Intracranial hypertension

A relação entre o conteúdo da caixa intracraniana e o seu volume determina a pressão intracraniana (PIC), que tem como referência a pressão atmosférica. Em condições normais, a pressão intracraniana tem flutuações determinadas pelos ciclos respiratório e cardíaco. Várias doenças determinam o aumento da pressão intracraniana, sendo a mais freqüente o traumatismo craniencefálico. Para o diagnóstico da hipertensão intracraniana (HIC) deve-se valorizar o quadro clínico, constituído de cefaléia, vômitos e papiledema. Dos exames subsidiários, os mais importantes são os métodos de imagem principalmente Tomografia Computadorizada (TC) e Ressonância Nuclear Magnética (RNM). Para os casos graves de HIC, o ideal durante o tratamento é que a PIC esteja monitorizada. Diversas modalidades podem ser utilizadas, como a hipocapnia induzida pela hiperventilação, os diuréticos osmóticos, a hipotermia e cuidados especiais no tratamento geral dos pacientes.The relation between the volume of the brain and the skull determines the intracranial pressure, that has as reference the atmospheric pressure. In normal conditions the intracranial pressure has oscillations determined by the breathing and heart cycles. Several pathologies determine the increase of the intracranial pressure, the most frequent the head trauma. Should be valued for the diagnosis of the intracranial hypertension (ICH) the clinical picture of headache, vomiting and papilledema. The most important subsidiary exams are the image methods mainly the Computed Tomography (CT) and the Magnetic Resonance Imaging (MRI). Monitorization of the intracranial pressure is important for severe cases of ICH. Several therapeutic modalities can ben used, as hypocarbia induced by hyperventilation, osmotics diuretics, barbiturates, hypothermia and special general measures with the patient

Selection of suitable housekeeping genes for expression analysis in glioblastoma using quantitative RT-PCR

Background: Considering the broad variation in the expression of housekeeping genes among tissues and experimental situations, studies using quantitative RT-PCR require strict definition of adequate endogenous controls. for glioblastoma, the most common type of tumor in the central nervous system, there was no previous report regarding this issue.Results: Here we show that amongst seven frequently used housekeeping genes TBP and HPRT1 are adequate references for glioblastoma gene expression analysis. Evaluation of the expression levels of 12 target genes utilizing different endogenous controls revealed that the normalization method applied might introduce errors in the estimation of relative quantities. Genes presenting expression levels which do not significantly differ between tumor and normal tissues can be considered either increased or decreased if unsuitable reference genes are applied. Most importantly, genes showing significant differences in expression levels between tumor and normal tissues can be missed. We also demonstrated that the Holliday Junction Recognizing Protein, a novel DNA repair protein over expressed in lung cancer, is extremely over-expressed in glioblastoma, with a median change of about 134 fold.Conclusion: Altogether, our data show the relevance of previous validation of candidate control genes for each experimental model and indicate TBP plus HPRT1 as suitable references for studies on glioblastoma gene expression.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAEPA-FMRUniv São Paulo, Fac Med, Dept Surg & Anat, BR-14049090 Ribeirao Preto, SP, BrazilUniv São Paulo, Fac Med, Dept Cellular & Mol Biol, BR-14049090 Ribeirao Preto, SP, BrazilUniv São Paulo, Fac Med, Dept Pathol, BR-14049090 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, BR-04023900 São Paulo, BrazilUniv São Paulo, Sch Med, Dept Neurol, BR-01246903 São Paulo, BrazilUniv São Paulo, Fac Med, Dept Pediat, BR-14049090 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, BR-04023900 São Paulo, BrazilFAPESP: 04/12133-6FAPESP: 06/57602-9CNPq: 485342/2006Web of Scienc

Reconfigurable spin-wave propagation in magnetic stripe domains in hybrid system

Resumen del trabajo presentado a la INTERMAG Conference - IEEE International Magnetics, celebrada on-line del 26 al 30 de abril de 2021.Very recently magnetic stripe domains, characterized by alternating up and down out-of-plane orientation of the magnetization, have received great interest due to the possibility to use stripe patterns to manipulate spin-wave (SW) propagation as in artificial magnonic crystals. In this work, we demonstrate the control of the SW propagation by using reconfigurable regular stripe-pattern domain structure in the hybrid system. The investigated system consists of 64-nm-thick NdCo layer and 10-nm-thick NiFe layer, coupled through an Al layer of different thicknesses. Magnetic force microscopy (MFM) measurements show that, due to the perpendicular magnetic anisotropy of the NdCo film, the system develops stripe domains aligned with the last in-plane saturation direction. The domain pattern is found to have a period of about 140 nm, which is almost independent on the thickness of the Al layer. The magnetization reversal of the trilayer system was investigated by vibrating sample magnetometer, showing that the hysteresis loop is characterized by a two-step process, due to the different coercivity of the NiFe and NdCo films. Detailed analysis of the hysteresis loops along with micromagnetic simulations indicates that the stray magnetic field coming from the NdCo layer induces a regular domain structure also in the NiFe layer, which is tuned by the thickness of Al spacer. In addition, upon reversing the applied magnetic field, an antiparallel state, characterized by an antiparallel alignment of the magnetization component parallel to the domain axis in the NdCo and NiFe stripes, is formed. Then, Brillouin light scattering spectroscopy has been used to measure the spectra of the SWs propagating in the direction perpendicular to stripe domains for the parallel and the antiparallel state. For both configurations, the dispersion relation shows a strongly nonreciprocal mode. However, in the parallel state SWs propagating with positive and negative wavevector are both characterized by a positive dispersion, while in the reversed state SWs propagating with negative wavevector show a negative dispersion. The above experimental results have been satisfactorily reproduced by numerical simulations. The latter show that the detected SW mode is mainly localized in the NiFe layer and its frequency nonreciprocity can be ascribed to the static magnetization configuration as well as to the interaction with the NdCo induced by the SWs via the dynamic stray field.PID2019-104604RBPeer reviewe

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence

Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression

Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global <it>HDAC </it>expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.</p> <p>Methods</p> <p>Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV <it>HDACs </it>was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene <it>β-glucuronidase</it>. Protein levels were evaluated by western blotting.</p> <p>Results</p> <p>We found that mRNA levels of class II and IV <it>HDACs </it>were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, <it>p </it>< 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue.</p> <p>Conclusion</p> <p>Our study establishes a negative correlation between <it>HDAC </it>gene expression and the glioma grade suggesting that class II and IV <it>HDACs </it>might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of <it>HDAC </it>mRNA in glioblastomas.</p

Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin