Genetic and Genomics of Uterine Myomas

Vergara, Daniele; Greco, Margherita

doi:10.1007/978-3-319-10305-1_2

Cited by 3 publications

(1 citation statement)

References 75 publications

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“…Uterine leiomyomas (fibroids or myomas) are very common benign gynecological tumors affecting women of reproductive age (Stewart, 2001; Laganà et al, 2017). Approximately 25% of women have clinically significant lesions (Tinelli and Malvasi, 2015), and pathological examinations of surgical specimens suggest that the prevalence of myomas is as high as 77% (Cramer and Patel, 1990).…”

Section: Introductionmentioning

confidence: 99%

Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) Ameliorates Human Uterine Myomas via Apoptosis

Lee

Choi

et al. 2019

Front. Pharmacol.

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Uterine leiomyomas are the most common benign neoplasms in women of reproductive age. However, non-surgical treatments for uterine myomas have not been fully evaluated. In Korea and China, Gyejibongnyeong-hwan (GBH) is widely used to treat gynecological diseases. Thus, we investigated the effects of GBH in human uterine myoma cells (hUtMCs). The hUtMCs were collected from patients undergoing curative surgery. Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The expression levels of p53, Bax, Bcl-2, cleaved-caspase-3, and caspase-9 were determined by Western blotting. Apoptosis and ROS levels were evaluated by fluorescence microscopy. First, we determined the adequate concentration that did not affect normal cells, and then investigated the time-dependent anti-neoplastic effect of GBH to decide the appropriate treatment time under a non-toxic concentration. Cell viability and number were significantly reduced by GBH at 48 h in a dose-dependent manner (0–200 µg/ml). The ratio of Bax to Bcl2 and expression of p53, cleaved-caspase-3, and caspase-9 increased, representing GBH induced apoptosis in uterine leiomyomas. In addition, preliminary tests using pan-caspase inhibitor/p53 inhibitor with GBH rescued the GBH-mediated apoptotic effect. Furthermore, GBH significantly increased the mitochondrial ROS concentration, and preliminary test showed that mitochondria ROS scavenger reduced the percentages of early apoptosis cell. These results suggest that GBH may induce apoptosis of leiomyomas and demonstrated that GBH can be a potential therapeutic and/or preventive agent for uterine leiomyomas.

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Section: Introductionmentioning

confidence: 99%

Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) Ameliorates Human Uterine Myomas via Apoptosis

Lee

Choi

et al. 2019

Front. Pharmacol.

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Physiology and Importance of the Myoma’s Pseudocapsule

et al. 2017

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The Biological Impact of Ulipristal Acetate on Cellular Networks Regulating Uterine Leiomyoma Growth

Tinelli

Kosmas

Mynbaev

et al. 2020

CPD

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Uterine Fibroids (UFs), or leiomyomas, represent the most frequent pelvic tumor in reproductive-aged women. Although of benign origin, UFs decrease fertility and cause significant reproductive dysfunctions. Compared to normal myometrium, UFs are characterized by a clinical and molecular heterogeneity as demonstrated by the presence of multiple genetic alterations and altered signaling pathways. Recently, selective progesteronereceptor modulators (SPRM), as ulipristal acetate (UPA), have demonstrated their clinical benefits by reducing tumor growth and extracellular matrix deposition. For these reasons, UPA is used in the clinical practice as an intermittent treatment for women symptomatic for UFs or, sometimes, before a myomectomy. However, drug effects on signaling pathways frequently upregulated in UFs remain largely unknown. In fact, the mechanisms of action of the UPA on UFs and on the surrounding areas are not yet understood. To learn more about UPA molecular mechanisms, UF samples were treated ex vivo with UPA and profiled for drug effects on selected markers. During this preliminary ex vivo UPA administration, significant changes were observed in the expression levels of proteins related to cell cycle regulation, cytoskeleton remodeling, and drug resistance. The UPA administration reduced cofilin, Erk and Src phosphorylation, p27 and ezrin protein levels, but not Akt phosphorylation and cyclin D1 and β-catenin levels. This preliminary ex vivo biological analysis provided new insights into the mechanism of action of UPA in the treatment of UFs, which could better explain the biological functioning of the drug on UFs.

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Genetic and Genomics of Uterine Myomas

Cited by 3 publications

References 75 publications

Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) Ameliorates Human Uterine Myomas via Apoptosis

Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) Ameliorates Human Uterine Myomas via Apoptosis

Physiology and Importance of the Myoma’s Pseudocapsule

The Biological Impact of Ulipristal Acetate on Cellular Networks Regulating Uterine Leiomyoma Growth

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