Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis

Most non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitor (TKI) therapy. However, about 30% exhibit primary resistance to EGFR TKI therapy. Here we report that Met protein expression and phosphorylation were associated with primary resistance to EGFR TKI therapy in NSCLC patients harboring EGFR mutations, implicating Met as a de novo mechanism of resistance. In a separate patient cohort, Met expression and phosphorylation were also associated with development of NSCLC brain metastasis and were selectively enriched in brain metastases relative to paired primary lung tumors. A similar metastasis-specific activation of Met occurred in vitro in the isogenous cell lines H2073 and H1993, which are derived from the primary lung tumor and a metastasis, respectively, from the same patient. We conclude that Met activation is found in NSCLC before EGFR-targeted therapy and is associated with both primary resistance to EGFR inhibitor therapy and with the development of metastases. If confirmed in larger cohorts, our analysis suggests that patient tumors harboring both Met activation and EGFR mutation could potentially benefit from early intervention with a combination of EGFR and Met inhibitors

Micro-CT - A Digital 3D Microstructural Voyage into Scaffolds: A Systematic Review of the Reported Methods and Results

Background: Cell behavior is the key to tissue regeneration. Given the fact that most of the cells used in tissue engineering are anchorage-dependent, their behavior including adhesion, growth, migration, matrix synthesis, and differentiation is related to the design of the scaffolds. Thus, characterization of the scaffolds is highly required. Micro-computed tomography (micro-CT) provides a powerful platform to analyze, visualize, and explore any portion of interest in the scaffold in a 3D fashion without cutting or destroying it with the benefit of almost no sample preparation need. Main body: This review highlights the relationship between the scaffold microstructure and cell behavior, and provides the basics of the micro-CT method. In this work, we also analyzed the original papers that were published in 2016 through a systematic search to address the need for specific improvements in the methods section of the papers including the amount of provided information from the obtained results.FROnTHERA Project (NORTE-01-0145-FEDER-000023) within the Norte Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement, through ERDF, and Portuguese Foundation for Science and Technology (SFRH/BD/99555/2014, IF/00423/2012, and IF/01285/2015).info:eu-repo/semantics/publishedVersio