19 research outputs found

    Reprogramación metabólica en cáncer

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    This article reviews the molecular mechanisms that regulate the metabolism of cancer cells, as well as the possible therapeutic targets that could be exploited to interfere with their growth and survival. The article begins by explaining the Warburg effect, which is the preference of cancer cells for anaerobic glycolysis instead of oxidative respiration, even in the presence of oxygen. The article argues that this effect not only has an energetic purpose, but also a biosynthetic one, as it allows cancer cells to obtain the precursors necessary for the synthesis of lipids, nucleotides and proteins. Next, the article analyzes the intrinsic and extrinsic factors that contribute to metabolic reprogramming in cancer, such as mutations in oncogenic or tumor suppressor genes, the tumor microenvironment, inflammation and metabolic diseases. Finally, the article describes some of the therapeutic strategies that are being developed to inhibit or reverse metabolic reprogramming in cancer, such as inhibitors of glycolysis, glutaminolysis, lipogenesis and nucleotide biosynthesis.El artículo revisa los mecanismos moleculares que regulan el metabolismo de las células cancerosas, así como las posibles dianas terapéuticas que se podrían explotar para interferir con su crecimiento y supervivencia. El artículo comienza explicando el efecto Warburg, que es la preferencia de las células cancerosas por la glucolisis anaeróbica en lugar de la respiración oxidativa, incluso en presencia de oxígeno. El artículo argumenta que este efecto no solo tiene un propósito energético, sino también biosintético, ya que permite a las células cancerosas obtener los precursores necesarios para la síntesis de lípidos, nucleótidos y proteínas. A continuación, el artículo analiza los factores intrínsecos y extrínsecos que contribuyen a la reprogramación metabólica en el cáncer, como las mutaciones en genes oncogénicos o supresores de tumores, el microambiente tumoral, la inflamación y las enfermedades metabólicas. Finalmente, el artículo describe algunas de las estrategias terapéuticas que se están desarrollando para inhibir o revertir la reprogramación metabólica en el cáncer, como los inhibidores de la glucolisis, la glutaminolisis, la lipogénesis y la biosíntesis de nucleótidos

    Antiangiogenic potential of an anthraquinone metabolite isolated from a marine fungus.

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    This is a communication in the format of a posterThe potential of marine organisms to yield bioactive molecules is vast and largely unexplored. Significantly, certain bioactive compounds derived from the marine environment have already received approval as anticancer drugs1. Among the multitude of bioactive compounds found in marine organisms, anthraquinones represent a notable class of molecules, with over 200 structurally related compounds having been isolated from diverse species of marine fungi2. Danthron (1,8-dihydroxy-9,10-anthraquinone) serves as an exemplary member of anthraquinones, possessing anti-tumoral and anti-angiogenic properties that have yet to be fully elucidated. Therefore, the primary objective of this study was to comprehensively investigate and understand these specific properties.Funding: Funding: Projects PID2019-105010RB-I00 (Ministry of Science and Innovation, Government of Spain), UMA18-FEDERJA-220 and P20_00257 (Junta de Andalucía-FEDER) The assistance to the congress has an help from the Plan Propio de Investigación (UMA). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Antioxidant potential of an anthraquinone metabolite isolated from a marine fungus.

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    Marine ecosystem is a fruitful source of many pharmacologically active. In particular, a number of marine anthraquinones and their derivatives, have been studied for their potential as anticancer and antimetastatic agents, although little is known about their antiangiogenic activities. In addition, there is some controversy regarding the poor antioxidant effect of these marine secondary metabolites. In this study, we describe for the first time the antiangiogenic activity of an anthraquinone, isolated from a marine fungus, which was evidenced in vitro by the inhibition of the activated endothelial cells survival, proliferation, and differentiation into tubelike structures. Furthermore, we have demonstrated its protective effect against reactive oxygen species (ROS), especially in presence of hydrogen peroxide, a potent prooxidant agent. These results were evidenced by a reduced ROS production and an increased redox capacity of cells after treatment with this anthraquinone, evidenced through the staining with DCFHDA and the sulfhydryl groups determination, respectively. The observation that this compound appears to present a more potent effect in tumor than in endothelial cells, suggests a putative selectivity. All these results highlight the need for further study of this molecule as a potential therapeutic agent for cancer and other angiogenesisdependent diseases.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Danthron, an Anthraquinone Isolated from a Marine Fungus, Is a New Inhibitor of Angiogenesis Exhibiting Interesting Antitumor and Antioxidant Properties

