The complex life of DICKKOPF-1 in cancer cells

This work is licensed under a Creative Commons Attribution 4.0 International License.The role of DICKKOPF (DKK)-1 in human cancer is controversial. DKK-1 behaves as an inhibitor of the canonical Wnt/β-catenin signaling pathway acting at the plasma membrane, although several studies have proposed effects that are independent of the inhibition of β-catenin transcriptional activity, in some cases mediated by the activation of c-Jun N-terminal kinase (JNK). Recently, a proportion of DKK-1 protein has been found within the nucleus of human intestinal epithelial cells following an apical-to-basal crypt decreasing gradient, and in that of colon carcinoma cells. Moreover, we show here that in the human mammary gland DKK-1 is also present within the nucleus of many differentiated luminal epithelial cells and in that of a small proportion of myoepithelial cells. Nuclear DKK-1 binds to actively transcribed chromatin and regulates the expression of specific genes, some of which are involved in cell proliferation, survival and stemness, and in the defense against xenobiotics. This may explain the finding that while DKK-1 is downregulated more rapidly in the nucleus than in the cytosol during colon carcinoma progression, its expression remains high in a percentage of patients who do not respond to chemotherapy. Available data suggest that the accumulation of DKK-1 in the nucleus of colon carcinoma cells depends on signals from the surrounding tumor microenvironment.Work in authors' laboratories is supported by grants from Ministerio de Economía y Competitividad of Spain-Fondo Europeo de Desarrollo Regional (FEDER) (SAF2013-43468-R), Comunidad de Madrid (S2010/BMD-2344 Colomics2), and FEDER-Instituto de Salud Carlos III (RD12/0036/0021; RD12/0036/0051, PT13/0010/0012 and PI12/01552).Peer reviewe

SIVIM – das Online-Datenbank-System zur Vegetation der iberischen Halbinsel und der Makaronesischen Inseln

SIVIM (Sistema de Información de la Vegetación Ibérica y Macaronésica) is an information system designed for capturing, hosting, editing, analyzing and outputting georeferenced plot data of Iberian and Macaronesian vegetation. It currently hosts 86,000 relevés, mainly from the northern half of the Iberian Peninsula and the Balearic Islands, and will grow to 100,000 relevés in the near future. SIVIM has been conceived to offer direct and free on-line access to relevés, tables, as well as to floristic, syntaxonomical and bibliographical records. The system also offers on-line software for edition and analysis of vegetation data. The main characteristics of SIVIM are presented, and its particular technical solutions to typical data banking problems as well as its future objectives are briefly commented.SIVIM ist ein Informationssystem, mit welchem georeferenzierte Daten zur iberischen und makaronesischen Vegetation erfasst, gehostet, editiert, analysiert und ausgegeben werden können. Momentan umfasst das System 86.000 Aufnahmen. In naher Zukunft soll die Anzahl der Aufnahmen auf 100.000 steigen, hauptsächlich durch Daten aus dem Norden der Iberischen Halbinsel und von den Balearen. SIVIM wurde initiiert, um einen direkten, freien Online-Zugang zu Vegetationsaufnahmen, Vegetationstabellen, sowie zu floristischen, syntaxonomischen und bibliographischen Daten anzubieten. Außerdem bietet es Online-Software, um Vegetationsdaten zu editieren und zu analysieren. Dieser Beitrag gibt eine Übersicht über die wesentlichen Eigenschaften von SIVIM und erläutert die implementierten technischen Lösungen typischer Datenbankprobleme sowie die zukünftigen Ziele

Pseudo-optimal five-level DCC modulation based on machine learning

This paper presents a method for the control design of five-level DCC converters based on mixed-integer optimization and machine learning. The resulting controller is computationally simple and can be easily implemented on low-resource control hardware using simple nested “if-else” statements. The optimization problem is recalled from previous work by modifying the cost function to further enhance the dynamic performance. Additionally, and in contrast to previous works, the online implementation accomplished in this paper allows the system to cover a wider range of operating points. For this, the optimization problem is solved offline for several operating conditions, and the results are gathered into a dataset to train classification and regression trees (CARTs), which are later used online. Due to the generalization capability of the CARTs, a more flexible and less resource-intensive implementation is achieved which is capable of operating at points outside the ones considered in the training dataset. The resulting control strategy is compared in simulation and experiments with several alternative approaches found in the literature. This approach can be extended to other power converter topologies, allowing the implementation of optimized modulations

MicroRNAs in rectal cancer: Functional significance and promising therapeutic value

It is well-known that microRNAs (miRNAs) are critical mediators of initiation and disease progression in many human cancers. Rectal cancer is a highly prevalent tumor, accounting for around one third of newly diagnosed colorectal cancers. The usefulness of miRNAs as clinical biomarkers predictive of the outcome and response to chemoradiotherapy has been well-reported for rectal cancer. However, the existing literature on their functional and therapeutic impact needs to be put in context to clarify their role in disease pathogenesis. Therfore, this review is focused on the functional relevance of miRNAs as key regulators of signaling pathways in rectal cancer and their potential therapeutic value as novel molecular targets in this disease.This research was funded by PI18/00382 and PI16/01468 grants from “Instituto de Salud Carlos III FEDER”

Association of acute equine leukoencephalomalacia (ELEM) with fumonisins concentrations in corn stover in an outbreak in the state of Jalisco, Mexico

Fumonisins are mycotoxins responsible for equine leukoencephalomalacia (ELEM) and they are produced by Fusarium species of high incidence in corn crops. In Jalisco (Mexico), six cases were confirmed by histopathological and neurological findings and fumonisins analysis. This is the first report of fumonisins in corn stover associated to ELEM cases

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

Reparació per recombinació homòloga; Càncer de pròstata metastàtic; Inhibidors de la poli(ADP-ribosa) polimerasaReparación por recombinación homóloga; Cáncer de próstata metastásico; Inhibidores de la poli(ADP-ribosa) polimerasaHomologous recombination repair; Metastatic prostate cancer; Poly(ADP-ribose) polymerase inhibitorsAnalysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of patients with mCRPC to identify those who can benefit from targeted therapies. Best practice guidelines in overall biospecimen collection and processing for molecular analysis are widely available for several tumour types. However, there is no standard protocol for molecular diagnostic testing in prostate cancer. Here, we provide a series of recommendations on specimen handling, sample pre-analytics, laboratory workflow, and testing pathways to maximise the success rates for clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team of pathologists, urologists, oncologists, radiologists, nurses, molecular scientists, and laboratory staff is key to enable optimal workflow for specimen selection and preservation at the time of diagnosis so that samples are available for molecular analysis when required. Given the improved outcome of patients with mCRPC and homologous recombination repair gene alterations who have been treated with PARP inhibitors, there is an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of these patients.JM has served on advisory boards for Amgen, AstraZeneca, Clovis Oncology, Janssen, Merck/MSD, and Roche; has participated in speaker bureaus for AstraZeneca, Pfizer, Janssen, Sanofi, and Astellas Pharma; and has received research funding from AstraZeneca and Pfizer Oncology through grants to his institution

Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer

Background: Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug. The purpose of this study was to quantitatively assess the impact of TYMS gene expression in tumor cells as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer (NSCLC) treated at our institution. Methods: Sixty-two NSCLC patients were included in this study: 16 patients received platins-pemetrexed as first-line NSCLC, and 46 pemetrexed in monotherapy as second- or subsequent-line treatment. Total mRNA was isolated and the expression of TYMS was analyzed by RT-qPCR. TYMS levels were calibrated against expression in normal lung tissue. Results: TYMS overexpression was detected in 61 % of patients and low expression in 39 %. The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025). A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002). Conclusions: TYMS overexpression in tumor cells correlated with a reduced response to pemetrexed-containing chemotherapy and might be used as a predictive biomarker in advanced NSCLC patientsThe present work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (AES Program, grant PI12/01552); the Ministerio de Sanidad (Cancer Network); and the Comunidad de Madrid (S2010/BMD-2344). The Fundacion Jimenez Diaz Biobank is funded by a grant from the MINECO (Instituto de Salud Carlos III, RETICS Red de Biobancos, with FEDER funds, RD09/0076/00101). S.Z. and C.C. are supported by grants from the same Biobanks initiativ

Desempeño de actividades y habilidades gerenciales para la gestión del cuidado enfermero : Estudio descriptivo transversal a realizar con profesionales de Enfermería, Clínica Santa María, Alta Gracia, Córdoba, segundo semestre del año 2022

La profesión de enfermería se desarrolla en diversos contextos, por lo que evidentemente las acciones se caracterizan por ser polivalentes, con un alto grado y valor de formación académica, contenido multidisciplinario con el propósito esencial de impartir cuidados de calidad. Es por esta razón, que la disciplina se sustenta en paradigmas y teorías que aportan al crecimiento y la producción de nuevos conocimientos respecto al objeto de estudio, que, en esencia, es el cuidado de las personas desde un marco integral. Así mismo, es imprescindible destacar la preponderancia de los servicios de enfermería a través de la gestión del cuidado en las organizaciones sanitarias, lo cual simboliza la unificación de todas las intervenciones, cuidados y actividades que prestan a la sociedad en general, acudiendo al manejo de habilidades necesarias, para direccionar no solo a un grupo de personas, sino que simultáneamente recursos materiales y económicos; impartiendo innumerables esfuerzos tanto cognitivos, como individuales marcando la transcendencia en el sector salud. Los gestores de enfermería que se desempeñan en las diversas áreas de acción necesitan ciertas competencias esenciales para la práctica profesional, que son fundamentales para realizar la labor de gestión en forma eficiente, lo que radica en el nivel de responsabilidad exigente como así los imperativos que devienen de las cuestiones ético legales. La gestión, profundiza las innovaciones puestas en marcha; así mismo reconoce los procesos y conocimientos que asienten como herramientas esenciales para seguir avanzando a través de operaciones que posibiliten su consolidación integrándolas en la cultura profesional. Es así, por lo que se destaca la relevancia de estudio, fijando especial atención, a la dirección del departamento de enfermería, la cual supone desplegar un tipo de liderazgo democrático, con la posibilidad de desarrollar prácticas del cuidado, proporcionando satisfacción, a razón de las necesidades que exhiban los pacientes. El enfermero/a responsable de la gestión tiene que tener en cuenta valores, actitudes y fundamentos de la profesión, lo que de este modo le brindara una visión más específica respecto a la gestión y administración como su alcance y valor, remarcando la funcionalidad, sistematización y organización que conlleva dicho proceso. 2 El presente trabajo de investigación, de tipo descriptivo-transversal, el cual se llevará a cabo con los profesionales enfermeros de la Clínica Santa María en la localidad de Alta Gracia, provincia de Córdoba durante el segundo semestre del año 2021, tiene como propósito proveer conocimientos sobre la importancia del desempeño de las actividades y habilidades gerenciales de los profesionales enfermeros gestores, las cuales influyen directamente en el comportamiento y bienestar de los pacientes. El desarrollo del mismo se organiza en dos capítulos: Capítulo I: Planteo del problema; donde se expone la temática en estudio, incluyendo la descripción de la problemática planteada, contextualización de lugar, antecedentes, observaciones de la realidad, justificación y definición. Por consiguiente, el marco teórico, mediante el cual, a través de la búsqueda de información, se desarrollan las bases teóricas que sustentan la investigación como así también la definición conceptual de la variable en estudio con sus respectivas dimensiones e indicadores, de la cual se desprenden los objetivos del mismo. Capítulo II: Diseño Metodológico, mismo que describe la metodología que se empleará para el desarrollo del mismo, el tipo de estudio, la técnica e instrumento a utilizar, la operacionalización de la variable en estudio y las etapas de recolección, procesamiento, presentación y análisis de la información a recopilar. Además, se encuentran disponibles las referencias bibliográficas consultadas y los anexos que sirven de respaldo al proyecto de investigación.Fil: Ferreira, Leonela Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Enfermería; Argentina.Fil: Prienza, Melanie Maricel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Enfermería; Argentina.Fil: Rojo, Federico Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Enfermería; Argentina

Basement membrane-rich Organoids with functional human blood vessels are permissive niches for human breast cancer metastasis

Metastasic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention

Functional and clinical impact of circRNas in oral cancer

The increasing number of recently published works regarding the role of circular RNAs (circRNAs) in oral cancer highlights the key contribution of this novel class of endogenous noncoding RNAs as regulators of critical signaling pathways and their clinical value as novel biomarkers. This review summarizes and puts into context the existing literature in order to clarify the relevance of circRNAs as novel mediators of oral cancer pathogenesis as well as their potential usefulness as predictors of clinical outcome and response to therapy in this disease.This research was funded by PI18/00382 and PI16/01468 grants from Instituto de Salud Carlos III FEDE