Effects of matcha tea extract on cell viability and estrogen receptor-ß expression on MCF-7 breast cancer cells.

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.

Galectin-10 Expression in Placentas of Women with Gestational Diabetes.

Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM. It is hypothesized that the difference in galectin-10 expression will raise the pathophysiological understanding of gestational diabetes. The study population consists of 80 women: 40 healthy mothers and 40 women suffering from gestational diabetes mellitus. The expression of galectin-10 was analyzed in the syncytiotrophoblast (SCT) and the decidua of the placenta via immunohistochemistry and immunofluorescence double staining. The immunoreactivity score (IRS) was used for evaluation. The results in this study were significant for an overexpression of galectin-10 in GDM placentas compared with the control group. The syncytiotrophoblast showed overexpression in the nucleus and the cytoplasm, whereas expression of galectin-10 in the decidua was significant in the cytoplasm only. This study identified the expression changes in galectin-10 in placental tissue between healthy and GDM mothers and intensified the understanding of gestational diabetes. Assuming that gestational diabetes mellitus is involved in inflammatory processes, galectin-10 might play a role in the development and maintenance of GDM. Further investigation is required to strengthen these findings.

[Pruritus in pregnancy: consider the intrahepatic cholestasis of pregnancy]. / Juckreiz, das Leitsymptom der Schwangerschaftscholestase.

In the case of generalized pruritus in pregnancy, dermatological diseases are often considered primarily and the patient is treated topically. In any case, intrahepatic cholestasis of pregnancy (ICP) should be clarified as a potentially child- and pregnancy-threatening disease. The leading symptoms are pruritus, especially on the palms and feet, and laboratory elevated bile acids (GS) and transaminases. Feared perinatal complications include prematurity, green/meconium-containing amniotic fluid, respiratory distress syndrome, or even intrauterine fetal death.

Increase of the T-reg-recruiting chemokine CCL22 expression in a progressive course of cervical dysplasia.

PURPOSE: An increasing infiltration of FoxP3-positive T-regs is associated with a higher grade of cervical intraepithelial neoplasia. The T-reg-recruiting chemokine CCL22 is expressed in various tumour entities. Aim of our study was to investigate the role of CCL22 in the progression and regression of cervical intraepithelial neoplasias, especially in patients with intermediate cervical intraepithelial neoplasias (CIN II). Furthermore, our aim was to characterize the CCL22-producing cells and explore the role of innate immunity in the process of cells recruitment. METHODS: CCL22 expression was analyzed immunohistochemically in 169 patient samples. The immunoreactive score as well as the median numbers of positive cells were calculated in each slide and correlated with the histological CIN grade and FoxP3 expression. Additionally, CD68/CCL22 as well as CD68/PPARγ and CD68/FoxP3 expression were examined by double immunofluorescence. Statistical analysis was performed by SPSS 26. RESULTS: A significantly higher expression of epithelial CCL22 in CIN II with progression in comparison to CIN II with regression (p = 0.006) could be detected. CCL22 was correlated with FoxP3 (Spearman's Rho: 0.308; p < 0.01). In 88%, CCL22-positive cells were positive for CD68, and 71% of CD68-positive macrophages expressed PPARγ. Colocalization of CD68 and FoxP3 was detected in 12%. CONCLUSION: We could demonstrate that increased expression of CCL22, mainly produced by macrophages, correlates with elevated potential of malignancy. CCL22 expression could act as a predictor for regression and progression in cervical intraepithelial neoplasia, and it may help in the decision process regarding surgical treatment versus watchful waiting strategy in order to prevent conisation-associated risks. Furthermore, our findings support the potential of CCL22-producing cells as a target for immune therapy in cervical cancer patients.

Risk of postpartum depressive symptoms is influenced by psychological burden related to the COVID-19 pandemic and dependent of individual stress coping.

PURPOSE: There are different studies worldwide, which have shown a higher risk of mental disorders due to the COVID-19 pandemic. One aim of this study was to identify influencing factors of the psychological burden related to the COVID-19 pandemic and the impact on the development of postpartum depression. Further, the role of individual stress and coping strategies was analyzed in this context. MATERIALS AND METHODS: Between March and October 2020, 131 women in obstetric care at the LMU Clinic Munich completed a questionnaire at consecutive stages during their perinatal period. The times set for the questionnaire were before birth, 1 month, 2 months, and 6 months after birth. The questionnaire was designed to evaluate the psychological burden related to the COVID-19 pandemic. For this a modified version of the Stress and coping inventory (SCI) and the Edinburgh Postnatal Depression Scale (EPDS) was used. RESULTS: We could show that the psychological burden related to the COVID-19 pandemic influenced the EPDS score 1, 2 and 6 months after birth. In addition, the prenatal stress and individual coping strategies affected the EPDS and the burden related to the COVID-19 pandemic before and after birth significantly. CONCLUSION: An association of the psychological burden related to the COVID-19 pandemic with the risk of developing postpartum depressive symptoms could be shown in this study. In this context, the separation of the partner and the family was recognized as an important factor. Furthermore, the SCI was identified as an effective screening instrument for identifying mothers with an increased risk of postpartum depression. Hereby allowing primary prevention by early intervention or secondary prevention by early diagnosis.

Trends among patients with endometriosis over a 7-year period and the impact of the COVID-19 pandemic: experience from an academic high-level endometriosis centre in Germany.

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.

High RIG-I and EFTUD2 expression predicts poor survival in endometrial cancer.

PURPOSE: Endometrial cancer is the most common gynecological malignancy. The helicase RIG-I, a part of the innate immune system, and EFTUD2, a splicing factor which can upregulate RIG-I expression, are shown to influence tumor growth and disease progression in several malignancies. For endometrial cancer, an immunogenic cancer, data about RIG-I and EFTUD2 are still missing. The aim of this study was to examine the expression of RIG-I and EFTUD2 in endometrial cancer. METHODS: 225 specimen of endometrial cancer were immunohistochemically stained for RIG-I and EFTUD2. The results were correlated to clinicopathological data, overall survival (OS) and progression-free survival (PFS). RESULTS: High RIG-I expression correlated with advanced tumor stages (FIGO: p = 0.027; pT: p = 0.010) and worse survival rates (OS: p = 0.009; PFS: p = 0.022). High EFTUD2 expression correlated to worse survival rates (OS: p = 0.026; PFS: p < 0.001) and was determined to be an independent marker for progression-free survival. CONCLUSION: Our data suggest that the expression of RIG-I and EFTUD2 correlates with survival data, which makes both a possible therapeutic target in the future.

Blood group antigens SLeX, SLeA, and LeY as prognostic markers in endometrial cancer.

PURPOSE: Endometrial cancer (EC) is the most common gynecological cancer worldwide. Treatment has been improved in recent years, but, in advanced stages, therapeutical options are still limited. It has been reported that the expression of the blood group antigens Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA) and Lewis Y (LeY) is associated with prognosis in several tumors. Large studies on endometrial and cervical cancer are still pending. METHODS: Specimens of 234 patients with EC were immunohistochemically stained with antibodies for SLeX, SLeA and LeY. Expression was correlated to histopathological variables. RESULTS: High expression of SLeX was correlated to low pT-stage (p = 0.013), low grade (p < 0.001), low FIGO-stage (p = 0.006) and better overall survival rates (OS; p = 0.023). High expression of SLeA was associated with low pT-stage (p = 0.013), low grade (p = 0.001) and better progression-free survival (PFS; p = 0.043). LeY staining was correlated to pN + (p = 0.038), low grade (p = 0.005) and poorer PFS (p = 0.022). CONCLUSION: This is the first study examining the expression of SLeX, SLeA and LeY in EC, which can serve as additional future prognostic markers. Further studies are necessary to understand the underlying mechanisms. The study was approved by the local ethics committee of the Ludwig-Maximilians University Munich (reference number 19-249).

Overexpression of galectin-4 in placentas of women with gestational diabetes.

OBJECTIVE: Galectins are known for their immunomodulatory functions in placentas. They are associated with pregnancy disorders such as preeclampsia, HELLP-Syndrome and intrauterine growth restriction (IUGR). In addition, galectins seem to be overexpressed in placentas of women with gestational diabetes mellitus (GDM). STUDY DESIGN: The collective consisted of 40 women diagnosed with GDM and 40 healthy expectant mothers. The expression of Gal-4 was investigated in syncytiotrophoblast (SCT), representing the fetal part of the placenta, and decidual tissues, representing the maternal part of the placenta, by immunohistochemistry and immunofluorescence double staining. Expression levels were evaluated using the immunoreactive score (IRS). RESULTS: Nuclear IRS of Gal-4 is significantly higher in SCT cells of placentas of expectant mothers diagnosed with GDM. Overexpression of Gal-4 observed in the decidua of women with GDM by significant higher nuclear and cytoplasmatic IRS of Gal-4. Multivariate regression showed that Gal-4 is significantly overexpressed in the nucleus of SCTs and cytoplasm of decidual cells of placentas with GDM. GDM could be identified as a significant predictor for both cases. CONCLUSION: The results of this study provide further evidence for the involvement of galectins in the processes of chronic inflammation throughout a pregnancy with GDM. These findings are also in line with the known overexpression of galectin-1 in placental tissues of GDM women. Further evaluation of the role of galectins in this process is warranted.

Implementation of an Electronic Patient-Reported Outcome App for Health-Related Quality of Life in Breast Cancer Patients: Evaluation and Acceptability Analysis in a Two-Center Prospective Trial.

BACKGROUND: One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. OBJECTIVE: The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. METHODS: Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. RESULTS: Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app's evaluation parameters. CONCLUSIONS: The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

Role of FoxP3-positive regulatory T-cells in regressive and progressive cervical dysplasia.

PURPOSE: Forkhead Box Protein 3 (FoxP3) is known as a key mediator in the immunosuppressive function of regulatory T-cells (Tregs). The aim of our study was to investigate whether FoxP3-positive Tregs have the potential to act as an independent predictor in progression as well as in regression of cervical intraepithelial neoplasia, especially in patients with intermediate cervical intraepithelial neoplasia (CIN II). METHODS: Nuclear FoxP3 expression was immunohistochemically analysed in 169 patient samples (CIN I, CIN II with regressive course, CIN II with progressive course, CIN III). The median numbers were calculated for each slide and correlated with the histological CIN grade. Statistical analysis was performed by SPSS 26 (Mann-Whitney U test, Spearman's rank correlation). RESULTS: An increased FoxP3 expression in CIN II with progression could be detected in comparison to CIN II with regression (p = 0.003). Total FoxP3 expression (epithelium and dysplasia-connected stroma) was higher in more advanced CIN grades (p < 0.001 for CIN I vs. CIN II; p = 0.227 for CIN II vs. CIN III). A positive correlation could be detected between FoxP3-positive cells in epithelium and total FoxP3 expression (Spearman's Rho: 0,565; p < 0.01). CONCLUSION: Expression of FoxP3 could be a helpful predictive factor to assess the risks of CIN II progression. As a prognosticator for regression and progression in cervical intraepithelial lesions it might thereby help in the decision process regarding surgical treatment vs. watchful waiting strategy to prevent conisation-associated risks for patients in child-bearing age. In addition, the findings support the potential of Tregs as a target for immune therapy in cervical cancer patients.

Epigenetic changes occur in placentas of spontaneous and recurrent miscarriages.

