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1.
Front Oncol ; 11: 684700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026657

RESUMO

INTRODUCTION: to assess incidence, prognosis and obstetric outcome of patients treated for gestational trophoblastic disease GTD in a twenty-year period. Incidence, prognosis and obstetric outcome of gestational throphoblastic disease. METHODS: retrospective study. RESULTS: Fifty-four cases of GTD: 46 (85.18%) cases of Hydatidiform mole (HM); 8 cases of Persistent Gestational Trophoblastic Neoplasia (GTN) (14.81%): 6/8 cases (75%) GTN not metastatic; 2/8 cases (25%) GTN metastatic. In both cases, the metastases occurred in the lungs. In 3 out of 8 GTN cases (37.5%) a histological picture of choriocarcinoma emerged. The incidence of GTD cases treated from 2000 to 2020 was 1.8 cases per 1000 deliveries and 1.3 cases per 1000 pregnancies. Of the 54 patients, 30 (55.56%) presented showed normal serum hCG levels without the need for chemotherapy. On the other hand, 24 patients (44.44%) developed a persistent trophoblastic disease and underwent adjuvant therapy. The negative prognostic factors that affected the risk of persistence of GTD were: serum hCG levels at diagnosis > 100,000 mUI/ml; characteristic "snow storm" finding at the ultrasound diagnosis; a slow regression of serum hCG levels during follow-up; the persistence of high serum hCG levels (especially if > 1000 mUI/ml one month after suction curettage) that was the main risk factor for resistance to first-line chemotherapy. There were 10 pregnancies in total following treatment. Patients' survival in our study was 100%. DISCUSSION: Although GTD is a rare disease, its incidence was 1.3 cases per 1,000 pregnancies in Sardinia, Italy, higher if compared with mean national and worldwide incidence.

2.
Semin Cancer Biol ; 77: 194-202, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33607247

RESUMO

In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contrasting evidences have suggested a potential role in this clinical setting of SCS combined with intraperitoneal hyperthermic chemotherapy. In this complex scenario we review here the available evidences regarding the role surgery in ovarian cancer patients with platinum resistant disease, trying also to understand which patients may benefit from this challenging, experimental approach.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/cirurgia , Animais , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Compostos de Platina
3.
Cells ; 9(8)2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806709

RESUMO

Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (DNMT1, SIRT1), miRNAs (miR-145, miR-148, and miR-185) related to stemness, exosomes, the cell-cycle regulators p21 (WAF1/CIP1) and p53, and the senescence-associated genes (p16, p19, and hTERT). Cells were cultured in the presence or absence of the human hepatocarcinoma cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of SIRT1 and reduced levels of p21 mRNA. Moreover, we observed a downregulation of DNMT1, and a simultaneous overexpression of Oct-4 and c-Myc. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.


Assuntos
Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Geleia de Wharton/citologia , Diferenciação Celular/genética , Senescência Celular/genética , Meios de Cultivo Condicionados , Inibidor de Quinase Dependente de Ciclina p21/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , MicroRNAs/genética , Fator 3 de Transcrição de Octâmero/genética , Proteínas Proto-Oncogênicas c-myc/genética , Sirtuína 1/genética
4.
Arch Gynecol Obstet ; 302(3): 665-670, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32506173

RESUMO

PURPOSE: To evaluate the feasibility and safety of laparoscopic excision of endometriotic lesions in obese women. METHODS: Retrospective analysis of prospectively collected data involving consecutive women scheduled for complete laparoscopic removal of macroscopic endometriotic lesions between January 2012 and November 2018. Operative time, laparotomic conversion rates, complication rates, and length of hospital stay were recorded. RESULTS: One thousand two hundred thirty women were enrolled and divided into two main groups, according to the World Health Organization classification of obesity, obese (body mass index ≥ 30 kg/m2) and non-obese (body mass index < 30 kg/m2). During the study period, 91 (7.4% of overall study cohort) obese women underwent surgery. At univariate analyses, significant differences between the two groups were found in terms of age, rates of severe endometriosis, American Society of Anesthesiologists physical status classification ≥ III, and different surgical procedures. Significant differences in terms of median operative time [125 (interquartile range (IQR) 85-165) in obese group vs 110 min (IQR 75-155) in non-obese group, P = 0.04] were observed. There were no significant differences between the obese and non-obese groups with respect to the other variables of interest. After adjusted multivariable regression models for potential confounders, difference in operating time (coefficient of 13.389; 95% CI 1.716, 25.060) was still found to be significant. CONCLUSION: In our tertiary care referral center, laparoscopic removal of endometriosis is feasible and safe, except for a slight increase of operative time and conversion rate.


