Search

Additional file 10. Figure S6. PD-L1 expression contributes to cisplatin resistance in an in vitro model of acquired resistance.

Additional file 12. Figure S8. Analysis of miR-455-5p and PD-L1 association in post-chemotherapy samples of NSCLC patients.

Additional file 5. Figure S1. Whole miRNA expression profile of chemo-naïve metastatic tissue from stage III NSCLC patients.

Additional file 16. Supplemental Material.

Additional file 9. Figure S5. Higher basal levels of PD-L1 are associated to cisplatin resistance in NSCLC in vitro.

Additional file 7. Figure S3. Implantation analysis of CDX in zebrafish.

Additional file 15. Figure S11. miR-455-5p is not involved in the regulation of NOTCH-1 and HOXA-AS3 expression in NSCLC.

Additional file 6. Figure S2. Biological characterization of Cisplatin resistant cells.

Additional file 14. Figure S10. Estimation of immune features of chemo-naïve lung metastatic tumor tissue.

Additional file 13. Figure S9. miR-455-5p regulates IRF2 expression in NSCLC cell lines.

Additional file 11. Figure S7. Gating strategy used to analyze Jurkat T cells apoptosis after co-culture with NCIH1975 tumor cells.

Additional file 8. Figure S4. miR-455-5p overexpression decreases the proliferation rate of NSCLC cells.

The article is focused on the analysis of flexicurity arrangements in the Italian case with a twofold aim. The first aim is substantive, i.e. analyzing and evaluating recent labour market reforms in Italy with particular reference to the possible emergence of a new flexicurity model. The second goal is to contribute to the debate on labour market development and flexicurity by enriching and refining the available analytical tools. More specifically, we argue that the traditional conceptual "lenses' focusing on the "insiders"/"outsiders" divide are inadequate to grasp the ongoing changes in the Italian labour market. This leads us to identify a third category of workers, the "mid-siders", which are increasingly relevant in the Italian case and may prove to be relevant also in other labour markets. Moreover, we introduce the concept of "selective flexicurity", referring to the fact that in the Italian case flexibility and security measures have been applied differently across the various categories of workers.

La política latinoamericana desde una perspectiva comparada ha adquirido en los últimos tiempos una mayor centralidad e importancia dentro de las ciencias sociales, generando la necesidad de reflexionar acerca de su desarrollo histórico, su estado actual y su derrotero futuro. Política Latinoamericana Comparada es un libro que busca realizar un aporte en este sentido, acercando múltiples vías de entrada y análisis de la temática, ya que conjuga miradas panorámicas, diagnósticos regionales y perspectivas ancladas en la observación de realidades nacionales, proponiendo un escenario común en el cual dialogar, debatir y encontrar puntos de encuentro y de fuga entre especialistas. Fil: Geary, Mirta. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Lucca, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Universidad Nacional de Rosario; Argentina. Fil: Pinillos, Cintia. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Fanelli, Lucrecia. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales. Fil: Schreiner, Federico. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Perbellini, Melina. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Fernández, Elías. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Ruiz, Valeria. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales; Argentina. Fil: Orta, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Universidad Nacional de Rosario; Argentina. Fil: Kestler, Thomas. Würzburg University; Germany. Fil: Lauth, Hans-Joachim. Würzburg University; Germany. Fil: Mohamad-Klotzbach, Christoph. Würzburg University; Germany. Fil: Borrell, Mariana. Universidad Nacional de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina Fil: Heinisch, Reinhard. Universidad de Salzburgo; Austria. Fil: Gugliano, Alfredo Alejandro. Universidade Federal do Rio Grande do Sul; Brasil. Fil: Rodrigues, Priscila. Universidade Federal do Rio Grande do Sul; Brasil. Fil: Batlle, Margarita. Universidad Externado, Colombia. Fil: Cascante, María José. Universidad de Costa Rica. Fil: Basabe-Serrano, Santiago. Facultad Latinoamericana de Ciencias Sociales (FLACSO), Ecuador. Fil: Caballero Santos, Sergio. Universidad Autónoma de Madrid; España. Fil: Graziano, Paolo. Universidad Bocconi, Italia. Fil: Vidal de la Rosa: Godofredo. Universidad Autónoma Metropolitana; México. Fil: Duarte Recalde, Liliana Rocío. Universidad Católica “Nuestra Señora de la Asunción”; Paraguay. Fil: Camerlo, Marcelo. Universidad de Lisboa; Portugal. Fil: Malamud, Andrés. Universidad de Lisboa; Portugal. Fil: Chasquetti, Daniel. Universidad de la República; Uruguay. Fil: Castiglioni, Rossana. Universidad Diego Portales; Chile.

The striking clinical outcomes of antibody-based immunotherapy, through the inhibitors of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) axis, have driven research aimed at identifying further clinically relevant tumor antigens that can serve as targets in solid tumors. B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family overexpressed in tumor tissues, including non-small cell lung cancer (NSCLC), while showing limited expression in normal tissues, becoming an attractive and promising target for cancer immunotherapy. B7-H3 expression in tumors has been demonstrated to be associated with poor prognosis. In addition to its role in immune modulation, B7-H3 also promotes pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. In this review, we will provide an overview of this newly characterized immune checkpoint molecule and its development in the management of metastatic NSCLC.

AimsHeterogeneous implementation of molecular tests in current diagnostic algorithm at a European and international level is emerging as a major issue for efficient lung cancer molecular profiling.MethodsFrom May 2017 until October 2017, N=1612 patients referring to 13 Italian institutions were selected, at advanced stage non-small cell lung cancer (NSCLC), and prospectively evaluated. Principal endpoints were: the percentage of diagnoses performed on cytological and histological material, the proportion of requests for epidermal growth factor receptor (EGFR) mutational status, and resistance mutations detected on tissue and/or liquid biopsy samples after first-generation or second-generation tyrosine kinase inhibitors, the proportion of requests for anaplastic lymphoma kinase (ALK) gene rearrangements, ROS proto-oncogene 1 (ROS1) and Kirsten Rat Sarcoma (KRAS) determinations, the proportion of requests for programmed death-ligand1 (PD-L1) evaluation and, finally, the different assays used for the detection of EGFR mutations, ALK and ROS1 gene rearrangements and PD-L1 expression.ResultsOf 1325 patients finally included, only 50.8% requests were related to driver mutations with target agents already available in first-line at that preplanned time, while 49.2% were associated with PD-L1, ROS1, KRAS and others. Multiplex genomic assays (such as next-generation sequencing) were considered by all participating centres.ConclusionsTo the best of our knowledge, this is the first study in a ‘real-life daily practice’ involving both pathologists and oncologists evaluating routinely workflow and trends towards improvements in molecular requests. Collected data aim to describe the applied algorithms and evolution of molecular screening for stage IV NSCLC in clinical practice.

Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs PAs and in metastatic PCs vs non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.

Large cell carcinomas (LCCs) of the lung are heterogeneous and may be of different cell lineages. We analyzed 56 surgically resected lung tumors classified as LCC on the basis of pure morphologic grounds, using a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, cytokeratin 7, and napsin A; squamous cell carcinoma [SQCC]-specific, p63, cytokeratin 5, desmocollin 3, and Delta np63) and the quantitative analysis of microRNA-205 (microRNA sample score [mRSS]). Based on immunoprofiles 19 (34%) of the cases were reclassified as ADC and 14 (25%) as SQCC; 23 (41%) of the cases were unclassifiable. Of these 23 cases, 18 were classified as ADC and 5 as SQCC according to the mRSS. Our data show that an extended panel of immunohistochemical markers can reclassify around 60% of LCCs as ADC or SQCC. However, a relevant percentage of LCCs may escape convincing immunohistochemical classification, and mRSS could be used for further typing, but its clinical relevance needs flirt her confirmation.