Long noncoding RNA HOTAIR promotes breast cancer development through the lncRNA HOTAIR/miR-1/GOLPH3 axis

Background The lncRNA HOTAIR is frequently overexpressed in breast cancer tissues and plays an important role in the development of breast cancer. Here, we investigated the effect of the lncRNA HOTAIR on the biological behaviour of breast cancer cells and its molecular mechanism. Methods We investigated the level of HOTAIR in breast cancer and its clinical pathological characteristics by bioinformatic methods. Then, we evaluated the effects of HOTAIR and miRNA-1 expression on the biological behaviour of breast cancer cells by qPCR, Cell Counting Kit-8 (CCK-8) assay, clonogenic assays, Transwell assay and flow cytometry for cell proliferation, invasion migration and apoptosis, and cell cycle analysis. Finally, the target genes of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis were validated by luciferase reports. Results The expression of HOTAIR in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05). Silencing of HOTAIR suppressed cell proliferation, invasion and migration, promoted apoptosis and induced G1 phase block in breast cancer (P < 0.0001). We also verified that miR-1 is a target of HOTAIR and that GOLPH3 is a target of miR-1 by luciferase reporter assays (P < 0.001). Conclusions The expression of HOTAIR was significantly elevated in breast cancer tissues. Reducing the expression of HOTAIR inhibited the proliferation, invasion and migration of breast cancer cells and promoted apoptosis, and the mechanism was mainly the effect of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis on the biological behaviour of breast cancer cells (AU)

Research progress on the role of Ndfip1 (Nedd4 family interacting protein 1) in immune cells

Nedd4 family interacting protein 1 (Ndfip1) was first mentioned in an article in 2000. Since its discovery, related studies have shown that this protein is associated with apoptosis, neuroprotection, substance transport, ubiquitination, and immune regulation. It is noteworthy that the lack of Ndfip1 can lead to death in fetal mice. Researchers generally believe that the function of Ndfip1 is closely related to individual immune capacity and have published a large number of articles. However, a comprehensive classification of the immune regulatory function of Ndfip1 is still lacking. In this review, we will overview and discuss this new perspective, focusing on the role of Ndfip1 in the proliferation, differentiation, and cell activity of CD4+ T cells, CD8+ T cells, mast cells, and eosinophils. This review provides an updated summary of Ndfip1, which will unveil novel therapeutic targets. Finally, the conclusion is that Ndfip1 mainly plays a negative regulatory role in immune cells by maintaining the stability of the immune response and limiting its overexpression (AU)

MG53 alleviates airway inflammatory responses by regulating nuclear factor-kB pathway in asthmatic mice

Background: Asthma is a common lung disease with increasing incidence and prevalence globally, thereby imposing a substantial global health and economic burden. Recently, studies have shown that Mitsugumin 53 (MG53) exhibits multiple biological functions and plays a protective role in a variety of diseases. However, the role of MG53 in asthma remained unknown; hence, in the present study we aimed to explore the functioning of MG53 in asthma. Methods: Using ovalbumin and aluminum hydroxide adjuvant, an OVA-induced asthmatic animal model was constructed and administered with MG53. After establishing mice model, inflammatory cell counts and the levels of type 2 inflammatory cytokines were examined and histological staining of lung tissues were performed. The levels of key factors associated with the nuclear factor-κB (NF-κB) pathway were detected. Results: Asthmatic mice displayed a remarkable accumulation of white blood cells, neutrophils, macrophages, lymphocytes, and eosinophils in bronchoalveolar lavage fluid, compared to control mice. MG53 treatment lowered the number of these inflammatory cells in asthmatic mice. The level of type 2 cytokines in asthmatic mice was higher than that in control mice, and was lessened by MG53 intervention. In asthmatic mice, airway resistance was elevated, which was reduced by MG53 treatment. In addition, inflammatory cell infiltration and mucus secretion were aggravated in the lung tissues of asthmatic mice, and both were attenuated by MG53 intervention. The levels of phosphorylated p65 and phosphorylated inhibitor of nuclear factor kappa-B kinase were elevated in asthmatic mice, but were downregulated by MG53 supplement. Conclusion: The aggravated airway inflammation was observed in asthmatic mice; however, MG53 treatment suppressed airway inflammation by targeting the NF-κB pathway (AU)

Circular RNA circHIPK3 modulates prostate cancer progression via targeting miR-448/MTDH signaling

Purpose Prostate cancer (PCa) is one of the most diagnosed cancers in men worldwide. Several studies have identified that circular RNAs (circRNAs) have a crucial impact on the biological processes in PCa. Therefore, it is necessary to study the molecular mechanism of circRNAs in tumor progression and metastasis. Methods RNA interference was used to decrease circHIPK3 and MTDH expression. Overexpression vector was used to increase circHIPK3 and MTDH expression. Luciferase reporter assay were used to detect the relationship between circHIPK3 and miR-448 or between miR-448 and MTDH. MTT assay, colony formation assay and transwell assay were used to measure proliferation and migration of PCa cells. Results Circular RNA circHIPK3 was significantly increased in PCa tissues and cell lines. And overexpression of circHIPK3 promoted the migration, proliferation, and invasion of PC-3 and 22Rv1 cells, while knockdown of circHIPK3 markedly repressed the above-mentioned series of biological processes. Furthermore, circHIPK3 promoted metadherin (MTDH) expression by sponging miR‐448. In vivo experiments, it was also found that overexpression of circHIPK3 significantly promoted tumor growth. Conclusions Our research shows that circHIPK3 plays a carcinogenic effect in PCa by regulating the miR-448/MTDH axis, indicating that circHIPK3 may be a potential therapeutic target for PCa (AU)

Mutations in chronic myelomonocytic leukemia and their prognostic relevance

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (~ 60%), ASXL1 (~ 40%), SRSF2 (~ 50%), and the RAS pathways (~ 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Cytogenetic abnormalities and the size of genome are also associated with prognosis. Meanwhile, cases with ASXL1, DNMT3A, NRAS, SETBP1, CBL and RUNX1 mutations may have inferior prognoses, but only ASXL1 mutations were confirmed to be independent predictors of the patient outcome and were included in three prognostic models. Novel treatment targets related to the various gene mutations are emerging. Therefore, this review provides new insights to explore the correlations among gene mutations, clinical phenotypes, prognosis, and novel drugs in CMML (AU)

Cancer cell intrinsic sting is associated with CD8T cell infiltration and might serve as a potential immunotherapeutic target in hepatocellular carcinoma

Purpose The activation of stimulator of interferon genes (STING) pathway triggers the antitumor immunity by CD8 + T cells. However, the differentiated antitumor effects of STING activation in different cell types is still unclear. We aimed to investigate the expression and potential prognostic value of cancer cell-intrinsic STING in hepatocellular carcinoma (HCC), and whether STING could be a potential immunotherapeutic target of HCC was then evaluated. Methods We separately assessed the expression of STING in cancer cells and infiltrating immune cells in HCC tissues. The independent clinicopathological factors associated with survival outcomes were evaluated by the multivariable analysis. The HCC orthotopic mice model were used to confirm the immunotherapeutic effects of STING agonists, and CD8 + T-cell infiltration level was analyzed through immunofluorescence and flow cytometry. Results The expression of cancer cell-intrinsic STING was significantly reduced in HCC compared with adjacent tissues. Patients with low levels of cancer cell-intrinsic STING expression was associated with increased tumor volume (P = 0.009), higher serum AFP levels (P = 0.028), and decreased CD8 + T-cell infiltration (P = 0.002). Low levels of cancer cell-intrinsic STING expression indicated a poor overall survival (OS) and disease-free survival (DFS). Multivariate analysis demonstrated that low levels of cancer cell-intrinsic STING expression was an independent prognostic factor. Additionally, cancer cell-intrinsic STING expression was positively related with CD8 + T-cell infiltration levels in HCC patients (r = 0.308; P = 0.001). When mice with orthotopic HCC tumors treated with STING agonists, tumor growth was significantly reduced with enhanced levels of CD8 + T-cell infiltration. Conclusion Cancer cell-intrinsic STING might affect HCC tumor progression through enhancing CD8 + T-cell infiltration and can be an immunotherapeutic target for HCC (AU)

A novel JAG1 mutation causing Alagille syndrome presenting with giant hepatic nodules and discordant phenotype in monozygotic twins

No disponible

Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética / Megalencephalic leukoencephalopathy with cysts -the clinical importance in the genetic era

INTRODUCCIÓN: La leucoencefalopatía megalencefálica con quistes es una leucodistrofia de origen genético que produce una alteración de la homeostasis del agua e iones en el cerebro, generando formas vacuolares y edema crónico en la sustancia blanca con deterioro neurológico progresivo. Debe sospecharse en los lactantes que presentan macrocefalia progresiva durante el primer año de vida, retraso motor y hallazgos característicos en la resonancia magnética cerebral. CASO CLÍNICO: Niña en seguimiento desde los 9 meses por macrocefalia progresiva y retraso del desarrollo psicomotor con presencia en la resonancia magnética cerebral de hallazgos compatibles con leucoencefalopatía megalencefálica con quistes, y aparición de epilepsia en su evolución. Los estudios genéticos habituales (secuenciación de nueva generación y array) fueron negativos, pero, al cumplir los criterios diagnósticos, se procedió al estudio del ARN mensajero y el ADN complementario, que confirmó la presencia de dos variantes patogénicas en MLC1. CONCLUSIONES: La leucoencefalopatía megalencefálica con quistes es una entidad infrecuente. Es característica la macrocefalia progresiva en el primer año de vida, la ausencia de deterioro o deterioro lento, y la posibilidad de desarrollar epilepsia, espasticidad y ataxia en su evolución. Cobra importancia en dichos pacientes la realización de una prueba de imagen que muestre hallazgos propios de la entidad, lo que, junto con la clínica, permite diferenciarla de otras leucodistrofias y establecer un diagnóstico confirmatorio. Los estudios genéticos pueden constatar la mutación asociada que posibilita predecir el fenotipo clinicorradiológico

INTRODUCTION: Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans. CASE REPORT: We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development. The usual genetic studies (new generation sequencing and array) were negative, but as the diagnostic criteria were met, a complementary messenger RNA and DNA study was conducted, which confirmed the presence of two pathogenic variants in MLC1. CONCLUSIONS: Megalencephalic leukoencephalopathy with cysts is a rare condition. Progressive macrocephaly in the first year of life, the absence of deterioration or slow deterioration, and the possibility of developing epilepsy, spasticity and ataxia are characteristic signs in its course. It is important for these patients to undergo an imaging test that shows findings that characterise this condition, which, together with the clinical features, makes it possible to differentiate it from other leukodystrophies and to establish a confirmatory diagnosis. Genetic studies can confirm the associated mutation that makes it possible to predict the clinicoradiological phenotype

Policondritis recidivante y glomeruloesclerosis segmentaria y focal: coincidencia o causalidad / Relapsing polychondritis and focal segmental glomerulosclerosis: Coincidence or causality

No disponible

Encefalitis límbica asociada a anti-Caspr2: contribución del análisis visual ayudado de las imágenes PET con 18F-FDG mediante comparación con una base de datos de normalidad / Caspr2 antibody-associated limbic encephalitis: contribution of visual aided analysis of 18F-FDG PET images using normal database comparison

Un inicio temprano de la inmunoterapia es fundamental para mejorar el pronóstico de los pacientes con encefalitis aguda de origen autoinmune (EAI). Se ha propuesto un nuevo abordaje clínico para el diagnóstico temprano basado en aspectos clínicos y pruebas complementarias, pero estas pueden tener una sensibilidad limitada principalmente en las primeras semanas. Mientras que las formas más comunes de EAI (anti-LGI-1 y anti-NMDAR), muestran frecuentemente patrones de PET con 18Flúor-fluordeoxiglucosa (PET-FDG) consistentes, las anti-Caspr2 son menos frecuentes y los patrones de PET-FDG no están establecidos. En nuestra experiencia la PET-FDG en la EAI anti-Caspr2 presenta un hipermetabolismo temporal medial y un déficit difuso cortical, incluso con pruebas complementarias negativas. No obstante, es necesaria la estandarización del análisis de las imágenes PET mediante métodos basados en vóxeles con comparación con bases de datos de normalidad para definir con claridad las áreas de metabolismo alterado que pueden pasar desapercibidas al análisis visual

