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1.
Arch Gynecol Obstet ; 309(4): 1509-1514, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37737883

RESUMEN

PURPOSE: In the following work, we investigated the effect of matcha green tea extract (MTE) on MCF-7 breast cancer cell viability and estrogen receptor-beta expression (ERß). METHODS: MCF-7 cells were stimulated with MTE at concentrations of 5 and 10 µg/ml. Cell viability was assessed using a water-soluble tetrazolium assay (WST-1 assay) after an incubation time of 72 h. ERß was quantified at gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. RESULTS: The WST-1 test showed a significant inhibition of viability in MFC-7 cells after 72 h at 10 µg/ml. The WB demonstrated a significant quantitative decrease of ERß at protein level with MTE concentrations of 10 µg/ml. In contrast, the PCR did not result in significant downregulation of ERß. CONCLUSION: MTE decreases the cell viability of MCF-7 cells and furthermore leads to a decrease of ERß at protein level.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Células MCF-7 , Receptor beta de Estrógeno/genética , Supervivencia Celular , Antioxidantes/farmacología , , Receptor alfa de Estrógeno , Línea Celular Tumoral , Proliferación Celular
2.
Int J Gynecol Cancer ; 32(5): 662-668, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35185017

RESUMEN

OBJECTIVE: Because mucinous carcinomas are rare tumors that affect several organ sites and are known to originate from different tissues, leading to frequent misdiagnoses, the objective was to characterize the differences between primary mucinous tumors of the ovary and metastatic mucinous cancer to the ovary by studying the expression pattern of several candidate biomarkers. METHODS: Tissue samples of mucinous histology were obtained between 1985 and 2015. Individual ovary and colon tissue samples were analyzed, including standard (PAX8, CK20, CK7, CDX2, SATB2, estrogen/progesterone) and new (MUC1, MUC5AC) biomarkers, which were then scored for immunoreactivity semi-quantitatively. RESULTS: The study cohort included 98 mucinous tumor samples, including benign mucinous cystadenoma (n=24), mucinous borderline tumors (n=24), mucinous carcinomas (n=40), and metastatic mucinous ovarian carcinomas (n=10). A strong positive correlation was found between PAX8 scoring (p=0.003), CK7 scoring (p=0.0001), and MUC1 scoring (p=0.001) in primary mucinous ovarian cancer. Tumors of increasing invasiveness were analyzed and a significant decrease in the scoring of MUC5AC (p=0.001) was observed, with a stronger expression in adenomas (87%) and borderline tumors (75%), and a lower expression in mucinous cancers (42%). Patients survived significantly longer when their tumors expressed high PAX8 and showed an expansile invasion pattern (p=0.005 and p=0.015, respectively) compared with patients with PAX8-negative tumors and destructive invasion pattern. CONCLUSION: The study data support the diagnostic value of MUC1 as a new biomarker to differentiate between primary and metastatic mucinous ovarian cancer. In addition, the tumor growth pattern along with the PAX8 immunophenotype might represent potential prognostic biomarkers for primary mucinous ovarian carcinomas.


Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias Ováricas , Biomarcadores , Carcinoma Epitelial de Ovario , Femenino , Humanos , Mucina 5AC , Mucina-1 , Factor de Transcripción PAX8
3.
Arch Gynecol Obstet ; 305(3): 713-718, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34491417

RESUMEN

PURPOSE: With the beginning of 2021, the world has been suffering from the COVID-19 pandemic for more than 1 year. More and more, we are able to evaluate side effects of the pandemic in the healthcare sector. A negative impact on cancer diagnoses is one of them. Careful observation of trends in an academic gyneco-oncological context appears important to identify potential negative developments. METHODS: We analyzed the case number of gynecologic and breast cancer diagnoses in the period from January to June 2020 compared to 2019 and during the period of the first general German lockdown (March 22nd until May 5th 2020). Patients were characterized by age, tumor type, FIGO or TNM stage and presence of symptoms at initial hospital presentation. RESULTS: The frequency of newly diagnosed gynecologic and breast cancer cases from beginning of January until end of June changed by - 10% and by - 12% during the lockdown in 2020 compared to 2019. In both periods, reduction of breast cancer cases was relatively larger than decrease of gynecologic cancers. Moreover, median patient age decreased. For the first half of 2020, we found a shift towards higher tumor stages (N+/M1 or FIGO III-IV). During the lockdown period, the appearance of tumor-associated symptoms at diagnosis increased by about 12%. CONCLUSION: This analysis illustrates the anticipated general decrease in diagnoses of primary cancers during the lockdown periods in 2020 due to COVID-19 pandemic for gynecologic and breast cancer cases.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Femenino , Alemania/epidemiología , Humanos , Pandemias/prevención & control , SARS-CoV-2
4.
Arch Gynecol Obstet ; 306(2): 451-459, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35079875

