Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6iss) are widely used in first-line metastatic breast cancer. For patients with progression under CDK4/6is, there is currently no standard treatment recommended at the category 1 level in international guidelines. The purpose of this article is to review the cellular mechanisms underlying the resistance to CDK4/6is, as well as treatment strategies and the clinical data about the efficacy of subsequent treatments after CDK4/6is-based therapy. In the first part, this review mainly discusses cell-cycle-specific and cell-cycle-non-specific resistance to CDK4/6is, with a focus on early and late progression. In the second part, this review analyzes potential therapeutic approaches and the available clinical data on them: switching to other CDK4/6is, to another single hormonal therapy, to other target therapies (PI3K, mTOR and AKT) and to chemotherapy.

Whole-Blood Transcriptional Profiles Enable Early Prediction of the Presence of Coronary Atherosclerosis and High-Risk Plaque Features at Coronary CT Angiography.

Existing tools to estimate cardiovascular (CV) risk have sub-optimal predictive capacities. In this setting, non-invasive imaging techniques and omics biomarkers could improve risk-prediction models for CV events. This study aimed to identify gene expression patterns in whole blood that could differentiate patients with severe coronary atherosclerosis from subjects with a complete absence of detectable coronary artery disease and to assess associations of gene expression patterns with plaque features in coronary CT angiography (CCTA). Patients undergoing CCTA for suspected coronary artery disease (CAD) were enrolled. Coronary stenosis was quantified and CCTA plaque features were assessed. The whole-blood transcriptome was analyzed with RNA sequencing. We detected highly significant differences in the circulating transcriptome between patients with high-degree coronary stenosis (≥70%) in the CCTA and subjects with an absence of coronary plaque. Notably, regression analysis revealed expression signatures associated with the Leaman score, the segment involved score, the segment stenosis score, and plaque volume with density <150 HU at CCTA. This pilot study shows that patients with significant coronary stenosis are characterized by whole-blood transcriptome profiles that may discriminate them from patients without CAD. Furthermore, our results suggest that whole-blood transcriptional profiles may predict plaque characteristics.

Circulating MicroRNAs as Novel Biomarkers in Risk Assessment and Prognosis of Coronary Artery Disease.

Coronary artery disease is among the leading causes of death worldwide. Nevertheless, available cardiovascular risk prediction algorithms still miss a significant portion of individuals at-risk. Thus, the search for novel non-invasive biomarkers to refine cardiovascular risk assessment is both an urgent need and an attractive topic, which may lead to a more accurate risk stratification and/or prognostic score definition for coronary artery disease. A new class of such non-invasive biomarkers is represented by extracellular microRNAs (miRNAs) circulating in the blood. MiRNAs are non-coding RNA of 22-25 nucleotides in length that play a significant role in both cardiovascular physiology and pathophysiology. Given their high stability and conservation, resistance to degradative enzymes, and detectability in body fluids, circulating miRNAs are promising emerging biomarkers, and specific expression patterns have already been associated with a wide range of cardiovascular conditions. In this review, an overview of the role of blood miRNAs in risk assessment and prognosis of coronary artery disease is given.

Correlations Between Physical Activity Level, Quality of Life, and Cognitive Performance in Elderly Individuals Engaging in Multi-Year Dance Activities.

INTRODUCTION: It is well-acknowledged that cognitive and physical decline associated with aging can be prevented or reduced with the engagement in regular physical activity (PA). Dance activities combine cardiovascular, cognitive, and coordinative demands, providing a popular leisure PA among elderly. This study examined the correlations between quality of life (QoL), cognitive and physical performance, and PA level in older adults who participated in at least 10 years of amateur ballroom dancing.
Methods: The study was designed as an observational study. A sample of 20 (10 men; age range: 65 to 80 years; BMI: 26.3 ± 3.0 kg/m²) amateur senior dancers were compared with a sample of 18 (8 men; age range: 65 to 75 years; BMI: 25.5 ± 2.4 kg/m²) non-sedentary individuals (control group) following an adapted PA program. Quality of life and cognitive functioning assessment tools were administered: 36 Health Status Survey (SF-36v2), Montreal Cognitive Assessment (MoCA), and Cognitive Reserve Index questionnaire (CRIq). Physical performance was measured with their preferred walking speed (PWS), and level of moderate to vigorous physical activity (MVPA) was evaluated using a multi-sensor activity monitor.
Results: Participants presented a good SF-36v2 physical component and a very good mental com- ponent summary, a total MoCA score within the limits, and an average total CRIq score. Their PWS and daily MVPA were high. Differences neither in the three questionnaires nor in PWS and PA level were observed between groups. A significant, moderate, and positive correlation was found between PWS and SF-36v2 physical component summary score.
Conclusion: Ballroom dancing seems to allow elderly individuals to maintain good cognitive and physical abilities, QoL, an acceptable normal cognitive reserve, notable physical performance, and PA level to the same extent as an adapted PA program. Both types of PA seem to be able to contrast the mental and physical decline associated with aging.