Hypoxia-inducible Factor-1α and mTOR as a Potential Therapeutic Target in Endometriosis: An Immunohistochemical Study.

IF 1.3 4区 医学 Q3 ANATOMY & MORPHOLOGY
Dalia M Badary, Hisham A Abou-Taleb, Maha Ibrahim
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引用次数: 0

Abstract

Background and study aim: We aim to study the immunohistochemical expression of both hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) in endometriosis to provide new evidence for a targeted endometriosis therapy.

Patients and methods: This study comprised 106 endometriotic cases diagnosed clinically and histopathologically. The immunohistochemical method was done to determine the expression of HIF-1α and mTOR.

Results: Endometriotic glands showed significant cytoplasmic expression of both markers in patients with poor ovulation, severe endometriosis, and infertile for >2 years ( P <0.001). Also, patients with intense and worst pain show significant immunohistochemical expression of both markers ( P <0.001). There is a significant correlation between mTOR and HIF-1α expression in endometriotic tissue samples as P <0.001.

Conclusions: Our data suggest that both mTOR and its downstream target HIF-1α transcription factor are both disrupted in patients with endometriosis, which is consistent with aberrant activation of these pathways and their possible contribution to the pathogenesis of endometriosis. These results could offer a promising novel opportunity to be blocked therapeutically. As new management options need to be refined in particular in severe cases and infertile patients with endometriosis, therefore future studies are warranted to investigate treating endometriosis with mTOR inhibitors; the latter are already in clinical trials in phase III and IV, treating solid tumors as well as non-neoplastic disorders.

缺氧诱导因子-1α和mTOR作为子宫内膜异位症潜在治疗靶点的免疫组织化学研究。
背景和研究目的:我们旨在研究缺氧诱导因子-1α(HIF-1α)和哺乳动物雷帕霉素靶点(mTOR)在子宫内膜异位症中的免疫组织化学表达,为靶向治疗子宫内膜异位病提供新的证据。患者和方法:本研究包括106例经临床和组织病理学诊断的子宫内膜异位症病例。免疫组织化学方法检测HIF-1α和mTOR的表达。结果:子宫内膜异位腺在排卵不良、严重子宫内膜异位症患者的两种标志物的细胞质中均有显著表达,不孕超过2年(P结论:我们的数据表明,mTOR及其下游靶向HIF-1α转录因子在子宫内膜异位症患者中均被破坏,这与这些途径的异常激活及其对子宫内膜异位病发病机制的可能贡献一致。这些结果可能为治疗阻断提供了一个有希望的新机会s需要改进,特别是在子宫内膜异位症的严重病例和不孕患者中,因此未来的研究有必要研究用mTOR抑制剂治疗子宫内膜异位;后者已经在III期和IV期的临床试验中,治疗实体瘤和非肿瘤性疾病。
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来源期刊
Applied Immunohistochemistry & Molecular Morphology
Applied Immunohistochemistry & Molecular Morphology ANATOMY & MORPHOLOGY-MEDICAL LABORATORY TECHNOLOGY
CiteScore
3.20
自引率
0.00%
发文量
153
期刊介绍: ​Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist. Official Journal of the International Society for Immunohistochemisty and Molecular Morphology​.
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