| Project/Area Number |
13470351
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Gifu University |
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Principal Investigator |
TAMAYA Teruhiko Gifu Univ., OB/GYN., Prof, 大学院・医学研究科, 教授 (70079870)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Asushi Gifu Univ, OB/GYN, Ass.Prof, 大学院・医学研究科, 助教授 (40193643)
YOKOYAMA Yasuhiro Gifu Univ, OB/GYN, Ass.Prof, 医学附属病院, 助教授 (00200923)
FUJIMOTO Jiro Gifu Univ, OB/GYN, Assist Prof, 医学附属病院, 講師 (80199372)
NIWA Kenji Gifu Univ, OB/GYN, Research Associate, 大学院・医学研究科, 助手 (80218247)
伊藤 直樹 岐阜大学, 医学部・附属病院, 講師 (30184675)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | gnecologic tumors / hormone regulation / GnRH / estrogen receptor (ER) / ER-related receptor / PTEN / phytoestrogen / SHBG / gas6 / GnRH作用 / 血管新生因子 / 生薬 / 植物エストロゲン / エストロゲンリセプター / オルファンリセプター / 転写因子 / SHBGの相同性蛋白 / Gas6の発現 / プロゲステロンレセプターの発現 / 植物性エストロゲン生薬の抗腫瘍効果 |
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| Research Abstract |
The results of the titled study are as follows. In the gynecological tumor cells, GnRH activates serine/threonime phosphatase type2 for proliferative inhibition and LPA increases those growth via Gi-linked each receptor, suggesting the different signaling in different Gi subtypes. Expressions of estrogen receptor (ER) α and ER-related receptor (ERR) α/γ increase in human placentas during the early pregnancy, suggesting the growth potential of placenta by those receptors. As the malignant advance in the endometrial cancers, expression of ER α decreases, yet ERR α/γ increase, suggesting ERR is a poor prognostic indicator and a therapeutic target. In endometrial PTEN-introduced cancer cell line (Ishikawa), phosphorylated ERβ increases, yet phosphorylated ER α decreases, suggesting the effect of PTEN on estrogen receptor mechanism. Phytoestrogens (genistin/genistein and daizin/daidzen)and tremiphen as a SERM decrease the expressions of IL-1α, TNF-α, and c-fos/jun, resulting in decreased carcinogenesis in mouse endometrial carcinomas as an anti-estrogeic effect. Juzentaiho-to and its main component (Shimotu-to) decrease this carcinogenesis, with anti-estrogenic and anti-inflammatory (COX-2 inhibition) effects and will be the candidates of cancer prophylaxis. In gynecological cancer cells, SHBG has polymorphisms and mutations, and its splicing variant expression increases as the malignant advance. Growth arrest-specific gene6 (gas6), a homologic structure with SHBQ is a ligand of Axl/Sky family with phosphorylation, and is expressed in the estrogen-dependent, well differentiated endometrial cancers.
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