ABSTRACT
Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.
ABSTRACT
Industrial biotechnology gene expression systems relay on constitutive promoters compromising cellular growth from the start of the bioprocess, or on inducible devices, which require manual addition of cognate inducers. To overcome this shortcoming, we engineered an automata regulatory system based on cell-stress mechanisms. Specifically, we engineered a synthetic and highly portable phosphate-depletion library of promoters inspired by bacterial PHO starvation system (Pliar promoters). Furthermore, we fully characterized 10 synthetic promoters within the background of two well-known bacterial workhorses such as E. coli W and P. putida KT2440. The promoters displayed an interesting host-dependent performance and a wide strength spectrum ranging from 0.4- to 1.3-fold when compared to the wild-type phosphatase alkaline promoter (PphoA). By comparing with available gene expression systems, we proved the suitability of this new library for the automata and effective decoupling of growth from production in P. putida. Growth phase-dependent expression of these promoters could therefore be activated by fine tuning the initial concentration of phosphate in the medium. Finally, the Pliar library was implemented in the SEVA platform in a ready-to-use mode allowing its broad use by the scientific community.
Subject(s)
Escherichia coli , Phosphates , Escherichia coli/genetics , Gene Expression , Gene Expression Regulation, Bacterial , Gene Library , Promoter Regions, GeneticABSTRACT
BACKGROUND: The literature on occupational violence and even more the literature on violence against nurses in health settings have evidenced inconsistencies regarding how workplace violence has been conceptualized. PURPOSE: To review and discuss some inconsistencies regarding how workplace violence against nurses in health settings has been conceptualized paying special attention to the challenges posed to the health of nurses stemming from patients, visitors or co-workers. METHOD: Review of data of the European Working Conditions Surveys, and National Surveys on Working Conditions in Spain. DISCUSSION: It is necessary to overcome these conceptual inconsistencies on violence in order to carry out intervention programmes based on solid theoretical grounds. CONCLUSIONS: Violence against nurses takes place within an organisational climate defined by role relationships. The organizational climate can either reduce the likelihood of violence or, on the contrary, instigate violent behaviors.
