Development of the new diagnostic method and drug discovery based on metabolic loam analysis of the castration-resistant prostate cancer
Project/Area Number |
17K11125
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
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Research Institution | Chiba University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
今村 有佑 千葉大学, 大学院医学研究院, 助教 (10568629)
安西 尚彦 千葉大学, 大学院医学研究院, 教授 (70276054)
高山 達也 自治医科大学, 医学部, 准教授 (90324350)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 前立腺癌 / 去勢抵抗性 / アミノ酸トランスポーター / テストステロン / 前立腺がん / メタボローム / 血清テストステロン / 予後 / cf DNA / AR増幅 / バイオバンク / 血清 / タンパク質 / メタボロミクス / マーカー |
Outline of Final Research Achievements |
In the prostate cancer, I identified the importance in the tumor increase of 4F2hc which formed LAT1 and the heterodimer which were the amino acid transporter which was the control factor of the metabolic loam. The expression of 4F2hc in the prostatic complete removal specimen is related to a PSA recurrence (P = 0.0035). The overexpression of 4F2hc was related to the clinical tumors stage (p= 0.0255) and Gleason score (p= 0.0035). Si4F2hc controlled phosphorylation of MAPK and AKT in conjunction with G0/G1 Arrest. From RNA Seq analysis of Si4F2hc, I identified SKP-2 protein as the downstream signal.
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Academic Significance and Societal Importance of the Research Achievements |
前立腺癌におけるアミノ酸トランスポータ―LAT1/4F2hcの臨床的、基礎医学的意義を証明した。以前は、LAT1からの側面しか解析されていない中、結合蛋白である4F2hcの重要性を世界で初めて証明した。 また、LAT1阻害剤は前臨床段階でPhase I試験が終了し、Phase II試験を去勢抵抗性前立腺癌において計画している。今回の結果は、今後の臨床試験の申請に活用されると思われる。 平行して行った血清テストステロン値と去勢抵抗性前立腺癌患者の予後予測因子としての有用性の検討は、血清テストステロンの高低により新規AR剤か化学療法を選択すべきか示唆される実臨床に応用可能な内容であった。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma.2020
Author(s)
Maimaiti M, Sakamoto S, Yamada Y, Sugiura M, Rii J, Takeuchi N, Imamura Y, Furihata T, Ando K, Higuchi K, Xu M, Sazuka T, Nakamura K, Kaneda A, Kanai Y, Kyprianou N, Ikehara Y, Anzai N, Ichikawa T.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 1292-1292
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Biparametric Prostate Imaging, the Reporting and Data System, Version 2, and International Society of Urological Pathology Grade Predict for Biochemical Recurrence After Radical Prostatectomy.2018
Author(s)
Takeuchi N, Sakamoto S, Nishiyama A, Horikoshi T, Yamada Y, Iizuka J, Maimaiti M, Imamura Y, Kawamura K, Imamoto T, Komiya A, Ikehara Y, Akakura K, Ichikawa T.
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Journal Title
Clin Genitourin Cancer
Volume: 「印刷中」
Issue: 4
Pages: e817-e829
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Duration of androgen deprivation therapy and nadir of testosterone at 20 ng/dL predict testosterone recovery to supracastrate level in prostate cancer patients who received external beam radiotherapy.2018
Author(s)
Takei A, Sakamoto S, Wakai K, Tamura T, Imamura Y, Xu M, Maimaiti M, Kawamura K, Imamoto T, Komiya A, Akakura K, Ichikawa T.
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Journal Title
Int J Urol.
Volume: 25
Issue: 4
Pages: 352-358
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Testosterone Reduction of 480 ng/dL Predicts Favorable Prognosis of Japanese Men With Advanced Prostate Cancer Treated With Androgen-Deprivation Therapy.2017
Author(s)
Yamamoto S, Sakamoto S, Minhui X, Tamura T, Otsuka K, Sato K, Maimaiti M, Kamada S, Takei A, Fuse M, Kawamura K, Imamoto T, Komiya A, Akakura K, Ichikawa T.
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Journal Title
Clin Genitourin Cancer
Volume: 15
Issue: 6
Pages: e1107-e1115
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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