Aplicación del índice ECSI para analizar, según modelo PLS-SEM, la satisfacción de los operadores y usuarios de las OPFH en Cataluña

El objeto de esta comunicación es resumir la investigación sobre las OPFH en Cataluña, en lo que respecta al análisis de la satisfacción del operador y usuario de estas, según el European Customer Satisfaction Index (ECSI), aplicando el modelo PLS-SEM, y que será un apartado de una Tesis Doctoral. La PAC reconoce las intervinculaciones multisectoriales con sus objetivos de 1. “garantizar un suministro estable de alimentos asequibles”, 2. “mantener viva la economía rural mediante la promoción de empleos en la agricultura, las industrias agroalimentarias y los sectores asociados y de servicios” y 3. “promover, proteger y controlar la calidad y sanidad de los alimentos”, y para ello, los retos de su cumplimiento deben pasar por el asociacionismo profesional, sobre todo, en el primer eslabón de la cadena de valor, con el papel de las OPFH para imprimir eficiencia y resolver problemáticas sectoriales, a través de los Programas y Fondos Operativos. Es esencial testar y analizar las opiniones sobre el funcionamiento de las OPFH y los Programas Operativos. Para ello se ha diseñado una encuesta aplicada a 171 profesionales y usuarios de OPFH en Cataluña, y se ha aplicado el modelo ECSI para analizarlo con PLS-SEM a través del programa SmartPLS 3.3.3

Las organizaciones de productores de frutas y hortalizas en Europa y España: un modelo PAC para resolver los problemas sectoriales. El caso de las OPFH en España

El objetivo general de esta comunicación es estudiar y analizar el papel actual de las OPFH y AOP como figuras primordiales de la PAC de la Unión Europea, para tratar de resolver las problemáticas que año tras año están anidadas en el sector de frutas y hortalizas, estudiando con atención el caso de España. A través de datos e informaciones de la Comisión Europea, Eurostat, MAPA, FEGA y otras instituciones, se estudia cómo han evolucionado las OPFH en la UE y en nuestro país, se analizan las problemáticas del sector de Frutas y Hortalizas, y las herramientas fundamentales para su solución y avance por el camino de la eficacia-eficiencia, como son los Programas y Fondos Operativos, y su aplicación en las distintas CCAA españolas

TGFβ controls ovarian cancer cell proliferation

There have been no major improvements in the overall survival of ovarian cancer patients in recent decades. Even though more accurate surgery and more effective treatments are available, the mortality rate remains high. Given the differences in origin and the heterogeneity of these tumors, research to elucidate the signaling pathways involved is required. The Transforming Growth Factor (TGFβ) family controls different cellular responses in development and cell homeostasis. Disruption of TGFβ signaling has been implicated in many cancers, including ovarian cancer. This article considers the involvement of TGFβ in ovarian cancer progression, and reviews the various mechanisms that enable the TGFβ signaling pathway to control ovarian cancer cell proliferation. These mechanistic explanations support the therapeutic use of TGFβ inhibitors in ovarian cancer, which are currently in the early phases of development

Fusion of the human gene for the polyubiquitination coeffector UEV1 with Kua, a newly identified gene

UEV proteins are enzymatically inactive variants of the E2 ubiquitin-conjugating enzymes that regulate noncanonical elongation of ubiquitin chains. In Saccharomyces cerevisiae, UEV is part of the RAD6-mediated error-free DNA repair pathway. In mammalian cells, UEV proteins can modulate c-FOS transcription and the G2-M transition of the cell cycle. Here we show that the UEV genes from phylogenetically distant organisms present a remarkable conservation in their exon-intron structure. We also show that the human UEV1 gene is fused with the previously unknown geneKua. In Caenorhabditis elegans and Drosophila melanogaster, Kua and UEV are in separated loci, and are expressed as independent transcripts and proteins. In humans,Kua and UEV1 are adjacent genes, expressed either as separate transcripts encoding independent Kua and UEV1 proteins, or as a hybrid Kua-UEV transcript, encoding a two-domain protein. Kua proteins represent a novel class of conserved proteins with juxtamembrane histidine-rich motifs. Experiments with epitope-tagged proteins show that UEV1A is a nuclear protein, whereas both Kua and Kua-UEV localize to cytoplasmic structures, indicating that the Kua domain determines the cytoplasmic localization of Kua-UEV. Therefore, the addition of a Kua domain to UEV in the fused Kua-UEV protein confers new biological properties to this regulator of variant polyubiquitination

Integrating clinical, molecular, proteomic and histopathological data within the tissue context : tissunomics

