Hsa-miR-375/RASD1 Signaling May Predict Local Control in Early Breast Cancer

Background: In order to characterize the various subtypes of breast cancer more precisely and improve patients selection for breast conserving therapy (BCT), molecular profiling has gained importance over the past two decades. MicroRNAs, which are small non-coding RNAs, can potentially regulate numerous downstream target molecules and thereby interfere in carcinogenesis and treatment response via multiple pathways. The aim of the current two-phase study was to investigate whether hsa-miR-375-signaling through RASD1 could predict local control (LC) in early breast cancer. Results: The patient and treatment characteristics of 81 individuals were similarly distributed between relapse (n = 27) and control groups (n = 54). In the pilot phase, the primary tumors of 28 patients were analyzed with microarray technology. Of the more than 70,000 genes on the chip, 104 potential hsa-miR-375 target molecules were found to have a lower expression level in relapse patients compared to controls (p-value < 0.2). For RASD1, a hsa-miR-375 binding site was predicted by an in silico search in five mRNA-miRNA databases and mechanistically proven in previous pre-clinical studies. Its expression levels were markedly lower in relapse patients than in controls (p-value of 0.058). In a second phase, this finding could be validated in an independent set of 53 patients using ddPCR. Patients with enhanced levels of hsa-miR-375 compared to RASD1 had a higher probability of local relapse than those with the inverse expression pattern of the two markers (log-rank test, p-value = 0.069). Conclusion: This two-phase study demonstrates that hsa-miR-375/RASD1 signaling is able to predict local control in early breast cancer patients, which—to our knowledge—is the first clinical report on a miR combined with one of its downstream target proteins predicting LC in breast cancer.

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Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3

Breast Cancer ◽

10.1007/s12282-021-01308-y ◽

2021 ◽

Author(s):

Barbara Zellinger ◽

Ulrich Bodenhofer ◽

Immanuela A. Engländer ◽

Cornelia Kronberger ◽

Brane Grambozov ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Local Relapse ◽

Downstream Target ◽

Cellular Processes ◽

Target Molecules ◽

Regulatory Functions ◽

Breast Recurrence ◽

Independent Cohort

Abstract Background MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer. Results By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134). Conclusion The current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.

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Three-Dimensional Analysis of the In Vivo Motion of Implantable Cardioverter Defibrillator Leads

Cardiovascular Engineering and Technology ◽

10.1007/s13239-021-00557-4 ◽

2021 ◽

Author(s):

Tamas Szili-Torok ◽

Jens Rump ◽

Torsten Luther ◽

Sing-Chien Yap

Keyword(s):

Three Dimensional ◽

Second Phase ◽

Two Phase ◽

Maximum Curvature ◽

Phase Study ◽

Absolute Curvature ◽

Icd Leads ◽

Lead Testing ◽

Design And Testing

Abstract Better understanding of the lead curvature, movement and their spatial distribution may be beneficial in developing lead testing methods, guiding implantations and improving life expectancy of implanted leads. Objective The aim of this two-phase study was to develop and test a novel biplane cine-fluoroscopy-based method to evaluate input parameters for bending stress in leads based on their in vivo 3D motion using precisely determined spatial distributions of lead curvatures. Potential tensile, compressive or torque forces were not subjects of this study. Methods A method to measure lead curvature and curvature evolution was initially tested in a phantom study. In the second phase using this model 51 patients with implanted ICD leads were included. A biplane cine-fluoroscopy recording of the intracardiac region of the lead was performed. The lead centerline and its motion were reconstructed in 3D and used to define lead curvature and curvature changes. The maximum absolute curvature Cmax during a cardiac cycle, the maximum curvature amplitude Camp and the maximum curvature Cmax@amp at the location of Camp were calculated. These parameters can be used to characterize fatigue stress in a lead under cyclical bending. Results The medians of Camp and Cmax@amp were 0.18 cm−1 and 0.42 cm−1, respectively. The median location of Cmax was in the atrium whereas the median location of Camp occurred close to where the transit through the tricuspid valve can be assumed. Increased curvatures were found for higher slack grades. Conclusion Our results suggest that reconstruction of 3D ICD lead motion is feasible using biplane cine-fluoroscopy. Lead curvatures can be computed with high accuracy and the results can be implemented to improve lead design and testing.

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Depression in Patients with Schizophrenia in a Psychiatry Hospital in Lagos, Nigeria

10.26420/jpsychiatrymentaldisord.2021.1032 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Akinjola O ◽

◽

Lawal RA ◽

Ojo AM ◽

Adeosun II ◽

...

Keyword(s):

Social Support ◽

Depressive Symptoms ◽

Depressive Disorder ◽

Second Phase ◽

Two Phase ◽

Good Treatment Outcome ◽

Phase Study ◽

Poor Social Support ◽

Schizophrenic Patients

Schizophrenia is a devastating and highly disabling disorder associated with long-term consequences. Treatment is often made difficult by the presence of comorbidities like depression which when considered in management ensures good outcome. This study aimed to determine the prevalence and correlates of depression in schizophrenia. It is a two-phase study involving 320 outpatients recruited by consecutive sampling. The first phase entails confirming diagnosis with Mini International Neuropsychiatric Interview (MINI), psychotic disorder module, assessing socio-demographic characteristic and screening for depressive symptoms with the Beck Depression Inventory (BDI) by a trained assistant. In the second phase, the researcher then assesses for depressive disorder using MINI, depressive disorder module among subjects who screened positive with BDI together with 10% of those who screened negative. Over four-fifth (83.4%) of the participants were less than 50 years, they were mostly females (57.2%), of Yoruba ethnic group (59.7%), Christians (75.6%), and earn below ₦18,000 monthly or nothing (72.2%). Also, a large proportion (86.2%) had good social support. Over a third of the participants were married (38.1%) with about four-fifth of these living with their spouses. The prevalence of depressive symptoms and depressive disorder were 49.7% and 38.4% respectively. Logistic regression revealed that poor social support predicts depressive in Schizophrenia. In conclusion, Depression is common in patients with schizophrenia. Therefore, thorough evaluation of schizophrenic patients is necessary so that, co-morbid depression when present can be detected and considered in management to ensure good treatment outcome.

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Ontario’s Poverty Reduction Strategy

Canadian Journal of Nursing Research ◽

10.1177/0844562116684729 ◽

2016 ◽

Vol 48 (3-4) ◽

pp. 100-109 ◽

Cited By ~ 5

Author(s):

Sarah Benbow ◽

Carolyne Gorlick ◽

Cheryl Forchuk ◽

Catherine Ward-Griffin ◽

Helene Berman

Keyword(s):

Critical Discourse Analysis ◽

Poverty Reduction ◽

Second Phase ◽

Two Phase ◽

Policy Document ◽

Reduction Strategy ◽

Phase Study ◽

Poverty Reduction Strategy ◽

The Government ◽

Gender Neutrality

This article overviews the second phase of a two-phase study which examined experiences of health and social exclusion among mothers experiencing homelessness in Ontario, Canada. A critical discourse analysis was employed to analyze the policy document, Realizing Our Potential: Ontario’s Poverty Reduction Strategy, 2014–2019. In nursing, analysis of policy is an emerging form of scholarship, one that draws attention to the macro levels influencing health and health promotion, such as the social determinants of health, and the policies that impact them. The clear neo-liberal underpinnings, within the strategy, with a focus on productivity and labor market participation leave little room for an understanding of poverty reduction from a human rights perspective. Further, gender-neutrality rendered the poverty experienced by women, and mothers, invisible. Notably, there were a lack of deadlines, target dates, and thorough action and evaluation plans. Such absence troubles whether poverty reduction is truly a priority for the government, and society as a whole.

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Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer in the ECOG-ACRIN 5103 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.520 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 520-520

Author(s):

Joseph A. Sparano ◽

Anne M. O'Neill ◽

Noah Graham ◽

Donald W. Northfelt ◽

Chau T. Dang ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Propensity Score ◽

Propensity Score Matching ◽

Early Breast Cancer ◽

Inflammatory Cytokines ◽

Multiple Testing ◽

Distant Recurrence ◽

Stage Ii ◽

P Value

520 Background: Systemic inflammation may contribute to cancer progression (PMC2803035), including recurrence of early breast cancer (PMC4828958). We hypothesized that inflammatory cytokines and/or chemokines may be associated with distant recurrence (DR). Methods: We performed a case:control study in women with stage II-III Her2-negative breast cancer, all of whom had surgery and adjuvant chemotherapy (doxorubicin/cyclophosphamide, then weekly paclitaxel) with/without bevacizumab, plus endocrine therapy if ER-positive (PMC6118403). Propensity score matching was used to identify approximately 250 case:control pairs (with/without DR). Serum samples obtained before adjuvant chemotherapy were analyzed using the MSD V-Plex Human Cytokine 36-Plex Kit for detection of human cytokines and chemokines involved in the Th1/Th2 pathway, chemotaxis, the Th17 pathway, angiogenesis, and immune system regulation. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations. Due to skewed nature of cytokines, HRs are reported on log base 2 scale. If adjusted for multiple testing including 36 markers, a p value of < 0.0014 would be required for statistical significance. Results: A total 249 matched pairs (498 patients) were identified. Covariates used for propensity score matching included age, menopausal status (post 54% vs. pre/peri 46%), ER/PR status (one/both pos 64% vs. both neg 36%) tumor size ( < = 2cm 17%, > 2-5cm 67%, > 5cm 16%) nodal status (neg 15%,1-3+ 32%, 4+ 53%), and grade (low 3%, int. 31%, high 66%). The only biomarker associated with a significantly increased DR risk when adjusted for multiple testing was the proinﬂammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). Others associated with a 2-sided p value < 0.05 included the chemokine MDC(macrophage-derived chemokine/CCL22) (1.90, 95% CI 1.17, 3.1, p = 0.0098), the T helper cell inﬂammatory cytokine IL-17A (HR 1.36, 95% CI 1.10, 1.67, p = 0.0052), and the cytokine VEGF-A (HR 1.13 for, 95% CI 1.01, 1.27, p = 0.037). There was no statistical interaction between VEGF-A and bevacizumab benefit. The median and mean value for IL-6 was 0.95 and 7.5 pg/ml (range 0.04-2761.24 pg/ml). Conclusions: This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher DR risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy. This provides a foundation for confirmatory validation of IL-6 as a prognostic biomarker, and potentially as a predictive biomarker for testing therapeutic interventions targeting the IL-6/JAK/STAT3 pathway. Supported by NCI U10CA180820,180794,180821; UG1CA189859,232760,233290, 233196; Komen Foundation; Breast Cancer Research Foundation. Clinical trial information: NCT00433511.

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