Early immunotherapy is of paramount importance for a positive outcome in patients suffering acute encephalitis of autoimmune origin (AIE). A new approach for early diagnosis based on clinical presentation and complementary tests has been proposed, but not all these tests show positive findings in the first weeks. While common forms of AIE (anti-LGI-1 and anti-NMDAR antibodies) exhibit consistent 18Fluor-fluorodeoxiglucose (FDG-PET) patterns in many cases, the anti-Caspr2 form of AIE is infrequent and FDG-PET patterns have not been well characterized. In our experience, FDG-PET in anti-Caspr2 limbic encephalitis shows medial temporal hypermetabolism and diffuse cortical hypometabolism, even in the absence of findings in these tests. However, it is necessary to standardize PET image analysis by means of visual and voxel-based methods compared to normal databases to define the areas of pathological metabolism that may go unnoticed when using visual analysis exclusively

Elevación de CA 19-9 en procesos benignos / Elevation of CA 19-9 in benign processes

No disponible

Effect of potential probiotic Leuconostoc mesenteroides FB111 in prevention of cholesterol absorption by modulating NPC1L1/PPARalpha/SREBP-2 pathways in epithelial Caco-2 cells

Mustard kimchi consumption reduces cholesterol levels in rats. To identify lactic acid bacteria (LAB) in kimchi which exert this effect, 20 LAB isolates were evaluated for cholesterol reduction in an in vitro screen. The FB111 strain showed the highest cholesterol-lowering activity and was identified as Leuconostoc mesenteroides. This strain was characterized as a potential probiotic through sequential analyses for resistance to gastrointestinal digestion and bile salts, and adhesion to Caco-2 cells. The Caco-2 cells treated with L. mesenteroides FB111 (6-8 log CFU/mL) showed toxicological effect. The reduction of cholesterol uptake in these cells was inhibited by 48.6% compared to the control and significantly higher than that of the Lactobacillus rhamnosus GG (LGG) strain-treated group after 2-h incubation. The levels of NPC1L1, ABCG5, ABCG8, SREBP-1, SREBP-2, and PPARalpha gene expression were determined by reverse transcription-quantitative polymerase chain reaction analysis. The L. mesenteroides FB111 and LGG inhibited the mRNA expression of NPC1L1 (P < 0.05), whereas the expression of PPARalpha was increased. Moreover, the FB111 strain also inhibited the expression of SREBP-2 mRNA. Overall, we found that L. mesenteroides FB111 has efficient cholesterol-lowering effects and might be useful as a probiotic in the food industry

No disponible

Alpha-syntrophin dependent expression of tubulin alpha 8 protein in hepatocytes

The scaffold protein alpha-syntrophin (SNTA) is a component of the dystrophin glycoprotein complex and has been comprehensively studied in skeletal muscle and adipocytes. SNTA is further expressed in the liver where its biological role remains unclear. Unpublished data from our group suggested that SNTA deficiency is associated with altered tubulin alpha 8 (TUBA8) levels in fat. TUBA8 is highly expressed in different cell lines including hepatoma cells, and here we analyzed whether SNTA has a role herein. In Hepa1-6 cells, TUBA8 protein levels were increased upon SNTA knock down and were reduced upon overexpression of SNTA. This regulation was not identified when analyzing mRNA expression. In the liver of SNTA-deficient mice, TUBA8 protein was higher compared to the respective wild-type controls while RNA expression was even suppressed. Using the HaloTag platform, TUBA8 was found to form a complex with SNTA in Hepa1-6 cells. In the hepatic stellate cell line LX-2, the lack or overexpression of SNTA did, however, not change TUBA8 protein expression. SNTA and TUBA8 are described to regulate cell proliferation. Yet, knock down of SNTA did neither affect proliferation nor viability of Hepa1-6 cells. The present study shows that SNTA protein levels are inversely related to TUBA8 protein expression in the hepatocyte cell line Hepa1-6

PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition

Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma. We also produced a recombinant PTRF (rPTRF) and examined its impact on the functional interactions between the adipocyte and the hepatocyte in vitro. We demonstrated that PTRF can be found in human plasma, and is at least in part, carried by exosomes. In vitro treatment with rPTRF increased the hypertrophy and senescence of 3T3-L1 adipocytes. In turn, those rPTRF-treated adipocytes increased lipid accumulation in hepatocytes. Lastly, we found a positive correlation between circulating PTRF and the concentration of PTRF in the visceral fat depot. All these findings point toward the presence of an enlarged and dysfunctional visceral adipose tissue which secretes PTRF. This circulating PTRF behaves as an adipokine and may partially contribute to the well-known detrimental effects of visceral fat accumulation

Update on the diagnosis and prognosis of pre-eclampsia in singleton pregnancies based on the sFlt-1/PlGF ratio / Actualización del diagnóstico y el pronóstico de la preeclampsia en embarazos únicos con la ayuda del cociente sFlt-1/PlGF

Pre-eclampsia belongs to a group of obstetric complications that are closely related through placental insufficiency, which also includes intrauterine growth restriction and placental abruption. Timely and accurate detection and treatment of pre-eclampsia is usually difficult, since diagnostic criteria are still based on nonspecific signs and symptoms and there is no clear association between the usual criteria for severity and unfavorable outcomes for mother and fetus. The discovery of the role of angiogenic factors (sFlt-1 y PlGF) in the pathophysiology of placental insufficiency is a key step toward improving early diagnosis and establishing a prognosis in cases occurring before week 34 of pregnancy. At present, ≤ 38 is widely accepted to be threshold value of the sFlt-1/PlGF ratio that rules out suspected pre-eclampsia. The use of the ratio is considered cost-effective. However, current data on the treatment and prognosis of women with an abnormally high sFlt1/PlGF ratio are more limited. The present article summarizes current knowledge on the clinical application of the sFlt-1/PlGF for the diagnosis and prognosis of pre-eclampsia and highlights those areas that should be addressed with respect to biomarkers, for example, their role as targets in the development and follow-up of new treatments

La preeclampsia pertenece a un grupo de complicaciones obstétricas estrechamente relacionadas entre ellas por la existencia de una insuficiencia placentaria, que incluye también la restricción del crecimiento intrauterino y el desprendimiento placentario. El reconocimiento y tratamiento oportuno y preciso de la preeclampsia suele ser difícil, ya que los criterios diagnósticos aún se basan en signos y síntomas inespecíficos y no existe una relación clara entre los criterios habituales de gravedad y los resultados desfavorables para la madre o el feto. El descubrimiento del papel que juegan los factores relacionados con la angiogénesis (sFlt-1 y PlGF) en la fisiopatología subyacente de la insuficiencia placentaria ha constituido un paso importante a la hora de mejorar el diagnóstico precoz y establecer un pronóstico en los casos que se presentan antes de la semana 34 de gestación. En la actualidad está ampliamente aceptado que el valor límite del cociente sFlt-1/PlGF que permite excluir la existencia de preeclampsia en pacientes en las que se sospecha esta enfermedad es de 38 o menos, y que el uso de este cociente resulta costo-eficiente. Sin embargo, los datos disponibles relativos al tratamiento y al pronóstico de las mujeres con niveles anormalmente altos del cociente sFlt1/PlGF son más limitados. Este artículo resume los conocimientos actuales relativos a la aplicación clínica del cociente sFlt-1/PlGF para diagnosticar y pronosticar el curso de la preeclampsia, y señala las próximas tareas que serán necesarias abordar en relación con estos biomarcadores, como por ejemplo el papel que pueden jugar como dianas para el desarrollo y el seguimiento de nuevos tratamientos

