34 results on '"Maria Magdalena Montt Guevara"'
Search Results
2. 49 - Prevalence of pelvic floor dysfunctions in women with endometriosis
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Maria Fernanda Brancalion, Eleonora Russo, Sara Gorini, Giulia Misasi, Maria Magdalena Montt Guevara, Cristina Zito, and Tommaso Simoncini
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2024
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3. 65 - Vaginal Erbium Laser as a non-hormonal therapeutical procedure for managing urinary symptoms in breast and gynecological cancer survivors
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Giulia Misasi, Vittoria Frisetti Carpani, Maria Magdalena Montt Guevara, Eleonora Russo, and Tommaso Simoncini
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2023
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4. 71 - Effects of intravaginal DHEA administration in women suffering from concomitant stress urinary incontinence and vulvo vaginal atrophy
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Eleonora Russo, Giulia Misasi, Maria Magdalena Montt Guevara, Veronica Tomatis, and Tommaso Simoncini
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2022
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5. Simulation training program for vacuum application to improve technical skills in vacuum-assisted vaginal delivery
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Paolo Mannella, Mario Giordano, Maria Magdalena Montt Guevara, Andrea Giannini, Eleonora Russo, Federica Pancetti, Marta Caretto, and Tommaso Simoncini
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Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Objective evaluation of technical skills of the operators during the obstetrical device application for operative vaginal delivery, named kiwi-cup in a simulation training program. Methods Thirty-five residents in obstetrics and gynecology of the University of Pisa, Italy were recruited and evaluated with an assessment scale on technical skills from 0 to 55 points. They performed various operative vaginal delivery simulations with kiwi-cup and were evaluated at time 0 by a tutor. After 8 weeks, simulation training was repeated and trainees were re-evaluated by the same tutor. Results after 8 weeks from the first simulation session, trainees have been shown to increase technical skills (46.27 ± 4.6 with p-value
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- 2021
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6. Minimal Invasive Abdominal Sacral Colpopexy and Abdominal Lateral Suspension: A Prospective, Open-Label, Multicenter, Non-Inferiority Trial
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Eleonora Russo, Maria Magdalena Montt Guevara, Koray Gorkem Sacinti, Giulia Misasi, Maria Falcone, Riccardo Morganti, Liliana Mereu, Francesca Dalprà, Saverio Tateo, and Tommaso Simoncini
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apical defect ,minimally invasive abdominal surgery ,lateral suspension ,sacral suspension ,Medicine - Abstract
Background: Abdominal minimally invasive surgery has become increasingly prominent for the treatment of prolapse. Abdominal sacral colpopexy (ASC) is the gold standard for the treatment of advanced apical prolapse; however, alternative surgical approaches such as the abdominal lateral suspension (ALS) have been developed to improve patient outcomes. This study aims to determine whether ALS improves outcomes compared to ASC in multicompartmental prolapse patients. Methods: A prospective, open-label, multicenter, non-inferiority trial was conducted in 360 patients who underwent ASC or ALS for the treatment of apical prolapse. The primary outcome was anatomical and symptomatic cure of the apical compartment at 1-year follow-up; secondary outcomes included prolapse recurrence, re-operation rate, and post-operative complications. A 300-patient cohort was subdivided into 200-patients who underwent ALS and 100-patients who underwent ASC. The confidence interval method was used to calculate the p-value of non-inferiority. Results: At the 12-months follow-up, the objective cure rate of the apical defect was 92% for ALS and 94% for ASC (recurrence rates were 8% and 6%, respectively, and the p-value for non-inferiority was
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- 2023
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7. Simulation as tool for evaluating and improving technical skills in laparoscopic gynecological surgery
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Paolo Mannella, Elisa Malacarne, Andrea Giannini, Eleonora Russo, Marta Caretto, Francesca Papini, Maria Magdalena Montt Guevara, Federica Pancetti, and Tommaso Simoncini
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Simulation ,Laparoscopy ,OSATS ,Training ,Surgery ,RD1-811 - Abstract
Abstract Background Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion. Methods Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale. Results Senior trainees had better score than junior trainees (p value
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- 2019
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8. Estetrol: A New Choice for Contraception
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Franca Fruzzetti, Tiziana Fidecicchi, Maria Magdalena Montt Guevara, and Tommaso Simoncini
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combined hormonal contraception ,estetrol ,metabolism ,SHBG ,cycle control ,hemostasis ,Medicine - Abstract
Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.
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- 2021
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9. Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users
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Tommaso Simoncini, Andrea Panattoni, Mustafa Aktas, Jozef Ampe, Cornelia Betschart, Alexander L. A. Bloemendaal, Stephan Buse, Giuseppe Campagna, Marta Caretto, Mauro Cervigni, Esther C. J. Consten, Hugo H. Davila, Jean Dubuisson, Eloy Espin-Basany, Bernardina Fabiani, Jean-Luc Faucheron, Andrea Giannini, Brooke Gurland, Dieter Hahnloser, Ralf Joukhadar, Paolo Mannella, Liliana Mereu, Jacopo Martellucci, Guillaume Meurette, Maria Magdalena Montt Guevara, Carlo Ratto, Barry A. O’Reilly, Christl Reisenauer, Eleonora Russo, Steven Schraffordt Koops, Shahab Siddiqi, Alessandro Sturiale, and Gabriele Naldini
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Rectal prolapse ,Delphi consensus ,Humans ,Robotics ,Pelvic Floor/surgery ,Delphi Technique ,Surgery, Plastic ,Robotic Surgical Procedures/methods ,Laparoscopy/methods ,Pelvic floor reconstructive surgery ,Pelvic organ prolapse ,Robotic surgery ,Settore MED/18 - CHIRURGIA GENERALE ,Surgery - Abstract
Background Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion. Methods We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons’ characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis. Results The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy. Conclusion Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit.
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- 2023
10. Music Modulates Autonomic Nervous System Activity in Human Fetuses
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Francesca Massimello, Lucia Billeci, Alessio Canu, Maria Magdalena Montt-Guevara, Gaia Impastato, Maurizio Varanini, Andrea Giannini, Tommaso Simoncini, and Paolo Mannella
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musical stimulation ,autonomic nervous system evaluation ,fetal autonomic nervous system ,fetal nervous system ,heart rate variability (HRV) ,non-invasive evaluation ,General Medicine - Abstract
ContextFetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby.ObjectiveAim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability.MethodsThirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was “Clair de lune” Debussy, played through headphones on the mother’s abdomen (CTR: 31927).ResultsMusic does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037).ConclusionMusic can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition.
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- 2022
11. Abstract P2-05-07: Differential expression and localization of beta-catenin and HSP27 after cisplatin/doxorubicin treatment in triple negative breast cancer cells
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Martin E. Guerrero-Gimenez, D Cuello-Carrion, ME Cordoba, GE Pennacchio, ML Vargas Roig, Maria Magdalena Montt-Guevara, Silvina B. Nadin, and Mariel A. Fanelli
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Cancer Research ,Beta-catenin ,Oncology ,biology ,Hsp27 ,business.industry ,biology.protein ,Cancer research ,Medicine ,Cisplatin/doxorubicin ,Differential expression ,business ,Triple-negative breast cancer - Abstract
The treatment of triple-negative breast cancers (TNBC) involves the administration of the conventional chemotherapeutic drug doxorubicin, given the lack of specific targeted agents. Novel therapeutic strategies, such as cisplatin, are currently being tested for these patients. Many studies have demonstrated that aberrant Wnt/β-catenin signaling serves a role in the development of breast cancer, while others have concluded that abnormal regulation of Wnt pathway induces tumor cell chemoresistance. The small heat shock protein 27 (HSP27) is overexpressed in human breast cancer cells. As a result, cancer cells may suppress apoptosis and develop resistance to antineoplastic agents, such as doxorubicin. The present study sought to examine the role of the Wnt/β-catenin and HSP27 signaling pathway in response to cisplatin (CisPt)/ doxorubicin (Doxo) treatment in human triple-negative (TN) breast cancer cell lines. Material and Methods: MDA-MB231 (TN) and MCF10A cell lines were used. Cell viability was measured using MTT assay and IC50 values were obtained after 48 h of CisPt or Doxo exposition. Cellular senescence was assayed by measuring SAbeta-galactosidase (SA-beta-Gal) activity. Total and active β-catenin, HSP27, phospho HSP27, GSK3β, phospho GSK3β, p38 and phospho p38 expressions were measured by western blot and immunofluorescence. Apoptosis was measured by cleaved Caspase-3 immunofluorescence. Results: MDA-MB231 cells showed higher IC50 values for CisPt and Doxo than the MCF10A cell line. Increased numbers of senescent cells (larger and flatter) were observed in both MDA-MB231 and MCF10A cells exposed to the IC50 dose of Doxo. In MDA-MB231 cells, CisPt treatment induced caspase-3 cleavage. In MDA-MB231 cells, the expression of β-catenin, active β-catenin, total and phospho-GSK3β and total HSP27 significantly decreased in the CisPt group (p Conclusions: CisPt treatment was associated with absence of senescence, and decreased expression of β-catenin and HSP27. While in Doxo-treated cells, senescence phenomenon was related to stable levels of β-catenin and increased expression of HSP27. The differential expression and localizations of β-catenin and HSP27 could be related to a differential cellular response depending on the cytotoxicity mechanism of chemotherapeutic agent used, that in turns affect the cell fate decision. Our preliminary data indicate that β-catenin and HSP27 may be potential therapeutic targets in TNBC. G.E.P. and M.E.C. contributed equally to this work. Citation Format: Pennacchio GE, Cordoba ME, Guerrero-Gimenez ME, Montt-Guevara MM, Cuello-Carrion D, Nadín SB, Vargas Roig ML, Fanelli MA. Differential expression and localization of beta-catenin and HSP27 after cisplatin/doxorubicin treatment in triple negative breast cancer cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-07.
