Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.

Background: Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrP) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrP can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating -secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Effect of atorvastatin on muscle tissues of dermatomyositis and antisynthetase syndrome patients with dyslipidemia.

Introduction: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients.

Methods: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo].

Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis.

Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs).

Patients And Methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.

GBM Cells Exhibit Susceptibility to Metformin Treatment According to TLR4 Pathway Activation and Metabolic and Antioxidant Status.

Glioblastoma (GBM) is an aggressive brain cancer associated with poor overall survival. The metabolic status and tumor microenvironment of GBM cells have been targeted to improve therapeutic strategies. TLR4 is an important innate immune receptor capable of recognizing pathogens and danger-associated molecules.

Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status.

Tumor cell infiltrative ability into surrounding brain tissue is a characteristic of diffusely infiltrative astrocytoma and is strongly associated with extracellular matrix (ECM) stiffness. Collagens are the most abundant ECM scaffolding proteins and contribute to matrix organization and stiffness. LOX family members, copper-dependent amine oxidases, participate in the collagen and elastin crosslinking that determine ECM tensile strength.

Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma.

Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state.

Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma.

Objective: The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcriptome, and protein expressions.

Methods: The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequencing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity.

Identification of two patterns of mitochondrial DNA-copy number variation in postcentral gyrus during aging, influenced by body mass index and type 2 diabetes.

Aims: Mitochondrial (mt) DNA replication is strongly associated with oxidative stress, a condition triggered by aging and hyperglycemia, both of which contribute to mitophagy disruption and inflammation. This observational exploratory study evaluated mtDNA-copy number (mtDNA-CN) and expression of genes involved in mitochondriogenesis (PPARGC1A, TFAM, TFB1M, TFB2M), mitophagy (PINK1, PRKN), and inflammatory pathways triggered by hyperglycemia (TXNIP, NLRP3, NFKB1), in the postcentral gyrus of adults and older individuals with and without type 2 diabetes mellitus (T2D).

Main Methods: Quantitative real-time PCR was employed to evaluate mtDNA-CN and gene expression; tissue autofluorescence, a marker of aging and of cells with damaged organelles, was also quantified.

Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma.

Background: Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.

Exercise Training Attenuates Ubiquitin-Proteasome Pathway and Increases the Genes Related to Autophagy on the Skeletal Muscle of Patients With Inflammatory Myopathies.

Background/objective: The aim of this study was to evaluate the effects of exercise training on the ubiquitin-proteasome system (UPS) and genes related to autophagy on the skeletal muscle of patients with dermatomyositis (DM) and immune-mediated necrotizing myopathies (IMNMs).

Methods: Seven DM patients and 6 IMNM patients were treated for 12 weeks with a twice-weekly aerobic and resistance training exercise program. Aerobic capacity, muscle strength, and expression of genes in the skeletal muscle related to UPS and to autophagy were evaluated at the baseline and after the intervention.

Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness.

Background: Glioblastoma is the most frequent and high-grade adult malignant central nervous system tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer.

A coordinated approach for the assessment of molecular subgroups in pediatric ependymomas using low-cost methods.

Although ependymoma (EPN) molecular subgroups have been well established by integrated high-throughput platforms, low- and middle-income countries still need low-cost techniques to promptly classify these molecular subtypes. Here, we applied low-cost methods to classify EPNs from a Brazilian cohort with 60 pediatric EPN patients. Fusion transcripts (C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B) were investigated in supratentorial EPN (ST-EPNs) samples through RT-PCR/Sanger sequencing and immunohistochemistry (IHC) for p65/L1CAM.

CXCR7, CXCR4, and Their Ligand Expression Profile in Traumatic Brain Injury.

Objective: Traumatic brain injury (TBI) is a health problem worldwide, and therapeutic strategies to enhance brain tissue repair to lessen neurologic sequels are imperative. We aimed to analyze the impact of the inflammatory process in TBI through CXCR4 and CXCR7 chemokine receptors and their ligands' CXCL11 and CXCL12 expression profile in search for potential new druggable targets.

