Project/Area Number |
26462519
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | Gifu University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
古井 辰郎 岐阜大学, 大学院医学系研究科, 准教授 (00313883)
牧野 弘 岐阜大学, 医学部附属病院, 助教 (20649107)
鈴木 紀子 岐阜大学, 大学院医学系研究科, 学術研究補佐員 (40642096)
水野 智子 岐阜大学, 医学部附属病院, 医員 (60444262)
川島 英理子 (佐藤英理子 / 川島 英理子(佐藤英理子)) 岐阜大学, 医学部附属病院, 助教 (80444264)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 卵巣癌 / 癌幹細胞 / 明細胞癌 / 卵巣がん / 明細胞腺癌 / 活性酵素 / 活性酸素 |
Outline of Final Research Achievements |
We investigated the relationship between a CSC marker, aldehyde dehydrogenase1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. As a result, high ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. In vitro study revealed that ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. In conclusion, ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.
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