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- 2019
12. Simulation training program for vacuum application to improve technical skills in vacuum-assisted vaginal delivery
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Mario Giordano, Eleonora Russo, Tommaso Simoncini, Marta Caretto, Paolo Mannella, Andrea Giannini, Maria Magdalena Montt Guevara, and Federica Pancetti
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medicine.medical_specialty ,Vacuum Extraction, Obstetrical ,Vacuum assisted ,education ,Obstetrical ,Session (web analytics) ,Simulation training ,03 medical and health sciences ,0302 clinical medicine ,Obstetrics and gynaecology ,Medicine ,Humans ,Medical physics ,Clinical Competence ,Gynecology ,Italy ,Obstetrics ,Simulation Training ,Internship and Residency ,030212 general & internal medicine ,Technical skills ,TUTOR ,computer.programming_language ,030219 obstetrics & reproductive medicine ,business.industry ,Vaginal delivery ,Research ,Obstetrics and Gynecology ,Gynecology and obstetrics ,Assessment scale ,RG1-991 ,business ,Vacuum Extraction ,computer - Abstract
Objectiveevaluation of technical skills of the operators during the obstetrical device application for operative vaginal delivery, named kiwi-cup in a simulation training program.MethodsThirty-five residents in obstetrics and gynecology of the University of Pisa, Italy were recruited and evaluated with an assessment scale on technical skills from 0 to 55 points. They performed various operative vaginal delivery simulations with kiwi-cup and were evaluated at time 0 by a tutor. After 8 weeks, simulation training was repeated and trainees were re-evaluated by the same tutor.Resultsafter 8 weeks from the first simulation session, trainees have been shown to increase technical skills (46.27 ± 4.6 withp-value p-value 0.0161).) and to reduce the time to complete the procedure (86.2 ± 29.9 s withp-value Conclusionsimulation training on operational vaginal delivery significantly increases technical skills, improves successful rate, and reduces the time taken to complete the procedure.Clinical trial registrationNot applicable.
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- 2021
13. Impact of Polycystic Ovarian Syndrome, Metabolic Syndrome, and Obesity on Women’s Health
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Giulia Palla, Paolo Mannella, Andrea Giannini, Marta Caretto, Maria Magdalena Montt Guevara, and Tommaso Simoncini
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medicine.medical_specialty ,business.industry ,Medicine ,Disease ,Metabolic syndrome ,business ,Psychiatry ,medicine.disease ,Obesity ,World health - Abstract
The definition of health given by the World Health Organization is that “Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” Being a man or a woman has a significant impact on health, as a result of both biological and gender-related differences.
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- 2021
14. Impact of Polycystic Ovary, Metabolic Syndrome and Obesity on Women Health
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Maria Magdalena Montt Guevara
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- 2021
15. D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes
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Maria Magdalena Montt-Guevara, Tiziana Fidecicchi, Michele Finiguerra, Alessandro D. Genazzani, Tommaso Simoncini, Ilaria Marzi, and Amerigo Ferrari
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medicine.medical_specialty ,insulin receptor substrate (IRS1) ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,insulin pathway ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Cell Line ,chemistry.chemical_compound ,Endocrinology ,Adipocyte ,Internal medicine ,Lipid droplet ,Adipocytes ,medicine ,Simpson–Golabi–Behmel syndrome cells (SGBS) ,Humans ,Insulin ,Original Research ,Cell Proliferation ,17β-estradiol (E2) ,D-Chiro-Inositol (D-Chiro-Ins) ,lcsh:RC648-665 ,Glucose Transporter Type 4 ,biology ,D-chiro-Inositol ,Cell Differentiation ,Polycystic ovary ,IRS1 ,Insulin receptor ,chemistry ,Insulin Receptor Substrate Proteins ,biology.protein ,Proto-Oncogene Proteins c-akt ,Inositol ,GLUT4 ,Signal Transduction - Abstract
D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.
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- 2021
16. Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism
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I Grijalva-Grijalva, Faustino R. Pérez-López, Danny Salazar-Pousada, Peter Chedraui, Maria Magdalena Montt-Guevara, Cecibel Ramírez-Morán, Giulia Palla, Tommaso Simoncini, and Jorge Eduardo Shortrede
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Adipokine ,030209 endocrinology & metabolism ,Pilot Projects ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Metabolic Diseases ,Adipokines ,Internal medicine ,Medicine ,Humans ,Insulin ,Excessive body weight ,Adiposity ,Cervantes Scale ,Digestive metabolism ,Inflammation ,Menopausal symptoms ,Triglyceride ,business.industry ,Leptin ,Middle Aged ,medicine.disease ,Metabolic syndrome ,Perimenopause ,Cross-Sectional Studies ,chemistry ,Adipose Tissue ,030220 oncology & carcinogenesis ,Resistin ,Digestion ,Female ,medicine.symptom ,Inflammation Mediators ,Menopause ,business ,Weight gain ,Body mass index ,Biomarkers - Abstract
Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI–MetS). Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI–MetS women as compared to NBMI ones. Spearman’s correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.
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- 2020
17. Simulation of childbirth improves clinical management capacity and self-confidence in medical students
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Andrea Giannini, Paolo Mannella, Giulia Palla, Marta Caretto, Armando Cuttano, Tommaso Simoncini, Maria Magdalena Montt-Guevara, Federica Pancetti, and Rachele Antonelli
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Medical education ,Normal cycle ,030219 obstetrics & reproductive medicine ,media_common.quotation_subject ,030208 emergency & critical care medicine ,Health Informatics ,Education ,Comprehension ,03 medical and health sciences ,0302 clinical medicine ,Self-confidence ,Modeling and Simulation ,Childbirth ,Psychology ,Competence (human resources) ,Original Research ,media_common - Abstract
Background The learning process of physiological mechanisms of childbirth and its management are important elements in the education of medical students. In this study, we verify how the use of a high-fidelity simulator of childbirth improves competence of students in this regard.Methods A total of 132 medical students were recruited for the study in order to attend a physiological childbirth in a no-hospital environment after being assigned to two groups. The control group received only a normal cycle of lectures, while the simulation (SIM) group followed a specific training session on the simulator. Subsequently, both groups were assessed for their technical and non-technical skills in a simulated childbirth. Also, a self-assessment test regarding their self-confidence was administrated before and after simulation, and repeated after 8 weeks.Results The SIM group showed better performance in all the domains with a better comprehension of the mechanisms of childbirth, managing and assistance of labour and delivery. In addition, compared to the control group, they presented a better self-related awareness and self-assurance regarding the possibility of facing a birth by themselves.Conclusion The present study demonstrated that the use of a high-fidelity simulator for medical students allows a significant improvement in the acquisition of theoretical and technical expertise to assist a physiological birth.
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- 2018
18. Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration
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Jorge Eduardo Shortrede, Tommaso Simoncini, Adrian Esteban Campelo, Alessio Canu, Stefania Spina, Maria Magdalena Montt-Guevara, Guja Bernacchi, Giulia Palla, and Elena Cecchi
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Genetics and Molecular Biology (all) ,0301 basic medicine ,medicine.medical_treatment ,PAI-1 ,Ciencias de la Salud ,Biochemistry ,Tissue plasminogen activator ,Umbilical vein ,ESTETROL ,chemistry.chemical_compound ,HUVEC ,0302 clinical medicine ,Cell Movement ,u-PA ,Cells, Cultured ,Cultured ,Estradiol ,Blotting ,Estetrol ,Fibrinolysis ,Obstetrics and Gynecology ,Endothelial stem cell ,ESTROGEN ,Selective estrogen receptor modulator ,Tissue Plasminogen Activator ,030220 oncology & carcinogenesis ,Female ,Western ,medicine.drug ,Selective Estrogen Receptor Modulators ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,medicine.drug_class ,Cells ,Blotting, Western ,U-PA ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Vascular ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Estrogen ,t-PA ,Endothelial Cells ,Endothelium, Vascular ,Estrogens ,Urokinase-Type Plasminogen Activator ,Biochemistry, Genetics and Molecular Biology (all) ,Endothelium ,Salud Ocupacional ,T-PA ,030104 developmental biology ,Endocrinology ,chemistry ,Plasminogen activator - Abstract
BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17β-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration. Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Università degli Studi di Pisa; Italia Fil: Palla, Giulia. Università degli Studi di Pisa; Italia Fil: Spina, Stefania. Università degli Studi di Pisa; Italia Fil: Bernacchi, Guja. Università degli Studi di Pisa; Italia Fil: Cecchi, Elena. Università degli Studi di Pisa; Italia Fil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina. Università degli Studi di Pisa; Italia Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; Italia Fil: Canu, Alessio. Università degli Studi di Pisa; Italia Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
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- 2017
19. Simulation as tool for evaluating and improving technical skills in laparoscopic gynecological surgery
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Eleonora Russo, Marta Caretto, Paolo Mannella, Andrea Giannini, Francesca Papini, Federica Pancetti, Tommaso Simoncini, Maria Magdalena Montt Guevara, and Elisa Malacarne
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Laparoscopic surgery ,medicine.medical_specialty ,medicine.medical_treatment ,lcsh:Surgery ,Appropriate use ,03 medical and health sciences ,Gynecologic Surgical Procedures ,0302 clinical medicine ,Obstetrics and gynaecology ,Laparoscopy ,OSATS ,Simulation ,Training ,Clinical Competence ,Gynecology ,Humans ,Italy ,Surgeons ,Internship and Residency ,Simulation Training ,medicine ,Surgical skills ,Surgical technical ,Medical physics ,030212 general & internal medicine ,Technical skills ,Gynecological surgery ,medicine.diagnostic_test ,business.industry ,lcsh:RD1-811 ,General Medicine ,Surgery ,030220 oncology & carcinogenesis ,business ,Research Article - Abstract
Background Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion. Methods Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale. Results Senior trainees had better score than junior trainees (p valuep Conclusions In this study, we demonstrated the role of simulation as powerful tool to evaluate and to self-assess surgical technical skills and to improve own capacities, with the use of a modified OSATs scale adapted to specific exercises.