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    The role played by a sustained angiogenesis in cancer and other diseases stimulates the interest in the search for new antiangiogenic drugs. In this manuscript, we provide evidence that 1,8- dihydroxy-9,10-anthraquinone (danthron), isolated from the fermentation broth of the marine fungus Chromolaenicola sp. (HL-114-33-R04), is a new inhibitor of angiogenesis. The results obtained with the in vivo CAM assay indicate that danthron is a potent antiangiogenic compound. In vitro studies with human umbilical endothelial cells (HUVEC) reveal that this anthraquinone inhibits certain key functions of activated endothelial cells, including proliferation, proteolytic and invasive capabilities and tube formation. In vitro studies with human breast carcinoma MDA-MB231 and fibrosarcoma HT1080 cell lines suggest a moderate antitumor and antimetastatic activity of this compound. Antioxidant properties of danthron are evidenced by the observation that it reduces the intracellular reactive oxygen species production and increases the amount of intracellular sulfhydryl groups in endothelial and tumor cells. These results support a putative role of danthron as a new antiangiogenic drug with potential application in the treatment and angioprevention of cancer and other angiogenesis-dependent diseases.Partial funding for open access charge: Universidad de Málag

    The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer

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    Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.MRI experiments were performed in the ICTS “NANBIOSIS”, more specifically in the U28 Unit at the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND). Cell cultures were performed in the Cell Culture Service at the Central Support Services of Research (SCAI) of the University of Málaga. // Partial funding for open access charge: Universidad de Málaga / CBUA

    Role of age and comorbidities in mortality of patients with infective endocarditis

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    [Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

    Métodos y mediciones

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    Actitud y conducta hacia la salud oral en estudiantes de la comuna de AraucoAn&aacute;lisis de instrumentos de registro odontol&oacute;gicos en la red de APS de la Regi&oacute;n MetropolitanaAn&aacute;lisis de la eficiencia relativa del Hospital de Cabildo mediante la aplicaci&oacute;n del an&aacute;lisis de fronteraAn&aacute;lisis de letalidad intrahospitalaria y acumulada a 30 d&iacute;as de eventos IAM, 2003-2007An&aacute;lisis del programa de c&aacute;ncer cervicouterino en Chile con metodolog&iacute;a de marco l&oacute;gicoA&ntilde;os de vida perdidos por muerte prematura: efecto de diferentes criterios de correcci&oacute;n de subregistrosCalidad global de la alimentaci&oacute;n de mujeres asistidas por el sistema de salud p&uacute;blico chilenoCarga de mortalidad para el estado de R&iacute;o de Janeiro, BrasilCausas de extracciones permanentes en adultos atendidos en la Posta Central, ChileComparaci&oacute;n del consumo de drogas en escolares hombres utilizando metodolog&iacute;a de pares y cuestionario autoregistradoCuidado hospitalario de pacientes con accidente cerebrovascular isqu&eacute;mico atendidos bajo r&eacute;gimen GESDescripci&oacute;n de dimensiones del constructo de calidad de vida en ni&ntilde;os de 2-5 a&ntilde;osDistribuci&oacute;n de benzodiacepinas en establecimientos del SNSS, per&iacute;odo 2006-2008Evaluaci&oacute;n de calidad, implementaci&oacute;n del control odontol&oacute;gico del ni&ntilde;o sano en CAP'S, Regi&oacute;n del MauleEvaluaci&oacute;n de la satisfacci&oacute;n del usuario interno de la Unidad de Cuidados B&aacute;sicos del Hospital MetropolitanoEvaluaci&oacute;n del protocolo de referencia de cefalea tensional y migra&ntilde;a en consultorio Llay-LlayEvaluaci&oacute;n econ&oacute;mica del Programa de Fluoraci&oacute;n del Agua en ChileFactores de riesgo de enfermedad hipertensiva del embarazo en la UCI del H.G EcatepecImpacto de reforma sanitaria en autorizaciones sanitarias y de desempe&ntilde;o en instalaciones de radiodiagn&oacute;stico dentalInstitucionalidad de la investigaci&oacute;n en salud p&uacute;blica en ChileLetalidad intrahospitalaria y a 30 d&iacute;as de los eventos de accidente cerebrovascular isqu&eacute;mico en ChileLimitaciones y desaf&iacute;os de la investigaci&oacute;n en salud p&uacute;blica en ChileMejora de agudeza visual y utilizaci&oacute;n cirug&iacute;a de segundo ojo en pacientes con cataratas GESMortalidad infantil en la Regi&oacute;n Metropolitana II del Estado de R&iacute;o de Janeiro, 1981-2008Mortalidad por c&aacute;ncer de tiroides en Chile en el per&iacute;odo 1985-2007Mortalidad por tumores cerebrales en poblaci&oacute;n infantil y adolescente, ciudad R&iacute;o de Janeiro, 1980-2007Mortalidad por tumores del sistema nervioso central en adultos, R&iacute;o de Janeiro, 1980 a 2007Prevalencia de anemia ferropriva en una muestra representativa de beneficiarios del PNACPrevalencia de caries y fluorosis previo a la fluoruraci&oacute;n del agua potable en TemucoPrevalencia de traumatismos dentoalveolares en ni&ntilde;os del Hospital Dr. S&oacute;tero del R&iacute;o, enero-junio 2010Propuesta de un indicador de la calidad para los centros de salud familiarSalud p&uacute;blica y la emergencia del dispositivo cl&iacute;nico en la modernidad nacionalSatisfacci&oacute;n de funcionalidad familiar en adolescentes entre 12 y 18 a&ntilde;os consumidores de drogasValidaci&oacute;n cualitativa del cuestionario ASAQ para la determinaci&oacute;n de la conducta sedentaria en escolare

