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Introduction: Targeting Kirsten Rat Sarcoma (KRAS) has been deemed impossible for long time, but new drugs have recently demonstrated promising results. Evidence on the outcome of KRAS-mutant advanced-NSCLC treated with new standard regimens are still scarce. Thus, we aimed at assessing the incidence and clinical impact of KRAS mutations in a real-life population of advanced-NSCLC, exploring the prognostic significance of distinct alterations., Materials and Methods: The present multicenter retrospective study, conducted by 5 Italian Centers from January 2018 to February 2020, involved 297 advanced KRAS mutant NSCLC. Complete clinico-pathological data were evaluated., Results: Out of 297 patients, 130 carried KRAS_G12C mutation, while 167 presented with mutations other than G12C. Within KRAS_non-G12C group, 73%, 16.8% and 8.9% harboured G12X, codon 13 and Q61H alterations, respectively. No significant differences in survival outcome and treatment response were documented according to KRAS_G12C versus non-G12C, nor KRAS_G12C versus G12X versus other mutations. On univariate analysis ECOG PS, number and sites of metastatic lesions and PD-L1 status significantly impacted on survival. A clear trend towards worse prognosis was apparent in chemotherapy-treated patients, while immunotherapy-based regimens were associated to prolonged survival. Investigating the outcome of PD-L1 ≥ 50% population, we did not detect any significant difference between KRAS_G12C and non-G12C subsets., Conclusion: Here, we report on real-life data from a large retrospective cohort of advanced NSCLC harbouring KRAS alterations, with particular attention to G12C mutation. Our study offers useful clues on survival outcome, therapeutic response and clinico-pathological correlations in KRAS-mutant setting, especially in the upcoming era of KRAS G12C targeting therapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients whose disease has progressed during treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired resistance mechanism. The objective of this study was to assess a real-life picture of EGFR T790M detection in LB., Materials and Methods: Liquid biopsies performed between June 2016 and October 2018 for advanced EGFR-mutated NSCLC at disease progression during treatment with first- and second-generation TKIs were retrospectively evaluated in 5 Italian centers. Circulating tumor DNA was extracted from plasma and tested with different commercial kits. The detection rate in LBs and the patients' characteristics were correlated., Results: We enrolled 120 consecutive patients. The overall T790M detection rate observed using LB was 25.8%. Fifty-four of 89 (60.7%) patients with negative LB results underwent tissue rebiopsy, and 56% were positive for T790M. The overall rate of T790M positivity in the study cohort was 49.2%. LB performed before formal tumor progression according to Response Evaluation Criteria In Solid Tumors criteria was negative for T790M in all patients (n = 21; P = .012). T790M positivity was statistically significantly higher in cases of disease progression at extrathoracic metastatic sites (P = .008) and, specifically, in the case of worsening bone disease (P = .003)., Conclusion: Our study shows that the detection of T790M-positive patients whose disease progressed during treatment with first- and second-generation TKIs in real life was according to the literature. However, this result was obtained with a specific clinical course (repeat LBs and tissue rebiopsy), thus implying the necessity for multidisciplinary management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Transbronchial cryobiopsy, a new diagnostic procedure in patients with diffuse lung disease, provides larger and better-preserved lung specimens compared to forceps biopsy. The diagnostic yield of cryobiopsy is much better than that of forceps biopsy and slightly lower than that of surgical lung biopsy, but with a lower complication rate compared to the latter. Literature suggests that in the multidisciplinary approach to patients with diffuse lung disease cryobiopsy provides diagnostic and prognostic information similar to surgical lung biopsy. Cryobiopsy can also be performed in some patients unsuitable for surgical biopsy, yet in whom histologic input is needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In view of the potential use of pyrolysis-based technologies, it is crucial to understand the environmental hazards of pyrolysis-derived products, in particular bio-oils. Here, three bio-oils were produced from fast pyrolysis of pine wood and intermediate pyrolysis of corn stalk and poultry litter. They were fully characterized by chemical analysis and tested for their biodegradability and their ecotoxicity on the crustacean Daphnia magna and the green alga Raphidocelis subcapitata. These tests were chosen as required by the European REACH regulation. These three bio-oils were biodegradable, with 40-60% of biodegradation after 28 days, and had EC50 values above 100mgL(-1) for the crustacean and above 10mgL(-1) for the alga, showing low toxicity to the aquatic life. The toxic unit approach was applied to verify whether the observed toxicity could be predicted from the data available for the substances detected in the bio-oils. The predicted values largely underestimated the experimental values., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this study we have explored the effects of different groups of ionic liquids (ILs) on membrane fusion. The ILs used contain different head groups: N-methylimidazolium, 3-methylpyridinium and N-methylpyrrolidinium; short alkyl or ether functionalized side chains (with one or two ethoxy functionalities), paired with chloride anion. These ILs have been compared with 1-dodecyl-3-methylimidazolium bromide as example of a highly lipophilic IL. The effect of ILs on membrane fusion was investigated through pyrene steady state fluorescence probing, using the IE factor and excimer/monomer ratio (IE/IM) as parameters. The ratio between the vibronic bands of pyrene (I1/I3 ratio) has been used to monitor the effect of ILs on the aggregation properties of egg-PC liposomes. The effect of different ILs' families was evident; the pyridinium ILs induced a greater extent of fusion than pyrrolidinium and imidazolium ILs having the same side chain. Marginal effect could be attributed to different anions. ILs with short alkyl chains were usually more effective than ether functionalized ones. The aggregation behaviors of ILs having dioxygenated chains have been measured in buffer solution., (Copyright © 2014 Elsevier B.V. All rights reserved.)

EDDHSA/Fe is a promising substitute of EDDHA/Fe to fight iron chlorosis. o,o-EDDHSA structure contains two chiral carbons giving the racemic and meso couples of stereoisomers. Ion-pair HPLC and UHPLC-UV/Vis-ESI-MS/MS methods were developed for the determination of racemic and meso-o,o-EDDHSA/Fe in commercial samples of chelates. The lack of a commercial EDDHSA standard was overcome by sulfonation of a commercial available o,o-EDDHA standard and subsequent quantification by (1)H-NMR. Assignment of configurations was carried out starting from racemic and meso-o,o-EDDHA/Fe by direct sulfonation to give the corresponding o,o-EDDHSA/Fe isomers. The performances of these methods were assessed in terms of intra and inter-day precision, linearity and selectivity. The high selectivity and lower detection limit (nanomolar) of the UHPLC-ESI-MS/MS method could allow to deepen the knowledge relative to meso and rac-o,o-EDDHSA/Fe interactions with plants, its fate in different soil conditions, its mobility and other environmental aspects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Adenomas are the easily identifiable precursors of the vast majority of colorectal cancers. Some of their morphological features, such as dysplasia, are predictive of their biological evolution toward adenocarcinomas. A large body of evidence has demonstrated that the epidermal growth factor receptor (EGFR) signaling pathway is commonly activated in colorectal cancer and EGFR-target therapies have improved the outcome for colorectal cancer patients. Nevertheless, the mechanisms underlying the role of EGFR in the adenoma-carcinoma sequence are not entirely clear. We retrospectively analyzed EGFR gene copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tissue from 215 patients recruited through a prospective colorectal cancer screening procedure and undergoing surgical colectomy. We observed that in human colorectal carcinogenesis, EGFR copy number increases progressively, from adenomas with high-grade dysplasia to locally advanced adenocarcinomas, through early invasive adenocarcinomas, suggesting that deregulation of EGFR may correlate with the malignant progression., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The biological effects of a class of oxygenated imidazolium ionic liquids were studied in comparison with alkyl imidazolium salts (BMIM BF4 and BMIM N(CN)2).The cellular and subcellular effects were evaluated on rat pheochromocytoma PC12 cell lines, through MTT test, lactate dehydrogenase release and acetylcholinesterase inhibition; the eco-toxicological responses were assessed through the acute toxicity tests towards Daphnia magna and Vibrio fischeri. The introduction of ethoxy moieties in the lateral chain of imidazolium cations reduced the biological effects in all the tests. The acute toxicity towards D. magna was not affected by the number of ethoxy units, but the crustacean seemed to be sensitive to the type of anion; on the contrary, a further addition of ethoxy moieties increased the toxicity towards V. fischeri, M(OE)4MIM N(CN)2 being the most toxic oxygenated ionic liquid. In the cytotoxicity assays the salts with oxygenated cations resulted ineffective compared to BMIMs, independently from the anion and the number of ethoxy units in the lateral chain. In order to estimate the influence on membrane fluidity, an analysis of fluorescence anisotropy was done and it indicated that BMIM BF4, the most toxic ionic liquid among the tested ones, led to a destabilization of the model membranes at any molarity., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)