14 research outputs found
Programa de intervención de Terapia Ocupacional en pacientes con fibromialgia.
El objeto de este trabajo consiste en realizar un programa de intervención desde terapia ocupacional en pacientes con fibromialgia. Se quiere determinar si la participación de estos pacientes, les produce mejorÃa en su calidad de vida y salud. Para ello se ha planteado como objetivo principal: valorar si un programa de intervención desde Terapia Ocupacional mejora la calidad de vida del paciente con fibromialgia, y los siguientes objetivos especÃficos: evaluar desde Terapia Ocupacional la calidad de vida y el grado de autonomÃa de los pacientes con fibromialgia y establecer un plan de intervención y desarrollar un sistema de evaluación de resultados. La metodologÃa se ha basado en los siguientes instrumentos de evaluación: Fibromyalgia Impact Questionnaire (FIQ) versión español, Barthel-Lawton, Escala de Intensidad de la fatiga y el inventario de la depresión de Beck, posteriormente deben ser de nuevo utilizados para realizar una reevaluación y comprobar si se han cumplido los objetivos. Con este programa de intervención se podrá ver la eficacia del programa, de los resultados y los efectos en los usuarios con fibromialgia que reciben intervención desde Terapia ocupacional. Finalmente se pretende recoger la satisfacción de los pacientes con el programa. Esto se evaluará con un cuestionario ad hoc.<br /
Development and characterization of cell models harbouring mtDNA deletions for <i>in vitro</i> study of Pearson syndrome
Pearson syndrome is a rare multisystem disease caused by single large-scale mitochondrial DNA deletions (SLSMDs). The syndrome presents early in infancy and is mainly characterised by refractory sideroblastic anaemia. Prognosis is poor and treatment is supportive, thus the development of new models for the study of Pearson syndrome and new therapy strategies is essential. In this work, we report three different cell models carrying an SLMSD: fibroblasts, transmitochondrial cybrids and induced pluripotent stem cells (iPSCs). All studied models exhibited an aberrant mitochondrial ultrastructure and defective oxidative phosphorylation system function, showing a decrease in different parameters, such as mitochondrial ATP, respiratory complex IV activity and quantity or oxygen consumption. Despite this, iPSCs harbouring ‘common deletion’ were able to differentiate into three germ layers. Additionally, cybrid clones only showed mitochondrial dysfunction when heteroplasmy level reached 70%. Some differences observed among models may depend on their metabolic profile; therefore, we consider that these three models are useful for the in vitro study of Pearson syndrome, as well as for testing new specific therapies.
This article has an associated First Person interview with the first author of the paper
Diagnóstico molecular de enfermedades mitocondriales: sÃndrome de MELAS y sÃndrome de Leigh
El ADN mitocondrial tiene unas caracterÃsticas propias y su localización en un orgánulo citoplasmático implica que la herencia de este genoma difiera de la del ADN nuclear en el modo de herencia, la poliplasmia, la segregación mitótica, la expresión umbral y la alta tasa de mutación. Las enfermedades causadas por mutaciones en el ADNmt tienen como caracterÃstica común el estar producidas por una deficiente sÃntesis de ATP. Las mitocondrias son componentes fundamentales de todos los tejidos y órganos, por lo que estas enfermedades serán, en general, multisistémincas y darán lugar a amplio espectro de fenotipos. El sÃndrome de Leigh o encefalomiopatÃa mitocondrial necrotizante infantil subaguda es una enfermedad neurodegenerativa, genéticamente heterogénea causada por mutaciones tanto en el genoma nuclear como en el mitocondrial, por lo que puede presentar diversos tipos de herencia. El sÃndrome de MELAS es uno de los sÃndromes mitocondriales multisistémicos mejor definidos desde el punto de vista clÃnico. Los criterios invariables son episodios de accidentes cerebrovasculares antes de los 40 años, encefalopatÃa caracterizada por crisis epilépticas focales o generalizadas, acidosis láctica y/o fibras rojo rasgadas, además de dos de los siguientes sÃntomas: baja estatura, demencia, cefaleas recurrentes y vómitos. El objetivo de este estudio de este estudio es el análisis genetico-molecular del ADNmt de varios pacientes con sÃndrome de Leigh y sÃndrome de MELAS. Asimismo, se ha realizado la búsqueda de mutaciones en familiares relacionados por la vÃa materna. En este estudio se ha realizado el análisis genético mitocondrial de 22 personas, 20 pacientes y 2 familiares, principalmente por las técnicas de RFLP-PCR de los cuales se han obtenido 9 positivos
ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells.
Metastasis, the spread of malignant cells from a primary tumour to distant sites, causes 90% of cancer-related deaths. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake. The functional requirement for ITGB3 derives from its interactions with heparan sulfate proteoglycans (HSPGs) and the process of integrin endocytosis, allowing the capture of extracellular vesicles and their endocytosis-mediated internalization. Key for the function of ITGB3 is the interaction and activation of focal adhesion kinase (FAK), which is required for endocytosis of these vesicles. Thus, ITGB3 has a central role in intracellular communication via extracellular vesicles, proposed to be critical for cancer metastasis.S
GDF15 is an eribulin response biomarker also required for survival of DTP breast cancer cells
Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after drug treatment. We performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. We showed that the growth differentiation factor 15 (GDF15) is a protein significantly over-secreted upon eribulin treatment. The biomarker potential of GDF15 was confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. We also found that GDF15 is required for survival of DTP cells. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function assays. Finally, we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired resistance
GDF15 is an Eribulin Response Biomarker also required for Survival of DTP Breast Cancer Cells.
Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after drug treatment. We performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. We showed that the growth differentiation factor 15 (GDF15) is a protein significantly over-secreted upon eribulin treatment. The biomarker potential of GDF15 was confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. We also found that GDF15 is required for survival of DTP cells. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function assays. Finally, we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired resistance