Assuntos
Endometriose/cirurgia , Laparoscopia/métodos , Obesidade/complicações , Adulto , Estudos de Viabilidade , Feminino , Humanos , Análise de Regressão , Estudos Retrospectivos
5.
Maturitas ; 133: 13-31, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005420

RESUMO

The objective of this systematic review and meta-analysis was to evaluate the efficacy and the effectiveness, as well as the safety and tolerability, of urethral bulking agents (UBAs) in women with mixed or stress urinary incontinence. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were used to identify relevant articles. In total, 3510 records were found. A total of 42 full texts were evaluated but only 21 (48.8 %) were selected for the qualitative and quantitative analysis. The pooled improvement rate in studies with a follow-up of ≤1 and >1 year was 46.0 % (95 % CI: 37.0 %-57.0 %; I2: 88.9 %) and 57.0 % (95 % CI: 39.0 %-74.0 %; I2: 89.6 %), respectively. The outcome 'cure/dryness' ranged from 9.1 % to 56.7 %. The pooled cure rate was 26.0 % (95 % CI: 21.0 %-32.0 %; I2: 89.9 %) and 21.0 % (95 % CI: 16.0 %-27.0 %; I2: 34.2 %) in females with a follow-up of ≤1 and >1 year, respectively. The treatment success rate ranged from 32.7 % to 93.3 % in 12 studies; it was objectively assessed with different tools (e.g., the Stamey scale in 5 studies). The pooled objective treatment success rate was 7.0 % (95 % CI: 59.0.0 %-75.0 %; I2: 82.4 %) and 46.0 % (95 % CI: 37.0 %-55.0 %; I2: 55.3 %) in women with a follow-up of ≤12 and >12 months, respectively. The percentage of adverse events was 0.4 % (vaginal infection, irritation, lichen sclerosus, worsening urinary incontinence). However, the use of UBAs as the first-line therapy should be demonstrated in more comparative studies (randomized studies MUSs vs. UBAs). UBAs should be considered a first-line surgical therapy only for women with SUI and mixed UI with high anaesthesia risk, elderly patients, or patients reluctant to undergo surgery. Thus, UBAs should not be offered as first-line therapy for those women desiring a "one-time" durable solution for primary or recurrent SUI.


Assuntos
Hidrogéis/uso terapêutico , Polímeros/uso terapêutico , Incontinência Urinária/terapia , Humanos , Resultado do Tratamento , Uretra
6.
Vaccines (Basel) ; 8(1)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991753

RESUMO

The aim of this study was to assess the role of a human papilloma virus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) in reducing recurrent cervical dysplasia. A series of 503 women with cervical dysplasia received LEEP between January 2012 and October 2018. Of these patients, 379 were treated between January 2012 and June 2017, thus ensuring an adequate follow-up time. We made three attempts to establish telephone contact with each patient; 77 women did not respond and were excluded from the final study population, which consisted of 302 patients. One hundred eighty-two (60.7%) women were vaccinated with an HPV vaccine within 4 weeks of LEEP and 103 (34.3%) were followed up with but not vaccinated. Recurrence of cervical dysplasia requiring a further LEEP procedure occurred in 30 (10.5%) women, of whom 17 (16.5%) were not vaccinated and 13 (7.1%) were vaccinated (p-value = 0.010). At univariate analysis, HPV vaccination after LEEP (odds ratio (OR) = 0.4, p-value = 0.020) emerged as an independent protective factor. Choosing as an outcome of the analysis only recurrence as severe cervical lesions, the protective role of HPV vaccination after LEEP was found to be much more relevant with an odds ratio of 0.2 (95% CI = 0.1-0.6, p-value = 0.02). Administration of an HPV vaccine after LEEP seems to reduce the risk of recurrence, thus suggesting that HPV vaccination has a role as an adjuvant treatment after LEEP.

