Search results for "Bioinformatics"
showing 10 items of 1632 documents
Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma out…
2012
BACKGROUND: Using mRNA expression-derived signatures as predictors of individual patient outcome has been a goal ever since the introduction of microarrays. Here, we addressed whether analyses of tumour mRNA at the exon level can improve on the predictive power and classification accuracy of gene-based expression profiles using neuroblastoma as a model. METHODS: In a patient cohort comprising 113 primary neuroblastoma specimens expression profiling using exon-level analyses was performed to define predictive signatures using various machine-learning techniques. Alternative transcript use was calculated from relative exon expression. Validation of alternative transcripts was achieved using q…
Translation of genomics-guided RNA-based personalised cancer vaccines: towards the bedside
2014
Cancer is a disease caused by DNA mutations. Cancer therapies targeting defined functional mutations have shown clinical benefit. However, as 95% of the mutations in a tumour are unique to that single patient and only a small number of mutations are shared between patients, the addressed medical need is modest. A rapidly determined patient-specific tumour mutation pattern combined with a flexible mutation-targeting drug platform could generate a mutation-targeting individualised therapy, which would benefit each single patient. Next-generation sequencing enables the rapid identification of somatic mutations in individual tumours (the mutanome). Immunoinformatics enables predictions of mutat…
The genetic landscape of clinical resistance to RAF inhibition in melanoma.
2013
11009 Background: Although single-agent RAF inhibition has proved effective in metastatic BRAFV600-mutant melanoma, most patients relapse and some are intrinsically resistant. While several genetic resistance effectors have been identified, a comprehensive assessment of the genetic resistance spectrum in a large patient cohort may further inform resistance patterns and treatment strategies. Methods: Pre-treatment and post-relapse biopsies were obtained from BRAFV600melanoma patients treated with vemurafenib or dabrafenib. Whole exome sequencing of tumor and normal samples was performed to identify exome-wide mutations, insertion/deletions, and chromosomal copy number alterations. Since som…
Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life/Death Decisions by Tumor Cells with Potential Clinical Applications
2010
Parathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal- as well as midregion- and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treat…
Clinical impact of the immunome in lymphoid malignancies: the role of Myeloid-Derived Suppressor Cells
2015
The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of myeloid-derived suppressor cells in the settings of lymphoid malignancies.
Large-scale proteomic identification of S100 proteins in breast cancer tissues
2010
Abstract Background Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. Methods Samples of breast cancer t…
ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer
2010
AbstractPurpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis…
MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?
2012
Recently, the hypothesis that colorectal tumors originate from a subpopulation of cells called ‘cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit stem-like features, has been confirmed experimentally in various human cancers. Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have demonstrated that this rare cell population can be isolated by the expression of specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are crucial for post-transcriptional regulation of gene expression and participate in a wide variety of biological functions, including development, cell proliferation, differentiation, metabolism…
Abstract 3193: Development of a colon cancer model system reveals epithelial contribution to poor-prognosis gene signatures
2016
Abstract Background: Recent consensus on molecular classification categorizes colorectal cancer (CRC) into 4 robust subtypes: CMS1 (epithelial-MSI), CMS2 (epithelial-canonical), CMS3 (epithelial-metabolic) and CMS4 (mesenchymal)1. CMS4 is linked to poor cancer prognosis and characterized by mesenchymal and epithelial-to-mesenchymal transition (EMT) gene expression2,3. Recent attempts to deconvolute the transcriptome from CRC tumors have suggested that the mesenchymal gene expression results from a large stromal compartment and is not due to epithelial cells with EMT-like features4,5. This challenges the classic notion that tumor cells activate the EMT program to undergo trans-differentiatio…
Abstract 2679: Virtual screening of small molecule inhibitors towards the tumor suppressor p53 to overcome radioresistance of nasopharyngeal carcinom…
2010
Abstract The tumor suppressor p53 belongs to the most frequently mutated genes in cancer, including nasopharyngeal carcinoma (NPC). p53 is over-expressed in NPC, but the mutation rate is lower than in other tumor types. Therefore, it can be hypothesized that p53 might be involved in repair of DNA-damage after radiotherapy and causes recrudescence. Hence, the aim of the present investigation was to identify small molecule inhibitors for p53 to inhibit DNA repair after ionizing radiation of NPC. Approximately 260.000 2D-structures from NCI database were downloaded and different tautomers and charged stages between pH 5 and 9 were calculated for each compound. A total number of 906.587 drugs i…