Association of high miR-27a, miR-206, and miR-214 expression with poor patient prognosis and increased chemoresistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, associated with early metastasis and recurrence as well as poor patient outcome. TNBC does not or weakly respond to hormonal or HER2-targeted therapies. Therefore, there is a strong need to identify other potential molecular targets for TNBC therapy. Micro-RNAs play important roles in the post-transcriptional regulation of gene expression. Thus, micro-RNAs, displaying an association between elevated expression and poor patient prognosis, may represent candidates for such novel tumor targets. In the present study, we evaluated the prognostic impact of miR-27a, miR-206, and miR-214 in TNBC via qPCR in tumor tissue (n=146). In univariate Cox regression analysis, elevated expression of all three analyzed micro-RNAs was significantly associated with shortened disease-free survival (hazard ratio [HR] for miR-27a: 1.85, P=0.038; miR-206: 1.83, P=0.041; miR-214: 2.06, P=0.012). In multivariable analysis, the micro-RNAs remained independent biomarkers for disease-free survival (HR for miR-27a: 1.99, P=0.033; miR-206: 2.14, P=0.018; miR-214: 2.01, P=0.026). Furthermore, our results suggest that elevated levels of these micro-RNAs are linked to enhanced resistance to chemotherapy. Based on the association of high expression levels with shortened patient survival and increased chemoresistance, miR-27a, miR-206, and miR-214 may represent novel molecular targets for TNBC.

A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin.

Many mechanobiological processes that govern development and tissue homeostasis are regulated on the level of individual molecular linkages, and a number of proteins experiencing piconewton-scale forces in cells have been identified. However, under which conditions these force-bearing linkages become critical for a given mechanobiological process is often still unclear. Here, we established an approach to revealing the mechanical function of intracellular molecules using molecular optomechanics. When applied to the integrin activator talin, the technique provides direct evidence that its role as a mechanical linker is indispensable for the maintenance of cell-matrix adhesions and overall cell integrity. Applying the technique to desmoplakin shows that mechanical engagement of desmosomes to intermediate filaments is expendable under homeostatic conditions yet strictly required for preserving cell-cell adhesion under stress. These results reveal a central role of talin and desmoplakin as mechanical linkers in cell adhesion structures and demonstrate that molecular optomechanics is a powerful tool to investigate the molecular details of mechanobiological processes.

[Prevention of chronic pain in the German healthcare system : Current state and perspective]. / Vermeidung chronischer Schmerzen in der deutschen Gesundheitsversorgung : Derzeitiger Stand und Ausblick.

The current healthcare provision in Germany is established, in particular, for the diagnostics and treatment of chronic pain conditions; however, the current aim is to initiate the diagnostic and therapeutic approaches oriented towards the biopsychosocial pain model in the early stages of pain, i.e. before the onset of chronification, for patients with pain and a risk of chronification in order to actively avoid chronification processes. In this context, multiple risk factors play an important role for the diagnostic and therapeutic approaches as well as for the interdisciplinary multimodal pain therapy developed for this purpose. The Global Year of the International Association for the Study of Pain (IASP) 2020 addressed the prevention of (chronic) pain, a welcome opportunity to provide a short review of the evidence for and clinical experiences with timely diagnostic and therapeutic options and to summarize the current framework conditions and scientific recommendations for Germany. At the end of this article the implications for future research are summarized, particularly for the treatment of patients with pain and risk of chronification.