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

Hdl Handle:
http://hdl.handle.net/10147/229134
Title:
Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.
Authors:
Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena
Affiliation:
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. paula.kinsella@dcu.ie
Citation:
Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib. 2012, 318 (5):641-52 Exp. Cell Res.
Journal:
Experimental cell research
Issue Date:
10-Mar-2012
URI:
http://hdl.handle.net/10147/229134
DOI:
10.1016/j.yexcr.2012.01.014
PubMed ID:
22285130
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.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Cell Proliferation; Female; Gene Expression; Glioma; Humans; Male; Middle Aged; PTEN Phosphohydrolase; Piperazines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-abl; Proto-Oncogene Proteins c-kit; Pyrimidines; Quinazolines; Receptor, Epidermal Growth Factor; Receptor, Platelet-Derived Growth Factor alpha; Receptor, Platelet-Derived Growth Factor beta; Survival Rate; Tumor Cells, Cultured; Young Adult
ISSN:
1090-2422

Full metadata record

DC FieldValue Language
dc.contributor.authorKinsella, Paulaen_GB
dc.contributor.authorHowley, Rachelen_GB
dc.contributor.authorDoolan, Padraigen_GB
dc.contributor.authorClarke, Colinen_GB
dc.contributor.authorMadden, Stephen Fen_GB
dc.contributor.authorClynes, Martinen_GB
dc.contributor.authorFarrell, Michaelen_GB
dc.contributor.authorAmberger-Murphy, Verenaen_GB
dc.date.accessioned2012-06-15T13:27:21Z-
dc.date.available2012-06-15T13:27:21Z-
dc.date.issued2012-03-10-
dc.identifier.citationCharacterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib. 2012, 318 (5):641-52 Exp. Cell Res.en_GB
dc.identifier.issn1090-2422-
dc.identifier.pmid22285130-
dc.identifier.doi10.1016/j.yexcr.2012.01.014-
dc.identifier.urihttp://hdl.handle.net/10147/229134-
dc.description.abstractHigh-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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Experimental cell researchen_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBrain Neoplasms-
dc.subject.meshCell Proliferation-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshGlioma-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPTEN Phosphohydrolase-
dc.subject.meshPiperazines-
dc.subject.meshProtein Kinase Inhibitors-
dc.subject.meshProto-Oncogene Proteins c-abl-
dc.subject.meshProto-Oncogene Proteins c-kit-
dc.subject.meshPyrimidines-
dc.subject.meshQuinazolines-
dc.subject.meshReceptor, Epidermal Growth Factor-
dc.subject.meshReceptor, Platelet-Derived Growth Factor alpha-
dc.subject.meshReceptor, Platelet-Derived Growth Factor beta-
dc.subject.meshSurvival Rate-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshYoung Adult-
dc.titleCharacterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.en_GB
dc.typeArticleen
dc.contributor.departmentNational Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. paula.kinsella@dcu.ieen_GB
dc.identifier.journalExperimental cell researchen_GB
dc.description.provinceLeinsteren

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