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.

Health-related quality of life and patient-centred outcomes with COVID-19 vaccination in patients with breast cancer and gynaecological malignancies.

Introduction: Safety and tolerability of COVID-19 vaccines were demonstrated by several clinical trials which led to the first FDA/EMA approvals in 2021. Because of mass immunizations, most social restrictions were waived with effects on quality of life. Therefore, our a-priori hypothesis was that COVID-19 vaccination impacted the health-related quality of life (HR-QoL) in patients with breast and gynecological cancer. Methods: From March 15th until August 11th, 2022, fully vaccinated patients with breast and gynecological cancer treated in the oncological outpatient clinics of the Department of Obstetrics and Gynecology, LMU University Hospital, Munich, Germany filled out a vaccine related QoL survey. Patients were asked about demographics (age, comorbidities), clinical parameters related to previous COVID-19 infections, and HR-QoL related parameters (living situation, responsibilities in everyday life). Subsequently, a questionnaire with 12 items was designed using a 5-point Likert scale (0 - strongly disagree/4 - strongly agree), covering the aspects health and therapy, social environment, participation in everyday life and overall assessment. Results: By August 11th, 2022, 108 out of 114 (94.7%) patients had received at least three doses of COVID-19 vaccine and six patients at least two doses. More than half of the surveyed patients were >55y (52.6%; mean: 55.1y, range 29-86y). Patients with breast cancer (n= 83) had early (59.0%) or metastatic cancer (41.0%); gynecological cancers (n=31) also included metastatic (54.8%) and non-metastatic cancer (45.2%). 83.3% of the patients stated that COVID-19 vaccination had a positive impact on their HR-QoL. Furthermore, 29 patients (25.4%) had undergone a COVID-19 infection. These patients reported self-limiting symptoms for a median duration of 5.9 days and no hospital admissions were registered. Conclusions: Our study demonstrates that vaccination against COVID-19 was positively associated with HR-QoL in patients with breast and gynecological cancer. Furthermore, vaccinated patients who underwent COVID-19 disease experienced only self-limiting symptoms.

Effects of matcha tea extract on cell viability and peroxisome proliferator-activated receptor γ expression on T47D breast cancer cells.

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.

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer.

The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

Identification of a Novel Tumor Microenvironment Prognostic Signature for Advanced-Stage Serous Ovarian Cancer.

(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.

The Prognostic Impact of Retinoid X Receptor and Thyroid Hormone Receptor alpha in Unifocal vs. Multifocal/Multicentric Breast Cancer.

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.

IFN Regulatory Factor 4 Controls Post-ischemic Inflammation and Prevents Chronic Kidney Disease.

Ischemia reperfusion injury (IRI) of the kidney results in interferon regulatory factor 4 (IRF4)-mediated counter-regulation of the acute inflammatory response. Beyond that, IRF4 exerts important functions in controlling the cytokine milieu, T-cell differentiation, and macrophage polarization. The latter has been implicated in tissue remodeling. It therefore remains elusive what the role of IRF4 is in terms of long-term outcome following IRI. We hypothesized that an inability to resolve chronic inflammation in Irf4-/- mice would promote chronic kidney disease (CKD) progression. To evaluate the effects of IRF4 in chronic upon acute injury in vivo, a mouse model of chronic injury following acute IRI was employed. The expression of Irf4 increased within 10 days after IRI in renal tissue. Both mRNA and protein levels remained high up to 5 weeks upon IRI, suggesting a regulatory function in the chronic phase. Mice deficient in IRF4 display increased tubular cell loss and defective clearance of infiltrating macrophages. These phenomena were associated with increased expression of pro-inflammatory macrophage markers together with reduced expression of alternatively activated macrophage markers. In addition, IRF4-deficient mice showed defective development of alternatively activated macrophages. Hints of a residual M1 macrophage signature were further observed in human biopsy specimens of patients with hypertensive nephropathy vs. living donor specimens. Thus, IRF4 restricts CKD progression and kidney fibrosis following IRI, potentially by enabling M2 macrophage polarization and restricting a Th1 cytokine response. Deteriorated alternative macrophage subpopulations in Irf4-/- mice provoke chronic intrarenal inflammation, tubular epithelial cell loss, and renal fibrosis in the long course after IRI in mice. The clinical significance of these finding for human CKD remains uncertain at present and warrants further studies.