 128-134

    • DOI

      10.1016/j.bbrc.2020.03.043

    • NAID

      120006839258

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Off‐clamp tumor excision using soft coagulation in laparoscopic and robotic partial nephrectomy2020

    • Author(s)
      Yoshida Tetsuya、Okinaka Yuki、Tomita Keiji、Tsuru Teruhiko、Kageyama Susumu、Narita Mitsuhiro、Kawauchi Akihiro
    • Journal Title

      Asian Journal of Endoscopic Surgery

      Volume: - Issue: 4 Pages: 519-525

    • DOI

      10.1111/ases.12775

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] DRUG-INDUCED INTERSTITIAL LUNG DISEASE DURING COMBINED ANDROGEN BLOCKADE WITH BICALUTAMIDE AND LEUPRORELIN ACETATE FOR PROSTATE CANCER2019

    • Author(s)
      Maeda Koki、Osafune Takashi、Masuda Yoshikata、Takeda Takayuki、Kageyama Susumu、Narita Mitsuhiro、Kawauchi Akihiro
    • Journal Title

      The Japanese Journal of Urology

      Volume: 110 Issue: 1 Pages: 36-40

    • DOI

      10.5980/jpnjurol.110.36

    • NAID

      130007787602

    • ISSN
      0021-5287, 1884-7110
    • Year and Date
      2019-01-20
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blockade of γ-Glutamylcyclotransferase Enhances Docetaxel Growth Inhibition of Prostate Cancer Cells2019

    • Author(s)
      TAKAGI HIROKO、II HIROMI、KAGEYAMA SUSUMU、HANADA EIKI、TANIGUCHI KEIKO、YOSHIYA TAKU、CHANO TOKUHIRO、KAWAUCHI AKIHIRO、NAKATA SUSUMU
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 9 Pages: 4811-4816

    • DOI

      10.21873/anticanres.13666

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Depletion of gamma-glutamylcyclotransferase inhibits cancer cell growth by activating the AMPK?FOXO3a?p21 axis2019

    • Author(s)
      Taniguchi Keiko、Ii Hiromi、Kageyama Susumu、Takagi Hiroko、Chano Tokuhiro、Kawauchi Akihiro、Nakata Susumu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 517 Issue: 2 Pages: 238-243

    • DOI

      10.1016/j.bbrc.2019.07.049

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of an OCT3/4 reporter cynomolgus monkey ES cell line using CRISPR/Cas9.2019

    • Author(s)
      Kobayashi K, Tsukiyama T, Nakaya M, Kageyama S, Tomita K, Murai R, Yoshida T, Narita M, Kawauchi A, Ema M.
    • Journal Title

      Stem cell research

      Volume: Epub Pages: 101439-101439

    • DOI

      10.1016/j.scr.2019.101439

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth2019

    • Author(s)
      HANADA EIKI、KAGEYAMA SUSUMU、MURAI RYOSUKE、KUBOTA SHIGEHISA、II HIROMI、NAKATA SUSUMU、KITA HIROKO、KAWAUCHI AKIHIRO、CHANO TOKUHIRO
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 4 Pages: 1893-1898

    • DOI

      10.21873/anticanres.13297

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy2018

    • Author(s)
      Kageyama Susumu、Ii Hiromi、Taniguchi Keiko、Kubota Shigehisa、Yoshida Tetsuya、Isono Takahiro、Chano Tokuhiro、Yoshiya Taku、Ito Kosei、Yoshiki Tatsuhiro、Kawauchi Akihiro、Nakata Susumu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 7 Pages: 2054-2054

    • DOI

      10.3390/ijms19072054

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Superoxide dismutase 2 expression can predict prognosis of renal cell carcinoma patients2018

    • Author(s)
      Yoshida Tetsuya、Kageyama Susumu、Isono Takahiro、Yuasa Takeshi、Kushima Ryoji、Kawauchi Akihiro、Chano Tokuhiro
    • Journal Title

      Cancer Biomarkers

      Volume: 22 Issue: 4 Pages: 755-761

    • DOI

      10.3233/cbm-181308

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] RAB39A: a Rab small GTPase with a prominent role in cancer stemness2018

    • Author(s)
      Chano Tokuhiro、Avnet Sofia
    • Journal Title

      The Journal of Biochemistry

      Volume: 164 Issue: 1 Pages: 9-14

    • DOI

      10.1093/jb/mvy041

    • NAID

      40021625260

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Gamma-glutamylcyclotransferase阻害剤pro-GAの開発とその抗癌効果の検討2020

    • Author(s)
      影山 進、花田英紀, 飯居宏美, 吉矢 拓, 谷口恵香, 高木寛子, 中田 晋, 河内明宏
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] トランスクリプトーム解析を用いたGGCT発現阻害による抗腫瘍メカニズムの解明2020

