Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Ciebiera, Michał; Włodarczyk, Marta; Wrzosek, Małgorzata; Słabuszewska-Jóźwiak, Aneta; Jakiel, Grzegorz

doi:10.1016/j.fertnstert.2017.11.023

Cited by 18 publications

(19 citation statements)

References 61 publications

(119 reference statements)

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“…In their study, TGF-β3 was inhibited by increased concentrations of vitamin D [ 98 ]. Their results further confirmed our belief that research about the role of vitamin D in the UF biology is the right direction because TGF-β is considered to be one of the most relevant factors in the pathogenesis of fibrosis-associated diseases [ 46 ], while TGF-β3 is one of the most important TGF-β isoforms in UF biology [ 99 , 100 , 101 ]. Its increased serum levels constitute a risk factor for UF incidence [ 6 ].…”

Section: Discussionsupporting

confidence: 65%

Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts

Ciebiera

Włodarczyk

Ciebiera

et al. 2018

IJMS

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This article provides a detailed review of current knowledge on the role of vitamin D and its receptor in the biology and management of uterine fibroids (UFs). Authors present ideas for future steps in this area. A literature search was conducted in PubMed using the following key words: “uterine fibroid” and “vitamin D”. The results of the available studies, published in English from January 2002 up to April 2018, have been discussed. Vitamin D is a group of steroid compounds with a powerful impact on many parts of the human body. This vitamin is believed to regulate cell proliferation and differentiation, inhibit angiogenesis, and stimulate apoptosis. Nowadays, hypovitaminosis D is believed to be a major risk factor in the development of UFs. In many studies vitamin D appears to be a powerful factor against UFs, resulting in inhibition of tumor cell division and a significant reduction in its size, however, the exact role of this compound and its receptor in the pathophysiology of UFs is not fully understood. According to available studies, vitamin D and its analogs seem to be promising, effective, and low-cost compounds in the management of UFs and their clinical symptoms, and the anti-tumor activities of vitamin D play an important role in UF biology. The synergy between vitamin D and selected anti-UF drugs is a very interesting issue which requires further research. Further studies about the biological effect of vitamin D on UF biology are essential. Vitamin D preparations (alone or as a co-drugs) could become new tools in the fight with UFs, with the additional beneficial pleiotropic effect.

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Section: Discussionsupporting

confidence: 65%

Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts

Ciebiera

Włodarczyk

Ciebiera

et al. 2018

IJMS

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“…These observations are also supported by some of the effects of ulipristal acetate (UPA) on UF tumors [133]. Despite the fact that UPA has a potent effect on one of the major UF pathophysiological pathways—progesterone and is TGF-β dependent [27], it also increases the activity of alkaline phosphatase, upregulates caspases, and downregulates TNF-α expression [134]. According to Ciarmela et al, UPA was also found to inhibit the expression and functions of activin A and activin receptor in UF tumor cells [135].…”

Section: Discussionmentioning

confidence: 91%

“…According to the available sources, elevated levels of TGF-β play an important role in UF growth and clinical symptom progression [7,26,27,29,103], which appears to be one of the key factors in myofibroblast transformation and fibrosis progression [17,29,35,37]. Activin A is yet another factor, by no means less important, which was found to be involved in cell proliferation, differentiation, death signaling, and metabolism [81,104].…”

Section: Discussionmentioning

confidence: 99%

“…We know many paths of action of UPA, both biochemical and genetic [133,206,207]. In the studies published by our team, we obtained preliminary results that UPA may influence some growth factors, e.g., TGF-β3 [27]. Research on other factors is ongoing and the results will be presented in the nearest future.…”

Section: Discussionmentioning

confidence: 99%

“…The main mechanism of action of progesterone in tumorigenesis is its effect on the increase in the concentration of selected growth factors [12,23,24,25]. Disturbances in growth factors (e.g., transforming growth factor β (TGF-β)) [26,27,28,29] and cytokine secretion may be the cause of UF-derived symptoms [7,20,30]. Some of the UF properties might also be regulated by different miRNAs in order to alter their effect on structural homeostasis of female genital tract [31].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms

Ciebiera

Włodarczyk

Zgliczyńska

et al. 2018

IJMS

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Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25–80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an “inflammation-like” state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.

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Ulipristalacetat – aktueller Stellenwert in der Myombehandlung

Römer

2019

Gynäkologische Endokrinologie

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Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Abstract: Reduction of serum and tissue TGF-β3 concentrations in UFs may be an important component of the effect of UPA on UF biology. Further research in this area is necessary.

Cited by 18 publications

References 61 publications

Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts

Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms

Ulipristalacetat – aktueller Stellenwert in der Myombehandlung

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