The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries.

The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2- positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2- dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Comportamiento prooxidante y antioxidante de hierbas aromáticas en queso

Los quesos de cabra, con mejores cualidades funcionales provienen de leche de cabras en pastoreo, esto obedece al mayor contenido de ácidos grasos ω-3 y ω-6 en una relación óptima para la salud, sumado a un menor contenido de grasa y colesterol. Saborizar quesos con especias, otorga beneficios sensoriales y saludables al producto. Las especias son usadas para realzar el flavor de los alimentos además presentan beneficios antioxidantes. Sin embargo, se reportaron evidencias del doble papel de los flavonoides como antioxidantes o prooxidantes en función de la concentración de uso. El objetivo del trabajo es evaluar el efecto de distintas concentraciones de especias aromáticas con capacidad antioxidante, frente a las reacciones de deterioro que ocurren en el almacenamiento de quesos de cabra. Se estudió la actividad antirradicalaria (AAR) de 18 especias. Para evaluar la actividad antioxidante (AA0) se usó la técnica de desaparición de un radical libre estable el 2,2-difenil-1-picril hidrazilo (DPPH) y se calculó la AAR porcentual. Definido el queso base estándar (control), se ensayaron tres variedades con especies, elegidas de entre las de mayor AAR (orégano, romero y tomillo) y se adicionaron con las concentraciones 0,4 – 1 % p/p. Estos, fueron madurados 30 días y almacenados 7 meses a 4 °C. Se analizaron cada 4 semanas. Se realizaron pruebas sensoriales de aceptabilidad con 60 consumidores de queso (condición), usando planillas, con escala hedónica. Se trabajó sobre los lípidos extraídos de los quesos. El rancidez y deterioro fueron evaluados con análisis de acidez; índice peróxido y sustancias reactivas al ácido TBA. Los resultados se compararon con el comportamiento sensorial del producto en el tiempo de almacenamiento. En los quesos adicionados al 1 %, la acidez se incrementó con el almacenamiento. El máximo valor corresponde al queso con orégano (3,72 % de ac. láctico a los 126 días). En el control, la acidez inicial fue inferior y alcanzó 1,05 g de ác. láctico % a los 166 días. El IP más alto corresponde a los quesos con orégano al 1% , resultado que se contrapone a la actividad antirradicalaria de esta especia. Al 0,4 %, tanto el IP como el número de TBA son menores en quesos adicionados, respecto del control. En los quesos de cabra analizados las especias agregadas al 1% ejercieron acción prooxidante, mientras que al ser agregadas al 0,4% la acción es antioxidante, lo que indica la importancia de la selección de concentraciones adecuadas.Goat cheeses with better functional qualities, due to greater fatty acid content ω 3 and ω 6, come from free-range goat milk in an optimal relation for health, besides having a smaller content of fat and cholesterol. The spices, which present antioxidant benefits, are used to heighten the flavor of foods. Nevertheless, evidence of the double role of the flavonoids as antioxidant or prooxidant was reported based on their use concentration. Flavoring cheeses with spices gives sensory and healthy benefits to the product. The objective of the present work is to evaluate the effect of different aromatic spice concentrations with antioxidant capacity, as opposed to the deterioration reactions that happen in the goat cheese storage. The antiradical capacity (ARA) of 18 spices was studied. In order to evaluate the Antioxidant activity (AOA) the technique of disappearance of a stable free radical was used and the 2,2-diphenyl-2-picrylhydrazyl (DPPH) and the percentage ARA were calculated as well. Once the standard basic cheese (control) was defined, we tried three varieties with species, chosen from among those of greater AAR (oregano, rosemary and thyme) and were added with 0,4 - 1% p/p concentrations. These ripened in 30 days and were stored for 7 months at 4 °C. Every 4 weeks they were analyzed. Sensory tests of acceptability with 60 cheese consumers were carried out (condition), using checklists, with the hedonic scale. The work was performed on lipids extracted of cheeses according to Bligh Dyer method. The rancid flavor and deterioration were evaluated with the analysis of acidity; peroxide index (PI), and reactive substances to TBA acid. The results were compared with the sensory behavior of the product during the time of storage. All the assays were produced in triplicate. The data were put under the descriptive statistical and variance analysis. In cheeses, to which spices were added to 1%, the acidity increased with the storage. The maximum value was the cheese with oregano (3.72% of ac. lactic to the 126 days). In the control, the initial acidity was inferior and reached 1.05 g % of lactic acid to the 166 days. The PI in cheeses to 1% with oregano was higher, result that is opposed to the antiradical activity of this spice. To 0.4%, both the PI and the number of TBA are smaller in added cheeses, with respect to the control. In goat cheeses the spices added to 1% exert prooxidating action. However, to 0.4% it is AAO, which indicates the importance of the selection of suitable concentrations. Key words: antioxidant capacity - prooxidant- spices - goat cheese – rancid flavo

Tumor-infiltrating (TINKs) and tumor-associated (TANKs) natural killer cells: a new player in the inflammatory orchestration of tumor angiogenesis in colon cancer

Natural Killer (NK) cells are lymphocytes of innate immunity that can potentially control tumors by their cytotoxic activity. The NK cells of patients with NSCLC, both tumor infiltrating (TINKs) and tumor associated (TANKs, from peripheral blood), are poorly cytotoxic, CD56brightCD16-, producing substantial levels of VEGF, PlGF, IL-8 and induce angiogenesis in vitro. In the present study we extended our analysis on colorectal cancer (CRC) TINKs and TANKs. NK cell were isolated from blood and tissue (adjacent-normal and tumor tissues) from patients with CRC then phenotypically and functionally characterized for surface antigen expression and cytokine profiling by multiparametric flow cytometry. Functional angiogenesis assays were performed on human umbilical vein cells, using conditioned media derived from isolated NK cells. We found that the CD56brightCD16- NK cells predominate in both the tumors and adjacent tissues derived from CRC samples. The CRC TINKs are poorly cytotoxic and express markers of decidual NK cells (CD9 and CD49a). TINKs produce pro-angiogenic factors, including VEGF, PlGF and IL-8, associated with induction of migration and capillary-like structure formation of endothelial cells in vitro. TANKS also produced VEGF. The \u201cswitched\u201d phenotype and function of tumor infiltrating NK cells acquire a broad implications in the role of immune response against tumors and this places NK cells as a new playe r in the inflammatory promotion of tumor angiogenesis

Neuroprem: the Neuro-developmental outcome of very low birth weight infants in an Italian region

The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome