Search results for "Informatics"

Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools

2019

BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

2014

Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is impli…

Abstract LB-287: Identification of patients at risk for tumor predisposition syndromes based on the evaluation of sporadic cancer exome sequencing da…

2017

Abstract The MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Program of the NCT (National Center for Tumor Diseases) Heidelberg and the DKTK (German Cancer Consortium) is situated at the interface of cancer genomics and clinical oncology to provide whole exome/genome and transcriptome sequencing to selected patients with unmet medical need, and to evaluate the utility of such an approach regarding molecular stratification and individualized, biology-guided treatment. The program has enabled implementation of a shared, DKTK-wide workflow for rapid-turnaround clinical sequencing, comprising all steps from sample processing to reporting of results by a dedicated molecu…

Computational Methods for Gene Expression Profiling Using Next-Generation Sequencing (RNA-Seq)

2014

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

2006

Contains fulltext : 35205.pdf (Publisher’s version ) (Closed access) Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, nor…

Genome-wide association scan of attention deficit hyperactivity disorder

2008

Contains fulltext : 70191.pdf (Publisher’s version ) (Closed access) Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present t…

MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer

2021

Summary We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interaction network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overexpress an exogenous MYC, leading to overexpression of the three microRNAs …

GIST: Particular aspects related to cell cultures, xenografts, and cytogenetics

2006

In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged from historical anonymity to become a model of kinase-targeted therapies. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic value. In this regard, the in vitro and in vivo models have provided valuable tools for understanding the molecular pathology of this interesting neoplasm. This review charts particular aspects in the field of cell cultures and tumor xenografts in nude mice in GIST and their implication in the establishment of appropriate models for discovering and testing therapy. The cytogenetic featu…

Pharmacogenomics: a tool to prevent and cure coronary heart disease.

2007

Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- …

Gene expression profiles in irradiated cancer cells

2013

Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell …