Mecanismos de señalización intracelular en cáncer de tiroides

ResumenAntecedentesEl cáncer de tiroides es el tumor maligno más frecuente del sistema endocrino; la variante papilar representa entre el 80 y el 90% de todos los casos diagnosticados. En el desarrollo del cáncer papilar de tiroides están afectados principalmente 2genes llamados BRAF y RAS, que alteran el sistema de señalización intracelular de las proteínas conocidas como «cinasas de proteínas activadas por mitógenos» (MAPK, por sus siglas en inglés para mitogen-activated protein kinase) y que se componen de «módulos» de proteínas de señalización interna (Receptor/Ras/Raf/MEK/ERK), que van de la membrana celular al núcleo y que en el cáncer de tiroides regulan diversos procesos celulares, como la diferenciación, crecimiento, desarrollo y apoptosis. Tienen un papel importante en la patogénesis del cáncer de tiroides, debido a que son usados como biomarcadores moleculares, como elementos de diagnóstico, pronóstico y como posibles blancos terapéuticos moleculares.ObjetivoRevisar los mecanismos moleculares que intervienen en las vías de señalización, en las que están involucradas las proteínas de los genes BRAF y RAS, en el cáncer de tiroides.ConclusionesLas mutaciones en el gen BRAF han sido correlacionadas con una pobre respuesta al tratamiento con quimioterapia tradicional, además de ser un índice de mal pronóstico. La terapia molecular es de gran interés en este tipo de cáncer, ya que se han desarrollado medicamentos que actúan inhibiendo alguno de los componentes de la vía de señalización (RET/PTC)/Ras/Raf/MEK/ERK, con especial énfasis en la sección (RET/PTC)/Ras/Raf, que constituye un efector principal de la vía ERK.AbstractBackgroundThyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis.ObjectiveTo review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer.ConclusionsMolecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway

Relación entre la resistencia a antibióticos y la producción de biofilm de aislados de Staphylococcus aureus provenientes de mastitis bovina

The objective was to analyze the relationship between the antibiotic-resistance profile and the biofilm formation of S. aureus isolates from bovine mastitis. Thirty (30) isolates of S. aureus from cases of subclinical mastitis in dairy farms in semi-intensive production and backyard production systems, located in the states of Guanajuato and Michoacán, Mexico, were analyzed. An antibiogram was performed by the Kirbi-Bauer disc-diffusion method. Biofilm formation was determined by the violet crystal staining method. For the evaluation of antibiotic resistance genes and biofilm formation, genomic DNA was obtained from a colony for the identification of the genes: blaZ, mecA, tetK, tetM, gyrA and gyrB, and icaA and icaD. The results showed that 100 % of the isolates were resistant to penicillin and dicloxacillin, followed by cefotaxime (86.6 %), ampicillin and cephalotin (83.3 %) and ceftazidime (80.0 %), while a 36.6 % resistance to oxacillin was observed. It was identified that all isolates of S. aureus had the ability to form biofilm with a range between 20 to 98 %. It was also observed that isolates with a high multi-resistance presented a greater formation of biofilm, establishing a significant positive correlation. In conclusion, S. aureus isolates from bovine mastitis presented high levels of antibiotic resistance; as well as an important biofilm-forming capacity, demonstrating the existence of a positive correlation between these two factors.El objetivo fue analizar la relación entre el perfil de resistencia a antibióticos y la formación de biofilm de aislados de S. aureus provenientes de mastitis bovina. Se analizaron 30 aislados de S. aureus procedentes de casos de mastitis subclínica en granjas lecheras en sistemas de producción semi-intensivo y de traspatio ubicadas en los estados de Guanajuato y Michoacán, México. Se realizó un antibiograma por el método de difusión en disco Kirbi Bauer. La formación de biofilm se determinó por el método de tinción con cristal violeta. Para la evaluación de genes de resistencia a antibióticos y de formación de biofilm se obtuvo ADN genómico de una colonia para la identificación de los genes: blaZ, mecA, tetK, tetM, gyrA y gyrB, y icaA e icaD. Los resultados mostraron que el 100 % de los aislados fueron resistentes a penicilina  y dicloxacilina, seguidos  por cefotaxima  (86.6 %),  ampicilina y cefalotina (83.3 %) y ceftazidima (80.0 %), mientras que se observó un 36.6 % de resistencia a oxacilina. Se identificó que todos los aislados de S. aureus presentaron la capacidad de formar biofilm con un rango del 20 a 98 %. Se observó además que los aislados con una multirresistencia elevada presentaron una mayor formación de biofilm; estableciéndose una correlación positiva significativa. En conclusión, los aislados de S. aureus provenientes de mastitis bovina presentaron elevados niveles de resistencia a antibióticos; así como una importante capacidad formadora de biofilm, demostrando la existencia de una correlación positiva entre estos dos factores