    Métodos y mediciones

    Get PDF
    Actitud y conducta hacia la salud oral en estudiantes de la comuna de AraucoAn&aacute;lisis de instrumentos de registro odontol&oacute;gicos en la red de APS de la Regi&oacute;n MetropolitanaAn&aacute;lisis de la eficiencia relativa del Hospital de Cabildo mediante la aplicaci&oacute;n del an&aacute;lisis de fronteraAn&aacute;lisis de letalidad intrahospitalaria y acumulada a 30 d&iacute;as de eventos IAM, 2003-2007An&aacute;lisis del programa de c&aacute;ncer cervicouterino en Chile con metodolog&iacute;a de marco l&oacute;gicoA&ntilde;os de vida perdidos por muerte prematura: efecto de diferentes criterios de correcci&oacute;n de subregistrosCalidad global de la alimentaci&oacute;n de mujeres asistidas por el sistema de salud p&uacute;blico chilenoCarga de mortalidad para el estado de R&iacute;o de Janeiro, BrasilCausas de extracciones permanentes en adultos atendidos en la Posta Central, ChileComparaci&oacute;n del consumo de drogas en escolares hombres utilizando metodolog&iacute;a de pares y cuestionario autoregistradoCuidado hospitalario de pacientes con accidente cerebrovascular isqu&eacute;mico atendidos bajo r&eacute;gimen GESDescripci&oacute;n de dimensiones del constructo de calidad de vida en ni&ntilde;os de 2-5 a&ntilde;osDistribuci&oacute;n de benzodiacepinas en establecimientos del SNSS, per&iacute;odo 2006-2008Evaluaci&oacute;n de calidad, implementaci&oacute;n del control odontol&oacute;gico del ni&ntilde;o sano en CAP'S, Regi&oacute;n del MauleEvaluaci&oacute;n de la satisfacci&oacute;n del usuario interno de la Unidad de Cuidados B&aacute;sicos del Hospital MetropolitanoEvaluaci&oacute;n del protocolo de referencia de cefalea tensional y migra&ntilde;a en consultorio Llay-LlayEvaluaci&oacute;n econ&oacute;mica del Programa de Fluoraci&oacute;n del Agua en ChileFactores de riesgo de enfermedad hipertensiva del embarazo en la UCI del H.G EcatepecImpacto de reforma sanitaria en autorizaciones sanitarias y de desempe&ntilde;o en instalaciones de radiodiagn&oacute;stico dentalInstitucionalidad de la investigaci&oacute;n en salud p&uacute;blica en ChileLetalidad intrahospitalaria y a 30 d&iacute;as de los eventos de accidente cerebrovascular isqu&eacute;mico en ChileLimitaciones y desaf&iacute;os de la investigaci&oacute;n en salud p&uacute;blica en ChileMejora de agudeza visual y utilizaci&oacute;n cirug&iacute;a de segundo ojo en pacientes con cataratas GESMortalidad infantil en la Regi&oacute;n Metropolitana II del Estado de R&iacute;o de Janeiro, 1981-2008Mortalidad por c&aacute;ncer de tiroides en Chile en el per&iacute;odo 1985-2007Mortalidad por tumores cerebrales en poblaci&oacute;n infantil y adolescente, ciudad R&iacute;o de Janeiro, 1980-2007Mortalidad por tumores del sistema nervioso central en adultos, R&iacute;o de Janeiro, 1980 a 2007Prevalencia de anemia ferropriva en una muestra representativa de beneficiarios del PNACPrevalencia de caries y fluorosis previo a la fluoruraci&oacute;n del agua potable en TemucoPrevalencia de traumatismos dentoalveolares en ni&ntilde;os del Hospital Dr. S&oacute;tero del R&iacute;o, enero-junio 2010Propuesta de un indicador de la calidad para los centros de salud familiarSalud p&uacute;blica y la emergencia del dispositivo cl&iacute;nico en la modernidad nacionalSatisfacci&oacute;n de funcionalidad familiar en adolescentes entre 12 y 18 a&ntilde;os consumidores de drogasValidaci&oacute;n cualitativa del cuestionario ASAQ para la determinaci&oacute;n de la conducta sedentaria en escolare
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