11. Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : an observational studyMaximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Lara Wang, Amanda Golembesky, Angela Märten, Tanja Čufer, 2018, izvirni znanstveni članek Povzetek: Aim: To assess outcomes in patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer receiving sequential afatinib and osimertinib in a real-world clinical setting. Materials & methods: In this retrospective, observational, multicenter study, patients (n = 204) had T790M-positive disease following first-line afatinib and started osimertinib treatment [>/=]10 months prior to data entry. Primary outcome was time on treatment. Results: Overall median time on treatment was 27.6 months (90% CI: 25.9-31.3), 30.3 months (90% CI: 27.6-44.5) in Del19-positive patients and 46.7 months (90% CI: 26.8-not reached) in Asians. The 2-year overall survival was 78.9%. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M acquired resistance, and is a potentially attractive strategy, especially for Del19-positive tumors.
Ključne besede: lung neoplasms -- therapy, non-small-cell lung cancer, afatinib, osimertinib, epidermal growth factor receptor, EGFR, observational study
Objavljeno v DiRROS: 09.11.2020; Ogledov: 1590; Prenosov: 949
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12. Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivityGregor Vlačić, Mir Alireza Hoda, Thomas Klikovits, Katharina Sinn, Elisabeth Gschwandtner, Katja Mohorčič, Karin Schelch, Christine Pirker, Barbara Peter-Vörösmarty, Jelena Brankovic, Tanja Čufer, Aleš Rozman, Izidor Kern, 2019, izvirni znanstveni članek Povzetek: Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines.
Ključne besede: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
Objavljeno v DiRROS: 07.10.2020; Ogledov: 12253; Prenosov: 1080
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13. Multicenter evaluation of the fully automated PCR-based Idylla EGFR Mutation Assay on formalin-fixed, paraffin-embedded Q1 tissue of human lung cancerSolène M. Evrard, Estelle T. Clermont, Isabelle Rouquette, Samuel Murray, Sebastian Dintner, Yun-Chung Nam-Apostolopoulos, Beatriz Bellosillo, Mar V. Rodriguez, Ernest Nadal, Klaus H. Wiedorn, Mitja Rot, Izidor Kern, 2019, izvirni znanstveni članek Povzetek: Before initiating treatment of advanced nonesmall-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15- center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from nonesmall-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.
Ključne besede: non-small cell lung carconima -- diagnosis -- genetics, ErbB receptors, sequence analysis, tyrosine kinase inhibitors, epidermal growth factor receptor
Objavljeno v DiRROS: 07.10.2020; Ogledov: 1516; Prenosov: 1048
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14. Trace elements and nitrogen content in naturally growing moss Hypnum cupressiforme in urban and peri-urban forests of the Municipality of Ljubljana (Slovenia)S. Berisha, Mitja Skudnik, Urša Vilhar, M. Saboljević, Saša Zavadlav, Zvonka Jeran, 2017, izvirni znanstveni članek Povzetek: We monitored trace metals and nitrogen using naturally growing moss Hypnum cupressiforme Hedw. in urban and peri-urban forests of the City Municipality of Ljubljana. The aim of this study was to explore the differences in atmospheric deposition of trace metals and nitrogen between urban and peri-urban forests. Samples were collected at a total of 44 sites in urban forests (forests within the motorway ring road) and peri-urban forests (forests outside the motorway ring road). Mosses collected in urban forests showed increased trace metal concentrations compared to samples collected from peri-urban forests. Higher values were significant for As, Cr, Cu, Hg, Mo, Ni, Pb, Sb, Tl and V. Within the motorway ring road, the notable differences in element concentrations between the two urban forests were significant for Cr, Ni and Mo. Factor analysis showed three groups of elements, highlighting the contribution of traffic emissions, individual heating appliances and the resuspension of contaminated soils and dust as the main sources of trace elements in urban forests.
Ključne besede: heavy metals, biomonitoring, Ljubljana, ICP-MS, elemental analysis, factor analysis, traffic emissions
Objavljeno v DiRROS: 12.07.2017; Ogledov: 3264; Prenosov: 1238
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