7.
J Invest Surg ; 33(4): 301-306, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30380354

RESUMO

Aim: To investigate regarding the safety and effectiveness of a balloon catheter (Aqueduct-100 device) to dilate the uterine cervix before operative hysteroscopies. Secondary objectives were to evaluate the duration of the dilatation procedure and to investigate on physicians' satisfaction with the device. Methods: Fifty women younger than 40 years, wishing pregnancies and diagnosed with apparently benign intrauterine lesions and/or uterine anomalies, were enrolled into this study and submitted to cervical priming with Aqueduct-100 device before operative hysteroscopy. Results: Initial cervical dilatation was ≤4 mm in all but one patient. Adequate (10 mm) cervical dilatation was achieved in only one patient, the remaining forty-nine needed additional cervical dilatation. All women, however, presented with a ≥6 mm cervical width after balloon catheter removal. The mean time to final cervical dilatation was 8.5 minutes. No perioperative complications occurred. Physicians reported, in the majority of cases, satisfaction for the dilatation achieved (66%), the ease of balloon catheter insertion/use (82%), and for the ease of additional dilatation (96%). Conclusions: Aqueduct-100 device before operative hysteroscopy is safe and useful to increase the baseline cervical width and facilitate additional dilatation, with good effects on physician satisfaction and acceptable dilatation times.


Assuntos
Dilatação/instrumentação , Histeroscopia/métodos , Complicações na Gravidez/diagnóstico por imagem , Cuidados Pré-Operatórios/instrumentação , Anormalidades Urogenitais/diagnóstico por imagem , Útero/anormalidades , Adulto , Colo do Útero , Dilatação/efeitos adversos , Feminino , Humanos , Projetos Piloto , Gravidez , Cuidados Pré-Operatórios/efeitos adversos , Útero/diagnóstico por imagem
8.
Int J Mol Sci ; 20(20)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615086

RESUMO

MiRNAs, a small family of non-coding RNA, are now emerging as regulators of stem cell pluripotency, differentiation, and autophagy, thus controlling stem cell behavior. Stem cells are undifferentiated elements capable to acquire specific phenotype under different kind of stimuli, being a main tool for regenerative medicine. Within this context, we have previously shown that stem cells isolated from Wharton jelly multipotent stem cells (WJ-MSCs) exhibit gender differences in the expression of the stemness related gene OCT4 and the epigenetic modulator gene DNA-Methyltransferase (DNMT1). Here, we further analyze this gender difference, evaluating adipogenic and osteogenic differentiation potential, autophagic process, and expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived from males and females. These miRNAs were selected since they are involved in OCT4 and DNMT1 gene expression, and in stem cell differentiation. Our results indicate a difference in the regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in male WJ-MSCs as compared to female cells. Moreover, no difference was detected in the expression of the two-differentiation regulating miRNA (miR-145 and miR-185). Taken together, our results highlight a different behavior of WJ-MSCs from males and females, disclosing the chance to better understand cellular processes as autophagy and stemness, usable for future clinical applications.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/genética , MicroRNAs/genética , Fator 3 de Transcrição de Octâmero/genética , Células-Tronco Pluripotentes/metabolismo , Adipogenia/genética , Autofagia/genética , Diferenciação Celular/genética , Epigênese Genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética
9.
Histol Histopathol ; 34(7): 723-730, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30656635

RESUMO

INTRODUCTION: Primary extranodal non-hodgkin vaginal lymphoma (PeNHVL) represents a rare entity, with few data published until now. We present here a series of patients with PeNHVL, analyzing our data as part of a detailed review of the available literature. METHODS: The study included a consecutive series of 6 patients with final diagnosis of PeNHVL admitted at our Institution between January 2000 and December 2017. The systematic review was conducted according to PRISMA guidelines. A literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed using the following terms: 'vaginal lymphoma'. Relevant data were collected and analyzed for the purposes of this study, reporting results through a narrative approach. RESULTS: In our series discomfort and vaginal pain, refractory to medical treatments represent the symptoms of disease presentation, and the presence of localized/diffused anelastic area in the vaginal wall with tactile sensation of cork emerges as diagnostic sign (Cork Wall sign). The literature revision included 41 studies, with an overall population of 74 patients. The vast majority of women were diagnosed as early stage disease (93.6%) and received chemotherapy (74.6%) with a very high response rate (96%). Death from disease occurred in 5 women (6.7%). CONCLUSIONS: Localized or diffused hard-ligneous vaginal areas with Cork Wall sign represent the typical sign of disease presentation. PeNHVL is characterized by a very high sensitivity to chemotherapy and very favourable prognosis; therefore, radical surgery is not indicated. Histotype characterization is crucial to identify those uncommon variants associated with a less favorable clinical outcome.