Lanthanide(III) Ions and 5-Methylisophthalate Ligand Based Coordination Polymers: An Insight into Their Photoluminescence Emission and Chemosensing for Nitroaromatic Molecules

The work presented herein reports on the synthesis, structural and physico-chemical characterization, luminescence properties and luminescent sensing activity of a family of isostructural coordination polymers (CPs) with the general formula [Ln2(μ4-5Meip)3(DMF)]n (where Ln(III) = Sm (1Sm), Eu (2Eu), Gd (3Gd), Tb (4Tb) and Yb (5Yb) and 5Meip = 5-methylisophthalate, DMF = N,N-dimethylmethanamide). Crystal structures consist of 3D frameworks tailored by the linkage between infinite lanthanide(III)-carboxylate rods by means of the tetradentate 5Meip ligands. Photoluminescence measurements in solid state at variable temperatures reveal the best-in-class properties based on the capacity of the 5Meip ligand to provide efficient energy transfers to the lanthanide(III) ions, which brings intense emissions in both the visible and near-infrared (NIR) regions. On the one hand, compound 5Yb displays characteristic lanthanide-centered bands in the NIR with sizeable intensity even at room temperature. Among the compounds emitting in the visible region, 4Tb presents a high QY of 63%, which may be explained according to computational calculations. At last, taking advantage of the good performance as well as high chemical and optical stability of 4Tb in water and methanol, its sensing capacity to detect 2,4,6-trinitrophenol (TNP) among other nitroaromatic-like explosives has been explored, obtaining high detection capacity (with Ksv around 105 M−1), low limit of detection (in the 10−6–10−7 M) and selectivity among other molecules (especially in methanol).This work has been funded by University of the Basque Country (GIU20/028), Gobierno Vasco/Eusko Jaurlaritza (IT1755-22 and IT1500-22), Junta de Andalucía (FQM-394 and B-FQM-734-UGR20, B-FQM-478-UGR20 and ProyExcel_00386) and the Spanish Ministry of Economy and Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052-B-C21 and PID2020-117344RB-I00)

Problemas encontrados en el proceso de traducción del Manual de procedimientos logísticos ACTED Monde problemas lingüísticos en la traducción

El manual de procedimientos logísticos ACTED es un documento especializado que cuenta con 115 páginas. En este documento se pueden apreciar diferentes temas relacionados al campo de la logística. Para la traducción de este manual se realizaron arduas investigaciones que permitieron adquirir nuevos conocimientos sobre palabras y términos utilizados en logística. La traducción de este manual de procedimientos logísticos es importante, ya que será de gran ayuda a personas que estén realizando algún tipo de trabajo relacionado a la logística e incluso a estudiantes que puedan apoyarse en este manual que por primera vez se ha traducido. Por otra parte, esta traducción proporcionará información de gran utilidad a diferentes ONG’S (Organizaciones no gubernamentales) que intervienen en Nicaragua. Gracias a los estudiantes de quinto año de la carrera de Traducción e Interpretación Francesa se realizó la traducción de este manual, a través de este ejercicio se adquirió experiencias a nivel profesional y personal. Además, se desarrollaron las relaciones interpersonales en el colectivo de traducción, se aprendió a trabajar en equipo, a tomar decisiones en conjunto, así como respetar las opiniones de cada uno. Un factor importante de esta tarea fue la constante comunicación que permitió la resolución de problemas y la culminación de esta traducción

