Molecular bases of cancer: new tools for diagnosis, prognosis and treatment

Curso docente.Peer Reviewe

Impacto de una intervención de fisioterapia en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Estudio de casos.

Título: Impacto de una intervención de fisioterapia en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Estudio de casos. Introducción: La fibromialgia es una enfermedad reumática crónica caracterizada por dolor generalizado y difuso, fatiga, alteraciones del sueño y alteraciones de tipo psicológico, como ansiedad y depresión, entre otros, que afecta significativamente a la calidad de vida. No se conoce ningún tratamiento totalmente eficaz. Los mejores resultados se obtienen con abordajes multidisciplinares que combinan terapia educativa y terapia farmacológica y no farmacológica, basada en tratamientos psicológicos y físicos, adaptados a cada caso particular. Objetivo: Conocer el efecto de una intervención de fisioterapia, basada en ejercicio aeróbico, ejercicio de fortalecimiento muscular y autoestiramientos, en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Material y métodos: Estudio de casos de once pacientes diagnosticados de FM. Se llevan a cabo dos valoraciones (pre-tratamiento y post-tratamiento) en las que se realiza una entrevista y examen físico y se utilizan las siguientes escalas: Cuestionario de Impacto de la Fibromialgia, Inventario de Depresión de Beck y Escala Hamilton de Ansiedad. La intervención se desarrolla a lo largo de 6 semanas, durante 50-60 minutos cada sesión, un día a la semana. Resultados: Nueve de los pacientes concluyeron la intervención. Puede decirse que siete de los pacientes muestran una disminución del impacto que tiene la enfermedad en su vida; seis de ellos han disminuido sus niveles de depresión y cinco de ellos sus niveles de ansiedad. La adherencia al tratamiento no ha sido muy alta. Conclusiones: Un tratamiento de fisioterapia basado en ejercicio aeróbico, ejercicios de fortalecimiento muscular y de flexibilidad, adaptados a cada paciente, puede constituir una herramienta eficaz en la mejora de los niveles de ansiedad y depresión, y en menor medida, en la calidad de vida de pacientes con fibromialgia.Title: Impact of a physiotherapy intervention on quality of life and levels of anxiety and depression in patients with fibromyalgia. A cases study. Background: Fibromyalgia is a chronic rheumatic disease characterized by widespread, diffuse pain, fatigue, sleep disturbances and psychological disorders such as anxiety and depression, among others, which significantly affects the quality of life. There is no known any treatment completely effective. The best results have been obtained with multidisciplinary approaches that combine educational therapy and pharmacological and no-pharmacological therapy, based on psychological and physical treatments, tailored to each particular case. Objective: To know the effect of a physiotherapy intervention based on aerobic exercise, strengthening and self-stretching exercises in the quality of life and the levels of anxiety and depression in patients with FM. Materials and methods: A cases study of eleven patients diagnosed with FM. Two assessments are conducted (pre-treatment and post-treatment) in which performs an interview and physical exam, and uses the following scales: Impact Questionnaire Fibromyalgia, Beck Depression Inventory and Hamilton Anxiety Scale. The intervention took place over six weeks, for 50-60 minutes each session, one day a week. Results: Nine patients completed the procedure. It can be said that seven of the patients showed a decrease of the impact of the disease on their lives; six of them have decreased their levels of depression and five of them their anxiety levels. Adherence to treatment has not been very high. Conclusions: A physiotherapy treatment based on aerobic exercise, strength and flexibility training, tailored to each patient, can be an effective tool in improving the levels of anxiety and depression, and to a lesser extent, on the quality of life in patients with FM.Grado en Fisioterapi

Impacto de una intervención de fisioterapia en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Estudio de casos.

Título: Impacto de una intervención de fisioterapia en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Estudio de casos. Introducción: La fibromialgia es una enfermedad reumática crónica caracterizada por dolor generalizado y difuso, fatiga, alteraciones del sueño y alteraciones de tipo psicológico, como ansiedad y depresión, entre otros, que afecta significativamente a la calidad de vida. No se conoce ningún tratamiento totalmente eficaz. Los mejores resultados se obtienen con abordajes multidisciplinares que combinan terapia educativa y terapia farmacológica y no farmacológica, basada en tratamientos psicológicos y físicos, adaptados a cada caso particular. Objetivo: Conocer el efecto de una intervención de fisioterapia, basada en ejercicio aeróbico, ejercicio de fortalecimiento muscular y autoestiramientos, en la calidad de vida y los niveles de ansiedad y depresión de pacientes con fibromialgia. Material y métodos: Estudio de casos de once pacientes diagnosticados de FM. Se llevan a cabo dos valoraciones (pre-tratamiento y post-tratamiento) en las que se realiza una entrevista y examen físico y se utilizan las siguientes escalas: Cuestionario de Impacto de la Fibromialgia, Inventario de Depresión de Beck y Escala Hamilton de Ansiedad. La intervención se desarrolla a lo largo de 6 semanas, durante 50-60 minutos cada sesión, un día a la semana. Resultados: Nueve de los pacientes concluyeron la intervención. Puede decirse que siete de los pacientes muestran una disminución del impacto que tiene la enfermedad en su vida; seis de ellos han disminuido sus niveles de depresión y cinco de ellos sus niveles de ansiedad. La adherencia al tratamiento no ha sido muy alta. Conclusiones: Un tratamiento de fisioterapia basado en ejercicio aeróbico, ejercicios de fortalecimiento muscular y de flexibilidad, adaptados a cada paciente, puede constituir una herramienta eficaz en la mejora de los niveles de ansiedad y depresión, y en menor medida, en la calidad de vida de pacientes con fibromialgia.Title: Impact of a physiotherapy intervention on quality of life and levels of anxiety and depression in patients with fibromyalgia. A cases study. Background: Fibromyalgia is a chronic rheumatic disease characterized by widespread, diffuse pain, fatigue, sleep disturbances and psychological disorders such as anxiety and depression, among others, which significantly affects the quality of life. There is no known any treatment completely effective. The best results have been obtained with multidisciplinary approaches that combine educational therapy and pharmacological and no-pharmacological therapy, based on psychological and physical treatments, tailored to each particular case. Objective: To know the effect of a physiotherapy intervention based on aerobic exercise, strengthening and self-stretching exercises in the quality of life and the levels of anxiety and depression in patients with FM. Materials and methods: A cases study of eleven patients diagnosed with FM. Two assessments are conducted (pre-treatment and post-treatment) in which performs an interview and physical exam, and uses the following scales: Impact Questionnaire Fibromyalgia, Beck Depression Inventory and Hamilton Anxiety Scale. The intervention took place over six weeks, for 50-60 minutes each session, one day a week. Results: Nine patients completed the procedure. It can be said that seven of the patients showed a decrease of the impact of the disease on their lives; six of them have decreased their levels of depression and five of them their anxiety levels. Adherence to treatment has not been very high. Conclusions: A physiotherapy treatment based on aerobic exercise, strength and flexibility training, tailored to each patient, can be an effective tool in improving the levels of anxiety and depression, and to a lesser extent, on the quality of life in patients with FM.Grado en Fisioterapi

Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-κB

11 pages, 9 figures.Aerobic cells adjust the expression of antioxidant enzymes to maintain reactive oxygen species within tolerable levels. In addition, phosphatidylinositol 3 kinase (PI3K) and its downstream protein kinase effector Akt adapt cells to survive in the presence of oxidative stress. Here we provide evidence for an association between these two defense systems via transcriptional regulation of Cu/Zn-superoxide dismutase (Cu/Zn-SOD). PC12 pheochromocytoma cells expressing active Akt1 exhibit lower ROS levels in response to hydrogen peroxide, as determined with the superoxide-sensitive probe hydroethidine. Transfection of constitutive or 4-hydroxytamoxifen-inducible versions of Akt1 results in higher messenger RNA and protein levels of Cu/Zn-SOD. Luciferase reporter constructs, carrying different length fragments of the human sod1 gene promoter, have identified a region between -552 and -355 that is targeted by PI3K and Akt and that contains a putative site of regulation by nuclear factor-kappaB (NF-kappaB). Nerve growth factor (NGF) and Akt augment the transactivating activity and produce higher nuclear levels of p65-NF-kappaB. Electrophoretic mobility shift assays indicate that the putative NF-kappaB regulatory sequence binds p65-NF-kappaB more efficiently in nuclear extracts from these cells. A dominant-negative mutant of IkappaBalpha further demonstrates that the PI3K/Akt axis targets the sod1 promoter at the level of the newly characterized NF-kappaB site. These results illustrate a new mechanism by which the PI3K/Akt pathway protects cells against oxidative stress, involving the upregulation of Cu/Zn-SOD gene expression, and the results identify NF-kappaB as a key mediator in the regulation of this gene.This work was supported by Grants SAF2001-0545 from Ministry of Science and Technology and 08.5/0048/2001 from Comunidad Autónoma of Madrid.Peer reviewe

Empleo de Trefoil Factor-Family 3 (TFF3) en el pronóstico de pacientes diagnosticados con cáncer colorrectal

Peer reviewedUniversidad Autónoma de Madrid, Fundación para la Investigación Biomédica del Hospital Universitario de la Paz, Consejo Superior de Investigaciones CientíficasT3 Traducción de patente europe

Harnessing PM2.5 Exposure Data to Predict Progression of Fibrotic Interstitial Lung Diseases Based on Telomere Length

Cross-analysis of clinical and pollution factors could help calculate the risk of fibrotic interstitial lung disease (ILD) development and progression. The intent of this study is to build a body of knowledge around early detection and diagnosis of lung disease, harnessing new data sets generated for other purposes. We cross-referenced exposure levels to particulate matter 2.5 (PM2.5) with telomere length of a cohort of 280 patients with fibrotic ILD to weigh impact and associations. There was no linear correlation between PM2.5 and telomere length in our data sets, as the value of the correlation coefficient was 0.08. This exploratory study offers additional insights into methodologies for investigating the development and prognosis of pulmonary fibrosis

XPA, XPC, and XPD modulate sensitivity in gastric cisplatin resistance cancer cells

Cisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecular processes involved in cisplatin-induced apoptosis in two gastric cancer cell lines with different sensitivity to the treatment: AGS and MKN45. The apoptosis induction is higher in MKN45 than in AGS cells in response to CDDP. The intrinsic apoptotic pathway study revealed that MKN45 cells undergo degradation of Mcl-1 together with an increase of Bid and Bad levels, which results in sensitivity to CDDP. In addition, DNA repair NER pathway is impair in MKN45 cells due to low levels of XPC and the absence of translocation of XPA and XPD to the nucleus after stimuli. Altogether, these results suggest that NER and Bcl-2 protein family proteins are potential targets to improve the response to cisplatin treatmentThis work was supported by PI1401495 and P17-01401 (supported by FEDER funds) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain and by CTQ2015- 68779R. JB-I was supported by a fellowship from Catedra Isaac Costero, funded by Banco Santander-UAM and Beca Nacional de Posgrado CONACYT. NP-L was supported by a fellowship Programa de Formación de Profesorado Universitario REF: FPU15/04669, Ministerio de Educación, Cultura y Deport

GSE4, a small dyskerin- and GSE24.2-related peptide, induces telomerase activity, cell proliferation and reduces DNA damage, oxidative stress and cell senescence in dyskerin mutant cells

Dyskeratosis congenita is an inherited disease caused by mutations in genes coding for telomeric components. It was previously reported that expression of a dyskerin-derived peptide, GSE24.2, increases telomerase activity, regulates gene expression and decreases DNA damage and oxidative stress in dyskeratosis congenita patient cells. The biological activity of short peptides derived from GSE24.2 was tested and one of them, GSE4, that probed to be active, was further characterized in this article. Expression of this eleven amino acids long peptide increased telomerase activity and reduced DNA damage, oxidative stress and cell senescence in dyskerin-mutated cells. GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and TERC expression. The level of biological activity of GSE4 was similar to that obtained by GSE24.2 expression. Incorporation of a dyskerin nuclear localization signal to GSE24.2 did not change its activity on promoter regulation and DNA damage protection. However, incorporation of a signal that increases the rate of nucleolar localization impaired GSE24.2 activity. Incorporation of the dyskerin nuclear localization signal to GSE4 did not alter its biological activity. Mutation of the Aspartic Acid residue that is conserved in the pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and TERC gene expression in dyskerin-mutated cells. These results indicated that GSE4 could be of great therapeutic interest for treatment of dyskeratosis congenita patients.This work was supported by grants PI1401495 (supported by FEDER funds) and ER15PR07ACC114/757 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III. Spain), 201320E075 (Consejo Superior de Investigaciones Científicas) and IPT-2012-0674- 090000 (Ministerio de Economía y Competitividad. Spain). CM-G is supported by the CIBER de Enfermedades Raras.Peer Reviewe

CHK1 expression in gastric cancer is modulated by p53 and RB1/E2F1: implications in chemo/radiotherapy response

This work is licensed under a Creative Commons Attribution 4.0 International License.-- et al.Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient's samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1's expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgery.This work was supported by Instituto de Salud Carlos III–Fondo de Investigación Sanitaria (PS09/1988 to ISP; PI11-00949, pI014-1495 and Feder Funds to RP); Comunidad Autónoma de Madrid-Universidad Autónoma de Madrid (CCG10-UAM/BIO-5871 to ISP); Fundación Leticia Castillejo Castillo and Ministerio de Ciencia e Innovación (SAF2012-30862 to RSP), Spain. JBI was supported by a fellowship from Catedra Isaac Costero, funded by Banco Santander UAM and is a doctoral student from a double doctorate program in Molecular Biosciences (UAM) and in Biomedical Sciences, (UNAM) and received fellowship CVU:607546 from CONACYT.Peer Reviewe

Molecular Diagnosis and Precision Therapeutic Approaches for Telomere Biology Disorders

Telomeres are nucleo-protein structures located at the end of chromosomes that protect them from degradation. Telomeres length is maintained by the activity of the telomerase complex. These structures are protected by a specialized protein complex named shelterin. In the absence of telomerase activity and/or protection telomeres are shortened after each round of DNA replication. When a critical size is reached, telomeres are recognized as damaged DNA by the cell p53-dependent DNA-repair system. Persistent activation of this pathway finally results in cell apoptosis or senescence