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22 papers found.
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Evaluation of the efficacy of dasatinib, a Src/Abl inhibitor, in colorectal cancer cell lines and explant mouse model

. Investigation: Eun-Kee Song, John Arcaroli, Wells A. Messersmith. Methodology: Kevin S. Quackenbush, Aik Choon Tan, John Arcaroli, Wells A. Messersmith. Project administration: John Arcaroli, Wells A ... Choon Tan, Hubert Fenton, John Arcaroli. Formal analysis: Stacey Bagby, Todd M. Pitts, Hubert Fenton, John Arcaroli, Wells A. Messersmith. Funding acquisition: John Arcaroli, Wells A. Messersmith

Systematic Analysis of Whole Exome Sequencing Determines RET G691S Polymorphism as Germline Variant in Melanoma

Abstract The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is...

Systems biology approaches for advancing the discovery of effective drug combinations

University of Colorado School of Medicine. Her research interests include systems biology, computational modeling, and bioinformatics. Aik Choon Tan is an Associate Professor of Bioinformatics at the

iCOSSY: An Online Tool for Context-Specific Subnetwork Discovery from Gene Expression Data

Pathway analyses help reveal underlying molecular mechanisms of complex biological phenotypes. Biologists tend to perform multiple pathway analyses on the same dataset, as there is no single answer. It is often inefficient for them to implement and/or install all the algorithms by themselves. Online tools can help the community in this regard. Here we present an online gene...

BEST: Next-Generation Biomedical Entity Search Tool for Knowledge Discovery from Biomedical Literature

As the volume of publications rapidly increases, searching for relevant information from the literature becomes more challenging. To complement standard search engines such as PubMed, it is desirable to have an advanced search tool that directly returns relevant biomedical entities such as targets, drugs, and mutations rather than a long list of articles. Some existing tools...

Automatic Context-Specific Subnetwork Discovery from Large Interaction Networks

Genes act in concert via specific networks to drive various biological processes, including progression of diseases such as cancer. Under different phenotypes, different subsets of the gene members of a network participate in a biological process. Single gene analyses are less effective in identifying such core gene members (subnetworks) within a gene set/network, as compared to...

BRONCO: Biomedical entity Relation ONcology COrpus for extracting gene-variant-disease-drug relations

Tan 0 Jaewoo Kang 1 0 Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus , 12801

Identifying kinase dependency in cancer cells by integrating high-throughput drug screening and kinase inhibition data

Motivation: Targeted kinase inhibitors have dramatically improved cancer treatment, but kinase dependency for an individual patient or cancer cell can be challenging to predict. Kinase dependency does not always correspond with gene expression and mutation status. High-throughput drug screens are powerful tools for determining kinase dependency, but drug polypharmacology can make...

Long Term Storage of Dry versus Frozen RNA for Next Generation Molecular Studies

The standard method for the storage and preservation of RNA has been at ultra-low temperatures. However, reliance on liquid nitrogen and freezers for storage of RNA has multiple downsides. Recently new techniques have been developed for storing RNA at room temperature utilizing desiccation and are reported to be an effective alternative for preserving RNA integrity. In this study...

BEReX: Biomedical Entity-Relationship eXplorer

Summary: Biomedical Entity-Relationship eXplorer (BEReX) is a new biomedical knowledge integration, search and exploration tool. BEReX integrates eight popular databases (STRING, DrugBank, KEGG, PhamGKB, BioGRID, GO, HPRD and MSigDB) and delineates an integrated network by combining the information available from these databases. Users search the integrated network by entering...

An integrated bioinformatics analysis to dissect kinase dependency in triple negative breast cancer

Background Triple-Negative Breast Cancer (TNBC) is an aggressive disease with a poor prognosis. Clinically, TNBC patients have limited treatment options besides chemotherapy. The goal of this study was to determine the kinase dependency in TNBC cell lines and to predict compounds that could inhibit these kinases using integrative bioinformatics analysis. Results We integrated...

From Bench to Bedside: Lessons Learned in Translating Preclinical Studies in Cancer Drug Development

The development of targeted agents in oncology has rapidly expanded over the past 2 decades and has led to clinically significant improvements in the treatment of numerous cancers. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. As preclinical studies shift toward defining proof of mechanism, patient selection, and...

An Inducible TGF-β2-TGFβR Pathway Modulates the Sensitivity of HNSCC Cells to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases

The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of...

Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer

Background Thyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients...

Dual Pharmacological Targeting of the MAP Kinase and PI3K/mTOR Pathway in Preclinical Models of Colorectal Cancer

Background The activation of the MAPK and PI3K/AKT/mTOR pathways is implicated in the majority of cancers. Activating mutations in both of these pathways has been described in colorectal cancer (CRC), thus indicating their potential as therapeutic targets. This study evaluated the combination of a PI3K/mTOR inhibitor (PF-04691502/PF-502) in combination with a MEK inhibitor (PD...

Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy

Motivation: Non–small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients...

Genomic Signatures of Pregnancy-Associated Breast Cancer Epithelia and Stroma and their Regulation by Estrogens and Progesterone

Pregnancy-associated breast cancers (PABC) generally present at advanced stages and have a poor prognosis. The reasons are unclear but we hypothesized that the continuous high levels of estrogens and progesterone were involved. We have now carried out a detailed analysis of PABC compared to tumors of age-matched nonpregnant (non-PABC) women. Malignant epithelia and tumor...

A short survey of computational analysis methods in analysing ChIP-seq data

Chromatin immunoprecipitation followed by massively parallel next-generation sequencing (ChIP-seq) is a valuable experimental strategy for assaying protein-DNA interaction over the whole genome. Many computational tools have been designed to find the peaks of the signals corresponding to protein binding sites. In this paper, three computational methods, ChIP-seq processing...

Resistance to ROS1 Inhibition Mediated by EGFR Pathway Activation in Non-Small Cell Lung Cancer

The targeting of oncogenic ‘driver’ kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies invariably arises and is a major limitation to patient care. ROS1 fusion proteins are a recently described class of oncogenic driver, and...