| Project/Area Number |
18K08659
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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 55020:Digestive surgery-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
Suzuki Shuji 東京医科大学, 医学部, 主任教授 (30246566)
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| Co-Investigator(Kenkyū-buntansha) |
本多 彰 東京医科大学, 医学部, 教授 (10468639)
宮崎 照雄 東京医科大学, 医学部, 准教授 (60532687)
下田 貢 東京医科大学, 医学部, 教授 (90332999)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 胆道がん / 27-ヒドロキシコレステロール / エストロゲン受容体 / 胆汁 / 胆道癌 |
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| Outline of Final Research Achievements |
27-Hydroxycholesterol (27HC) is one of the biliary oxysterols that activates estrogen receptors (ERs). Since 27HC stimulates breast cancer growth through the activation of ERs and about half of bile duct cancer also expresses ERs, we hypothesized that biliary 27HC modulates ER-positive bile duct cancer growth. A cell line (TFK-1) derived from human bile duct cancer expressing ERβ was cultured and incubated with 27HC. The cell growth was significantly promoted by adding more than 10 nM of 27HC. Besides, the addition of PHTPP, an antagonist of ERβ, canceled the growth promotion due to 27HC. Biliary concentrations of 27HC in bile duct cancer patients were 50-1000 nM, which was much higher than the levels added in cell culture media. These results suggest that biliary 27HC can stimulate the growth of ER-positive bile duct cancer in vivo. Therefore, the inhibition of ER activity may be a new strategy to inhibit the postoperative recurrence of ER-positive bile duct cancer in both genders.
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| Academic Significance and Societal Importance of the Research Achievements |
胆管癌は5年生存率が膵癌に次いで低い予後不良の癌である。本研究成果によって、病理組織学的にエストロゲン受容体を発現している胆管癌では、患者の性別にかかわらず、術後にエストロゲン受容体の阻害剤を用いることによって、再発のスピードを抑制できる可能性が示唆された。新たな治療方法の開発や、27-ヒドロキシコレステロールが多く存在する他臓器癌での検討など、応用範囲が広い研究成果と考えられる。
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