RESUMEN

PURPOSE: In the following work, we investigated the nuclear peroxisome proliferator-activated receptor gamma (PPARγ)-dependent proliferation behavior of breast cancer cells after stimulation with matcha green tea extract (MTE). METHODS: T47D cells were stimulated with MTE at concentrations of 5, 10 and 50 µg/ml. Cell viability was assessed using a WST-1 assay after an incubation time of 72 h. PPARγ expression was quantified at the gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. RESULTS: The WST-1 test showed a significant inhibition of viability in T47D cells after 72 h at 5, 10 and 50 µg/ml. The PCR showed an overexpression of PPARγ in T47D cells in all concentrations. At the concentration of 50 µg/ml the expression was significantly increased (p < 0.05). The WB demonstrated a significant quantitative increase of PPARγ at protein level with MTE concentrations of 10 and 50 µg/ml. In addition, there was a negative correlation between the overexpression of PPAR γ and the inhibition of proliferation. CONCLUSION: MTE decreases the cell viability of T47D cells and furthermore leads to an overexpression of PPARγ on protein and mRNA level.


Asunto(s)
Neoplasias de la Mama , PPAR gamma , Extractos Vegetales , Neoplasias de la Mama/tratamiento farmacológico , Supervivencia Celular , Femenino , Humanos , PPAR gamma/genética , Extractos Vegetales/farmacología , ARN Mensajero/genética ,
5.
Arch Gynecol Obstet ; 304(5): 1307-1314, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33861372

RESUMEN

PURPOSE: Enzymes with epigenetic functions play an essential part in development of cancer. However, the significance of epigenetic changes in cervical carcinoma as a prognostic factor has not been fully investigated. Nuclear receptor corepressor (NCoR) presents itself as a potentially important element for epigenetic modification and as a potential prognostic aspect in cervical cancer. METHODS: By immunohistochemical staining of 250 tumor samples, the expression strength of NCoR was measured and evaluated by immunoreactive score (IRS) in the nucleus and cytoplasm. RESULTS: A low expression of NCoR in our patients was a disadvantage in overall survival. Expression of NCoR was negatively correlated with viral oncoprotein E6, acetylated histone H3 acetyl K9 and FIGO status, and positively correlated to p53. CONCLUSIONS: Our study has identified epigenetic modification of tumor cells thus seems to be of relevance in cervical cancer as well for diagnosis, as a marker or as a potential therapeutic target in patients with advanced cervical carcinoma.


Asunto(s)
Proteínas Oncogénicas Virales , Neoplasias del Cuello Uterino , Proteínas Co-Represoras , Epigénesis Genética , Femenino , Humanos , Pronóstico , Neoplasias del Cuello Uterino/genética
6.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33671013

RESUMEN

Cervical cancer is primarily caused by the infection of high-risk human papillomavirus (hrHPV). Moreover, tumor immune microenvironment plays a significant role in the tumorigenesis of cervical cancer. Therefore, it is necessary to comprehensively identify predictive biomarkers from immunogenomics associated with cervical cancer prognosis. The Cancer Genome Atlas (TCGA) public database has stored abundant sequencing or microarray data, and clinical data, offering a feasible and reliable approach for this study. In the present study, gene profile and clinical data were downloaded from TCGA, and the Immunology Database and Analysis Portal (ImmPort) database. Wilcoxon-test was used to compare the difference in gene expression. Univariate analysis was adopted to identify immune-related genes (IRGs) and transcription factors (TFs) correlated with survival. A prognostic prediction model was established by multivariate cox analysis. The regulatory network was constructed and visualized by correlation analysis and Cytoscape, respectively. Gene functional enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 204 differentially expressed IRGs were identified, and 22 of them were significantly associated with the survival of cervical cancer. These 22 IRGs were actively involved in the JAK-STAT pathway. A prognostic model based on 10 IRGs (APOD, TFRC, GRN, CSK, HDAC1, NFATC4, BMP6, IL17RD, IL3RA, and LEPR) performed moderately and steadily in squamous cell carcinoma (SCC) patients with FIGO stage I, regardless of the age and grade. Taken together, a risk score model consisting of 10 novel genes capable of predicting survival in SCC patients was identified. Moreover, the regulatory network of IRGs associated with survival (SIRGs) and their TFs provided potential molecular targets.


