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BACKGROUND: In high-risk patients with cervical incompetence, laparoscopic cerclage is a promising treatment option. However, the procedure exhibits relevant surgical risks. AIMS: The purpose of this study was to evaluate a surgical "needle-free" technique for minimally invasive, laparoscopically placed cervico-isthmic cerclage in high-risk patients. METHODS: This was a retrospective observational study over a 10-year period of pre- and postconceptional cerclage placement. The included patients either experienced previous transvaginal cerclage (TVC) failure or were not eligible for TVC. Laparoscopic transabdominal cerclage using a needle-less mersilene tape was performed via a broad ligament window lateral to the uterine vessels. RESULTS: Laparoscopic transabdominal cerclage was successfully performed in all included women with a median operation time of 62 min. We did not observe any intra- or postoperative complications, particularly no bleeding complications. Nine of 11 women became pregnant and/or carried out a successful pregnancy, respectively. Importantly, we did not observe any cases of miscarriage or mid-trimester loss. Two patients did not conceive; however, their medical histories did include Asherman's syndrome and advanced maternal age. CONCLUSION: Transabdominal laparoscopic "needle-free" cerclage is a safe and effective treatment option for a well-selected group of women at high risk of cervical incompetence. It provides good obstetric results without increasing perioperative morbidity.
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Cerclaje Cervical/métodos , Incompetencia del Cuello del Útero/cirugía , Adulto , Femenino , Humanos , Laparoscopía/métodos , Tempo Operativo , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to investigate the performance of screening for open spina bifida (OSB) integrated into the routine first-trimester screening. METHOD: This is a prospective multicentre study of 4,755 women undergoing first-trimester ultrasound scans over a 4-year period. Measurements of the brainstem (BS) diameter and brainstem-to-occipital-bone (BSOB) distance were performed. The cisterna magna (CM) was measured in the tilted axial view. RESULTS: Pregnancy outcome data were available for 4,658 fetuses included in this study. There were 5 fetuses with OSB, and in all of them, the BS/BSOB ratio and the CM measurements were abnormal. The sensitivity and specificity of a BS/BSOB ratio >1 were 100%. The sensitivity of a CM width <5th centile was 100%, and the specificity was 95.1%. In 4.6% of cases, the BS/BSOB ratio was between the 95th percentile and 1. In 87.1% of these cases, the CM was normal, and 12.9% had a CM below the 5th percentile. CONCLUSION: Screening for OSB is feasible in routine first-trimester scans. The BS/BSOB ratio shows a very good sensitivity and specificity. In cases with near-normal values for the BS/BSOB ratio, the CM width might be helpful for further assessment.
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Endometrial cancer (EC) is the most common gynaecologic tumour in the Western world. Previous studies have implicated an imbalance of oestrogens and progestogens in the development of most ECs, while the role of low-grade tissue inflammation remains largely unexplored. We investigated the impact of tumour necrosis factor alpha (TNFα), a central mediator of inflammation and spermatogenesis-associated protein 2 (SPATA2), a regulator of TNF receptor signalling, on clinical outcomes in EC. We evaluated TNFA and SPATA2 transcript levels in 239 EC patients and 25 non-malignant control tissues. Findings were validated in a cohort of 332 EC patients from The Cancer Genome Atlas (TCGA). Expression of TNFA and SPATA2 was increased in EC when compared with control tissues (P < 0.001). TNFA expression correlated with SPATA2 expression in non-malignant (P = 0.003, rS = 0.568) and EC tissue (P = 0.005, rS = 0.179). High TNFA and SPATA2 expression were associated with poor recurrence-free survival (RFS; P = 0.049 and P = 0.018) and disease-specific (P = 0.034 and P = 0.002) survival. Increased SPATA2 expression was also associated with decreased overall survival (OS; P = 0.013). In multivariate analysis, both TNFA and SPATA2 were predictors of clinical outcome. The impact of SPATA2 on RFS and OS could be validated in the TCGA cohort. Our study demonstrates that ECs exhibit a TNF signature which predicts clinical outcome. These findings indicate that TNF signalling modulates the course of EC, which could be therapeutically utilized in the future.
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Neoplasias Endometriales/diagnóstico , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Conjuntos de Datos como Asunto , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Proteínas/genética , Proteínas/metabolismo , Transducción de Señal , Transcripción Genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Over the years, there has been an increasing interest in the assessment of maternal hemodynamic responses during pregnancy. With the use of both noninvasive devices and/or maternal echocardiography, it has been shown that mothers who have pregnancy complications have altered hemodynamics compared with those who have uncomplicated pregnancies. It also has been suggested that preexisting maternal cardiac changes might drive the development of complications in pregnancy that are associated with impaired placentation. To understand, however, this potential link in complicated pregnancies, it is important to clarify whether placental function is associated with maternal cardiac functional indices in normal pregnancies. OBJECTIVE: To determine whether placental function, perfusion, and fetal weight are associated with maternal cardiac hemodynamic responses at 35-36 weeks of gestation in normal pregnancies. STUDY DESIGN: Prospective screening of women attending Kings' College Hospital for routine hospital visit at 35-37 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure, uterine artery pulsatility index, sonographic estimated fetal weight, and serum placental growth factor and soluble fms-like tyrosine kinase 1. We also performed maternal echocardiogram to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function, including global longitudinal systolic function and left ventricular mass indexed to body surface area. RESULTS: We studied 1386 women. Maternal characteristics were associated with both maternal hemodynamics and functional and structural indices. Uterine artery pulsatility index was associated with left ventricular mass (P=.03) and global longitudinal systolic function (P=.017). There were significant nonlinear associations between placental growth factor and cardiac output and peripheral vascular resistance (P<.001 for both) and between soluble fms-like tyrosine kinase 1 and peripheral vascular resistance (P=.018). Estimated fetal weight was associated with maternal cardiac output (mean increase=0.186, 95% confidence interval, 0.133-0.238, P<.001) and peripheral vascular resistance (mean decrease=-0.164, 95% confidence interval, -0.217 to -0.111, P<.001). No association was noted between placental and fetal parameters and maternal cardiac functional and structural indices. In multivariable analysis, placental growth factor remained strongly associated with maternal cardiac output and peripheral vascular resistance (P=.002 for both) over and above maternal characteristics and estimated fetal weight. Estimated fetal weight was associated with left ventricular mass (0.102, 95% confidence interval, 0.044-0.162, P=.001). CONCLUSION: The results of this study suggest a strong link between maternal hemodynamic responses and fetoplacental needs across the whole spectrum in normal pregnancies. These findings would also indicate that to diagnose maternal cardiac dysfunction in pregnancies complicated by impaired placentation a more extensive echocardiographic assessment might be needed rather than relying on hemodynamics which are strongly associated with fetoplacental indices.
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Presión Arterial/fisiología , Gasto Cardíaco/fisiología , Peso Fetal/fisiología , Factor de Crecimiento Placentario/metabolismo , Arteria Uterina/diagnóstico por imagen , Resistencia Vascular/fisiología , Adulto , Ecocardiografía , Ecocardiografía Doppler , Femenino , Edad Gestacional , Ventrículos Cardíacos/diagnóstico por imagen , Hemodinámica , Humanos , Placenta/diagnóstico por imagen , Placenta/fisiología , Embarazo , Tercer Trimestre del Embarazo , Flujo Pulsátil , Ultrasonografía Doppler , Ultrasonografía Prenatal , Arteria Uterina/fisiología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Función Ventricular/fisiologíaRESUMEN
INTRODUCTION: Poor genital self-image is a common phenomenon leading to an increasing interest in female genital surgery over the last years. AIM: The aim was to correlate objective measurements of the labia minora with the individual subjective perception of the labial size. METHODS: In a cross-sectional study with 200 premenopausal women (median age 33.5 years) presenting for gynecological issues other than vulvar diseases, labial width and length were measured, and psychological and physical complaints were assessed. Multivariable logistic regression analyses were performed to identify factors that influenced self-reported complaints and subjective perception of labia size. MAIN OUTCOME MEASURE: The main outcome measure was labial appearance (width and length in mm, color), subjective perception of the labial size, and complaints. RESULTS: The median width of the labia minora was 19.0 mm (interquartile range = 12.6-27.5), and the median length was 35.5 mm (interquartile range = 27.8-48.9). The objective size of the labia was significantly associated with womens' subjective perception of the labial size, but not with self-reported complaints. Nearly one-third of the women (n = 53, 27%) reported complaints of their labia minora which were mainly physical (n = 41, 77%) or a combination of physical and psychological problems (n = 9, 17%), while only a small group reported experiencing only psychological complaints (n = 3, 6%). Predictors of complaints were previous cosmetic surgery and the subjective perception of the labia size. The latter was significantly associated with discomfort during intercourse and when visiting a sauna and by labia minora that protruded over the labia majora. CLINICAL IMPLICATIONS: Cutoff values to define labial hypertrophy and to justify labial reduction surgery should be avoided. STRENGTH & LIMITATIONS: This is a large sample of labial measurements in women not seeking labiaplasty. Standardized and validated questions regarding quality of life, sexuality, and body image could have provided more insight into psychological aspects. CONCLUSION: These data demonstrate the variability of labial anatomy and its perception. Widschwendter A, Riedl D, Freidhager K, et al. Perception of Labial Size and Objective Measurements-Is There a Correlation? A Cross-Sectional Study in a Cohort Not Seeking Labiaplasty. J Sex Med 2020;17:461-469.
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Imagen Corporal , Calidad de Vida , Vulva/anatomía & histología , Adolescente , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Hipertrofia/cirugía , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Vulva/cirugía , Adulto JovenRESUMEN
Recently L1CAM was shown to be a promising biomarker for early-stage endometrial carcinoma (EC). As L1CAM expression was found to be related to serous ECs and areas of serous differentiation in endometrioid carcinomas, there is evidence that L1CAM-positive cancers more likely resemble type II carcinomas. Furthermore, expression of growth factor receptor HER2 has been found to be closely associated with serous ECs. We conducted a retrospective study on 142 patients in FIGO stages I and II with endometrioid EC and analyzed L1CAM and HER2 expression by double-staining immunohistochemistry. The association between these 2 transmembrane molecules and their impact on patient outcome was analyzed. Both L1CAM and HER2 showed a significant association with recurrent disease (P<0.001 and P=0.007, respectively). We found 39 (27%) L1CAM-positive cases and 17 (12%) HER2-positive cases. About 6.3% of cases were positive for both biomarkers. Survival of L1CAM-positive patients showed a significant difference between HER2-positive and HER2-negative patients (P=0.019) regarding disease-free survival. The most unfavorable disease-free survival and overall survival was found for patients with L1CAM and HER2 double-positive tumors (P<0.001). Double immunostaining revealed a mutually exclusive staining pattern for L1CAM and HER2 expression on the level of tumor cells. In early endometrioid uterine carcinoma, an additional expression of HER2 to L1CAM seems to further worsen disease-free survival and overall survival. In terms of "personalized medicine," detection of these molecules in endometrioid ECs may open new avenues for targeted therapies with the newly available anti-HER2 drugs and/or with the upcoming humanized anti-L1CAM antibodies.
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Carcinoma Endometrioide/química , Neoplasias Endometriales/química , Molécula L1 de Adhesión de Célula Nerviosa/análisis , Receptor ErbB-2/análisis , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes. METHODS: One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique. RESULTS: Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05). CONCLUSION: We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer.
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Metilación de ADN/genética , MicroARNs/metabolismo , Neoplasias Ováricas/metabolismo , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Silenciador del Gen , Humanos , MicroARNs/análisis , MicroARNs/genética , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Ovario/química , Ovario/metabolismo , Regiones Promotoras Genéticas/genética , Análisis de Supervivencia , Análisis de Matrices TisularesRESUMEN
OBJECTIVE: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above. METHODS: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score. RESULTS: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups. CONCLUSION: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.