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients

Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was & GE;6 mm(2) in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events

HypoxamiRs Profiling Identify miR-765 as a Regulator of the Early Stages of Vasculogenic Mimicry in SKOV3 Ovarian Cancer Cells

Vasculogenic mimicry (VM) is a novel cancer hallmark in which malignant cells develop matrix-associated 3D tubular networks with a lumen under hypoxia to supply nutrients needed for tumor growth. Recent studies showed that microRNAs (miRNAs) may have a role in VM regulation. In this study, we examined the relevance of hypoxia-regulated miRNAs (hypoxamiRs) in the early stages of VM formation. Data showed that after 48 h hypoxia and 12 h incubation on matrigel SKOV3 ovarian cancer cells undergo the formation of matrix-associated intercellular connections referred hereafter as 3D channels-like structures, which arose previous to the apparition of canonical tubular structures representative of VM. Comprehensive profiling of 754 mature miRNAs at the onset of hypoxia-induced 3D channels-like structures showed that 11 hypoxamiRs were modulated (FC>1.5; p < 0.05) in SKOV3 cells (9 downregulated and 2 upregulated). Bioinformatic analysis of the set of regulated miRNAs showed that they might impact cellular pathways related with tumorigenesis. Moreover, overall survival analysis in a cohort of ovarian cancer patients (n = 485) indicated that low miR-765, miR-193b, miR-148a and high miR-138 levels were associated with worst patients outcome. In particular, miR-765 was severely downregulated after hypoxia (FC < 32.02; p < 0.05), and predicted to target a number of protein-encoding genes involved in angiogenesis and VM. Functional assays showed that ectopic restoration of miR-765 in SKOV3 cells resulted in a significant inhibition of hypoxia-induced 3D channels-like formation that was associated with a reduced number of branch points and patterned tubular-like structures. Mechanistic studies confirmed that miR-765 decreased the levels of VEGFA, AKT1 and SRC-α transducers and exerted a negative regulation of VEGFA by specific binding to its 3‘UTR. Finally, overall survival analysis of a cohort of ovarian cancer patients (n = 1435) indicates that high levels of VEGFA, AKT1 and SRC-α and low miR-765 expression were associated with worst patients outcome. In conclusion, here we reported a novel hypoxamiRs signature which constitutes a molecular guide for further clinical and functional studies on the early stages of VM. Our data also suggested that miR-765 coordinates the formation of 3D channels-like structures through modulation of VEGFA/AKT1/SRC-α axis in SKOV3 ovarian cancer cells

Guía Mexicana de Práctica Clínica de Inmunoterapia 2011

Existen varias guías internacionales para la práctica clínica de in- munoterapia, que aplican solo parcialmente en México. La primera guía mexicana de inmunoterapia data de 1998

Red de tutores del Programa de Acción Tutorial de la Facultad de Económicas (PATEC)

El Plan de Acción Tutorial (PAT, PATEC en la Facultad de Ciencias Económicas y Empresariales) se viene desarrollando en la Universidad de Alicante (UA) desde el curso 2005-2006. Tras más de una década de su puesta en marcha en la Facultad de Ciencias Económicas y Empresariales, el PATEC se ha ido consolidando año a año y, aunque son muchas sus fortalezas, existen aún ciertas debilidades que persisten a las que hay que dar respuesta. Para ello, en el curso 2013-2014 surge la Red de Tutores del PATEC como un punto de encuentro en el que reflexionar sobre el funcionamiento del Programa. En el curso 2015-2016 su objetivo es doble. Por un lado, y continuando la labor que comenzó en el curso anterior referida a analizar experiencias de acción tutorial en otras universidades españolas, extraer las buenas prácticas que supongan un nuevo impulso para el PATEC. Por otro, conocer la experiencia de la primera promoción de alumnos-tutores de la Facultad

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders