PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits

Abstract Background and aims Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another. Methods In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis. Results MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodi…

A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease

Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessin…

Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur

Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized. The frequency and delicate location of these tumors suggest that the risk of recurrence might be more accurately predicted. Herein, we show an easy way to evaluate the methylation status of meningiomas and its correlation with the prognosis of the disease. A series of 120 meningiomas, including primary tumors and recurrences, were analyzed histopathologically, and 24 tumor suppressor genes (TSGs) were studied by meth…

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

Identification of a Novel BRCA1 Alteration in Recurrent Melanocytoma Resulting in Increased Proliferation

Abstract Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency. Even less has been described about markers with prognostic value. Here we describe a patient who developed a primary meningeal melanocytoma, suffered 3 recurrences in a period of 6 years and died of the tumor. The genetic and epigenetic changes explored confirmed GNAQ mutation as an initiating event. We found an epigenetic alteration of GSTP1, a feature that has recently been described in meningiomas, from the beginning …

Production of soluble eukaryotic recombinant proteins in E. coli is favoured in early log-phase cultures induced at low temperature

Abstract Background Producing recombinant plant proteins expressed in Escherichia coli produce in high yields and in a soluble and functional form can be difficult. Under overexpression conditions, proteins frequently accumulate as insoluble aggregates (inclusion bodies) within the producing bacteria. We evaluated how the initial culture density, temperature and duration of the expression stage affect the production of some eukaryotic enzymes in E. coli. Findings A high yield of active soluble proteins was obtained by combining early-log phase cultures and low temperatures for protein induction. When IPTG was added at OD600 = 0.1 and cultures were maintained at 4°C for 48-72 h, the soluble …

Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

We report a case of a recurrent clear cell meningioma (CCM) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 CCM with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The las…

BRAF V600E Mutation in Two Distinct Meningeal Melanocytomas Associated With a Nevus of Ota

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after s…

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

Abstract Background Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. Methods In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and…

Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations…

Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro

Patients with Minimal Hepatic Encephalopathy Show Altered Thermal Sensitivity and Autonomic Function

Cirrhotic patients may experience alterations in the peripheral nervous system and in somatosensory perception. Impairment of the somatosensory system could contribute to cognitive and motor alterations characteristic of minimal hepatic encephalopathy (MHE), which affects up to 40% of cirrhotic patients. We assessed the relationship between MHE and alterations in thermal, vibration, and/or heat pain sensitivity in 58 cirrhotic patients (38 without and 20 with MHE according to Psychometric Hepatic Encephalopathy Score) and 39 controls. All participants underwent attention and coordination tests, a nerve conduction study, autonomic function testing, and evaluation of sensory thresholds (vibra…

Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status.

Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression. The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) …

Chromosomal and genetic changes produced in tumoral progression of embryonal rhabdomyosarcoma

The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting E…

Introducció a les alteracions equilibrades dels cromosomes

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticas que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL VALENCIANO

Reciprocal translocation

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL INGLÉS

Segregació cromosòmica de la traslocació recíproca

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057.ADAPTACIÓN AL VALENCIANO

Segregació cromosòmica de la traslocació robertsoniana

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL VALENCIANO

Robertsonian translocation

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL INGLÉS

Introducción a las alteraciones estructurales equilibradas de los cromosomas

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticas que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Música: Firefly by Techsmith library. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD17-724975