BACKGROUND: In contrast to genetic abnormalities which are well known to be responsible for around 50 % of human miscarriages, there is very few data about epigenetic alterations in spontaneous and recurrent miscarriages (SM, RM). The aim of this study was to analyze the histone modification marks H3K9ac and H3K4me3 in SM and RM. METHODS: The abundance of histone modifications H3K4me3/H3K9ac was analyzed by western blot in frozen abortion material of SM and RM compared to a control group of legal pregnancy terminations. Further, to characterize placental tissue cells expressing H3K4me3/H3K9ac immunohistochemistry (IHC) and immunofluorescence was performed in 20 SM, 19 RM and 26 controls. RESULTS: The western blot data showed a tendency to an overall reduction of H3K4me3/H3K9ac, in the placental tissue of particularly SM. Further we differentiated between syncytiotrophoblast, cytotrophoblast and decidual cells and found a significant decrease of H3K4me3 in SM in cytotrophoblast cells and syncytial stroma. In RM H3K4me3 was downregulated exclusively in the syncytiotrophoblast. H3K9ac was reduced in SM and RM in all evaluated compartments, except from the syncytiotrophoblast. CONCLUSION: Our study showed an overall reduced histone modification of H3K4me3 and H3K9ac in the placental tissue of SM. Concerning RM, particularly the reduction of H3K9ac was detected in the placental tissue, indicating that RM group has distinct profile in epigenetic regulation. Whether these histone modifications are part of a possible pathophysiologic cascade during SM and RM or are merely indicating a defective placentation, cannot be concluded from this study.

An Electronic Patient-Reported Outcome Tool for the FACT-B (Functional Assessment of Cancer Therapy-Breast) Questionnaire for Measuring the Health-Related Quality of Life in Patients With Breast Cancer: Reliability Study.

BACKGROUND: The most frequent malignant disease in women is breast cancer. In the metastatic setting, quality of life is the primary therapeutic goal, and systematic treatment has only a limited effect on survival rates; therefore, the concept of the health-related quality of life (HRQoL) and measurement of patient-reported outcomes (PROs) are gaining more and more importance in the therapy setting of diseases such as breast cancer. One of the frequently used questionnaires for measuring the HRQoL in patients with breast cancer is the Functional Assessment of Cancer Therapy-Breast (FACT-B). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. ePRO tools for the FACT-B questionnaire with proven reliability are missing so far. OBJECTIVE: The aim of this study was to analyze the reliability of tablet-based measurement of FACT-B in the German language in adjuvant (curative) and metastatic breast cancer patients. METHODS: Paper- and tablet-based questionnaires were completed by a total of 106 female adjuvant and metastatic breast cancer patients. All patients were required to complete the electronically based (ePRO) and paper-based version of the FACT-B. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability using Wilcoxon test and test of internal consistency using Spearman ρ) and agreement rates for single items, Kendall tau for each subscale, and total score were analyzed. RESULTS: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patients' response behavior between paper-based and electronically based questionnaires. Regarding the reliability test of parallel forms, no significant differences were found in 35 of 37 single items, while significant correlations in the test for consistency were found in all 37 single items, in all 5 sum individual item subscale scores, as well as in total FACT-B score. CONCLUSIONS: The ePRO version of the FACT-B questionnaire is reliable for patients with breast cancer in both adjuvant and metastatic settings, showing highly significant correlations with the paper-based version in almost all questions all subscales and the total score.

Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial.

BACKGROUND: Breast cancer represents the most common malignant disease in women worldwide. As currently systematic palliative treatment only has a limited effect on survival rates, the concept of health-related quality of life (HRQoL) is gaining more and more importance in the therapy setting of metastatic breast cancer. One of the major patient-reported outcomes (PROs) for measuring HRQoL in patients with breast cancer is provided by the European Organization for Research and Treatment of Cancer (EORTC). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. Facing the possibilities associated with evolving digitalization in medicine, validation of electronic versions of well-established PRO is essential in order to contribute to comprehensive and holistic oncological care and to ensure high quality in cancer research. OBJECTIVE: The aim of this study was to analyze the reliability of a tablet-based measuring application for EORTC QLQ-C30 in German language in patients with adjuvant and (curative) metastatic breast cancer. METHODS: Paper- and tablet-based questionnaires were completed by a total of 106 female patients with adjuvant and metastatic breast cancer recruited as part of the e-PROCOM study. All patients were required to complete the electronic- (e-PRO) and paper-based versions of the HRQoL EORTC QLQ-C30 questionnaire. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability [Wilcoxon test] and test of internal consistency [Spearman rho and agreement rates for single items, Pearson correlation and Kendall tau for each scale]) were analyzed. RESULTS: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patient's response behavior between paper- and electronic-based questionnaires. Regarding the test of parallel forms reliability, no significant differences were found in 27 of 30 single items and in 14 of 15 scales, whereas a statistically significant correlation in the test of consistency was found in all 30 single items and all 15 scales. CONCLUSIONS: The evaluated e-PRO version of the EORTC QLQ-C30 is reliable for patients with both adjuvant and metastatic breast cancer, showing a high correlation in almost all questions (and in many scales). Thus, we conclude that the validated paper-based PRO assessment and the e-PRO tool are equally valid. However, the reliability should also be analyzed in other prospective trials to ensure that usability is reliable in all patient groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03132506; https://clinicaltrials.gov/ct2/show/NCT03132506 (Archived by WebCite at http://www.webcitation.org/6tRcgQuou).

Electronic-Based Patient-Reported Outcomes: Willingness, Needs, and Barriers in Adjuvant and Metastatic Breast Cancer Patients.

BACKGROUND: Patient-reported outcomes (PROs) play an increasingly important role as an adjunct to clinical outcome parameters in measuring health-related quality of life (HRQoL). In fact, PROs are already the accepted gold standard for collecting data about patients' subjective perception of their own state of health. Currently, paper-based surveys of PRO still predominate; however, knowledge regarding the feasibility of and barriers to electronic-based PRO (ePRO) acceptance remains limited. OBJECTIVE: The objective of this trial was to analyze the willingness, specific needs, and barriers of adjuvant breast cancer (aBC) and metastatic breast cancer (mBC) patients in nonexposed (no exposure to electronic assessment) and exposed (after exposure to electronic assessment decision, whether a tablet-based questionnaire is favored) settings before implementing digital ePRO assessment in relation to health status. We also investigated whether providing support can increase the patients' willingness to participate in such programs. METHODS: The nonexposed patients only answered a paper-based questionnaire, whereas the exposed patients filled out both paper- and tablet-based questionnaires. The assessment comprised socioeconomic variables, HRQoL, preexisting technical skills, general attitude toward electronic-based surveys, and potential barriers in relation to health status. Furthermore, nonexposed patients were asked about the existing need for technological support structures. In the course of data evaluation, we performed a frequency analysis as well as chi-square tests and Wilcoxon signed-rank tests. Subsequently, relative risks analysis, univariate categorical regression (CATREG), and mediation analyses (Hayes' bias-corrected bootstrap) were performed. RESULTS: A total of 202 female breast cancer patients completed the PRO assessment (nonexposed group: n=96 patients; exposed group: n=106 patients). Self-reported technical skills were higher in exposed patients (2.79 vs 2.33, P ≤.001). Significant differences were found in relation to willingness to use ePRO (92.3% in the exposed group vs 59% in the nonexposed group; P=.001). Multiple barriers were identified, and most of them showed statistically significant differences in favor of the exposed patients (ie, data security [13% in the exposed patients vs 30% in the nonexposed patients; P=.003] and no prior technology usage [5% in the exposed group vs 15% in the nonexposed group; P=.02]), whereas the differences in disease burden (somatic dimension: 4% in the exposed group vs 9% in the nonexposed group; P=.13) showed no significance. In nonexposed patients, requests for support services were identified, which could increase their ePRO willingness. CONCLUSIONS: Significant barriers in relation to HRQoL, cancer-related restrictions, and especially the setting of the survey were identified in this trial. Thus, it is necessary to address and eliminate these barriers to ensure data accuracy and reliability for future ePRO assessments. Exposure seems to be a potential option to increase willingness to use ePRO and to reduce barriers.