2007 Fiscal Year Final Research Report Summary
Exploring the mechanism of cell proliferation and the novel molecular target therapy of endometriosis
| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Endometrinsis / TNFα / IL-8 / dienogest / NFkB pathway / ovarian endometrioma / GnRH antagonist / Cetrorelix |
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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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Research Products
(50 results)