Asunto(s)
Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Microambiente Tumoral/inmunología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Anciano , Biomarcadores de Tumor/inmunología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología
7.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33478016

RESUMEN

The aim of this study was to assess the prognostic value of the steroid hormone receptor expression, counting the retinoid X receptor (RXR) and thyroid hormone receptors (THRs), on the two different breast cancer (BC) entities: multifocal/multicentric versus unifocal. The overall and disease-free survival were considered as the prognosis determining aspects and analyzed by uni- and multi-variate analysis. Furthermore, histopathological grading and TNM staging (T = tumor size, N = lymph node involvement, M = distant metastasis) were examined in relation to RXR and THRs expression. A retrospective statistical analysis was carried out on survival-related events in a series of 319 sporadic BC patients treated at the Department of Gynecology and Obstetrics at the Ludwig-Maximillian's University in Munich between 2000 and 2002. The expression of RXR and THRs, including its two major isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed to have a significant correlation for both BC entities in regard to survival analysis. Patients with multifocal/multicentric BC were exposed to a significantly worse disease-free survival (DFS) when expressing RXR. Patients with unifocal BC showed a significantly worse DFS when expressing THRα1. In contrast, a statistically significant positive association between THRα2 expression and enhanced DFS in multifocal/multicentric BC was shown. Especially the RXR expression in multifocal/multicentric BC was found to play a remarkably contradictory role for BC prognosis. The findings imply the need for a critical review of possible molecular therapies targeting steroid hormone receptors in BC treatment. Our results strengthen the need to further investigate the behavior of the nuclear receptor family, especially in relation to BC focality.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Receptores X Retinoide/fisiología , Receptores alfa de Hormona Tiroidea/fisiología , Adulto , Anciano , Biomarcadores de Tumor/fisiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Alemania/epidemiología , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Carga Tumoral
8.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-34445181

RESUMEN

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman's rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.


Asunto(s)
Carcinoma Epitelial de Ovario/patología , Neoplasias Ováricas/patología , Receptores Acoplados a Proteínas G/análisis , Anciano , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/metabolismo , Pronóstico , Receptores Acoplados a Proteínas G/metabolismo , Tironinas/metabolismo
9.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33334070

RESUMEN

A coherence between thyroid dysfunction and breast cancer incidence exists. Thyroid hormone metabolites bind to TAAR1 (trace amine-associated receptor 1) and through that modulate the serotonergic and dopaminergic system. Catecholamines themselves are synthesized by the L-dopa decarboxylase (DDC). The aim of our study was to analyze the influence of catecholamines on the DDC expression in primary breast cancer patients and the role of DDC concerning overall survival (OS). DDC expression was analyzed by immunohistochemistry. The effect of epinephrine on the expression of DDC and the Gi- protein was analyzed on the protein level via Western blot. A viability assay was performed to test the metabolic cell viability. The overexpression of DDC in the primary tumor was associated with longer OS (p = 0.03). Stimulation with epinephrine induced the downregulation of DDC (p = 0.038) and significantly increased viability in T47D cells (p = 0.028). In contrast, epinephrine induced an upregulation of DDC and decreased the proliferation of MCF7 cells (p = 0.028). Epinephrine led to an upregulation of Gi protein expression in MCF7 cells (p = 0.008). DDC is a positive prognostic factor for OS in breast cancer patients, and it is regulated through epinephrine differently in MCF7 and T47D. DDC may represent a novel target for the treatment of breast cancer, especially concerning its interaction with epinephrine.


Asunto(s)
Descarboxilasas de Aminoácido-L-Aromático/metabolismo , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Epinefrina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Descarboxilasas de Aminoácido-L-Aromático/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Pronóstico , Receptores Acoplados a Proteínas G/genética , Carga Tumoral
10.
Int J Mol Sci ; 21(23)2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33271935

RESUMEN

(1) Background: Biomarkers might play a significant role in predicting the clinical outcomes of patients with ovarian cancer. By analyzing lipid metabolism genes, future perspectives may be uncovered; (2) Methods: RNA-seq data for serous ovarian cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The non-negative matrix factorization package in programming language R was used to classify molecular subtypes of lipid metabolism genes and the limma package in R was performed for functional enrichment analysis. Through lasso regression, we constructed a multi-gene prognosis model; (3) Results: Two molecular subtypes were obtained and an 11-gene signature was constructed (PI3, RGS, ADORA3, CH25H, CCDC80, PTGER3, MATK, KLRB1, CCL19, CXCL9 and CXCL10). Our prognostic model shows a good independent prognostic ability in ovarian cancer. In a nomogram, the predictive efficiency was notably superior to that of traditional clinical features. Related to known models in ovarian cancer with a comparable amount of genes, ours has the highest concordance index; (4) Conclusions: We propose an 11-gene signature prognosis prediction model based on lipid metabolism genes in serous ovarian cancer.


Asunto(s)
Biomarcadores de Tumor , Cistadenocarcinoma Seroso/etiología , Cistadenocarcinoma Seroso/metabolismo , Metabolismo de los Lípidos , Neoplasias Ováricas/etiología , Neoplasias Ováricas/metabolismo , Biología Computacional , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Bases de Datos Genéticas , Susceptibilidad a Enfermedades , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Pronóstico , Curva ROC , Transcriptoma
11.
J Obstet Gynaecol Res ; 45(5): 1066-1070, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30854740

RESUMEN

Serious hepatic complications, although rare, are one of the leading causes of maternofetal morbidity and mortality in hypertensive pregnancy disorders. A 28-year-old primigravida was transferred to our hospital complaining of refractory epigastric pain in the 29th week of pregnancy and was subsequently admitted due to superimposed pre-eclampsia and hemolysis, elevated liver enzyme levels, and low platelet count syndrome. Following a pathological cardiotocogram, a cesarean section was performed. The intra-abdominal situs presented with 1000 mL of blood and a bleeding rupture of the left lobe of the liver. The trauma to the liver was surgically repaired with a suture and the patient's state was stabilized. Following the surgical procedures and neonatal intensive care, mother and newborn both recovered without residues. In order to avoid unnecessary maternal morbidity, we therefore recommend an abdominal ultrasound, beyond an obstetric focus, as an additional and sensible means of diagnostic imaging in cases of hemolysis, elevated liver enzyme levels, and low platelet count syndrome.


Asunto(s)
Hemólisis , Hepatopatías/cirugía , Preeclampsia , Complicaciones del Embarazo/cirugía , Rotura Espontánea/cirugía , Adulto , Cesárea , Femenino , Humanos , Nacimiento Vivo , Hepatopatías/metabolismo , Paridad , Recuento de Plaquetas , Preeclampsia/metabolismo , Embarazo , Complicaciones del Embarazo/metabolismo , Rotura Espontánea/metabolismo
12.
J Med Case Rep ; 17(1): 286, 2023 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-37422672

RESUMEN

BACKGROUND: Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth. CASE PRESENTATION: We present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab. CONCLUSION: Rare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors.


Asunto(s)
Neoplasias Endometriales , Nacimiento Prematuro , Neoplasias Uterinas , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , Inestabilidad de Microsatélites , Cesárea , Neoplasias Endometriales/genética , Neoplasias Endometriales/terapia , Neoplasias Endometriales/patología
13.
J Med Case Rep ; 16(1): 119, 2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35313981

RESUMEN

PURPOSE: During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature. CASE REPORT: A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later. METHODS: We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles. RESULTS: We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor. CONCLUSION: Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required.


Asunto(s)
COVID-19 , Neoplasias de los Genitales Femeninos , Tromboembolia Venosa , Anciano , Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Humanos , Estudios Retrospectivos
14.
Clin Case Rep ; 9(4): 2369-2372, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33936697

RESUMEN

Heterotopic pregnancy is a rare event in natural conception (1:30000). We describe a case of a 36-year-old nulliparous. She presented to our department in the 4 + 6 gestational week with two simultaneous pregnancies intrauterine and extrauterine. Here, we compare treatment options and ultrasound findings to help examiners avoid inadequate therapeutic approaches.

15.
Front Endocrinol (Lausanne) ; 12: 564002, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679613

RESUMEN

Purpose: Wnt pathway modulator Dickkopf 2 (Dkk2) and signaling of the G protein-coupled estrogen receptor (GPER) seem to have essential functions in numerous cancer types. For epithelial ovarian cancer (EOC), it has not been proven if either Dkk2 or the GPER on its own have an independent impact on overall survival (OS). So far, the correlation of both factors and their clinical significance has not systematically been investigated before. Methods: Expression levels of Dkk2 were immunohistochemically analyzed in 156 patient samples from different histologic subtypes of EOC applying the immune-reactivity score (IRS). Expression analyses were correlated with clinical and pathological parameters to assess for prognostic relevance. Data analysis was performed using Spearman's correlations, Kruskal-Wallis-test and Kaplan-Meier estimates. Results: Highest Dkk2 expression of all subtypes was observed in clear cell carcinoma. In addition, Dkk2 expression differed significantly (p<0.001) between low and high grade serous ovarian cancer. A significant correlation of Dkk2 with the cytoplasmic GPER expression was noted (p=0.001) but not for the nuclear estrogen receptor alpha (ERα) or beta (ERß). Patients exhibiting both, high expression Dkk2 (IRS>4) and GPER (IRS>8), had a significantly better overall survival compared to patients with low expression (61 months vs. 33 months; p=0.024). Conclusion: Dkk2 and GPER expression correlates in EOC and combined expression of both is associated with improved OS. These findings underline the clinical significance of both pathways and indicate a possible prognostic impact as well as a potential for treatment strategies addressing interactions between estrogen and Wnt signaling in ovarian cancer.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Ováricas/diagnóstico , Receptores de Estrógenos/genética , Receptores Acoplados a Proteínas G/genética , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/mortalidad , Estudios de Cohortes , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/mortalidad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Pronóstico , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Análisis de Supervivencia
16.
J Reprod Immunol ; 144: 103283, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33545613

RESUMEN

BACKGROUND: Pregnancy is an extraordinarily complex immunological process. For successful pregnancy maintenance the maternal immune system must adapt to and tolerate the semi-allogenic fetus at the fetomaternal interface of the placenta. This balance is regulated by cytokines with a predominant T helper 2 (Th-2) system and a suppressed inflammatory T helper 1 (Th-1) response. This study investigates the role of the Th-1 pro-inflammatory cytokine Interleukin-1 beta (IL-1ß) and its role in early pregnancy loss. PATIENTS AND METHODS: In order to identify differences in IL- ß levels a TaqMan® Human Cytokine Network Array, with placental tissue obtained from patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15), was carried out. Protein expression of IL-1ß in the decidua of healthy pregnancies (n = 15), spontaneous (n = 18) and recurrent miscarriages (n = 15), was investigated by immunohistochemistry. The identification of IL-1ß expressing cells in the decidua was done with double-immunofluorescence. RESULTS: Gene expression analysis identified a nearly 54-times higher expression of IL-1ß in placental tissue of patients suffering from recurrent abortion. Immunohistochemistry confirmed a significant upregulation of IL-1ß in the decidua of recurrent miscarriage specimens (p = 0.01) as well as in the decidua of women with spontaneous abortion (p = 0.001). Double-immunofluorescence identified decidual stoma cells as IL-1ß expressing cells. CONCLUSION: Significant upregulation of IL-1ß may be associated with an imbalanced immune system and a procoagulant state that could be responsible for early pregnancy loss. These results provide new evidence of the complex interplay of IL-1ß at the fetomaternal interface and its crucial role in miscarriage processes.


Asunto(s)
Aborto Habitual/inmunología , Decidua/patología , Interleucina-1beta/metabolismo , Regulación hacia Arriba/inmunología , Aborto Habitual/patología , Adulto , Estudios de Casos y Controles , Decidua/inmunología , Femenino , Voluntarios Sanos , Humanos , Interleucina-1beta/análisis , Embarazo , Primer Trimestre del Embarazo , Adulto Joven
17.
Cancers (Basel) ; 13(13)2021 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-34283076

RESUMEN

(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer patients is already known. (2) Methods: Based on data from The Cancer Genome Atlas (379 RNA sequencing samples), we constructed a prognostic 11-gene signature (SNRPA1, CCL19, CXCL11, CDC5L, APCDD1, LPAR2, PI3, PLEKHF1, CCDC80, CPXM1 and CTAG2) for Fédération Internationale de Gynécologie et d'Obstétrique stage III and IV serous ovarian cancer through lasso regression. (3) Results: The established risk score was able to predict the 1-, 3- and 5-year prognoses more accurately than previously known models. (4) Conclusions: We were able to confirm the predictive power of this model when we applied it to cervical and urothelial cancer, supporting its pan-cancer usability. We found that immune checkpoint genes correlate negatively with a higher risk score. Based on this information, we used our risk score to predict the biological response of cancer samples to an anti-programmed death ligand 1 immunotherapy, which could be useful for future clinical studies on immunotherapy in ovarian cancer.

18.
Front Oncol ; 11: 713026, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34631538

RESUMEN

The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed in vitro upon siRNA knockdown of ACTBL2 and NFAT5. ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. In vitro analyses upon siRNA knockdown of ACTBL2 displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of NFAT5 proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.

19.
Breast ; 60: 214-222, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34736092

RESUMEN

INTRODUCTION: The side effects of systemic cancer therapy and the lack of clinical data on safety and efficacy of COVID-19 vaccination in cancer patients cause uncertainty among the patients about whether to get vaccinated or not. Here, we evaluated attitude towards and effects of COVID-19 vaccination in patients with breast and gynecological cancer undergoing systemic cancer therapy. METHODS: Since March 15th, 2021, cancer patients who received one of the approved COVID-19 vaccines were routinely interviewed about immediate and late side effects. Clinical parameters such as current therapy, time interval between therapy administration and vaccination, and changes in the therapy schedule due to vaccination were documented. The collected data were analyzed de-identified as a part of routine quality assurance. RESULTS: By July 27th, 2021, 218 patients (74.3% breast cancer patients) had received one of two COVID-19 vaccine doses, and 112 patients had received both doses: 77.5% received Conmirnaty (BioNTech/Pfizer), 16.1% Vaxzevria (Astra Zeneca) and 5.9% COVID-19 Vaccine Moderna. The COVID-19 vaccines had an acceptable safety profile with self-limiting local and systemic adverse events, which rarely lasted >48 h post vaccination. Symptoms occurred predominantly after the second dose of the vaccine and less frequently in older patients >55 years. No vaccine-related serious adverse events were reported, and only limited effects of vaccination on the therapy schedule were observed. CONCLUSIONS: Breast and gynecologic cancer patients tolerate the COVID-19 vaccination while undergoing systemic cancer therapy without any additional side effects beyond those reported in the general population.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias de los Genitales Femeninos , Vacuna nCoV-2019 mRNA-1273 , Anciano , Vacunas contra la COVID-19 , Femenino , Humanos , SARS-CoV-2 , Vacunación
20.
PLoS One ; 16(6): e0252356, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34101746

RESUMEN

BACKGROUND: Preliminary empirical data indicates a substantial impact of the COVID-19 pandemic on well-being and mental health. Individuals with minoritized sexual and gender identities are at a higher risk of experiencing such negative changes in their well-being. The objective of this study was to compare levels of well-being among cis-heterosexual individuals and individuals with minoritized sexual and gender identities during the COVID-19 pandemic. METHODS: Using data obtained in a cross-sectional online survey between April 20 to July 20, 2020 (N = 2332), we compared levels of well-being (WHO-5) across subgroups (cis-individuals with minoritized sexual identities, individuals with minoritized gender identities and cis-heterosexual individuals) applying univariate (two-sample t-test) and multivariate analysis (multivariate linear regression). RESULTS: Results indicate overall lower levels of well-being as well as lower levels of well-being in minoritized sexual or gender identities compared to cis-heterosexual individuals. Further, multivariate analyses revealed that living in urban communities as well as being in a relationship were positively associated with higher levels of well-being. Furthermore, a moderation analysis showed that being in a relationship reduces the difference between groups in terms of well-being. CONCLUSION: Access to mental healthcare for individuals with minoritized sexual and gender identities as well as access to gender-affirming resources should be strengthened during COVID-19 pandemic. Healthcare services with low barriers of access such as telehealth and online peer support groups should be made available, especially for vulnerable groups.


Asunto(s)
COVID-19/psicología , Salud Mental , Pandemias , Minorías Sexuales y de Género , Adolescente , Adulto , COVID-19/epidemiología , Estudios Transversales , Identidad de Género , Alemania/epidemiología , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Telemedicina/métodos , Adulto Joven
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