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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.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Células MCF-7 , Receptor beta de Estrógeno/genética , Supervivencia Celular , Antioxidantes/farmacología , Té , Receptor alfa de Estrógeno , Línea Celular Tumoral , Proliferación CelularRESUMEN
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.
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Neoplasias Endometriales , Nacimiento Prematuro , Neoplasias Uterinas , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , Inestabilidad de Microsatélites , Cesárea , Neoplasias Endometriales/genética , Neoplasias Endometriales/terapia , Neoplasias Endometriales/patologíaRESUMEN
PURPOSE: Endometriosis is known to be an underestimated disease. Lately the awareness of the disease seems to have improved. Aim of this analysis is to provide an overview of the development of treatment of patients diagnosed with endometriosis. This includes a special scope on implications of the COVID-19 pandemic since in multiple settings postponed treatments resulting in negative impact on prognosis were reported. MATERIALS AND METHODS: We analysed the development of numbers of patients treated for endometriosis in an academic centre within a 7-year period, 01/2015-12/2021, performing a systematic analysis of ICD-10-Codes from our computer system used in clinical routine. RESULTS: Treatment numbers increased over the past 7 years, i.e., 239 treated cases in 2015 vs. 679 in 2021. Following restrictions for outpatient evaluation and surgical capacity at our centre, during COVID-19 pandemic the numbers of treated patients were reduced, especially in the first lockdown period (03/22/2020-05/05/2020 vs. same period in 2019: outpatient clinic (9 vs. 36; p < 0.001), patients surgically treated (27 vs. 52; p < 0,001)). The comparison of 2020 to 2019 showed a reduction in April 2020 of - 37% in outpatient department and up to - 90% for surgically treated patients. Comparing to 2019, we found a reduction of surgical interventions in 2020 by - 9% and an increase by 83% in 2021. CONCLUSIONS: Raising numbers of patients treated for endometriosis point to a new awareness for the disease. After the decline during the lockdown period numbers raised again, leading to a delay, but not an omission of treatment. A certified endometriosis centre with established and well-organized structures is required to improve not only treatment results but also quality of life of those affected.
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COVID-19 , Endometriosis , Femenino , Humanos , Endometriosis/epidemiología , Endometriosis/cirugía , COVID-19/epidemiología , Calidad de Vida , Pandemias , Control de Enfermedades TransmisiblesRESUMEN
BACKGROUND: Preliminary research shows a substantial impact of the COVID-19 pandemic on women's sexual health, whereby empirical work on sexual well-being of minoritized sexual identities is still rare. AIM: The objective of this study was to explore sexual health in heterosexual, lesbian and bisexual cis women during the first wave of COVID-19 pandemic in Germany. METHODS: An anonymous nationwide online survey was conducted among cis women during the first nationwide lockdown in Germany from April 20th to July 20th, 2020. The questionnaire was distributed via e-mail, online chats and social-media platforms. OUTCOMES: Demographic variables and self-report measures from the Sexual Behavior Questionnaire (SBQ-G) "before the pandemic" and "since the pandemic" were collected. RESULTS: A total of 1,368 cis women participants were included: heterosexual women (n = 844), lesbian women (n = 293), bisexual women (n = 231). Results indicate overall decrease in frequency of sexual contacts and masturbation during the COVID-19 pandemic. Regarding differences before and during the pandemic lesbian women showed significant changes in sexual arousal whereas heterosexual women showed significant changes in all dimensions except capability to enjoy sexual intercourse. The data of bisexual women showed significant changes in almost all dimensions except for frequency of sexual intercourse and sexual arousal. Results of the multiple regression analysis revealed that being younger than 36 years-old, and being in a relationship as well as being heterosexual (compared with being lesbian) is positively associated with general satisfaction with sexual life during the pandemic. CLINICAL IMPLICATIONS: The findings suggest that during a pandemic sexual and mental health care for (cis) women should be provided and address the specific needs of sexual minority groups. STRENGTHS & LIMITATIONS: This is the first study to describe sexual behavior in heterosexual, lesbian and bisexual women during the COVID-19 pandemic in Germany. Limitations, however, include the fact that the data described were obtained at only one time point so there is a possibility of recall bias, and that the results cannot be generalized because of the underrepresentation of women over age 46. CONCLUSION: This study examined the impact of the COVID-19 pandemic and resulting social constraints on the sexual health of particular groups of lesbian and bisexual women, which may improve preparedness for future public health and policy crises. Batz F, Lermer E, Hatzler L, et al. The Impact of the COVID-19 Pandemic on Sexual Health in Cis Women Living in Germany. J Sex Med 2022;19:907-922.
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COVID-19 , Salud Sexual , Minorías Sexuales y de Género , Adulto , Bisexualidad/psicología , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Femenino , Alemania/epidemiología , Humanos , Persona de Mediana Edad , Pandemias , Conducta SexualRESUMEN
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.
