Exploring the mechanism of cell proliferation and the novel molecular target therapy of endometriosis

探索细胞增殖机制及子宫内膜异位症新型分子靶向治疗

• 批准号: 17390451
• 负责人: TERAKAWA Naoki
• 金额: $ 8.88万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390451/
• 关键词: 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

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.

我们先前报道说，促炎细胞因子（例如肿瘤坏死因子（TNF）-α和介盘（IL）-8在子宫内膜异位症女性的腹膜液中升高。此外，TNFα通过来自卵巢子宫内膜瘤（ESC）的子宫内膜内核基质细胞中NF-κB激活来增强有丝分裂活性，并通过NF-κB激活更新IL-8的表达。子宫内膜组织在卵巢立体激素上生长，尤其是雌激素。通过雌激素作用的TNFα诱导IL-8产生可能参与子宫内膜异位症开发的分子机制。子宫内膜异位症患者卵巢的巧克力囊肿衬里是子宫内膜异位组织的来源。通过NFκB途径添加TNFα与E2一起显着增强的细胞增殖和IL-8表达。相反，P4，Dienogest或Danazol减弱了NFκB激活和IL-8表达。这些数据表明，马酮治疗控制子宫内膜异位症生长的可能分子机制。我们进行了有关GNRH拮抗剂乙酸盐的临床试验。我们分析了子宫内膜异位症患者的血清IL-6和IL-8浓度。通过向患者注射Cetrorelix，疼痛和临床症状的评分得到了提高。 cetrorix治疗显着抑制了血清IL-6浓度。我们首次证明了GNRH拮抗剂，Cetrorelix改善了临床症状并改善了血清IL-6浓度，这表明这种新型药物可能有效地有效地治疗子宫内膜异位症。

项目成果

IL-10 attenuates TNFa-induced IL-6 production in endometriotic stromal cells.

IL-10 减弱子宫内膜异位基质细胞中 TNFa 诱导的 IL-6 产生。

• 发表时间: 2008
• 作者: 早川智;相澤志保子;早川智・相澤(小峯)志保子;早川智;Y. Ohama;F. Taniguchi;Y. Ohama;F. Taniguchi;F. Taniguchi;Y. Ohama;N. Miura;T. Shoji;N. Miura;T. Shoji;M.Izawa;M. Ito;M. Mitsunari;M. Izawa;M. Ito;M. Mitsunari;M.Izawa;I. Deura;S. Horie;I. Deura;S. Horie;I.Deura;S.Horie;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;T. Iwabe
• 通讯作者: T. Iwabe

Effects of low dose oral contraceptive pill for dysmenorrhea associated with endometriosis:A placebo controlled,double blind,randomized trial

小剂量口服避孕药对子宫内膜异位症相关痛经的影响：安慰剂对照、双盲、随机试验

• 发表时间: 2007
• 作者: 早川智;相澤志保子;早川智・相澤(小峯)志保子;早川智;Y. Ohama;F. Taniguchi;Y. Ohama;F. Taniguchi;F. Taniguchi;Y. Ohama;N. Miura;T. Shoji;N. Miura;T. Shoji;M.Izawa;M. Ito;M. Mitsunari;M. Izawa;M. Ito;M. Mitsunari;M.Izawa;I. Deura;S. Horie;I. Deura;S. Horie;I.Deura;S.Horie;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;T. Iwabe;I. Deura;A. Ikeda;T. Iwabe;I. Deura;A. Ikeda;寺川直樹;寺川直樹;谷口文紀;田頭由紀子;寺川直樹;M. Izawa;Y. Tagashira;T. Harada;M. Izawa;Y. Tagashira;T. Harada
• 通讯作者: T. Harada

Small bowel perforation from a thermal burn caused by contact with the end of a laparoscope during ovarian cystectomy.

卵巢囊肿切除术期间与腹腔镜末端接触造成热烧伤导致小肠穿孔。

• 发表时间: 2006
• 期刊: J. Obstet. Gynaecol. Res. 32
• 作者: 早川智;相澤志保子;早川智・相澤(小峯)志保子;早川智;Y. Ohama;F. Taniguchi;Y. Ohama;F. Taniguchi;F. Taniguchi;Y. Ohama;N. Miura;T. Shoji;N. Miura;T. Shoji;M.Izawa;M. Ito
• 通讯作者: M. Ito

卵巣チョコレート嚢胞に対する腹腔鏡下手術の予後

腹腔镜卵巢巧克力囊肿手术的预后

• 发表时间: 2007
• 作者: 早川智;相澤志保子;早川智・相澤(小峯)志保子;早川智;Y. Ohama;F. Taniguchi;Y. Ohama;F. Taniguchi;F. Taniguchi;Y. Ohama;N. Miura;T. Shoji;N. Miura;T. Shoji;M.Izawa;M. Ito;M. Mitsunari;M. Izawa;M. Ito;M. Mitsunari;M.Izawa;I. Deura;S. Horie;I. Deura;S. Horie;I.Deura;S.Horie;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;T. Iwabe;I. Deura;A. Ikeda;T. Iwabe;I. Deura;A. Ikeda;寺川直樹;寺川直樹;谷口文紀
• 通讯作者: 谷口文紀

子宮内膜症細胞のIL-6産生に対するIL-10の影響

IL-10 对子宫内膜异位症细胞 IL-6 产生的影响

• 发表时间: 2007
• 作者: 早川智;相澤志保子;早川智・相澤(小峯)志保子;早川智;Y. Ohama;F. Taniguchi;Y. Ohama;F. Taniguchi;F. Taniguchi;Y. Ohama;N. Miura;T. Shoji;N. Miura;T. Shoji;M.Izawa;M. Ito;M. Mitsunari;M. Izawa;M. Ito;M. Mitsunari;M.Izawa;I. Deura;S. Horie;I. Deura;S. Horie;I.Deura;S.Horie;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;M. Izawa;Y. Ohata;T. Harada;T. Harada;Y. Tagashira;T. Iwabe;I. Deura;A. Ikeda;T. Iwabe;I. Deura;A. Ikeda;寺川直樹;寺川直樹;谷口文紀;田頭由紀子
• 通讯作者: 田頭由紀子