The YB-1 downstream pathways- diagnostic and therapeutic approaches for endometriosis -

YB-1下游通路-子宫内膜异位症的诊断和治疗方法-

• 批准号: 229202485
• 负责人: Professorin Dr. Daniela Hornung
• 金额: --
• 依托单位: Klinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/229202485?language=en
• 关键词: YB; downstream; pathways; diagnostic; therapeutic

Endometriosis is a complex gynecological disease widely recognized as an important women s health issue. Although conservative surgery as laparoscopy procedure and medical therapies are still known to be the best available treatment of endometriosis, they are non-curative and cannot prevent the recurrence of disease as well as related painful symptoms at long-term follow-up. An increased understanding of the molecular aspects in endometriosis would be beneficial in searching novel therapeutic strategies. Particularly, YB-1 has been considered of particular interest in many types of human tumors due to its pivotal role in transcriptional and translational regulation of multiple molecules involved in cellular homeostasis, as well as its significant association with therapy resistance and recurrence. A previous study of our group has revealed the involvement of YB-1 in endometriosis pathogenesis and its critical role in endometriotic cell expansion and survival in vitro. From this knowledge, we believe that YB-1 deserves a special attention in endometriosis and we aim to explore the YB-1 downstream pathways with respect to mechanisms of endometriotic cell survival, progression and invasion. In addition, we are prompting to test the phosphoinositide-dependent kinase-1 inhibitor 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012) for endometriosis treatment in a mouse model based on its ability to indirectly block the function of YB-1 and, consequently, YB-1-responsive genes in cancer cells. This study could provide a novel and promising therapeutic approach for endometriosis patients.

子宫内膜异位症是一种复杂的妇科疾病，被广泛认为是重要的女性健康问题。尽管腹腔镜检查等保守手术和药物治疗仍然被认为是子宫内膜异位症的最佳治疗方法，但它们是非治愈性的，并且在长期随访中不能防止疾病复发以及相关的疼痛症状。加深对子宫内膜异位症分子方面的了解将有助于寻找新的治疗策略。特别是，YB-1 由于其在参与细胞稳态的多个分子的转录和翻译调节中的关键作用，以及与治疗抵抗和复发的显着相关性，被认为对多种类型的人类肿瘤特别感兴趣。我们课题组前期的一项研究揭示了YB-1参与子宫内膜异位症的发病机制及其在子宫内膜异位细胞体外增殖和存活中的关键作用。根据这些知识，我们认为 YB-1 在子宫内膜异位症中值得特别关注，我们的目标是探索 YB-1 下游通路与子宫内膜异位细胞存活、进展和侵袭的机制。此外，我们还建议测试磷酸肌醇依赖性激酶1抑制剂2-氨基-N-[4-[5-(2-菲基)-3-(三氟甲基)-1H-吡唑-1-基]苯基] -乙酰胺 (OSU-03012) 用于治疗小鼠模型的子宫内膜异位症，因为它能够间接阻断 YB-1 的功能，从而阻断 YB-1 反应基因在癌细胞中。这项研究可以为子宫内膜异位症患者提供一种新颖且有前景的治疗方法。

项目成果

Disrupting Y-Box-Binding Protein 1 Function Using OSU-03012 Prevents Endometriosis Progression in In Vitro and In Vivo Models

使用 OSU-03012 破坏 Y-Box 结合蛋白 1 功能可预防体外和体内模型中的子宫内膜异位症进展

• DOI: 10.1177/1933719116649695
• 发表时间: 2016
• 期刊: Reproductive Sciences
• 影响因子: 2.9
• 作者: Cassia GT Silveira; Gabriele Marschner; Geraldine O Canny; Silke Klocke; Peter Hunold; Frank Köster; Thorben Ahrens; Achim Rody; Daniela Hornung
• 通讯作者: Daniela Hornung

Evaluation of YB-1 levels in patients with endometriosis.

子宫内膜异位症患者YB-1水平的评价

• DOI: 10.1016/j.ejogrb.2015.05.008
• 发表时间: 2015
• 期刊: European journal of obstetrics, gynecology, and reproductive biology
• 作者: Thorben Ahrens; Cassia GT Silveira; Constanze Banz
• 通讯作者: Constanze Banz