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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 , TéRESUMEN
BACKGROUND: Circulating tumor cells (CTC) in the peripheral blood in women with breast cancer has been found to be an indicator of prognosis before the start of systemic treatment. The aim of this study is the assessment of specific cytokine profiles as markers for CTC involvement that could act as independent prognostic markers in terms of survival outcome for breast cancer patients. METHODS: Patients selected for this study were defined as women with breast cancer of the SUCCESS study. A total of 200 patients' sera were included in this study, 100 patients being positive for circulating tumor cells (CTC) and 100 patients being CTC negative. The matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification, and patient survival. Commercial ELISA with a multi cytokine/chemokine array was used to screen the sera for Interleukin 15 (IL-15) and eotaxin. RESULTS: Statistically significant concentrations were exposed for IL-15 levels regardless of the CTC-Status, lymph node involvement, or hormone receptor status. Significantly enhanced serum IL-15 concentrations were observed in those patients with worse overall survival (OS) and disease-free survival (DFS). Elevated serum concentrations of IL-15 significantly correlate with patients diagnosed with Grade 3 tumor and worse OS. In contrast, patients with a Grade 3 tumor with a favourable OS and DFS demonstrated significantly decreased IL-15 values. The CTC negative patient subgroup with a favourable OS and DFS, showed statistically significant elevated eotaxin values. CONCLUSION: These findings suggest a potential functional interaction of increased IL-15 concentrations in the peripheral blood of patients with a worse OS and DFS, regardless of prognostic factors at primary diagnosis. The increased levels of the chemokine eotaxin in CTC negative patients and a favourable OS and DFS, on the other hand, suggest that the overexpression inhibits CTCs entering the peripheral blood, thus emphasizing a significant inhibition of circulation specific metastasis. To sum up, IL-15 could be used as an independent prognostic marker in terms of survival outcome for breast cancer patients and used as an early indicator to highlight high-risk patients and consequently the adjustment of cancer therapy strategies.
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Neoplasias de la Mama/patología , Quimiocinas/sangre , Interleucina-15/sangre , Células Neoplásicas Circulantes/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carboplatino , Ciclofosfamida , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Análisis de Supervivencia , TiotepaRESUMEN
Subsequently to the publication of this paper, the authors have realized that the name of the fifth listed author, Theresa Vilsmaier, was spelt incorrectly (it appeared as "Vilsmeier" in print). The corrected author list, as it shown have appeared in the paper, is shown above. The authors regret that the name of the fifth author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused. [The original article was published in Oncology Reports 41: 387-396, 2019; DOI: 10.3892/or.2018.6789].
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Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the IRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score ≥2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS ≥2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations.
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Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Neoplasias/fisiología , Subtipo EP2 de Receptores de Prostaglandina E/fisiología , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Galectina 3/análisis , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Estadificación de Neoplasias , Pronóstico , Isoformas de Proteínas/análisis , Subtipo EP3 de Receptores de Prostaglandina E/deficiencia , Subtipo EP3 de Receptores de Prostaglandina E/genética , Método Simple Ciego , Tasa de Supervivencia , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
We investigated the anticarcinogenic potential of green tea and its components epigallocatechin gallate (EGCG) and quercetin, as well as tamoxifen, on MCF-7 and MDA-MB-23 breast cancer cells. Using high-performance liquid chromatography, the quantity of EGCG and quercetin in green tea was analyzed. The receptor status of the cells was confirmed immunohistochemically. Various viability and cytotoxicity tests were later performed to investigate the effects of the substances. After incubating the cells with green tea extract, EGCG, quercetin and tamoxifen, a decrease in viability (MTT test) or proliferation (BrdU assay) was found in all cell tests with varying effects, depending on the assay used. The effects were similar in both cell lines. This work confirmed that EGCG and quercetin are contained in green tea and that both substances in pure form and as green tea have an anticarcinogenic effect on both estrogen receptor-positive and -negative breast cancer cells. This effect could also be demonstrated with tamoxifen in both cell lines (MTT and BrdU assays). These results suggest that the effects observed in these experiments are not generated only via estrogen receptor-mediated pathways.
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Anticarcinógenos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Catequina/análogos & derivados , Quercetina/farmacología , Té/química , Antioxidantes/metabolismo , Neoplasias de la Mama/metabolismo , Catequina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Receptores de Estrógenos/metabolismo , Tamoxifeno/farmacologíaRESUMEN
PURPOSE: Cervical cancer is one of the most frequent cancers in women worldwide. In most of all cases, a persistent HPV infection is the leading cause. HPV-specific sequences are able to bind glucocorticoid receptor (GR). Dexamethasone can increase the activity of early promoters in HPV16 and HPV18 interfering in transcription control of viral oncogenes. The aim of our study was to evaluate glucocorticoid receptor as transcriptional factor in its active form in the nucleus of in cervical cancer cells and to correlate the results with clinical patient specific parameters. METHODS: A total of 250 paraffin-embedded cervical cancer samples obtained from patients having undergone surgery for cervical cancer were used for the study. The expression of GR was immunhistochemical examined and evaluated by a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. RESULTS: GR is frequently expressed in cervical carcinoma tissue in favor of squamous cell carcinoma (SCC). An enhanced expression is correlated with rather small clinical stages. The expression of the GR is correlated with better overall survival and progression-free survival. CONCLUSIONS: The glucocorticoid receptor is frequently expressed in cervical carcinoma tissue in favor of squamous cell carcinoma. An enhanced expression is correlated with rather small clinical stages. The expression of the analyzed receptor is correlated with better overall survival. Further studies are needed to determine useful treatment targets for glucocorticoid receptor manipulation.
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Carcinoma de Células Escamosas/patología , Receptores de Glucocorticoides/metabolismo , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Femenino , Papillomavirus Humano 16/genética , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Adhesión en Parafina/métodos , Regiones Promotoras Genéticas , Análisis de Supervivencia , Transcripción Genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: Phytoestrogens have controversial effects on hormone-dependent tumors. Herein we investigated the effects of parsley root extract (PCE) on DNA synthesis performance, metabolic activity and cytotoxicity in malignant and benign breast cells. MATERIALS AND METHODS: The PCE was prepared and analyzed by mass spectrometry. MCF7 and MCF12A cells were incubated with various concentrations of PCE and analyzed for DNA synthesis performance, metabolic activity and cytotoxicity by BrdU proliferation, MTT and LDH assays, respectively. RESULTS: PCE was found to contain a substantial ratio of lignans. At a concentration range of 0.01 µg/ml-100 µg/ml the LDH assay analysis showed no significant cytotoxicity of PCE in both cell lines. However, at 500 µg/ml PCE's cytotoxicity was well over 70% of total cell population in both cell lines. According to the BrdU proliferation assay analysis, PCE demonstrated significant DNA synthesis inhibition of up to 80% at concentrations of 10, 50, 100 and 500 µg/ml in both cell lines. Based on the MTT assay analysis, only at a concentration of 500 µg/ml, PCE demonstrated a statistically significant inhibition of cellular metabolic activity of 63% in MCF7 and 75% in MCF12A of their respective normal capacity. CONCLUSION: PCE showed antiproliferative effects in MCF7 and MCF12A cells. Further investigation is required to determine whether this effect can be solely attributed to its phytoestrogens.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Glándulas Mamarias Humanas/efectos de los fármacos , Petroselinum , Fitoestrógenos/farmacología , Extractos Vegetales/farmacología , Receptores de Estrógenos/efectos de los fármacos , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Metabolismo Energético/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Células MCF-7 , Glándulas Mamarias Humanas/metabolismo , Glándulas Mamarias Humanas/patología , Espectrometría de Masas , Petroselinum/química , Fitoestrógenos/aislamiento & purificación , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Plantas Medicinales , Receptores de Estrógenos/metabolismoRESUMEN
Hereinwe investigated the effect of elderflower extracts (EFE) and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ER/ER/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ER in JEG-3 cell lines. In MCF7 cells, a significant ER downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ER expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ER downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation.
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Estradiol/metabolismo , Fitoestrógenos/farmacología , Extractos Vegetales/farmacología , Sambucus/química , Neoplasias Trofoblásticas/tratamiento farmacológico , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Lignanos/farmacología , Células MCF-7/metabolismo , Embarazo , Progesterona/metabolismo , Receptores de Estrógenos/efectos de los fármacos , Neoplasias Trofoblásticas/metabolismo , Neoplasias Uterinas/química , Neoplasias Uterinas/tratamiento farmacológicoRESUMEN
BACKGROUND: Circulating tumor cells (CTCs) are cells that detach from a primary tumor, circulate through the blood stream and lymphatic vessels, and are considered to be the main reason for remote metastasis. Due to their origin, tumor cells have different gene expression levels than the surrounding blood cells. Therefore, they might be detectable in blood samples from breast cancer patients by real-time quantitative polymerase chain reaction (RT-qPCR). MATERIALS AND METHODS: Blood samples of healthy donors and adjuvant breast cancer patients were withdrawn and the cell fraction containing white blood cells and tumor cells was enriched by density gradient centrifugation. RNA was isolated and reverse transcribed to cDNA, which was then used in TaqMan real-time PCR against cytokeratin (CK)8, CK18 and CK19. 18S and GAPDH were used as controls. RESULTS: All 3 CKs were, on average, found to be significantly higher expressed in adjuvant breast cancer samples compared to negative controls, probably due to the presence of CTCs. Unfortunately, gene expression levels could not be correlated to tumor characteristics. CONCLUSIONS: RT-qPCR could make up a new approach for the detection of CTCs from blood samples of breast cancer patients, but a correlation of the PCR data to gold standard methods in CTC detection would help to further improve the informative value of the qPCR results.
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Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.