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- 2019
20. Metabolic Syndrome and Excessive Body Weight in Peri- and Postmenopausal Women
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Jorge Eduardo Shortrede, Giulia Palla, Peter Chedraui, Tommaso Simoncini, Andrea R. Genazzani, Maria Magdalena Montt-Guevara, and Andrea Giannini
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medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Physiology ,Type 2 Diabetes Mellitus ,Hormone replacement therapy (menopause) ,Disease ,medicine.disease ,Obesity ,Insulin resistance ,Medicine ,Metabolic syndrome ,business ,Adverse effect ,Lipid profile - Abstract
Metabolic syndrome (MetS) has been associated with the endocrine, metabolic, and immunological functions of the adipose tissue. In parallel, obesity is strongly associated with disorder of glucose, lipid metabolism, and insulin resistance, and it is considered a common predisposing factor for elevated risk of several serious health conditions including insulin resistance, type 2 diabetes mellitus, hypertension and other cardiovascular disease (CVD), fatty liver disease, and some types of cancer. The incidence of CVD in women increases substantially with aging, probably because the menopause diminishes the gender estrogenic protection, thus contributing to an adverse impact on cardiovascular risk variables. CVD has become the leading cause of death for women. In this setting, the perimenopause must be considered a critical period in women’s life because it leads to several adverse changes especially in the lipid profile and modifies cardiovascular risk factors. Therefore, it could be necessary to encourage lifestyle measures and therapeutic interventions such as personalized hormone replacement therapy (HRT) throughout the perimenopause in order to counteract or prevent these events. HRT for postmenopausal women has been available for more than 60 years. Ever since, HRT has been a subject of discussion and debate regarding its safety and efficacy; nowadays it is well established that timing in the initiation and the type, dose, and route of HRT are crucial for the success of therapy, as well as for the control of possible adverse effects.
- Published
- 2019
21. Anatomical and functional outcomes of robotic abdominal lateral suspension for high-stage anterior-apical prolapse: a case series of 93 patients
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Paolo Mannella, Eleonora Russo, Maria Magdalena Montt-Guevara, Andrea Giannini, Giulia Misasi, and Tommaso Simoncini
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Apical prolapse ,business.industry ,Medicine ,Anatomy ,Stage (cooking) ,business ,Suspension (vehicle) - Published
- 2021
22. Principal surgical steps of the robotic-assisted lateral suspension for the treatment of concomitant advanced apical-anterior pelvic organ prolapse
- Author
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Eleonora Russo, Paolo Mannella, Andrea Giannini, Tommaso Simoncini, Maria Magdalena Montt-Guevara, and Giulia Misasi
- Subjects
medicine.medical_specialty ,Pelvic organ ,pelvic organ prolapse (POP) ,business.industry ,Robotic assisted ,Lateral suspension ,reconstructive surgery ,Surgery ,Concomitant ,robotic surgery ,Materials Chemistry ,Medicine ,business ,Suspension (vehicle) - Published
- 2020
23. Polymorphisms of the FTO and MTHFR genes and vascular, inflammatory and metabolic marker levels in postmenopausal women
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Ar Genazzani, Jasson Espinoza-Caicedo, Tommaso Simoncini, Gustavo S. Escobar, Peter Chedraui, Faustino R. Pérez-López, and Maria Magdalena Montt-Guevara
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Visfatin ,030204 cardiovascular system & hematology ,Polymerase Chain Reaction ,0302 clinical medicine ,Endocrinology ,Medicine ,FTO ,Genotypes ,Metabolic syndrome ,MTHFR ,Polymorphisms ,Postmenopause ,sCD40L ,Adult ,Aged ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Biomarkers ,Case-Control Studies ,Female ,Humans ,Inflammation ,Metabolic Syndrome ,Methylenetetrahydrofolate Reductase (NADPH2) ,Middle Aged ,Obesity ,Polymorphism, Single Nucleotide ,Vascular Diseases ,biology ,Leptin ,Single Nucleotide ,Diabetes and Metabolism ,medicine.medical_specialty ,Single-nucleotide polymorphism ,03 medical and health sciences ,Internal medicine ,SNP ,Polymorphism ,Adiponectin ,business.industry ,medicine.disease ,030104 developmental biology ,Methylenetetrahydrofolate reductase ,biology.protein ,Resistin ,business - Abstract
To determine the prevalence of three single nucleotide polymorphisms (SNPs) in postmenopausal women with and without the metabolic syndrome (METS) and to explore levels of circulating biomarkers of inflammation, vascular and metabolic dysfunction according to SNP genotypes. DNA was extracted from the whole blood of 192 natural postmenopausal women (40 to 65 years) screened for the METS and tested for three gene SNPs related to obesity: the fat mass obesity (FTO: rs9939609) and the methylenetetrahydrofolate reductase (MTHFR: C677T and A1298C). Blood levels of angiopoietin, IL-8, sFASL, IL-6, TNF-α, sCD40L, PAI-1, u-PA, leptin, adiponectin, resistin, ghrelin, visfatin, adipsin and insulin were measured in a subgroup, with and without the METS, using multiplex technology (n = 100) and compared according to SNP genotypes. Genotype frequency of the three studied SNPs did not differ in relation to the presence of the METS. However, genotypes CT+TT (C677T) and AT (rs9939609) were more prevalent in women with high triglyceride levels. Pooled sub-analysis (n = 100) found that median sCD40L and visfatin levels were higher in women with genotypes AT+TT (rs9939609) as compared to AA (1178 vs. 937.0 pg/mL and 0.93 vs. 0.43 ng/mL, respectively, p
- Published
- 2016
24. Ulipristal acetate interferes with actin remodeling induced by 17β-estradiol and progesterone in human endometrial stromal cells
- Author
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Andrea Giannini, Jorge Eduardo Shortrede, Tommaso Simoncini, Gisela Pennacchio, Michele Finiguerra, Alessandro D. Genazzani, and Maria Magdalena Montt-Guevara
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0301 basic medicine ,Stromal cell ,ULIPRISTAL ACETATE (UPA) ,CIENCIAS MÉDICAS Y DE LA SALUD ,Endocrinology, Diabetes and Metabolism ,Moesin ,purl.org/becyt/ford/3.5 [https] ,17β-estradiol (E2) ,Actin remodeling ,Endometrial stromal cells (ESC) ,Progesterone (P4) ,Ulipristal acetate (UPA) ,macromolecular substances ,17Β-ESTRADIOL (E2) ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Focal adhesion ,03 medical and health sciences ,Endocrinology ,Selective progesterone receptor modulator ,Cytoskeleton ,PROGESTERONE (P4) ,Original Research ,progesterone (P4) ,ACTIN REMODELING ,ENDOMETRIAL STROMAL CELLS (ESC) ,lcsh:RC648-665 ,endometrial stromal cells (ESC) ,biology ,Chemistry ,Vinculin ,Actin cytoskeleton ,Cell biology ,Otras Ciencias Médicas ,Diabetes and Metabolism ,actin remodeling ,030104 developmental biology ,biology.protein ,purl.org/becyt/ford/3 [https] - Abstract
Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) used for emergency contraception and for the medical management of symptomatic uterine fibroids (UF). Treatment with UPA turns in amenorrhea and UF volume reduction. Treatment with UPA is associated with the frequent development of benign, transitory endometrial changes known as SPRM-associated endometrial changes (PAECs). Why PAECs develop and their biological or cellular basis is unknown. Sex steroids, including estrogen and progesterone, are established modulators of the actin cytoskeleton in various cells, including endometrial cells. This explains several morphological and functional changes in endometrial cells. We thus hypothesized that UPA may alter the appearance of the endometrium by interfering with the actions of 17β-estradiol (E2) or progesterone (P4) on actin dynamics. We isolated and cultured human endometrial stromal cells (ESC) from endometrial biopsies from healthy fertile women. Treatment with E2 or P4 stimulated visible actin rearrangements with actin remodeling toward the membrane. Activation through phosphorylation of the actin regulatory proteins, Moesin, and focal adhesion kinase (FAK), hacked actin remodeling induced by E2 and P4. Membrane re-localization of Paxillin and Vinculin were also induced by E2 and P4, showing the formation of focal adhesion complexes. All these E2 and P4 actions were inhibited by co-treatment with UPA, which was otherwise inactive if given alone. The cytoskeletal changes induced by E2 and P4 turned into increased motility of ESC, and UPA again blocked the actions E2 and P4. In conclusion, we find that UPA interferes with the cytoskeletal actions of E2 and P4 in ESC. This finding helps understanding the mode of actions of SPRMs in the endometrium and may be relevant for other potential clinical applications of UPA. Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; Italia Fil: Montt Guevara, Maria Magdalena. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Finiguerra, Michele. Università degli Studi di Pisa; Italia Fil: Giannini, Andrea. Università degli Studi di Pisa; Italia Fil: Genazzani, Alessandro D.. Universita Degli Studi Di Modena E Reggio Emilia; Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
- Published
- 2018
25. Src and phospho-FAK kinases are activated by allopregnanolone promoting Schwann cell motility, morphology and myelination
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Veronica Bonalume, Simona Melfi, Massimiliano Ruscica, Tommaso Simoncini, Valerio Magnaghi, Alessandra Colciago, and Maria Magdalena Montt Guevara
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0301 basic medicine ,Cells ,Schwann cell ,Motility ,Pregnanolone ,Biology ,Nerve Fibers, Myelinated ,Biochemistry ,Focal adhesion ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Nerve Fibers ,peripheral nervous system ,Cell Movement ,myelin ,neuroactive steroid ,Animals ,Cells, Cultured ,Enzyme Activation ,Focal Adhesion Protein-Tyrosine Kinases ,Rats ,Schwann Cells ,src-Family Kinases ,medicine ,Actin ,Cultured ,integumentary system ,Kinase ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Myelinated ,tissues ,Tyrosine kinase ,030217 neurology & neurosurgery ,Intracellular ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Schwann cells' (SCs) development and maturation require coordinate and complementary activation of several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs', participating in regulation of their adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SCs motility and proliferation, which are crucial processes for nerve development, maturation and regeneration. Herein, we investigate the hypothesis that the molecular mechanisms behind the ALLO's action on SCs involve the signalling intermediates Src and FAK. We first demonstrated that ALLO 10−6 M regulates SCs morphology, motility and myelination, also increasing the internode distance in the in vitro myelination model of neuron/SCs co-culture. ALLO's actions were mediated by the modulation of Src/FAK pathway, since they were counteracted by PP2 10−5 M, a selective inhibitor of Src kinase. Then, we proved that Src/FAK activation in SCs involves GABA-A dependent mechanisms and actin re-arrangements. In conclusion, our findings are the first to corroborate the importance of the neuroactive steroid ALLO in regulating SCs development and maturation via the Src and phospho-FAK signalling activation. Cover Image for this issue: doi: 10.1111/jnc.13795.
- Published
- 2017
26. Androgens regulate T47D cells motility and invasion through actin cytoskeleton remodeling
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Andrea Giannini, Jorge Eduardo Shortrede, Tommaso Simoncini, Alessandro D. Genazzani, Eleonora Russo, Maria Silvia Giretti, Maria Magdalena Montt-Guevara, and Paolo Mannella
- Subjects
0301 basic medicine ,medicine.medical_specialty ,cell migration ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Moesin ,Actin cytoskeleton ,Androgens ,Breast cancer ,Metastasis ,Estrogen receptor ,macromolecular substances ,Biology ,urologic and male genital diseases ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Endocrinology ,Internal medicine ,medicine ,skin and connective tissue diseases ,Original Research ,lcsh:RC648-665 ,Cell migration ,cell invasion ,Androgen ,medicine.disease ,Diabetes and Metabolism ,030104 developmental biology ,actin cytoskeleton ,androgens ,breast cancer ,metastasis ,Dihydrotestosterone ,Cancer research ,medicine.drug - Abstract
The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR) is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.
- Published
- 2016
27. Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
- Author
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Laura M. Vargas-Roig, Silvina B. Nadin, Antonella D Losinno, F. Darío Cuello-Carrión, Mariel A. Fanelli, Maria Magdalena Montt-Guevara, and Mayra L Sottile
- Subjects
Hyperthermia ,HEAT SHOCK RESPONSE ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,Cancer Research ,Fever ,Physiology ,DNA repair ,HSP27 Heat-Shock Proteins ,THERMOTOLERANCE ,Antineoplastic Agents ,HSP72 Heat-Shock Proteins ,Biology ,Immunofluorescence ,DNA DAMAGE/REPAIR ,DNA Mismatch Repair ,Flow cytometry ,Physiology (medical) ,Heat shock protein ,Cell Line, Tumor ,medicine ,Humans ,neoplasms ,Cisplatin ,medicine.diagnostic_test ,purl.org/becyt/ford/3.1 [https] ,medicine.disease ,Molecular biology ,digestive system diseases ,CHAPERONES ,HT RADIO-CHEMOSENSITIZATION ,MSH2 ,Colonic Neoplasms ,DNA mismatch repair ,purl.org/becyt/ford/3 [https] ,medicine.drug ,DNA Damage - Abstract
Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(-)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR-) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR- cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR-/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions. Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Fanelli, Mariel Andrea. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
- Published
- 2015
28. Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells
- Author
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Andrea Giannini, Paolo Mannella, Tommaso Simoncini, Maria Silvia Giretti, Eleonora Russo, Andrea R. Genazzani, Alessandro D. Genazzani, and Maria Magdalena Montt-Guevara
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Endothelial cells ,Context (language use) ,Endogeny ,Endometrium ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Umbilical vein ,Nitric oxide ,chemistry.chemical_compound ,Endocrinology ,nitric oxide ,Enos ,Internal medicine ,estrogen ,medicine ,Original Research ,endothelial nitric oxide synthase ,lcsh:RC648-665 ,biology ,business.industry ,Estetrol ,biology.organism_classification ,Estrogen ,endothelial cells ,estetrol ,Diabetes and Metabolism ,medicine.anatomical_structure ,chemistry ,Endothelial nitric oxide synthase ,business - Abstract
Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout ageing in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2 and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use.
- Published
- 2015
29. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton
- Author
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Elena Cecchi, Andrea R. Genazzani, Silvia Di Bello, Tommaso Simoncini, Maria Magdalena Montt Guevara, Giulia Palla, Paolo Mannella, Guja Bernacchi, Alessandro D. Genazzani, Maria Silvia Giretti, and Stefania Spina
- Subjects
medicine.medical_specialty ,actin cytoskeleton ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Moesin ,Estrogen receptor ,macromolecular substances ,Biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Cell membrane ,chemistry.chemical_compound ,Endocrinology ,breast cancer ,Internal medicine ,medicine ,estrogen ,Cytoskeleton ,Original Research ,lcsh:RC648-665 ,Actin remodeling ,Actin cytoskeleton ,cancer progression ,Cell biology ,estetrol ,Estetrol ,medicine.anatomical_structure ,chemistry ,Estrogen - Abstract
Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2) on T47-D estrogen receptor (ER) positive breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, redistribution of actin fibers towards the cell membrane was observed. However, when E4 was added to E2, a inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin (ERM) family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr558, which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of ERα. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring estrogen receptor modulator in the breast.
- Published
- 2014
30. Menopause, Aging, Pelvic Organ Prolapse, and Dysfunction
- Author
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Adrian Esteban Campelo, Tommaso Simoncini, Giulia Palla, Guja Bernacchi, Silvia Pisaneschi, Stefania Spina, Maria Magdalena Montt Guevara, Silvia Di Bello, Elena Cecchi, Genazzani, Andrea R., and Brincat, Mark
- Subjects
Gynecology ,medicine.medical_specialty ,Pelvic organ ,CIENCIAS MÉDICAS Y DE LA SALUD ,Pelvic floor ,IRRITABLE BOWEL SYNDROME ,business.industry ,Urology ,Urinary incontinence ,Medicina Clínica ,URINARY INCONTINENCE ,medicine.disease ,Menopause ,STRESS URINARY INCONTINENCE ,medicine.anatomical_structure ,Endocrinología y Metabolismo ,PELVIC ORGAN PROLAPSE ,Medicine ,PELVIC FLOOR ,medicine.symptom ,business ,Irritable bowel syndrome - Abstract
The female pelvic floor is a complex functional unit involved in many undertakings. Pelvic floor dysfunction affects micturition, defecation, and sexual activity. Evolutionary adaptation, such as the acquisition of the upright standing position, walking, and delivery of fetuses with larger head diameters, made the fascial and the muscle support of the pelvic floor more vulnerable, predisposing women to pelvic organ prolapse and incontinence. In addition, the female pelvic floor (differently than in males) undergoes a number of adaptive changes related to life and endocrine events. Many of these clinical manifestations become apparent after menopause and aging in women. This chapter summarizes the key aspects of the pathophysiology and the clinics of the changes of the pelvic floor in women, in particular focusing on the association between endocrine changes of aging women and urinary problems and bowel dysfunctions. Fil: Pisaneschi, Silvia. Universitá di Pisa; Italia Fil: Palla, Giulia. Universitá di Pisa; Italia Fil: Spina, Stefania. Universitá di Pisa; Italia Fil: Bernacchi, Guja. Universitá di Pisa; Italia Fil: Cecchi, Elena. Universitá di Pisa; Italia Fil: Di Bello, Silvia. Universitá di Pisa; Italia Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universitá di Pisa; Italia Fil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina. Università di Pisa; Italia Fil: Simoncini, Tommaso. Universitá di Pisa; Italia
- Published
- 2014
31. Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
- Author
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F. Darío Cuello-Carrión, Marcela Leuzzi, Laura M. Vargas-Roig, Francisco E. Gago, Pedro Daguerre, Mayra L Sottile, Daniel R. Ciocca, Maria Magdalena Montt-Guevara, Jorge Ibarra, Silvina B. Nadin, and Gisel V. Gauna
- Subjects
Oncology ,Adult ,HEAT SHOCK PROTEINS ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Cyclophosphamide ,Anthracycline ,medicine.medical_treatment ,HSP27 Heat-Shock Proteins ,Breast Neoplasms ,Medicina Clínica ,Biochemistry ,NEOADJUVANT CHEMOTHERAPY ,Breast cancer ,BREAST CANCER ,Internal medicine ,PROGNOSTIC FACTORS ,Medicine ,Humans ,Doxorubicin ,Anthracyclines ,HSP70 Heat-Shock Proteins ,Breast ,Neoadjuvant therapy ,Aged ,Epirubicin ,Chemotherapy ,Original Paper ,Antibiotics, Antineoplastic ,business.industry ,Cancer ,Cell Biology ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Neoadjuvant Therapy ,Immunology ,Female ,Medicina Critica y de Emergencia ,ANTHRACYCLINES ,business ,medicine.drug ,Follow-Up Studies - Abstract
Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance. Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Daguerre, Pedro. Hospital Luis Lagomaggiore; Argentina Fil: Leuzzi, Marcela. Hospital Luis Lagomaggiore; Argentina Fil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina Fil: Ibarra, Jorge. Hospital Luis Lagomaggiore; Argentina Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
- Published
- 2013
32. Editorial: Endocrine aspects of gynaecological cancers
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Bastian Czogalla, Maria Magdalena Montt-Guevara, and Udo Jeschke
- Subjects
gynecological cancer ,endocrinology ,hormones ,pathways ,diagnostics ,therapy ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2024
- Full Text
- View/download PDF
33. Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model
- Author
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Ana Sofia Zabala, Rocío Ayelem Conforti, María Belén Delsouc, Verónica Filippa, Maria Magdalena Montt-Guevara, Andrea Giannini, Tommaso Simoncini, Sandra Silvina Vallcaneras, and Marilina Casais
- Subjects
endometriosis ,estetrol ,apoptosis ,proliferation ,hormone receptors ,oxidative stress ,Microbiology ,QR1-502 - Abstract
Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo.
- Published
- 2024
- Full Text
- View/download PDF
34. ANDROGENS REGULATE T47D CELLS MOTILITY AND INVASION THROUGH ACTIN CYTOSKELETON REMODELLING
- Author
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Maria Magdalena Montt-Guevara, Jorge Eduardo Shortrede, Maria Silvia Giretti, Andrea Giannini, Paolo Mannella, Eleonora Russo, Alessandro David Genazzani, and Tommaso Simoncini
- Subjects
Actin Cytoskeleton ,Androgens ,cell migration ,breast cancer ,cell invasion ,moesin ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR) is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.
- Published
- 2016
- Full Text
- View/download PDF
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