Type

Journal Article

Authors

Verena Amberger-Murphy
Michael Farrell
Martin Clynes
Stephen F Madden
Colin Clarke
Padraig Doolan
Rachel Howley
Paula Kinsella

Subjects

Biochemistry

Topics
epidermal growth factor receptor viii tumor cells cultured cell proliferation adult gefitinib metabolism humans proto oncogene proteins c kit gene expression receptor platelet derived growth factor beta drug effects pyrimidines female receptor platelet derived growth factor alpha genetics pten protein human glioma protein kinase inhibitors receptor epidermal growth factor pathology antineoplastic agents male erlotinib quinazolines young adult survival rate mortality pharmacology aged middle aged piperazines imatinib pten phosphohydrolase brain neoplasms proto oncogene proteins c abl

Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib. (2011)

Abstract High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.
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Full list of authors on original publication

Verena Amberger-Murphy, Michael Farrell, Martin Clynes, Stephen F Madden, Colin Clarke, Padraig Doolan, Rachel Howley, Paula Kinsella

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
Stephen F Madden
Dublin City University
Total Publications: 42
 
3
Colin Clarke
Dublin City University
Total Publications: 26
 
4
Padraig Doolan
Dublin City University
Total Publications: 37