Development of a new biomarker for urothelial carcinoma using urinary protein kinase C alpha
Project/Area Number |
19H04488
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 90130:Medical systems-related
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Research Institution | Kyushu University |
Principal Investigator |
Eto Masatoshi 九州大学, 医学研究院, 教授 (90315078)
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Co-Investigator(Kenkyū-buntansha) |
村田 正治 九州大学, 先端医療オープンイノベーションセンター, 教授 (30304744)
姜 貞勲 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50423512)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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Keywords | 癌 / 膀胱 / バイオマーカー / 尿 |
Outline of Research at the Start |
リン酸化酵素であるプロテインキナーゼCα(PKCα)はがん化の初期段階から過剰発現することが知られている。本研究では尿路上皮がん患者における尿中の活性型PKCαのバイオマーカーとしての臨床的有用性について検討する。測定法については、我々が開発したPKCα特異的な基質ペプチドを用いて、尿中PKCαによるそのリン酸化を質量分析装置にて定量化する。尿路上皮がん患者に加えて、腎がん等、他の泌尿器疾患患者の尿サンプルを用いても同様な実験を実施し、泌尿器科領域におけるPKCαの臨床的意義を詳細に調査する。これに並行して、活性型PKCαをより簡便に測定できる診断システムの開発も進める。
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Outline of Final Research Achievements |
Cystoscopy is considered the gold standard for the diagnosis and continuous monitoring of bladder cancer. However, cystoscopy is invasive and relatively expensive. Thus, there is a need for non-invasive, relatively inexpensive urinary biomarker-based diagnoses of bladder cancer. This study aimed to investigate the presence of activated protein kinase C (PKC) in urine samples and the possibility of PKC as a urinary biomarker for bladder cancer diagnosis. Activated PKC was found to be present at higher levels in bladder cancer tissues than in normal bladder tissues. Furthermore, high levels of activated PKC were observed in urine samples collected from orthotopic xenograft mice carrying human bladder cancer cells compared to urine samples from normal mice. These results suggest that activated PKC can be used as a urinary biomarker to diagnose bladder cancer.
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Academic Significance and Societal Importance of the Research Achievements |
尿路上皮癌患者数は増加傾向にあり、尿路上皮癌を見逃さないための簡便な診断・スクリーニング法の開発は喫緊の課題である。また尿路上皮癌の標準検査である尿細胞診は低悪性度癌に対する感度が低く、臨床上の大きな問題となっている。本研究では膀胱癌においても活性型PKCαが発現していることを見出し、さらに尿中活性型PKCα が高悪性度だけでなく低悪性度の尿路上皮癌のバイオマーカーとなり得ることを示した。この成果を実臨床に応用すれば尿路上皮癌の再発の早期発見につながるだけでなく、検診において血尿や尿潜血患者からの尿路上皮癌患者のスクリーニングにつながる可能性があり、社会的な意義は非常に大きいと思われる。
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced pact carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis.2022
Author(s)
Tomita Y, Yamamoto Y, Tsuchiya N, Kanayama H, Eto M, Miyake H, Thomas P, Yoshida M, Koide Y, Umeyama Y, Pietro AD, Uemura H.
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Journal Title
Int J Clin Oncol
Volume: 27 (2)
Issue: 2
Pages: 383-395
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of HLA genotype on intravesical recurrence after bacillus Calmette-Guerin therapy for non-muscle-invasive bladder cancer.2022
Author(s)
Kobayashi M, Fujiyama N, Tanegashima T, Narita S, Yamamoto Y, Fujimoto N, Ueda S, Takeuchi A, Numakura K, Habuchi T, Matsuyama H, Eto M, Shiota M.
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Journal Title
Cancer Immunol Immunother
Volume: 71 (3)
Issue: 3
Pages: 727-736
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical Practice Guidelines for Bladder Cancer 2019 edition by the Japanese Urological Association: Revision working position paper.2020
Author(s)
Matsumoto H, Shiraishi K, Azuma H, Inoue K, Uemura H, Eto M, Ohyama C, Ogawa O, Kikuchi E, Kitamura H, Shinohara N, Takahashi S, Tsuzuki T, Nakagawa M, Narumi Y, Nishiyama H, Habuchi T, Hinotsu S, Fujii Y, Fujimoto K, Fujimoto H, Mizowaki T, Matsuyama H
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Journal Title
Int J Urol
Volume: 27 (5)
Issue: 5
Pages: 362-368
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical Practice Guidelines for Bladder Cancer 2019 update by the Japanese Urological Association: Summary of the revision.2020
Author(s)
Matsumoto H, Shiraishi K, Azuma H, Inoue K, Uemura H, Eto M, Ohyama C, Ogawa O, Kikuchi E, Kitamura H, Shinohara N, Takahashi S, Tsuzuki T, Nakagawa M, Narumi Y, Nishiyama H, Habuchi T, Hinotsu S, Fujii Y, Fujimoto K, Fujimoto H, Mizowaki T, Matsuyama H
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Journal Title
Int J Urol
Volume: 27 (9)
Issue: 9
Pages: 702-709
DOI
Related Report
Peer Reviewed
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[Journal Article] Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses.2019
Author(s)
Ohyama C, Kojima T, Kondo T, Naya Y, Inoue T, Tomita Y, Eto M, Hisasue S, Uemura H, Obara W, Kikuchi E, Sharma P, Galsky MD, Siefker-Radtke A, Grossfeld G, Collette S, Gooden K, Kimura G:
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Journal Title
Int J Clin Oncol
Volume: 24 (9)
Issue: 9
Pages: 1089-1098
DOI
Related Report
Peer Reviewed
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[Journal Article] Impact of Previous, Simultaneous or Subsequent Bladder Cancer on Prognosis after Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.2019
Author(s)
Kuroiwa K, Inokuchi J, Nishiyama H, Kojima T, Kakehi Y, Sugimoto M, Tanigawa T, Fujimoto H, Gotoh M, Masumori N, Ogawa O, Eto M, Ohyama C, Yokomizo A, Matsuyama H, Ichikawa T, Mizusawa J, Eba J, Naito S; Urologic Oncology Study Group of the Japan Clinical Oncology Group (JCOG):
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Journal Title
J Urol
Volume: 202 (6)
Issue: 6
Pages: 1127-1135
DOI
Related Report
Peer Reviewed
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[Presentation] Phase I/II study to evaluate the efficacy of TAS0313, a cancer peptide vaccine, combined with pembrolizumab for locally advanced or metastatic urothelial carcinoma2021
Author(s)
Matsumoto R, Yonese J, Kawahara T, Miyake H, Matsubara N, Uemura H, Eto M, Azuma H, Obara W, Terai A, Fukasawa S, Suekane S, Nishiyama H
Organizer
2021 ASCO 57nd Annual Meeting
Related Report
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