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During the second covid-19 pandemic wave in November-December 2021 Prevention Departments had to face a hardly-sustainable workload of contact tracing and taking charge of the sars-cov2 positive case and of his or her close contacts. also laboratories have been stressed in their ability to process timely the extraordinary load of swabs performed. In this context of hazardous delays, the Prevention Department of Belluno (Italy) tested its resilience: a simple and effective method of taking charge was implemented, by initially phoning to the positive case and imposing the isolation measure on him or her and later on proceeding with the conventional contact tracing. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is the first cause of cancer‐related death among men and the second among women worldwide. It also poses an economic threat to the sustainability of healthcare services. This study estimated the direct costs of care for patients with NSCLC by stage at diagnosis, and management phase of pathway recommended in local and international guidelines. Methods: Based on the most up‐to‐date guidelines, we developed a very detailed "whole‐disease" model listing the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of each stage of NSCLC. We assigned a cost to each procedure, and obtained an estimate of the total and average per‐patient costs of each stage of the disease and phase of its management. Results: The mean expected cost of a patient with NSCLC is 21,328 € (95% C.I. −20 897−22 322). This cost is 16 291 € in stage I, 19530 € in stage II, 21938 € in stage III, 22175 € in stage IV, and 28 711 € for a Pancoast tumor. In the early stages of the disease, the main cost is incurred by surgery, whereas in the more advanced stages radiotherapy, medical therapy, treatment for progressions, and supportive care become variously more important. Conclusions: An estimation of the direct costs of care for NSCLC is fundamental in order to predict the burden of new oncological therapies and treatments on healthcare services, and thus orient the decisions of policy‐makers regarding the allocation of resources. Key points: Significant findings of the study: The high costs of surgery make the early stages of the disease no less expensive than the advanced stages. What this study adds: An estimation of the direct costs of care is fundamental in order to orient the decisions of policy‐makers regarding the allocation of resources. [ABSTRACT FROM AUTHOR]

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the stability of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpression or activation through growth arrest-specific 6 (Gas6) ligand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity. Upon activation, AXL stabilizes MDMX through a post-translational modification that involves phosphorylation of MDMX on the phosphosite Ser314, leading to increased affinity between MDMX and MDM2 and favouring MDMX nuclear translocation. Ser314 phosphorylation can also protect MDMX from MDM2-mediated degradation, leading to stabilization of the MDMX-MDM2 complex. We identified CDK4/6 and p38 MAPK as the two kinases mediating AXL-induced modulation of the MDMX-MDM2 complex, and demonstrated that suppression of AXL, either through siRNA silencing or pharmacological inhibition, increases expression levels of p53 target genes P21, MDM2, and PUMA, improves p53 pathway response to chemotherapy, and sensitizes cells to both Cisplatin and Vemurafenib. Our findings offer an insight into a novel signalling axis linking AXL to p53 and provide a potentially druggable pathway to restore p53 function in melanoma. [ABSTRACT FROM AUTHOR]