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选择性孕激素受体调节剂(醋酸乌利司他)治疗子宫肌瘤中细胞增殖、凋亡、雌激素/孕激素受体表达及纤维化的标志物

Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

作者信息

Szydłowska Iwona, Grabowska Marta, Nawrocka-Rutkowska Jolanta, Piasecka Małgorzata, Starczewski Andrzej

机构信息

Department of Gynecology, Endocrinology and Gynecological Oncology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland.

Department of Histology and Developmental Biology, Pomeranian Medical University, Żołnierska 48 Street, 71-210 Szczecin, Poland.

出版信息

J Clin Med. 2021 Feb 3;10(4):562. doi: 10.3390/jcm10040562.

Abstract

There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma.

摘要

关于选择性孕激素受体调节剂在子宫肌瘤中的具体作用机制,似乎只有极少的数据。本研究的目的是评估醋酸乌利司他(UPA)对肌瘤的影响,特别是对雌激素受体(ER)和孕激素受体(PR)免疫表达、增殖、凋亡及组织纤维化的影响,并比较未治疗(仅手术关注)和UPA治疗的平滑肌瘤中的上述参数。UPA治疗的患者分为三组:(1)良好反应组(肌瘤体积减少≥25%),(2)弱反应组(体积减少不显著),(3)治疗无反应组(肌瘤体积无减少或增加)。研究观察到,良好反应组的胶原体积分数百分比以及ER和PR免疫表达显著降低;良好反应组和弱反应组中增殖细胞核抗原(PCNA)和Ki67阳性细胞的百分比与对照组相比显著降低;良好反应组的凋亡指数(末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)阳性细胞)显著高于对照组。研究结果表明,对UPA的良好反应,表现为肌瘤体积减小,可能与肌瘤内纤维化、ER/PR和PCNA以及Ki67免疫表达降低和细胞凋亡增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fccd/7913139/b7782a9b2b22/jcm-10-00562-g001.jpg

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