Expresión del gen esp (enterococcus surface protein) de enterococcus faecalis en un modelo in vitro de dientes extraídos / Gene expression esp (enterococcus surface protein) of enterococcus faecalis in an in vitro model of extracted teeth

Objetivo: Determinar la presencia y expresión del gen esp en cepas clínicas de Enterococcus faecalis a partir de un modelo in vitro de dientes extraídos. Métodos: Se diseñó un sistema in vitro para evaluar la formación del biofilm mediante microscopía de fluorescencia y la expresión del gen esp. El sistema estuvo constituido por un diente humano previamente extraído, cortado y preparado que proporcionó, mediante su conducto radicular, una superficie adecuada para la formación del biofilm por parte de E. faecalis. El sistema dispuso de una cámara anaerobia que permitió el crecimiento de la bacteria en el caldo de cultivo y evitó su contaminación con otros microorganismos. Esta cámara estuvo constituida por un tubo de micro centrifuga estéril, cortado y unido por el extremo inferior al extremo apical del diente seccionado. Resultados: Los resultados que se obtuvieron tanto por microscopia de fluorescencia como por RT-PCR permitieron cuantificar el nivel de expresión del gen esp en las bacterias durante su crecimiento y formando el biofilm en la superficie de los conductos radiculares. Todas las cepas evaluadas presentan el gen esp. Sin embargo, el biofilm de la cepa CC02 expresó el gen esp cuatro veces más en comparación al gen esp de la cepa de referencia. Conclusión: La expresión del gen esp podría estar asociada con la formación de biofilm en E. faecalis y la adherencia a superficies abióticas. Podría convertirse en una diana terapéutica prometedora en los programas de control de infecciones persistentes por Enterococcus spp. asociados a la presencia de biofilm (AU)

Objective: To determine the presence and expression of Enterococcus faecalis Esp gene in several strains from an in vitro model on extracted teeth. Methods: An in vitro system was designed to evaluate the biofilm formation through fluorescence microscopy and gene expression that could be associated to biofilm formation. The system consisted of a previously extracted human tooth that was cut and prepared to provide by means of its root canal, an adequate surface for biofilm formation on behalf of Enterococcus faecalis. The system disposed an anaerobe chamber that allowed the growth of bacteria in broth culture and avoided contamination with other microorganisms. This chamber consisted of a sterile micro centrifuge tube, which was cut and united by its inferior end to the apical end of the sectioned tooth. Results: The results obtained with fluorescence microscopy and RT-PCR allowed the quantification of the Esp gene levels of expression in bacteria growing and forming biofilm in root canal surfaces. Conclusion: The expression of Esp gene is associated with biofilm formation in E. faecalis and in the adherence to abiotic surfaces. It could be a promising therapeutic target in control programs for the eradication of persistent infections associated with the presence of E faecalis in biofilm (AU)

Genome-wide association studies (GWAS) and their importance in asthma

Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease

No disponible

Validación externa de los ARNm: FXYD3 y KRT20 como biomarcadores predictivos de la presencia de micrometástasis en ganglios de pacientes con tumor vesical infiltrante / External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes

Introducción: Recientes estudios han propuesto que los ARNm FXYD3 y KRT20 cuantificados por qrtPCR en material parafinado podrían ser biomarcadores capaces de detectar los ganglios portadores de micrometástasis que se escapaban al análisis convencional por hematoxilina-eosina (HE). Se decidió hacer un estudio de validación en ganglios de pacientes a los que se les practicó una cistectomía radical. Objetivo: Clasificar el estado adenopático de una muestra de pacientes cistectomizados, según la expresión ganglionar de FXYD3 y KRT20. Como objetivo secundario valorar si existe una evolución oncológica diferencial de los pacientes, según la expresión ganglionar de dichas proteínas. Material y método: Se incluyeron ganglios linfáticos de 64 pacientes cistectomizados por tumor vesical infiltrante. El modelo se desarrolló a expensas de ganglios metastásicos de 15 pacientes y ganglios de 4 pacientes sin tumor conocido. La expresión génica se midió mediante PCR cuantitativa en tiempo real. Se calculó la expresión mediana mediante q-rtPCR de los ARNm de FXYD3 y KRT20 en el tejido ganglionar. Se continuó con un análisis de curvas ROC, según la función y = 0.1400 + 0.250FXYD3-2.532. Se estableció el punto de corte mediante una curva ROC. Dicha fórmula se aplicó al tejido ganglionar restante; en función del punto de corte antes establecido la muestra quedó clasificada en 4 subgrupos: HE- qrtPCR-, HE- qrtPCR+, HE+ qrtPCR+ y HE+ qrtPCR-. Se procedió a un análisis descriptivo, comparativo y a un análisis de supervivencia libre de progresión metastásica, calculando las curvas de Kaplan y Meyer para los 3 subgrupos establecidos. Los test se consideraron estadísticamente significativos cuando p < 0,05. Resultados: Mediante q-rtPCR se comprobó que había diferencias en la expresión mediana de FXYD3 (p = 0,05) y de KRT20 (p = 0,009) entre el tejido ganglionar de los pacientes con HBP y los pacientes con metástasis adenopáticas. Se asignó como punto de corte de 0,377. La muestra se clasificó en: un 37,5% de los pacientes eran pN0 por HE y pN0 por qrtPCR (-HE -qrtPCR), el 39,1% eran pN0 por HE pero eran metastásicos por qrtPCR (-HE +qrtPCR) y 15 pacientes (23,4%) eran metastásicos por ambas técnicas (+HE +qrtPCR). Las curvas de Kaplan y Meyer mostraron una peor supervivencia libre de progresión metastásica para los pacientes (+HE +qrtPCR) que para el resto de los subgrupos, no observando diferencias significativas entre (-HE +qrtPCR) y (-HE -qrtPCR). Conclusiones: Según nuestros resultados un 39,1% de los pacientes con tumor vesical infiltrante sobreexpresarían los biomarcadores FXYD3 y KRT20, siendo N0 por HE. No observamos un comportamiento clínico diferencial de los pacientes cistectomizados según su expresión de FXYD3 y KRT20 cuando son N0 por HE

Introduction: Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. Objective: To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. Material and method: The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y = 0.1400 + 0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P < .05. Results: Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P = .05) and KRT20 (P = .009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. Conclusions: According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE

Valoración de la superficie del dializador en la hemodiafiltración on-line. Elección objetiva de la superficie del dializador / Assessment of dialyzer surface in online hemodiafiltration; objective choice of dialyzer surface area

Introducción: La hemodiafiltración on-line (HDF-OL) es actualmente la técnica más efectiva. Varios estudios aleatorizados y metaanálisis han observado una reducción de la mortalidad, objetivándose una asociación en relación directa con el volumen convectivo. En el momento presente no está bien establecido si el aumento de superficie del dializador puede suponer mejores resultados en términos de eficacia convectiva y depurativa. El objetivo del estudio fue valorar el efecto del aumento de superficie del dializador sobre el volumen convectivo y la capacidad depurativa. Material y métodos: Se incluyeron 37 pacientes (31 varones y 6 mujeres) que se encontraban en programa de HDF-OL con monitor 5008Cordiax con autosustitución. Cada paciente fue analizado en 3 sesiones en las que solo se varió la superficie del dializador (1,0, 1,4 o 1,8m2). En cada sesión se determinaron la concentración de urea (60Da), creatinina (113Da), β2-microglobulina (11.800Da), mioglobina (17.200Da) y α1-microglobulina (33.000Da) en suero al inicio y al final de cada sesión, para calcular el porcentaje de reducción de estos solutos. Resultados: El volumen convectivo alcanzado fue de 29,8±3,0 con 1,0m2, de 32,7±3,1 (incremento del 6%) con 1,4m2 y de 34,7±3,3l (incremento del 16%) con 1,8m2 (p<0,001). El incremento de la superficie del dializador mostró un aumento de la dosis de diálisis y de la depuración de urea y creatinina. El porcentaje de reducción de β2-microglobulina se incrementó de 80,0±5,6 con 1,0m2, a 83,2±4,2 con 1,4m2 y a 84,3±4,0% con 1,8m2. Respecto a la mioglobina y la a1-microglobulina, se observaron diferencias significativas entre la menor superficie (1,0m2) 65,6±11 y 20,1±9,3; y las otras 2 superficies 70,0±8,1 y 24,1±7,1 (1,4m2) y 72,3±8,7 y 28,6±12 (1,8m2). Conclusión: El incremento del 40% y el 80% de la superficie conlleva un aumento del volumen convectivo de un 6 y un 16% respectivamente, aunque se evidenció una reducción en su máximo rendimiento, mostrando mínimas diferencias tanto en el volumen convectivo como en la capacidad depurativa cuando el CUF era superior a 45 ml/h/mmHg. Es recomendable optimizar el rendimiento de los dializadores a la mínima superficie posible adecuando la prescripción de tratamiento (AU)