Assuntos
Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Pessoa de Meia-Idade , Prognóstico , Vagina/patologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/terapia
10.
Eur J Obstet Gynecol Reprod Biol ; 234: 143-148, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30690190

RESUMO

OBJECTIVE: To study the molecular features of mesenchymal stem cells from Wharton Jelly (WJ-MSCs) of umbilical cord to predict their differentiation capacity. DESIGN: Comparison of gene expression from mesenchymal stem cells of male and female umbilical cord SETTING: University hospital PATIENT (S): umbilical cords (n = 12, 6 males and 6 females) retrieved from spontaneous full-term vaginal delivery of healthy women INTERVENTION: we analyzed the expression of the stemness related genes C-MYC, OCT4, SOX2 and NANOG and of the epigenetic modulating gene DNA-methyltransferase 1 (DNMT1). MEAN OUTCOME MEASURE: WJ-MSCs were isolated by standard procedures and immunophenotypically characterized. Gene expression analysis of stemness related genes and the epigenetic modulating gene DNMT1 were performed by real-time PCR RESULTS: expression of the OCT4 and DNMT1 genes was significantly higher in WJ- MSCs isolated from male subjects, as compared to MSCs isolated from female-derived WJ. The resulting higher expression of OCT4 and DNMT1 in WJ-MSCs from males as compared with female WJ-MSCs for the first time identifies a specific relationship between stemness genes, an epigenetic modulator, and gender differences. CONCLUSION: our findings disclose novel biomedical implications in WJ-MSCs related to the sex of the donor, thus providing additional cues to exploit their regenerative potential in allogenic transplantation.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Caracteres Sexuais , Cordão Umbilical/citologia , Geleia de Wharton/citologia , Diferenciação Celular , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Feminino , Expressão Gênica/fisiologia , Genes myc/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Gravidez , Fatores de Transcrição SOXB1/metabolismo , Vagina
11.
Arch Gynecol Obstet ; 296(3): 405-419, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28643028

RESUMO

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD). METHODS: A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulin resistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included. RESULTS: PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle. CONCLUSION: The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.


Assuntos
Tecido Adiposo/fisiopatologia , Resistência à Insulina , Síndrome Metabólica/complicações , Síndrome do Ovário Policístico/complicações , Adipocinas , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Estilo de Vida , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Síndrome do Ovário Policístico/patologia
12.
J Vasc Res ; 52(4): 273-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26855429

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) are key elements in vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA; an agonist of ER-ß and agonist and antagonist of ER-α) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC; an agonist of ER-α and antagonist of ER-ß) on human EPCs is unknown. We analyzed whether BPA and THC influence the migration of human EPCs, an essential process in endothelial regeneration, in both male and female EPCs. METHODS: EPCs isolated from healthy adult men and women were assayed for ER expression by Western blotting and chemotaxis assay. RESULTS: Male and female EPCs similarly expressed ERs and did not differ in basal migration. Interestingly, 17-ß-estradiol (10(-9) and 10(-10) M) significantly inhibited migration in female EPCs but not in males. Moreover, both 10(-5) M THC and 10(-8) M BPA blocked migration in female EPCs, allowing us to hypothesize that the effect is mediated by ER-α. CONCLUSIONS: Estrogenic compounds have a sex divergent effect which could help in understanding differences in the pathophysiology of endothelial function observed between men and women.


Assuntos
Quimiotaxia/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Estrogênios/farmacologia , Adolescente , Adulto , Células Cultivadas , Relação Dose-Resposta a Droga , Células Progenitoras Endoteliais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Fatores Sexuais , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
13.
Arch Gynecol Obstet ; 291(1): 19-30, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25234517

