The molecular mechanisms and morphological manifestations of leiomyoma reduction induced by selective progesterone receptor modulators

Демура, Т. А.; Kogan, E. A.; Adamyan, L. V.

doi:10.17116/patol201779319-26

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…To date, data on the effects of SPRM on the expression of estrogen and progesterone receptors in myomas remain scanty and somewhat ambiguous. In 2017, Demura et al—in addition to increased apoptosis and reduced leiomyoma proliferation and angiogenesis induced by UPA—noted no effect on the expression of PRs and ERs in myoma tissue [ 23 ]. Tinelli et al [ 24 ], in their study on the effects of UPA treatment on myomas ex vivo, noticed significant differences in the expression patterns of proteins related to regulation of the cell cycle, remodeling of the cell cytoskeleton and also drug resistance.…”

Section: Discussionmentioning

confidence: 99%

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

Szydłowska

Grabowska

Nawrocka-Rutkowska

et al. 2021

JCM

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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.

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Section: Discussionmentioning

confidence: 99%

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

Szydłowska

Grabowska

Nawrocka-Rutkowska

et al. 2021

JCM

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“…These authors also suggested that simultaneous evaluation of the clinical-pathological markers such as tumor size, mitotic index, and IHC Ki-67, Bcl-2 greatly increases statistical significance ( p = 0.001) [75]. Recently, Demura et al (2017), reported lower Ki-67 expression in those patients treated with selective progesterone receptor modulators (SPRMs) whose tumor volume significantly decreased, and claimed it was an antiproliferative and a proapoptotic effect of the treatment [32].…”

Section: Available Immunohistochemical Markersmentioning

confidence: 99%

“…(a) proteins that control the cell cycle and have a direct influence on the dynamics of proliferation, e.g., p16 [32,33,34]; cyclin D1 [35,36]; Bcl-2 [37]; proliferating cell nuclear antigen (PCNA) [38];…”

Section: Introductionmentioning

confidence: 99%

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

Rubisz

Ciebiera

Hirnle

et al. 2019

IJMS

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Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

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“…25 , 26 More recently, UPA was shown to impact cell proliferation and angiogenesis by decreasing Ki-67 activity and reducing expression of vascular endothelial growth factor. 27 Ulipristal acetate has been compared to other therapeutic approaches, evaluated for presurgical administration, and has shown considerable effectiveness when used long term in patients with leiomyomas. 23,24,28 Ulipristal acetate negatively impacts collagen deposition, and results in a decrease in the expression of both fibronectin and versican proteoglycan in a randomized controlled study.…”

Section: Introductionmentioning

confidence: 99%

Ulipristal Acetate Mediates Decreased Proteoglycan Expression Through Regulation of Nuclear Factor of Activated T-Cells (NFAT5)

et al. 2019

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Nuclear factor of activated T-cells (NFAT5) is a tissue specific, osmoadaptive transcription factor essential for the control of hydration homeostasis in mammalian cells. Nuclear factor of activated T-cells regulates osmolyte transporters aldo-keto reductase family 1 member B1 (AKR1B1) and solute carrier family 5 member 3 (SLC5A3) to maintain fluid equilibrium in cells. The osmotic potential of the extracellular matrix of leiomyomas is attributed to the role of proteoglycans. In leiomyoma cells, NFAT5 is overexpressed compared to myometrial cells. The selective progesterone receptor modulator, ulipristal acetate, has been reported to decrease the size of leiomyomas in clinical trials. When treated with ulipristal acetate, both patient leiomyoma tissue and leiomyoma cells grown in 3-dimensional cultures show a decrease in the expression of NFAT5 protein, solute transporters AKR1B1 and SLC5A3, and results in an associated decline in the expression of proteoglycans, versican, aggrecan, and brevican. In summary, ulipristal acetate induces changes in leiomyoma cell osmoregulation which result in a decrease in proteoglycan expression.

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The molecular mechanisms and morphological manifestations of leiomyoma reduction induced by selective progesterone receptor modulators

Cited by 8 publications

References 31 publications

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

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

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

Ulipristal Acetate Mediates Decreased Proteoglycan Expression Through Regulation of Nuclear Factor of Activated T-Cells (NFAT5)

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