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

2021 ◽  
Vol 10 (4) ◽  
pp. 562
Author(s):  
Iwona Szydłowska ◽  
Marta Grabowska ◽  
Jolanta Nawrocka-Rutkowska ◽  
Małgorzata Piasecka ◽  
Andrzej Starczewski
Keyword(s):  
Progesterone Receptor ◽  
Cellular Proliferation ◽  
Volume Fraction ◽  
Receptor Expression ◽  
Volume Reduction ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Ulipristal Acetate ◽  
Receptor Modulator

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.

scholarly journals Markers of Inflammation and Vascular Parameters in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids

2021 ◽  
Vol 10 (16) ◽  
pp. 3721
Author(s):  
Iwona Szydłowska ◽  
Marta Grabowska ◽  
Jolanta Nawrocka-Rutkowska ◽  
Andrzej Kram ◽  
Małgorzata Piasecka ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Inflammatory Markers ◽  
Uterine Fibroids ◽  
Response To Treatment ◽  
Control Group ◽  
Ulipristal Acetate ◽  
Weak Response ◽  
Receptor Modulator ◽  
Markers Of Inflammation ◽  
Response Group

The exact mechanism of selective progesterone receptor modulator action in leiomyoma still challenges researchers. The aim of the study was to assess the effects of ulipristal acetate (UPA) on immunoexpression of inflammatory markers and vascularization in fibroids. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction), (3) and no response to treatment (no decrease or increase in fibroid volume). The percentage of TGFβ, IL6, IL10, CD117, and CD68-positive cells were significantly lower in the group with a good response to treatment vs. the control group. Moreover, the percentage of IL10 and CD68-positive cells in the group with a good response to treatment were also significantly lower compared to the no response group. Additionally, a significant decrease in the percentage of IL10-positive cells was found in the good response group vs. the weak response group. There were no statistical differences in the percentage of TNFα-positive cells and vessel parameters between all compared groups. The results of the study indicate that a good response to UPA treatment may be associated with a decrease of inflammatory markers, but it does not influence myoma vascularization.

scholarly journals Predictive Factors of Response to Selective Progesterone Receptor Modulator (Ulipristal Acetate) in the Pharmacological Treatment of Uterine Fibroids

2020 ◽  
Vol 17 (3) ◽  
pp. 798
Author(s):  
Iwona Szydłowska ◽  
Aleksandra Marciniak ◽  
Jolanta Nawrocka-Rutkowska ◽  
Aleksandra Rył ◽  
Andrzej Starczewski
Keyword(s):  
Blood Flow ◽  
Progesterone Receptor ◽  
Predictive Factors ◽  
Uterine Fibroids ◽  
Volume Number ◽  
Ulipristal Acetate ◽  
Uterine Arteries ◽  
Receptor Modulator ◽  
Estradiol Concentration ◽  
Status Of Women

Background: Selective progesterone receptor modulator ulipristal acetate (UPA) is a drug used in management of symptomatic myomas. It was observed that the response to UPA treatment in uterine myomas varied amongst patients. An attempt was thus made at establishing predictive factors conducive to better reaction to treatment with UPA. The aim of this study was to assess the efficacy of UPA treatment in women with myomas, depending on pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Materials and methods: The study included patients with one to four myomas. The UPA treatment was a preparation stage for surgical treatment in all patients. The study group was divided into the subgroups according to pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Results: A better effect of reduction in size of myomas after UPA treatment was noted when pretreatment myomas’ volume was lower than 30 cm3. A significant reduction in fibroids’ size was observed after UPA therapy independently of the number of myomas and age of patients. A good response after the UPA therapy was observed when pretreatment estradiol concentration was below 50 pg/mL and when uterine artery resistance index (RI) was above 0.8. Conclusions: Our research demonstrates that treatment with ulipristal acetate is an efficient method in preoperative preparation of patients with uterine fibroids. The most important factor of positive response to UPA therapy is myoma volume. The number of myomas and patient’s age do not interfere with effects of UPA therapy. Pretreatment estradiol concentration is significant, yet secondary for the effects of therapy. The UPA therapy has no impact on blood flow in the uterine arteries and no adverse influence on estradiol concentrations.

scholarly journals Selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA) and its effects on the human endometrium

2017 ◽  
Author(s):  
L.H.R. Whitaker ◽  
A.A. Murray ◽  
R. Matthews ◽  
G. Shaw ◽  
A.R.W. Williams ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Human Endometrium ◽  
Ulipristal Acetate ◽  
Receptor Modulator

scholarly journals Maternal Antibiotic Treatment Disrupts the Intestinal Microbiota and Intestinal Development in Neonatal Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Chung-Ming Chen ◽  
Hsiu-Chu Chou ◽  
Yu-Chen S. H. Yang
Keyword(s):  
Drinking Water ◽  
Antibiotic Treatment ◽  
Intestinal Microbiota ◽  
Relative Abundance ◽  
Cellular Proliferation ◽  
Nuclear Antigen ◽  
Control Group ◽  
Antibiotic Administration ◽  
Intestinal Development ◽  
Neonatal Mice

Maternal antibiotic treatment (MAT) during prenatal and intrapartum periods alters the bacterial composition and diversity of the intestinal microbiota of the offspring. The effect of MAT during pregnancy on the intestinal microbiota and its relationship with intestinal development remain unknown. This study investigated the effects of MAT during pregnancy on intestinal microbiota, injury and inflammation, vascularization, cellular proliferation, and the intestinal barrier in neonatal mice. At timed intervals, we fed pregnant C57BL/6N mice sterile drinking water containing antibiotics (ampicillin, gentamicin, and vancomycin; all 1 mg/ml) from gestational day 15 to delivery. The control dams were fed sterile drinking water. Antibiotic administration was halted immediately after birth. On postnatal day 7, the intestinal microbiota was sampled from the lower gastrointestinal tract and the ileum was harvested for histology, Western blot, and cytokines analyses. MAT significantly reduced the relative abundance of Bacteroidetes and Firmicutes and significantly increased the relative abundance of Proteobacteria in the intestine compared with their abundances in the control group. MAT also significantly increased intestinal injury score and cytokine levels, reduced the number of intestinal goblet cells and proliferating cell nuclear antigen-positive cells, and reduced the expressions of vascular endothelial growth factor and tight junction proteins. Therefore, we proposed that maternal antibiotic exposure during pregnancy disrupts the intestinal microbiota and intestinal development in neonatal mice.

scholarly journals The role of Ulipristal Acetate in infertile women with submucous fibroids

2020 ◽  
Author(s):  
Giuseppe Morgante ◽  
Gabriele Centini ◽  
Libera Troìa ◽  
Raoul Orvieto ◽  
Vincenzo De Leo
Keyword(s):  
Uterine Cavity ◽  
Volume Reduction ◽  
Ulipristal Acetate ◽  
Receptor Modulator ◽  
Biochemical Pregnancy ◽  
Infertile Patients ◽  
Fibroid Volume

Abstract Background The presence of submucous fibroids strongly impacts on IVF results, therefore, this patients should be considered for surgical or medical treatment. The aim of this study was to assess the role of Ulipristal acetate (UPA), a selective progesterone receptor modulator, in restoring uterine cavity deformation due to submucous fibroids, in infertile patients attempting an IVF treatment. Methods Infertile patients with submucosal fibroid (Type 1 and Type 2 according to FIGO classification) were enrolled and received 1 to 3 treatment cycles of UPA, according to their response, as reflected by fibroid volume reduction and restoration of normal uterine cavity. Results 26 patients underwent UPA treatment revealed a mean volume reduction of their fibroids of 41%. A total of 15 (57.6%) biochemical pregnancy were obtained, resulting in 13 (50%) ongoing pregnancy and 9 (34.6%) healthy babies were already delivered. Conclusion Restoration of normal uterine cavity by UPA treatment prior to IVF treatment avoids surgery and enhances the pregnancy rate.

GnRH-a induced changes in endometrial pinopodes

2020 ◽  
Author(s):  
Weiqin Zhou ◽  
Dawei Li ◽  
Zhao Ziwei ◽  
Yanping Pan ◽  
Yali Jiang ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Subcutaneous Injection ◽  
Receptor Expression ◽  
Control Group ◽  
Serum Progesterone ◽  
Luteal Support ◽  
Group Protein ◽  
Induced Changes ◽  
And Control ◽  
Experimental Group

Abstract Our aim was to study the effect of GnRH-a on pinopodes during luteal phase support and explore the possible mechanism. Forty women with primary infertility due to male factors were enrolled for ART, and randomly divided into experimental and control groups. Seven days after ovulation, the experimental group received a subcutaneous injection of 0.1 mg GnRH-a, while the control group received a subcutaneous injection of 2 ml of 0.9% saline. Serum progesterone levels in the experimental group were significantly ( P < 0.05) higher 3 days after compared with before treatment, and were higher ( P < 0.05) compared with the control group. Protein expression levels of the progesterone receptor in the experimental group were significantly ( P < 0.05) lower after compared with before treatment, and lower than the control group ( P < 0.05). The number of pinopodes and the percentage of pinopode maturation were significantly higher in the experimental compared with control group ( P < 0.05). The luteal support provided by GnRH-a may act through the corpus luteum, which may promote the secretion of progesterone, down-regulate progesterone receptor expression, increase the growth of pinopodes and improve endometrial receptivity, which ultimately increase the rates of clinical pregnancy, continuous pregnancy and live birth.

Cell Kinetics and Apoptosis in Laryngeal Carcinoma Patients

2003 ◽  
Vol 112 (3) ◽  
pp. 206-213 ◽  
Author(s):  
Anastasia Georgiou ◽  
Ilias P. Gomatos ◽  
John Giotakis ◽  
Nikolaos B. Pararas ◽  
Eleutherios Ferekidis
Keyword(s):  
Clinical Outcome ◽  
Laryngeal Carcinoma ◽  
Cellular Proliferation ◽  
Prognostic Significance ◽  
Treatment Protocol ◽  
High Risk Group ◽  
Nuclear Antigen ◽  
Control Group ◽  
Proliferation Markers ◽  
Unfavorable Clinical Outcome

Cellular proliferation and apoptosis are both implicated in the process of carcinogenesis. The objective of this study was to access the prognostic significance of the expression of proliferating cell nuclear antigen (PCNA) and the apoptosis-related genes (bax, bcl-2, and p53) in laryngeal carcinoma patients. Thirty consecutive patients with stage I to IV squamous cell laryngeal carcinoma were treated in our department from 1992 to 1994. We immunohistochemically studied the expression of PCNA and bax, bcl-2, and p53 genes in their tumor specimens. Five healthy men were used as the control group. The staining results were correlated with clinicopathologic data. The PCNA protein expression was correlated with a significantly worse survival in those patients who were bax-negative (0% versus 42.86%, p =.0445). Similarly, the presence of PCNA led to an unfavorable clinical outcome in those patients who were bax-negative, bcl-2-negative, and p53-negative (0% versus 50%, p =.0278). Expression of bcl-2 protein was found to be an independent prognostic factor related to an unfavorable clinical outcome (p =.0262). The expression of bcl-2 protein appears to predict survival in laryngeal carcinoma patients. Furthermore, the combined study of proliferation markers and apoptosis-related genes helped us to identify a high-risk group of patients who may benefit from a more aggressive treatment protocol.

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