Linked Life Data

20443891

Source:http://linkedlifedata.com/resource/pubmed/id/20443891

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-5-6
pubmed:abstractText
Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1752-8062
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
183-92
pubmed:meshHeading
pubmed-meshheading:20443891-Antineoplastic Agents, pubmed-meshheading:20443891-Cell Line, Tumor, pubmed-meshheading:20443891-DNA Mutational Analysis, pubmed-meshheading:20443891-Drug Resistance, Neoplasm, pubmed-meshheading:20443891-Drug Screening Assays, Antitumor, pubmed-meshheading:20443891-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:20443891-Gene Dosage, pubmed-meshheading:20443891-Gene Expression Profiling, pubmed-meshheading:20443891-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20443891-Genome, Human, pubmed-meshheading:20443891-Head and Neck Neoplasms, pubmed-meshheading:20443891-Humans, pubmed-meshheading:20443891-Neoplasm Proteins, pubmed-meshheading:20443891-Quinazolines, pubmed-meshheading:20443891-RNA, Messenger, pubmed-meshheading:20443891-Tumor Markers, Biological
pubmed:year
2009
pubmed:articleTitle
Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.
pubmed:affiliation
Fomerly of AstraZeneca, Alderly Park, Macclesfield, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't