Development of anticancer therapy with the GGCT inhibitor for urothelial carcinoma
| Project/Area Number |
18K09192
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| Keywords | γ-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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(32 results)
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[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
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 4
Pages: 1805-1805
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
in vivo
Volume: 35
Issue: 2
Pages: 1141-1145
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Biochem Biophys Res Commun.
Volume: 526
Issue: 1
Pages: 128-134
DOI
NAID
Related Report
Peer Reviewed
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