    • Author(s)
      窪田成寿,礒野高敬,永澤誠之,和田晃典,影山 進,河内明宏
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遺伝子発現データ解析に基づく腎細胞癌のバイオマーカーの同定とリスクモデルの構築2019

    • Author(s)
      窪田成寿,礒野高敬,吉田哲也,影山 進,成田充弘,茶野徳宏,湯浅 健,米瀬淳二,河内明宏
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 低リスクNMIBCに対するTHP短時間単回膀胱内注入療法: MMCとの比較2019

    • Author(s)
      影山 進,窪田成寿,前田航規,長船 崇,西川全海,瀧本啓太,坂野祐司,曽我弘樹,金 哲將,吉田哲也,成田充弘,河内明宏
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCT発現低下はAMPK-FOXOa-p21経路を介して膠芽腫細胞株の増殖を抑制する ―GGCT阻害による抗がん効果のメカニズム解明―2019

    • Author(s)
      遠藤百華,安藤孝太,松田凌平,谷口恵香,飯居宏美,影山 進,高木寛子,茂山千愛美,安藤翔太,中田 晋
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pro-GAの抗腫瘍効果のメカニズムには細胞周期停止と細胞老化の誘導が関与する2019

    • Author(s)
      小川遥香,高木寛子,谷口恵香,吉矢 拓,影山 進,中田 晋
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCT阻害とドセタキセルの併用は前立腺がん細胞に対する増殖抑制を増強する2019

    • Author(s)
      高木寛子,飯居宏美,影山 進,谷口恵香,吉矢 拓,中田 晋
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCT発現低下でがん細胞に誘導されるオートファジーはAMPKを介して調節される ―GGCT阻害による抗がん効果のメカニズム解明―2019

    • Author(s)
      谷口恵香,飯居宏美,影山 進,高木寛子,安藤翔太,茂山千愛美,芦原英司,中田 晋
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCT阻害により誘導されるMCF7がん細胞増殖抑制は、N-アセチルシステイン添加により回復する2019

    • Author(s)
      飯居宏美,谷口恵香,高木寛子,茂山千愛美,影山 進,中田 晋
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCTの発現低下はAMPK-FOXO3a-p21経路を介してがん細胞の増殖を抑制する2019

    • Author(s)
      谷口恵香,飯居宏美,影山 進,茂山千愛美、安藤翔太、芦原英司、茶野徳宏、河内明宏、中田 晋
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規阻害剤pro-GAによるMCF7乳がん細胞のCDK阻害因子p21誘導と増殖抑制はN-アセチルシステイン添加により解除される2019

    • Author(s)
      中島里菜,早川詩乃,飯居宏美,高木寛子,谷口恵香,吉矢 拓,影山 進,中田 晋
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] GGCTを治療標的とした尿路上皮癌治療の基礎的検討2019

    • Author(s)
      影山 進,窪田成寿,村井亮介,吉田哲也,成田充弘,茶野徳宏,河内明宏
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Gamma-glutamylcyclotransferase(GGCT)欠乏で誘導されるp21発現上昇は乳癌細胞においてProhibitin-2を介して調節される2019

    • Author(s)
      1)谷口恵香,影山 進,高木寛子,飯居宏美,芦原英司,茶野徳宏,河内明宏,中田 晋
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規阻害剤によるGGCT酵素活性阻害効率の評価とPC3ヒト前立腺がん細胞に対する抗腫瘍効果の解析2019

    • Author(s)
      2)延原真之,坂本 唯,飯居宏美,谷口恵香,高木寛子,吉矢 拓,津田修吾,望月雅允,影山 進,中田 晋
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規GGCT阻害剤は細胞周期停止および細胞老化を誘導しMCF7乳がん細胞の増殖を抑制する2019

    • Author(s)
      3)金谷賢吾,早川詩乃,飯居宏美,高木寛子,谷口恵香,吉矢 拓,津田修吾,望月雅允,影山 進,中田 晋
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] γ-グルタミルシクロトランスフェラーゼを標的とした新規抗がん剤開発2018

    • Author(s)
      28)飯居宏美,中田 晋,谷口恵香,高木寛子,茂山千愛美,影山 進,吉貴達寛
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 乳癌細胞においてGGCT欠乏で誘導されるp21はprohibitin-2を介して調節される2018

    • Author(s)
      29)谷口恵香,松村健吾,影山 進,飯居宏美,芦原英司,茶野徳宏,河内明宏,吉貴達寛,中田 晋
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] GGCT(γ-グルタミルシクロトランスフェラーゼ)阻害を作用機序とした新規抗癌剤の開発2018

    • Author(s)
      37)影山 進,窪田成寿,村井亮介,吉矢 拓,飯居宏美,中田 晋,吉貴達寛,河内明宏
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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