58 research outputs found

    miR-203 drives breast cancer cell differentiation

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    Breast cancer; Cell differentiationCáncer de mama; Diferenciación celularCàncer de mama; Diferenciació cel·lularA hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.This work has been in part financed by the crowdfunding project “Match point against breast cancer” (PRECIPITA PR242, 2019; FECYT; Spanish Ministry of Science and Innovation, MICINN, led by MS-R) and donations to Asociación Española contra el Cáncer (AECC). The work has been funded also by the Comunidad de Madrid (Y2020/BIO-6519 and S2022/BMD-7437) to MM, the Spanish Ministry of Science and Innovation through CNS2022-135364 to MS-R and PID2021-128726 to MM and the Spanish Ministry of Economy and Competitiveness by Instituto de Salud Carlos III (ISC III) through PI20/00590 to CS and co-funded by the European Union. MS-R was supported by AECC (AIOA120833SALA and INVES18005SALA), a Juan de la Cierva Incorporación and a Ramón y Cajal contract (RYC2020-028929-I, from the MICINN, FSE/ Agencia Estatal de Investigación). NGM-I was supported by AECC (PRDMA19003GARC)

    Valor de la morfina liofilizada en la revascularización miocárdica

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    Introduction: epidural analgesia is a mainstay in cardiac surgery. Objectives: The aim of this study was to compare the use of lyophilized morphine and epidural bupivacaine in postoperative analgesia of myocardial revascularization. Method: A comparative and prospective study was conducted in 160 patients. They were divided into two groups: group M received epidural analgesia with morphine (2 mg) associated with 100 mg of bupivacaine, and group B bupivacaine only. Results: there was a prevalence of males. The ages and the average weights of both groups were similar (p>0.05). In group M, 90% of patients had excellent analgesia eight hours after the intervention, and it was good to excellent after 12 and 24 hours. On the other hand, 50% of patients in group B talked of an average analgesia eight hours after the operation –which extended to 80% of patients after 12 hours– and, after 24 hours, all the patients in group B complained of an inadequate or poor analgesia (p0.05); el 90% de los enfermos del grupo M tenían una analgesia excelente ocho horas después de la intervención y entre buena y excelente a las 12 y 24 horas, mientras que el 50% de los pacientes del grupo B referían una analgesia regular a las ocho horas de operados -lo que se extendió al 80% de los enfermos a las 12 horas- y, a las 24 horas, la totalidad de los enfermos del grupo B se aquejaban de una analgesia insuficiente o mala (p<0.05); el promedio de analgesia postoperatoria obtenida del grupo M fue de 29,41 horas y del grupo B de 9,76 horas (p<0.01) y los principales efectos adversos fueron la hipotensión arterial y la bradicardia. Conclusiones: la morfina demostró su utilidad como agente analgésico en la operación de las arterias coronarias. Los pacientes con bupivacaína y morfina epidural tuvieron mejor analgesia con tiempos más prolongados que los tratados con bupivacaína

    Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

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    © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    Estudios en Historia Moderna desde una visión Atlántica. Libro homenaje a la trayectoria de la profesora María Inés Carzolio

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    Fil: Tarragó, Griselda Beatriz. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Gentinetta, Martín. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Este libro homenaje se formula como un diálogo abierto entre grupos de investigación europeos y americanos sobre problemáticas referidas a una visión Atlántica de la proyección de los Imperios Ibéricos en la Edad Moderna. Los ejes convocantes son aquellos que a lo largo de su dilatada trayectoria en la investigación histórica ha desarrollado y publicado la Dra. María Inés Carzolio, tanto en Argentina como en el extranjero: Las raíces medievales de la Europa Moderna, las monarquías del Antiguo Régimen, la organización del espacio social y los agentes sociales en la modernidad, cuestiones sobre creencias y religiosidad, estudios urbanos y, finalmente, problemáticas en torno al campo discursivo y cultural.http://www.libros.fahce.unlp.edu.ar/index.php/libros/catalog/book/94Fil: Tarragó, Griselda Beatriz. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Gentinetta, Martín. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Otras Historia y Arqueologí

    Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

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    From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

    La alfabetización informacional: una necesidad no reconocida por todos

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    Bibliometric study of CorSalud Journal

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    Objetivos: Fez-se um estudo bibliométrico de alguns indicadores nos primeiros 199 artigos publicados em CorSalud, com o objetivo de conhecer o estado atual e a evolução de seus conteúdos. Método: Realizou-se de um estudo descritivo e transversal de forma retrospectiva, analisando os artigos publicados na Revista CorSalud entre o primeiro trimestre do ano 2009 e o primeiro trimestre do ano 2013 ambos inclusive, por origem de procedência do primeiro autor, tema de publicação, composição e atualização das fontes de referência e número de autores firmadores. Resultados: Analisaram-se um total de 199 artigos, o 73,36% dos mesmos proviam de Vila Clara, a Cardiologia predominou com um 50,25% da temática, as fontes de referências mais utilizadas foram as revistas impressas 79,96% e a atualização das mesmas teve uma tendência decrescente anual do 7,78% ainda que se manteve com uma média do 47,05% e o Índice de Colaboração entre os autores atingiu uma média de 3,75%. Conclusões: A maioria dos artigos proviam a região central, os artigos originais, breves, de revisão e especiais foram a generalidade. Preponderaron os temas de Cardiologia, as fontes de referências utilizadas mayormente foram as revistas impressas, a atualização das mesmas se mantém em níveis comparáveis internacionalmente, ao igual do Índice de Colaboração entre os autores que mostrou ademais, uma tendência crescente.Objetivos: Se hizo un estudio bibliométrico de algunos indicadores en los primeros 199 artículos publicados en CorSalud, con el objetivo de conocer el estado actual y la evolución de sus contenidos. Método: Se realizó de un estudio descriptivo y transversal de forma retrospectiva, analizando los artículos publicados en la Revista CorSalud entre el primer trimestre del año 2009 y el primer trimestre del año 2013 ambos inclusive, por origen de procedencia del primer autor, tema de publicación, composición y actualización de las fuentes de referencia y número de autores firmantes. Resultados: Se analizaron un total de 199 artículos, el 73,36% de los mismos provenían de Villa Clara, la Cardiología predominó con un 50,25% de la temática, las fuentes de referencias más utilizadas fueron las revistas impresas 79,96% y la actualización de las mismas tuvo una tendencia decreciente anual del 7,78% aunque se mantuvo con una media del 47,05% y el Índice de Colaboración entre los autores alcanzó una media de 3,75%. Conclusiones: La mayoría de los artículos provenían la región central, los artículos originales, breves, de revisión y especiales fueron la generalidad. Preponderaron los temas de Cardiología, las fuentes de referencias utilizadas mayormente fueron las revistas impresas, la actualización de las mismas se mantiene en niveles comparables internacionalmente, al igual del Índice de Colaboración entre los autores que mostró además, una tendencia creciente.Objectives: We conducted a bibliometric indicators in the first 199 articles published in CorSalud, in order to meet the current and evolving content. Methods: We conducted a descriptive study retrospectively analyzing the articles published in the Journal CorSalud between the first quarter of 2009 and the first quarter of 2013 inclusive, by source of origin of the first author, publication issue composition and update of reference sources and number of authors signing. Results: We analyzed a total of 199 articles, the 73.36% of them came from Villa Clara, the Cardiology prevailed with 50.25% of the thematic references sources used were 79.96% printed journals and the updating of them had an annual downward trend but remained 7.78% with an average of 47.05% and the Index of Collaboration between the authors reached an average of 3.75%. Conclusions: Most of the items were from the Midwest, original articles, brief review were the general and special. Cardiology predominated issues, sources of references used were mostly printed magazines, updating them remains at levels comparable internationally as Collaboration Index authors also showed an increasing trend
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