Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells.

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients' outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer.

Qualitative evaluation of a complex intervention to implement health promotion activities according to healthcare attendees and health professionals: EIRA study (phase II).

OBJECTIVE: To evaluate the implementation and development of a complex intervention on health promotion and changes in health-promoting behaviours in primary healthcare according to healthcare attendees and health professionals. DESIGN: Descriptive qualitative evaluation research conducted with 94 informants. Data collection techniques consisted of 14 semistructured individual interviews, 9 discussion groups, 1 triangular group and 6 documents. Three analysts carried out a thematic content analysis with the support of Atlas.ti software. This evaluation was modelled on Proctor and colleagues' concept of outcomes for implementation research. SETTING: 7 primary care centres from seven Spanish regions: Andalusia, Aragon, Balearic Islands, Basque Country, Castilla-La Mancha, Castilla-Leon and Catalonia. PARTICIPANTS: The study population were healthcare attendees (theoretical sampling) and health professionals (opportunistic sampling) who had participated in the exploratory trial of the EIRA intervention (2015). RESULTS: Healthcare attendees and professionals had a positive perception of the study. Healthcare attendees even reported that they would recommend participation to family and friends. Health professionals became aware of the significance of the motivational interview, especially for health promotion, and emphasised social prescribing of physical activity. They also put forward recommendations to improve recruitment, screening and retention of participants. Healthcare attendees modified behaviours and health professionals modified working practices. To achieve sustainability, health professionals believe that it is crucial to adapt agendas and involve all the staff. CONCLUSIONS: The discourses of all stakeholders on the intervention must be taken into consideration for the successful, setting-specific implementation of adequate, acceptable, equitable and sustainable strategies aimed at health promotion and well-being.

Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer.

Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a "liquid biopsy" for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination.

El perfil cronobiológico de tensión arterial y de frecuencia cardiaca en un grupo familiar, determinado mediante monitorización automática / The chronobiological profile of blood pressure and cardiac frequency in a family group, determinated via automatic monitoring

Durante una semana se determinaron: la tensión arterial (sistólica, media y diastólica) y la frecuencia cardiaca de los miembros de una familia mediante monitorización automática ininterrumpida. Se elaboró el perfil cronobiológico de cada uno de los miembros de la familia en series de tiempo de diversas periodicidades, identificándose un amplio componente circádico y otro circaseptano de menor amplitud. Se encontraron claras diferencias de fase entre los ritmos de las cuatro variables cardiovasculares estudiadas, y el perfil cronobiológico de los hijos, mostró mayor semejanza con el del padre que con el de la madre