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1.
Int J Gynaecol Obstet ; 161(3): 820-826, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36637220

RESUMO

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.


Assuntos
Bexiga Urinária , Retenção Urinária , Gravidez , Feminino , Humanos , Volume Residual , Parto Obstétrico/efeitos adversos , Retenção Urinária/diagnóstico por imagem , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Período Pós-Parto , Fatores de Risco
2.
J Cancer ; 11(6): 1446-1456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047551

RESUMO

The tumor suppressor miR-34 family is transcriptionally induced by p53. Clinical significance of the various miR-34 family members has not been studied in ovarian cancer. In 228 ovarian cancers and in 19 non-neoplastic fallopian tube samples we analysed miR-34 a/b/c expression in relation to clinicopathological characteristics and clinical outcome. We found significantly lower levels of miR-34 a/b/c in ovarian cancers as compared to control-tissues (P=0.002, P<0.001, P<0.001, respectively). Expression of miR-34 b/c revealed an inverse correlation with BRCA1/2 mRNA-expression (BRCA1: miR34 b/c P=0.002 each; BRCA2: miR-34 b/c P<0.001 each), the same was true for miR-34a and BRCA2 mRNA-expression (P<0.001). The miR-34 family expression was found to be significantly lower in type 2 in comparison to type 1 cancers (P<0.001) and in TP53-mutated compared with TP53-wild-type ovarian cancers (P<0.001, P=0.002, P=0.004, respectively). When low grade serous ovarian cancers were compared with high grade serous cancers the respective miR-34 a/b/c expression was 2.6-, 40.8- and 32.3-fold higher. The expression of each of the miR-34 family members was revealed to be of independent prognostic relevance regarding progression free survival (PFS); miR-34a: HR 0.6, P=0.033; miR-34b: HR 0.2, P=0.001 and miR-34c: HR 0.3, P=0.002, respectively). For overall survival (OS) independency of the prognostic value was confined to miR-34b (HR 0.4, P=0.016) and miR-34c (HR 0.6, P=0.049). The independency of the prognostic value of our identified thresholds was confirmed for PFS for miR-34c in a publicly available dataset (NCBI Gene Expression Omnibus GSE73582). Our findings suggest that downregulation of miR-34 family is a crucial part in ovarian cancer development. Low miR-34 levels are linked to a worse overall survival and progression free survival and may indicate a more aggressive disease.

3.
Tumour Biol ; 41(2): 1010428319830002, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813866

RESUMO

The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. DNA methylation of the NOX4 promoter was determined by means of MethyLight PCR. Data were correlated with clinicopathological parameters and analyzed in the context of diabetes and body mass index. In the normal endometrium, NOX4 microRNA expression was significantly higher in the secretory transformed compared with proliferative endometrium ( p = 0.008). In endometrial cancer specimens, NOX4 expression did not differ between diabetic and non-diabetic patients, but was the highest in patients with a body mass index ≤ 26 ( p = 0.037). The lowest NOX4 expression was found in carcinosarcomas ( p = 0.007). High NOX4 expression predicted poorer clinical outcome with regard to overall survival, especially in non-diabetic patients and those with a body mass index > 20. Independent prognostic significance of NOX4 transcripts was retained in type I endometrial cancer and was the most meaningful in patients with a body mass index > 20. No prognostic impact was shown for NOX4 promoter methylation in endometrial cancer. For the first time, we demonstrate that NOX4 plays a considerable role in the cycle-dependent changes in the normal endometrium and in the biology of endometrial cancer.


Assuntos
Neoplasias do Endométrio/enzimologia , Endométrio/enzimologia , NADPH Oxidase 4/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , NADPH Oxidase 4/análise , NADPH Oxidase 4/genética , RNA Mensageiro/análise , Transcriptoma
4.
Cancer Sci ; 110(3): 1117-1126, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30697874

RESUMO

Inflammation plays a crucial role in the pathogenesis of cancer with tumor necrosis factor-α (TNF-α) as a key mediator. Recently, spermatogenesis-associated protein 2 (SPATA2) was identified as a TNF receptor modulator which is required for TNF-induced inflammation and apoptosis. The available data on TNF-α in ovarian cancer (OC) are inconsistent, and SPATA2 is completely uncharacterized in tumorigenesis. We analyzed expression of SPATA2 and TNFA by quantitative real-time polymerase chain reaction in tissues of 171 patients with low-grade serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared with 28 non-malignant control tissues. We stimulated OC cells (OVCAR3) with pro-inflammatory (TNF-α, interleukin [IL]-1ß) and mitogenic stimuli (IL-6, lysophosphatidic acid) to establish a direct effect between inflammatory signaling and SPATA2. Pro-inflammatory, but not mitogenic stimuli, potently induced SPATA2 expression in OC cells. Expression of TNFA and SPATA2 was higher in OC compared with control tissues (P = 0.010 and P = 0.001, respectively) and correlated with each other (P = 0.034, rs  = 0.198). When compared with grade 1 cancers, SPATA2 was expressed higher in grade 2 and 3 tumors (P = 0.011) as well as in HGSOC compared with LGSOC (P = 0.024). Multivariate survival analyses revealed that OC with high SPATA2 expression were associated with reduced progression-free survival (P = 0.048) and overall survival (P < 0.001). In conclusion, SPATA2 expression is regulated by TNF-α and IL-1ß and is found to independently affect clinical outcome in OC patients. These data implicate a role of SPATA2 in tumorigenesis which warrants further investigation in gynecological malignancies.


Assuntos
Neoplasias Ovarianas/metabolismo , Proteínas/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Espermatogênese/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/metabolismo , Feminino , Humanos , Interleucina-1beta/metabolismo , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
5.
Br J Cancer ; 119(6): 683-692, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30111871

RESUMO

BACKGROUND: Mutations in BRCA1 and BRCA2 are associated with better survival in ovarian cancer (OC) patients due to a better response to platinum-based chemotherapy. However, the impact of the BRCA1/2 mRNA-expression is not well characterized in OC. PATIENTS AND METHODS: We investigated BRCA1/2 mRNA-expression in 12 non-neoplastic fallopian tubes and 201 epithelial OCs in relation to their clinical characteristics. RESULTS: We found higher BRCA1/2 mRNA-expression in OCs compared to controls (P = 0.011, P < 0.001, respectively). BRCA1 mutated OCs exhibited lower BRCA1 (P = 0.014) but higher BRCA2 mRNA-expression (P = 0.001). Low BRCA1-expression was associated with favorable overall survival (OS) (P = 0.012) and low BRCA2-expression with better progression-free survival (PFS) and OS (P = 0.004, P = 0.001, respectively). A subgroup-analysis showed that this effect was confined only to the BRCA1-wildtype cancers. Cox-regression confirmed the prognostic significance of BRCA1-expression for OS (P = 0.028). Independency of the prognostic value of BRCA2-expression for PFS (P = 0.045) and OS (P = 0.015) was restricted to high-grade serous OCs. Fully platinum-sensitivity was characterized by lower BRCA1/2 mRNA-expression in BRCA1-wildtype cancers in comparison to platinum-refractory OC. CONCLUSION: Our findings may reflect higher platinum-sensitivity due to reduced capacity of DNA damage repair in tissues with low BRCA1/2-expression. In this context, especially in BRCA-wildtype cancers both parameters could also be potential predictors for PARP-sensitivity.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/cirurgia , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Platina/uso terapêutico , Prognóstico , Resultado do Tratamento
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