Methods: Twelve pericontusional tissues from severe TBI patients submitted to surgical treatment, and 20 control brain tissues from normal autopsy were analyzed for expression profile by real-time quantitative-polymerase chain reaction.

SELAdb: A database of exonic variants in a Brazilian population referred to a quaternary medical center in São Paulo.

Objectives: High-throughput sequencing of genomes, exomes, and disease-focused gene panels is becoming increasingly common for molecular diagnostics. However, identifying a single clinically relevant pathogenic variant among thousands of genetic polymorphisms is a challenging task. Publicly available genomic databases are useful resources to filter out common genetic variants present in the population and enable the identification of each disease-causing variant.

Cyclin E1 expression and malignancy in meningiomas.

Objective: The aim of the present study was to analyze if the pathway Skp2-p27-cyclin E1 could also be a tumor progression marker for meningiomas.

Patients And Methods: We used quantitative real-time PCR to assess the relative expression levels of the genes coding for cyclin E1 (CCNE1), Skp2 (SKP2), and p27 (P27). The expression levels were compared in grades I to III meningiomas and among different histological subtypes of grade I meningiomas.

The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma.

Background: Ependymoma (EPN) is the third most common childhood cancer of the central nervous system. RELA fusion-positive EPN accounts for approximately 70% of all childhood supratentorial tumors and shows the worst prognosis among the supratentorial EPNs. TP53 mutation is infrequent in RELA fusions EPNs.

Associations of and single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas.

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of -2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and -604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls.

CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion.

Glioblastoma (GBM) is the most aggressive type of brain tumor, with an overall survival of 17 months under the current standard of care therapy. CD99, an over-expressed transmembrane protein in several malignancies, has been considered a potential target for immunotherapy. To further understand this potentiality, we analyzed the differential expression of its two isoforms in human astrocytoma specimens, and the CD99 involved signaling pathways in glioma model U87MG cell line.

A simplified approach using Taqman low-density array for medulloblastoma subgrouping.

Next-generation sequencing platforms are routinely used for molecular assignment due to their high impact for risk stratification and prognosis in medulloblastomas. Yet, low and middle-income countries still lack an accurate cost-effective platform to perform this allocation. TaqMan Low Density array (TLDA) assay was performed using a set of 20 genes in 92 medulloblastoma samples.

Comparison between treatment naive juvenile and adult dermatomyositis muscle biopsies: difference of inflammatory cells phenotyping.

Background: Different inflammatory cells (i.e., CD4, CD8, CD20 and CD68) are involved in pathogenesis of DM muscle.

A novel type of C11orf95-LOC-RELA fusion in a grade II supratentorial ependymoma: report of a case with literature review.

Background: Ependymoma (EPN) is the third most common central nervous system tumor in childhood. Recent advances in the molecular classification of EPN revealed a supratentorial (ST) ependymoma subgroup characterized by C11orf95-RELA fusion.

Case Report: We describe a novel RELA-fusion composed by a chimeric transcript C11orf95-LOC-RELA in a supratentorial WHO grade II EPN occurring in a 4-year-old child.

Molecular alterations in meningiomas: Literature review.

Meningiomas, tumors that originate from meningothelial cells, account for approximately 30% of all new diagnoses of central nervous system neoplasms. According to the 2016 WHO classification of central nervous system tumors meningiomas are classified into three grades: I, II, and III. Past studies have shown that the risk of meningiomas recurrence is strongly correlated with the molecular profile of the tumor.

Plasmatic membrane toll-like receptor expressions in human astrocytomas.

Toll-like receptors (TLRs) are the first to identify disturbances in the immune system, recognizing pathogens such as bacteria, fungi, and viruses. Since the inflammation process plays an important role in several diseases, TLRs have been considered potential therapeutic targets, including treatment for cancer. However, TLRs' role in cancer remains ambiguous.

A Brazilian family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia linked to the VCP pGly97Glu mutation.

The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). A systematic review of the literature on the valosin-containing protein (VCP) mutation was also performed. The proband (patient) was initially treated as a case of possible refractory polymyositis with Paget's disease and later as an inclusion body myopathy.