Malignant tumours show a marked degree of morphological, molecular and proteomic heterogeneity. This variability is closely related to microenvironmental factors and the location of the tumour. The activation of genetic alterations is very tissue-dependent and only few tumours have distinct genetic alterations. Importantly, the activation state of proteins and signaling factors is heterogeneous in the primary tumour and in metastases and recurrences. The molecular diagnosis based only on genetic alterations can lead to treatments with unpredictable responses, depending on the tumour location, such as the tumour response in melanomas versus colon carcinomas with mutations. Therefore, we understand that the correct evaluation of tumours requires a system that integrates both morphological, molecular and protein information in a clinical and pathological context, where intratumoral heterogeneity can be assessed. Thus, we propose the term 'tissunomics', where the diagnosis will be contextualised in each tumour based on the complementation of the pathological, molecular, protein expression, environmental cells and clinical data

Determinacions del perfil genètic de tumors sòlids de l’adult

Perfil genètic; Tumors sòlids; Adults; PrecisióPerfil genético; Tumores sólidos; Adultos; PrecisiónGenetic profile; Solid tumors; Adults; AccuracyEn aquest estudi s’ha definit la llista de gens per a cada patologia i tots ells han estat seleccionats atenent a; la seva utilitat diagnòstica per definir els subtipus tumorals en localitzacions tumorals molt concretes; la seva utilitat pronòstica i predictiva, sempre que això comporti un canvi d’actitud terapèutica; la seva utilitat terapèutica per a la indicació de l’ús de fàrmacs diana

Biomarkers of tumor-reactive CD4+ and CD8+ TILs associate with improved prognosis in endometrial cancer

Background: Despite the growing interest in immunotherapeutic interventions for endometrial cancer (EC), the prevalence, phenotype, specificity and prognostic value of tumor infiltrating lymphocytes (TILs) in this tumor type remains unclear. Methods: To better understand the role of TILs in EC, we analyzed the phenotypic traits of CD8+ and CD4+ EC-resident T cells from 47 primary tumors by high-dimensional flow cytometry. In addition, CD8+ and CD4+ TIL subpopulations were isolated based on the differential expression of programmed cell death protein-1 (PD-1) (negative, dim and high) and CD39 (positive or negative) by fluorescence activated cell sorting (FACS), expanded in vitro, and screened for autologous tumor recognition. We further investigated whether phenotypic markers preferentially expressed on CD8+ and CD4+ tumor-reactive TIL subsets were associated with the four distinct molecular subtypes of EC, tumor mutational burden and patient survival. Results: We found that CD8+TILs expressing high levels of PD-1 (PD-1hi) co-expressed CD39, TIM-3, HLA-DR and CXCL13, as compared with TILs lacking or displaying intermediate levels of PD-1 expression (PD-1- and PD-1dim, respectively). Autologous tumor reactivity of sorted and in vitro expanded CD8+ TILs demonstrated that the CD8+PD-1dimCD39+ and PD-1hiCD39+ T cell subsets both contained tumor-reactive TILs and that a higher level of PD-1 expression was associated with increased CD39 and a superior frequency of tumor reactivity. With respect to CD4+ T conventional (Tconv) TILs, co-expression of inhibitory and activation markers was more apparent on PD-1hi compared with PD-1- or PD-1dim T cells, and in fact, it was the CD4+PD-1hi subpopulation that accumulated the antitumor T cells irrespective of CD39 expression. Most importantly, detection of CD8+PD-1hiCD39+ and CD4+PD-1hi tumor-reactive T-cell subsets, but also markers specifically expressed by these subpopulations of TILs, that is, PD-1hi, CD39, CXCL13 and CD103 by CD8+ TILs and PD-1hi and CXCL13 by CD4+ Tconv TILs, correlated with prolonged survival of patients with EC. Conclusions: Our results demonstrate that EC are frequently infiltrated by tumor-reactive TILs, and that expression of PD-1hi and CD39 or PD-1hi can be used to select and expand CD8+ and CD4+ tumor-reactive TILs, respectively. In addition, biomarkers preferentially expressed on tumor-reactive TILs, rather than the frequency of CD3+, CD8+ and CD4+ lymphocytes, hold prognostic value suggesting their protective role in antitumor immunity

Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics

Purpose: Tumor antigens are central to antitumor immunity. Recent evidence suggests that peptides from noncanonical (nonC) aberrantly translated proteins can be presented on HLA-I by tumor cells. Here, we investigated the immunogenicity of nonC tumor HLA-I ligands (nonC-TL) to better understand their contribution to cancer immunosurveillance and their therapeutic applicability. Experimental Design: Peptides presented on HLA-I were iden-tified in 9 patient-derived tumor cell lines from melanoma, gyneco-logic, and head and neck cancer through proteogenomics. A total of 507 candidate tumor antigens, including nonC-TL, neoantigens, cancer-germline, or melanocyte differentiation antigens, were tested for T-cell recognition of preexisting responses in patients with cancer. Donor peripheral blood lymphocytes (PBL) were in vitro sensitized against 170 selected nonC-TL to isolate antigen-specific T-cell recep-tors (TCR) and evaluate their therapeutic potential.Rudolf Virchow Center, Center for Integrative and Transla- tional Bioimaging, Julius-Maximilians-University Wueurorzburg, Wueurorzburg, German