Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer

Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, and is often deregulated in cancer. In this study, we found that the gene encoding the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple‐negative breast cancer (TNBC) subtype. Ablation of FZD6 expression in mammary cancer cell lines: (1) inhibited motility and invasion; (2) induced a more symmetrical shape of organoid three‐dimensional cultures; and (3) inhibited bone and liver metastasis in vivo. Mechanistically, FZD6 signalling is required for the assembly of the fibronectin matrix, interfering with the organization of the actin cytoskeleton. Ectopic delivery of fibronectin in FZD6‐depleted, triple‐negative MDA‐MB‐231 cells rearranged the actin cytoskeleton and restored epidermal growth factor‐mediated invasion. In patients with localized, lymph node‐negative (early) breast cancer, positivity of tumour cells for FZD6 protein identified patients with reduced distant relapse‐free survival. Multivariate analysis indicated an independent prognostic significance of FZD6 expression in TNBC tumours, predicting distant, but not local, relapse. We conclude that the FZD6–fibronectin actin axis identified in our study could be exploited for drug development in highly metastatic forms of breast cancer, such as TNBC. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Prevalence of Co-morbidities and Severity of COPD

We aimed at exploring whether the prevalence of co-morbidities of chronic obstructive pulmonary disease (COPD) increases with COPD severity. Analysis of medical records of outpatients with established diagnosis of COPD was retrospectively performed. The lower limit of normality (LLN) for FEV1/FVC was applied to establish the occurrence of airway obstruction in the elderly population. The prevalence of co-morbidities was calculated, and the proportion of patients with each co-morbidity along with GOLD stages was analysed by chi-square for trend. A total of 326 (M/F: 256/70) consecutive outpatients with COPD (stage GOLD I to IV), aging 71.8 ± 9.2 years, were included in the analysis. The most frequent co-morbidities in the entire sample were systemic hypertension (64.7%), diabetes (28.5%), coronary artery disease (19.9%), arrhythmias (16.6%) and congestive heart failure (13.8%). Underweight patients were 8.0% of the sample while obese patients were 22.4%. None of the analyzed co-morbidities showed a trend towards increasing prevalence with COPD severity, except for nutritional problems. The current findings suggest that the occurrence and prevalence of co-morbidities is independent from the COPD severity, and encourage to assess co-morbidities even in the early stages of the COPD.     

Phonographic detection of mechanical heart valve thrombosis

The formation of thrombotic deposits affects the functionality of mechanical prosthetic heart valves; as a consequence, mechanical valves thrombosis needs early diagnosis to prevent thromboembolic events. This paper compares the acoustic signals produced by two commercial bileaflet mechanical heart valves in the closing phase to detect the presence of thrombi. The closing sounds were recorded in vitro by means of a phonocardiographic device under different hydrodynamic conditions. Thrombotic deposits of different weight and shape were applied onto the valve leaflet and the annular housing, until the movement of one leaflet was completely blocked. From the acoustic signals, the corresponding spectra were calculated and four diagnostic frequency bands were identified: their comparison allowed detecting malfunctioning valves because of the presence of thrombotic formations.