Background: The emergence of platinum resistance is a significant obstacle to clinical management of lung cancer. We aimed to analyze the EGFR signaling and efficacy of EGFR inhibitors in acquired cisplatin resistance. Better understanding forms a basis for the development of novel combination therapies that could enhance patient survival. Methods: An isogenic clinical model was used to induce resistance in a panel of cell lines (H838, HCC827, H1975 and H1650 NSCLC cells) and H1339, an SCLC cell line. Cells were exposed to cisplatin (1 μg/ml/3 hrs/week) followed by recovery periods over of 4 weeks, and cisplatin-resistant phenotype (CRP) derived from original, age-matched naïve cells. They were then characterized by survival, proliferation, colony formation, and apoptosis. EGFR family receptors, phosphorylation and downstream signalling was assessed by EGFR phosphorylation and the PathScan Signaling array. The effects of EGFR TKIs (erlotinib, gefitinib, afatinib, and rociletinib) on CRP cells was evaluated at clinical concentrations. Results: CRP cells demonstrated increased survival, proliferation and resistance to apoptosis against the cisplatin challenge. CRP cells displayed altered expression of EGFR receptor family and their phosphorylation and critical nodes of signaling. But their appearance varied from cell line to cell line in comparison to their respective controls. The EGFR TKIs (except erlotinib on H838 cells) showed similar effects on CRP and their naïve cells. Conclusions: Our results identified CRP of NSCLC cells, which exhibited enhanced total EGFR and Met protein expression and their phosphorylation. This altered the expression of critical oncoproteins. The information can be used to design combination therapies with other TKIs to improve patient life. Legal entity responsible for the study: Respiratory Medicine and Thoracic Oncology (LMU Klinikum der Universitaẗ Munchen) Funding: German Center for Lung Research (DZL), Germany Disclosure: All authors have declared no conflicts of interest.

This bionomic study of the detritic bottoms dominated by macroalgae from the south of Mallorca (Balearic Islands, Western Mediterranean) includes a quantitative description of the algal communities found in the area, as well as their bathymetric and geographical distribution. The results presented here are based on data collected in two oceanographic campaigns conducted in July 2012 and September 2014, using a Jennings beam trawl. A hierarchical group average agglomerative clustering, accompanied by the SIMPROF test, allowed the identification of seven different macroalgal communities, of which two are described here for the first time: the Cryptonemia longiarticulata fields and the Maërl beds of indeterminate rhodoliths. Depth and rhodolith abundance were the two main features driving the distribution of these communities. We found that seven species contributed 70% of the similarity between samples (SIMPER test), with the indeterminate species of rhodoliths (23.6%) and the encrusting fleshy red alga, Agissea inamoena (15.6%) being the most important. The methodology used for the sample selection and quantification processes turned out to be very efficient and faster than other methods used for the characterization of macroalgal communities from detritic bottoms, suggesting that this study could serve as a baseline for similar studies and for future management and conservation actions.