Introduction: Online hemodiafiltration (OL-HDF) is currently the most effective technique. Several randomized studies and meta-analyses have observed a reduction in mortality as well as a direct association with convective volume. Currently, it has not been well established whether a larger dialyzer surface area could provide better results in terms of convective and depurative effectiveness. The aim of this study was to assess the effect of larger dialyzer surface areas on convective volume and filtration capacity. Material and methods: A total of 37 patients were studied, including 31 men and 6 women, who were in the OL-HDF program using a 5008 Cordiax monitor with auto-substitution. Each patient was analyzed in 3 sessions in which only the dialyzer surface area varied (1.0, 1.4 or 1.8 m2). The concentrations of urea (60 Da), creatinine (113 Da), β2-microglobulin (11800 Da), myoglobin (17200 Da) and α1-microglobulin (33000 Da) were determined in serum at the beginning and end of each session in order to calculate the percent reduction of these solutes. Results: The convective volume reached was 29.8 ± 3.0 with 1.0 m2, 32.7 ± 3.1 (an increase of 6%) with 1.4 m2, and 34.7 ± 3.3 L (an increase of 16%) with 1.8 m2 (p<.001). The increased surface of the dialyzer showed an increase in the dialysis dose as well as urea and creatinine filtration. The percentage of β2m reduction increased from 80.0 ± 5.6 with 1.0 m2 to 83.2 ± 4.2 with 1.4 m2 and to 84.3 ± 4.0% with 1.8 m2. As for myoglobin and a1-microglobulin, significant differences were observed between smaller surface area (1.0 m2) 65.6 ± 11 and 20.1 ± 9.3 and the other two surface areas, which were 70.0 ± 8.1 and 24.1 ± 7.1 (1.4 m2) and 72.3 ± 8.7 and 28.6 ± 12 (1.8 m2). Conclusion: The 40% and 80% increases in surface area led to increased convective volumes of 6 and 16% respectively, while showing minimal differences in both the convective volume as well as the filtration capacity when the CUF was higher than 45 ml/h/mmHg. It is recommended to optimize the performance of dialyzers with the minimal surface area possible when adjusting the treatment prescription (AU)

PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer

PURPOSE: To identify biological markers related to the progression and prognosis of GBC. METHODS: The expressions of pyruvate kinase isoenzyme type M2 (PKM2) and activin A receptor type IC (ACVR 1C) in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry. RESULTS: Positive PKM2 and negative ACVR 1C expressions were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either elevated PKM2 or loss of ACVR 1C expression significantly correlated with shorter average survival times in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive PKM2 expression and loss of ACVR 1C expression were poor prognosis biomarkers in both SC/ASC and AC patients. CONCLUSIONS: Our study suggested that PKM2 overexpression is a marker of metastasis, invasion and poor prognosis of GBC. ACVR 1C is a tumor suppressor, and lowered ACVR 1C expression is an important marker for the metastasis, invasion, and prognosis of GBC (AU)

No disponible