RESUMO

INTRODUCTION: The accurate evaluation of tubal patency as well of the morphologic characteristics of the uterine cavity is a fundamental step in the diagnostic work-up for infertility. Hysteroscopy and laparoscopy and dye have long been regarded as the reference methods to assess uterine morphology and tubal patency, respectively. However, their technical and clinical limitations have supported the introduction of an emerging technique: hysterosalpingo contrast sonography (HyCoSy), which has recently been improved with the use of modern contrast agents and three-dimensional resolution. METHODS: A systematic literature search was performed in electronic databases (PubMed and Scopus). Key search terms included Hysterosalpingo contrast sonography (HyCoSy), Tubal patency, Infertility, Uterine cavity, Ultrasounds. RESULTS: HyCoSy has proved to be as reliable as laparoscopic techniques in the assessment of tubal patency and uterine morphology, and also it overcomes such major drawbacks as hospitalization, radiation exposure, anesthesia and use of iodinated contrast media. All in all, HyCoSy is considered as a safe and well tolerated outpatient procedure, which apparently favors the onset of spontaneous pregnancies. CONCLUSION: This paper provides a comprehensive overview of the literature dealing with HyCoSy to support its use as a first-line technique in standard infertility work-up.


Assuntos
Testes de Obstrução das Tubas Uterinas/métodos , Histerossalpingografia/métodos , Infertilidade Feminina/diagnóstico , Meios de Contraste/administração & dosagem , Feminino , Humanos , Histeroscopia/métodos , Laparoscopia/métodos , Gravidez , Ultrassonografia , Útero/diagnóstico por imagem
14.
Biol Sex Differ ; 5(1): 18, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25535548

RESUMO

BACKGROUND: Human umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3). Moreover, because autophagy is influenced by sex, its degree was analysed in male and female HUVECs (MHUVECs and FHUVECs). METHODS: Umbilical cords from healthy, normal weight male and female neonates born to healthy non-obese and non-smoking women were studied. HUVEC morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Gene and protein expression for oestrogen and androgen receptors and for NOS3 were evaluated by real-time PCR and Western blotting, respectively, and the expression of the primary molecules involved in autophagy regulation [protein kinase B (Akt), mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were detected by Western blotting. RESULTS: Cell proliferation, migration NOS3 mRNA and protein expression were significantly higher in FHUVECs than in MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating that male cells are more autophagic than female cells. The expression of oestrogen and androgen receptor genes and proteins, the protein expression of Akt and mTOR and cellular size and shape were not influenced by sex. Body weights of male and female neonates were not significantly different, but the weight of male babies positively correlated with the weight of the mother, suggesting that the mother's weight may exert a different influence on male and female babies. CONCLUSIONS: The results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease.

15.
Exp Cell Res ; 319(17): 2627-36, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23948303

RESUMO

The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals.


Assuntos
Núcleo Celular/metabolismo , Proteína de Suscetibilidade a Apoptose Celular/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ativação Transcricional , Transporte Ativo do Núcleo Celular , Linhagem Celular Tumoral , Movimento Celular , Proteína de Suscetibilidade a Apoptose Celular/genética , Citoplasma/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosforilação , Transcrição Gênica
17.
J Matern Fetal Neonatal Med ; 26(4): 369-72, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23039761

RESUMO

OBJECTIVE(S): The aim of this study was to explore the relationship between periodontal health and pregnancy outcomes in a large cohort of Italian postpartum women. METHODS: 750 postpartum women were enrolled in a case-control study within 5 days from delivery at three Italian obstetric clinics. Cases were defined as those mothers who delivered an infant weighing under 2500 g (LBW) and/or had premature delivery and/or delivered small for gestational age newborns (SGA) and/or experienced preeclampsia/pregnancy induced hypertension (PE/PIH) or preterm premature rupture of membranes (pPROM) during pregnancy. All women received comprehensive oral and dental examination. Associations between adverse pregnancy outcome and exposures of interest were evaluated by the use of multivariate logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was no significant difference between cases and controls with respect to country of birth, age, place of residence, educational achievement, smoking, and periodontal status. By definition, infant birth weight [2,750 g (IQR = 2,300-3,200 g) and 3,275, (IQR = 3,010-3,538 g) p < 0.001, respectively] and gestational age at delivery [259 days (IQR = 245-273) and 273 days (IQR = 266-280), p < 0.01, respectively] were significantly lower in cases than in controls. In multivariate analyses, a borderline association was found between poor obstetric outcomes and current smokers (OR: 1.5; 95% CI: 0.1-2.5). Finally, after adjusting for smoking status neither country of birth, nor age or place of residence or education or periodontitis were associated with a significantly increased risk of adverse pregnancy outcome. CONCLUSION(S): Our data failed to demonstrate the association between periodontitis and an adverse pregnancy outcome such as preterm birth, low birth weight, preeclampsia, intrauterine growth restriction, and premature rupture of membranes.


Assuntos
Periodontite/complicações , Periodontite/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Acebutolol , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Pessoa de Meia-Idade , Período Pós-Parto , Pré-Eclâmpsia/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Fumar/epidemiologia
18.
BMC Public Health ; 11: 785, 2011 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-21989375

RESUMO

BACKGROUND: Human papillomavirus (HPV) has been associated with several disorders of the genital tract, skin and oropharynx. The aims of our study were to evaluate the prevalence of HPV infection in women between 15 and 54 years of age in North Sardinia, Italy, to identify the prevalence of High Risk - Human papillomaviruses (HR-HPV) genotypes and to establish a correlation between molecular and cytological results. METHODS: From 2007 to 2009 we consecutively enrolled women aged 15-54 years admitted to public and private outpatient settings. All the participants filled in a questionnaire about the socio-cultural state, sexual activity and awareness about HPV. 323 cervical specimens were tested for HPV-DNA and HPV genotypes with INNO-LiPA HPV Genotyping CE Amp kit. Samples showing positivity to some HPV genotypes were re-tested using "in house" quantitative Real-Time PCR assays. RESULTS: Overall HPV-DNA positivity was detected in 35.9% of the women. The prevalence of HR-HPV infection among HPV positive samples was 93.1% with a specific prevalence of HPV 16, 51, 31, 53 and 18 of 54.3%, 37.9%, 10.3%, 6.9% and 5.2%, respectively. Co-infection with any HPV, HR-HPV, LR-HPV and HR/LR-HPV type was 18.3%, 14.9%, 0.9% and 2.5%, respectively; HPV 16/51 co-infection was detected in 64.6% of the HR-HPV co-infection group. The most frequent HPV-genotypes detected were 16 (32.5%) and 51 (22.7%). Among the 57 patients harboring mono-infection the most prevalent HPV genotypes were 16 (38.6%) and 31(10.5%). A multivariate analysis identified a statistical significant association between HPV infection and age and between HPV infection and previous sexual transmitted diseases. A statistically significant association between cytological cervical lesions and generic HPV exposure was identified. CONCLUSIONS: To our knowledge, this is the first survey evaluating the prevalence of HPV infection in Northern Sardinia and drawing attention to the unusual high proportion of genotype HPV 51. Given the recent implementation of a widespread immunization program with vaccines not containing HPV 51, it has been relevant to prove the high prevalence of this HPV genotype from the start of the vaccination campaign, in order to avoid in the future attributing to the vaccination program a possible selection effect (HPV replacement).


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Doenças do Colo do Útero/epidemiologia , Adolescente , Adulto , Coinfecção , DNA Viral/genética , Feminino , Genótipo , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Doenças do Colo do Útero/genética , Doenças do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
20.
Int J Gynecol Pathol ; 29(5): 423-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20736766

RESUMO

We present a unique case of bilateral gonadoblastoma in a 23-year-old patient with Swyer syndrome. The gonadoblastoma on both sides underwent synchronous neoplastic transformation, into a stage I germinoma in the right streak gonad and a highly differentiated Sertoli cell tumor in the left one. The latter was associated with a myriad of microscopic, Sertoli cell implants on the peritoneal surface, which were considered benign as they had a high grade of differentiation, minimal proliferative activity, and an absence of invasion. Most probably, the pathogenesis of this abdominal dissemination was iatrogenic, with implantation occurring mechanically as a result of the multiple laparoscopic biopsies performed on both of the streak gonads 2 months before the abdominal surgery. The pathogenesis of other benign abdominal implants is discussed.


Assuntos
Gonadoblastoma/patologia , Neoplasias Primárias Múltiplas/patologia , Tumor de Células de Sertoli/patologia , Neoplasias Urogenitais/patologia , Disgenesia Gonadal 46 XY/complicações , Disgenesia Gonadal 46 XY/patologia , Gonadoblastoma/complicações , Humanos , Masculino , Neoplasias Primárias Múltiplas/complicações , Peritônio/patologia , Tumor de Células de Sertoli/complicações , Neoplasias Urogenitais/complicações , Adulto Jovem
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