| Project/Area Number |
17390451
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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 | Tottori University |
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Principal Investigator |
TERAKAWA Naoki Tottori University, 医学部, Professor (90163906)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Tasuku Tottori University, Faculty of Medicine, Associate Professor (40218649)
IWABE Tomio Tottori University, Faculty of Medicine, Junior Associate Professor (10284001)
TANIGUCHI Fuminori Tottori University, Hospital, Junior Associate Professor (40322218)
吉田 壮一 鳥取大学, 医学部附属病院, 助手 (70304219)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,880,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Endometrinsis / TNFα / IL-8 / dienogest / NFkB pathway / ovarian endometrioma / GnRH antagonist / Cetrorelix / 酢酸セトロレリックス / 臨床試験 / 疼痛症状 / 血中CA-125濃度 / 血中IL-6濃度 / 血中IL-8濃度 / GrRHアンタゴニスト / 培養間質細胞 / 増殖・進展 / サイトカインファミリー / 転写因子NF-κB |
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| Research Abstract |
We previous reported that the proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-8 are elevated in the peritoneal fluid of women with endometriosis. In addition, TNFα enhances the mitogenic activity and upregulates IL-8 expression through NF-κB activation in endometriotic stromal cells from ovarian endometrioma (ESCs). Endometriotic tissue growth depends on ovarian steroid hormones, especially estrogen. TNFα induced-IL-8 production via estrogen action may be involved in the molecular mechanisms for development of endometriosis.
The chocolate cysts linings of the ovaries of patients with endometriosis were the source of endometriotic tissues. Adding TNFα together with E2 markedly enhanced cell proliferation and IL-8 expression via NFκB pathway. In contrast, P4, dienogest, or danazol attenuated NFκB activation and IL-8 expression. These data suggest that a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis.
Next, we performed the clinical trial regarding a GnRH antagonist, Cetrorelix Acetate. We analyzed that serum IL-6 and IL-8 concentration of the patients with endometriosis.
By the injection of Cetrorelix to the patients, the score of pain and of clinical symptoms were decreased. Cetrorelix therapy significantly suppressed the serum IL-6 concentration.
We demonstrated for the first time that a GnRH antagonist, Cetrorelix improved the clinical symptoms and decreased serum IL-6 concentration, suggesting this novel drug may be effective for the therapy of endometriosis.
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