Integration of gene expression and methylation to unravel biological networks in glioblastoma patients

ABSTRACT The vast amount of heterogeneous omics data, encompassing a broad range of biomolecular information, requires novel methods of analysis, including those that integrate the available levels of information. In this work, we describe Regression2Net, a computational approach that is able to integrate gene expression and genomic or methylation data in two steps. First, penalized regressions are used to build Expression‐Expression (EEnet) and Expression‐Genomic or Expression‐Methylation (EMnet) networks. Second, network theory is used to highlight important communities of genes. When applying our approach, Regression2Net to gene expression and methylation profiles for individuals with glioblastoma multiforme, we identified, respectively, 284 and 447 potentially interesting genes in relation to glioblastoma pathology. These genes showed at least one connection in the integrated networks ANDnet and XORnet derived from aforementioned EEnet and EMnet networks. Although the edges in ANDnet occur in both EEnet and EMnet, the edges in XORnet occur in EMnet but not in EEnet. In‐depth biological analysis of connected genes in ANDnet and XORnet revealed genes that are related to energy metabolism, cell cycle control (AATF), immune system response, and several cancer types. Importantly, we observed significant overrepresentation of cancer‐related pathways including glioma, especially in the XORnet network, suggesting a nonignorable role of methylation in glioblastoma multif...
Source: Genetic Epidemiology - Category: Epidemiology Authors: Tags: Research Article Source Type: research

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Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
Kruyt F, Dolga AM Abstract Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/KCa) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyP...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
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Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract PURPOSE: The 2-part, phase 1/2a, open-label study (NCT01677741) sought to determine the safety, tolerability, pharmacokinetics, and preliminary activity of dabrafenib in pediatric patients with advanced BRAF V600-mutated cancers. EXPERIMENTAL DESIGN: This phase 1 dose-finding part treated patients aged 1 to 52 weeks and 52% undergoing treatment at data cutoff date. The most common grade 3/4 adverse events suspected to be related to study drug were maculopapular rash and arthralgia (2 patients each). No dose-limiting toxicities were observed. Pharmacokinetic analyses showed a dose-dependent increase i...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractThe N-Myc downstream-regulated gene (NDRG) family consists of four members (NDRG1,NDRG2,NDRG3,NDRG4) that are differentially expressed in various organs and function in important processes, like cell proliferation and differentiation. In the last couple of decades, interest in this family has risen due to its connection with several disorders of the nervous system including Charcot-Marie-Tooth disease and dementia, as well as nervous system cancers. By combining a literature review with in silico data analysis of publicly available datasets, such as the Mouse Brain Atlas, BrainSpan, the Genotype-Tissue Expression (...
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research
In this study, we have aimed to show and compare the antileukemic effects of aprepitant and L-733,060 on acute and chronic myeloid leukemic cells by using in-vitro experiments, such as WST-1, cell imaging, annexin-V binding, soft agar colony formation, and Hoescht staining. As a result, we have determined that both aprepitant and L-733,060 had strong antiproliferative effects on K562 and HL-60 cells. Moreover, the two drugs caused significant apoptosis and decreased colony forming depending on concentration increase. These findings suggested that NK1R antagonists exhibited antileukemic activities and may be considered to h...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31278746 [PubMed - as supplied by publisher]
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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