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Neoplasias de la Mama , Crioterapia , Neoplasias de los Genitales Femeninos , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Enfermedades del Sistema Nervioso Periférico/terapia , Estudios Prospectivos , Crioterapia/métodos , Persona de Mediana Edad , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Adulto , Calidad de Vida , Antineoplásicos/efectos adversos , Resultado del Tratamiento , Taxoides/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Hidrocarburos Aromáticos con Puentes/efectos adversos , Hidrocarburos Aromáticos con Puentes/uso terapéuticoRESUMEN
OBJECTIVE: To create a reference curve for postvoid residual volume (PVRV) in asymptomatic postpartum women who are at low risk of developing postpartum urinary retention (PUR), a well-known complication in the immediate postpartum period. METHODS: This is a prospective observational study measuring PVRV after uncomplicated vaginal delivery. PVRV was assessed by transabdominal ultrasound using a portable ultrasound scanner within the first 26 h after delivery (PVRV 1) and on the day of discharge (day 2 or 3 postpartum) (PVRV 2). A PVRV of 150 mL or more was defined as the cut-off value for covert PUR. RESULTS: The prevalence of covert PUR was 7.1%. Primiparity, duration of second stage, and obstetric injury were correlated with higher PVRV 1. The median PVRV 1 was 21 mL and PVRV 2 was 11 mL. The subgroup of nulliparous women had a significantly higher PVRV 1 compared with multiparous women. At discharge, the majority (99.1%) of women had a PVRV of less than 150 mL. CONCLUSION: Asymptomatic women were at low risk of developing PUR. However, women with a prolonged second stage may benefit from a routine postpartum assessment. Our results allow for a better understanding of PVRV in the early postpartum period.
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Vejiga Urinaria , Retención Urinaria , Embarazo , Femenino , Humanos , Volumen Residual , Parto Obstétrico/efectos adversos , Retención Urinaria/diagnóstico por imagen , Retención Urinaria/epidemiología , Retención Urinaria/etiología , Periodo Posparto , Factores de RiesgoRESUMEN
Purpose: Alopecia has been reported a distressing side-effect of chemotherapy for breast cancer patients (BCP) that is highly relevant for quality of life during treatment. For the prevention of chemotherapy-induced alopecia, scalp cooling (SC) has been reported to be an effective and safe intervention. However, data on the patient's perspective on effectiveness and applicability of SC in a clinical routine setting are scarce. In this comparative study, we aimed at a longitudinal assessment of patient-reported outcome (PRO) data on the effect of SC on alopecia and its effect on symptoms and functional health when applied in clinical routine in BCP receiving taxane or anthracycline-based chemotherapy. Patients and Methods: Study participants were allocated either to the intervention group receiving SC or to the control group based on patient preference (non-randomized study). All patients completed PRO-measures on hair preservation (EORTC Item Library items on hair loss), symptom and functional health measures (EORTC QLQ-C30 and -BR23) and the Body Image Scale (BIS). Outcomes were assessed at chemotherapy start (baseline), mid-chemotherapy, last chemotherapy cycle, 3 months follow-up and 6-9 months follow-up. Results: Overall, we included 113 patients: 75 patients underwent SC (mean age = 51.3 years, 52.7% premenopausal); 38 patients standard care (mean age = 55.6 years, 39.5% premenopausal). A total of 53 patients (70.7%) discontinued SC, with 39 patients (73.5%) stating alopecia as the primary reason. On average, BCP stayed on treatment with the cooling cap for 40.2% of the duration of their chemotherapy (SD 25.3%). In an intention-to-treat analysis, we found no difference between the SC group and the control group with regard to their patient-reported hair loss (p=0.831) across the observation period, overall QOL (p=0.627), emotional functioning (p=0.737), social functioning (p=0.635) and body image (p=0.463) did not differ between groups. Conclusion: We found a high rate of SC-decliners and no beneficial effects of SC for patient-reported hair loss, symptoms and functional health. The efficacy and tolerability of SC applied in a clinical routine setting hence appeared to be limited. The further determination and up-front definition of criteria prognostic for effectiveness of SC may be helpful to identify patient subgroups that may experience a treatment benefit.
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The present article describes the facile one-step hydrothermal synthesis of single-crystalline ZnMoO4/AlPO4-5 nanorod composites. The physicochemical properties of the synthesized materials, such as structure, morphology, and bandgap, were determined using techniques such as X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), N2 adsorption-desorption isotherms, X-ray photoelectron (XPS), ultraviolet-visible (UV-vis), and photoluminescence (PL). The XRD pattern of synthesized ZnMoO4/AlPO4-5 verifies the synthesis of nanocomposites. Diffuse UV-vis spectra reveal that ZnMoO4/AlPO4-5 nanorod composites exhibit an indirect semiconductor with an optical bandgap between 3.15 and 3.7 eV depending on Mo : Zn ratio. In comparison to pure AlPO4-5, ZnMoO4/AlPO4-5 nanocrystal composites showed significantly higher photocatalytic activity for the degradation of para-nitrophenol (PNP, 0.04 g l-1), with 14, 99, 70, and 54% for AlPO4-5, Mo : Zn (2)/AlPO4-5, Mo : Zn (4)/AlPO4-5, and Mo : Zn (6)/AlPO4-5, respectively. This result might be attributed to the composite's efficient charge transfer and optimized electron-hole pair recombination. The supercapacitive ability of ZnMoO4/AlPO4-5 nanorod composites was also investigated in this work. For the prepared electrodes using AlPO4-5, Mo : Zn (2)/AlPO4-5, Mo : Zn (4)/AlPO4-5, and Mo : Zn (6)/AlPO4-5, the capacitance values were 400, 725, 450, and 481.25 F g-1, respectively, at a current density of 0.5 A g-1. This study shows that ZnMoO4/AlPO4-5 nanorod composites are a potential visible-light-responsive photocatalyst. The electrochemical results further demonstrate the high capacitance of ZnMoO4/AlPO4-5 nanorod composites toward energy-storage applications.
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Facile solvothermal techniques were used to manufacture ZnS/1T-2H MoS2 nanocomposite (ZMS) with outstanding adsorption-photocatalytic activity. The formed catalyst was characterized by different tools; XRD, HR-TEM, EDX, FTIR, Raman, N2adsorprion/desorption, Zeta potential, PL,and XPS. The analysis provided the formation on mixed phase of metallic 1Tand 2H phases. ZMS has a high porosity and large specific surface area, and it has a high synergistic adsorption-photocatalytic degradation effect for MB, with a removal efficiency of ≈100% in 45 minutes under visible light irradiation. The extraordinary MB removal efficiency of ZMS was attributed not only to the high specific surface area (49.15 m2/g) and precious reactive sites generated by ZMS, but also to the formation of 1T and 2H phases if compared to pristine MoS2 (MS). The best adsorption affinity was induced by the existance of 1T phase. The remarkably enhanced photocatalytic activity of ZMS nanocomposite can be ascribed to the 2D heterostructure which enhances the adsorption for pollutants, provides abundant reaction active sites, extends the photoresponse to visible light region.
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Endometrial carcinomas (ECs) are classified into type 1 (less aggressive) and type 2 (aggressive) tumours that differ in genetic alterations. So far, reliable immunohistochemical markers that can identify patients with high risk for recurrence are rare. We have defined the expression of L1 cell adhesion molecule (L1CAM), a biomarker previously identified for EC, and compared its expression to oestrogen receptor (ER)/progesterone receptor (PR) and E-cadherin. We found that L1CAM was absent in normal endometrium and the vast majority of endometrioid ECs (type 1) but was strongly expressed in serous and clear-cell ECs, considered as type 2. 78/272 cases were identified as L1CAM-positive endometrioid ECs that were correlated with a poor prognosis. Strikingly, we observed an inverse relationship between L1CAM and ER/PR/E-cadherin expression in all ECs. In mixed ECs, composed of endometrioid (L1CAM(-) ER/PR(+) E-cadherin(+)) and clear-cell/serous (L1CAM(+) ER/PR(-) E-cadherin(-)), both phenotypes were co-expressed. In some of these cases L1CAM was up-regulated at the leading edge of the tumour, where ER/PR and E-cadherin expression were selectively lost. In EC cell lines treated with the epithelial-mesenchymal transition (EMT) inducer TGFbeta1, L1CAM and vimentin were strongly up-regulated, while E-cadherin expression was reduced. The treatment also resulted in an increased expression of the EMT transcription factor Slug and an enhanced cell invasion. Depletion of Slug by siRNA knockdown prevented both L1CAM up-regulation and enhanced cell invasion. According to our analysis, we suggest that L1CAM is a novel marker for EMT in ECs and that L1CAM-typing could identify endometrioid ECs that have type 2-like features and are at high risk for recurrence.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Endometriales/metabolismo , Proteínas de Neoplasias/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/biosíntesis , Regulación hacia Arriba , Biomarcadores de Tumor/genética , Cadherinas/metabolismo , Neoplasias Endometriales/patología , Endometrio/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Técnicas para Inmunoenzimas , Invasividad Neoplásica/fisiopatología , Molécula L1 de Adhesión de Célula Nerviosa/genética , Pronóstico , ARN Neoplásico/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: The introduction of cell-free DNA into clinical practice has changed the screening approach. Healthcare professionals and future parents tend to overestimate NIPT (noninvasive prenatal testing) capabilities despite its relatively high cost and limited information. OBJECTIVE: In this review, our aim was to survey how various countries have introduced contingent screening models and to discuss the advantages and disadvantages of the combined screening test and the use of NIPT. DATA SOURCE: The Web of Science, PubMed database and institutional websites were searched for information regarding screening approaches and the implementation in different countries. RESULTS: There are nine countries and regions that have already approved contingent screening test, while others (e.g. Australia) are discussing the implementation of contingent screening versus universal use of NIPT. There are several recent meta-analyses debating whether to use NIPT for universal screening for trisomies and other fetal conditions. CONCLUSIONS: NIPT is a reasonable option as an advanced screening test for trisomy 21, 18 and 13 only. Introducing screening by NIPT instead of a first-trimester screening will cause the loss of other valuable information including accurate dating of pregnancy, diagnosing major structural fetal abnormalities and multiple pregnancies at an early gestational age. Additionally, the opportunity to screen for early preeclampsia will be lost. Currently, the price for NIPT is still high adding extra strain on publicly funded health systems.
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Ácidos Nucleicos Libres de Células , Diagnóstico Prenatal , Biomarcadores , Síndrome de Down/diagnóstico , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Trisomía/diagnósticoAsunto(s)
Antineoplásicos , Neoplasias de la Mama , Alopecia/inducido químicamente , Alopecia/prevención & control , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Cabello , Humanos , Estudios Prospectivos , Cuero Cabelludo , Taxoides/uso terapéuticoRESUMEN
BACKGROUND: High expression of L1 cell adhesion molecules (L1CAM) has been repeatedly shown to be associated with aggressive disease behavior, which translates in poor clinical outcome in various cancer entities. However, in ovarian cancer results based either on immunohistochemistry or cytosolic protein quantifications remained conflicting regarding clinical behavior. In the present work we assessed L1CAM expression on the transcriptome level with the highly sensitive quantitative real-time PCR (qRT-PCR) to define its relevance in ovarian cancer biology. RESULTS: There was a significant difference in L1CAM high and low mRNA expressing cancers with regard to disease-free (p=0.002) and overall survival (p=0.008). L1CAM proofed to be an independent predictor for disease progression (HR 1.8, p=0.01) and overall survival (HR 1.6, p=0.04). Furthermore, a significant positive correlation between the level of L1CAM and the grade of tumor differentiation (p=0.04), the FIGO stage (p=0.025) as well as the histological subtype (p= 0.002) was found. METHODS: This study included fresh frozen tissue samples of 138 patients with FIGO I-IV stage ovarian cancer. L1CAM mRNA expression was determined using qRT-PCR. In the calculations special attention was put on the various histological subtypes. In survival analysis median L1CAM mRNA expression obtained in the entire cohort of ovarian cancer samples was used as a cut-off to distinguish between high and low L1CAM mRNA expression. CONCLUSIONS: L1CAM mRNA expression appears to play a substantial role in the pathophysiology of ovarian cancer that is translated into poor clinical outcome. Additionally humanized L1CAM antibodies, which can serve as potential future treatment options are under testing.