{"id":{"repo_id":"dcu","oai_identifier":"oai:doras.dcu.ie:16061"},"canonical_url":"https://search.dev.ndltd.org/etd/dcu/oai:doras.dcu.ie:16061","repository":{"repo_id":"dcu","name":"Dublin City University","base_url":"http://doras.dcu.ie/cgi/oai2"},"display":{"title":"The Investigation of Targets for Therapy in Brain Tumours","abstract":"Gliomas are among the most difficult of tumours to treat. Their highly invasive nature leads to recurrence even after aggressive therapy including surgery, radiotherapy and chemotherapy. A promising target for new therapies are tyrosine kinases, because they regulate a large range of proteins involved in growth, metabolism and differentiation. The receptor tyrosine kinases, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR) and C-Kit, as well as the non-receptor tyrosine kinase C-Abl are often amplified, overexpressed, and/or mutated in gliomas and play an important role in glioma development. A number of tyrosine kinase inhibitors (TKIs) have been developed and tested in clinical trials with mixed results. In collaboration with Beaumont hospital 31 glioma cell cultures were established to identify molecular markers indicative of responsiveness to EGFR and PDGFR blockade. Each culture was characterised with regard to their protein expression profile, their proliferative and invasive behaviour and their responsiveness to three TKIs, erlotinib, gefitinib and imatinib, and two chemotherapy drugs, docetaxel and temozolomide. All data of 26 high-grade gliomas (20 primary glioblastomas, 2 secondary glioblastomas, and 4 grade III astrocytomas including medical history of the patients were analysed using hierarchical clustering analysis (HCA) and principal component analysis (PCA) employing multivariate statistics. Two distinct clusters of samples were found, which separated by the expression of PTEN and PDGFR-a in cluster 1 and predominately PDGFR-b, EGFR, phosphorylated C-Kit (p-C-Kit) and phosphorylated C-Abl (p-C-Abl) expression in cluster 2. Principal components analysis of the culture data captured 55% of the variance in the dataset showing PTEN, PGDFR-a and PGDFR-� loading vectors in approximately the same direction. Imatinib responsiveness was strongly correlated with high expression levels of PTEN and PDGFR-a. Responsiveness to erlotinib was correlated with the lack of expression of all proteins tested, while non-responders showed higher expression of PTEN and PDGFR-a. Responders to gefitinib fit into two groups, the majority (group 1) were influenced by the expression of the proteins tested, while the second smaller group correlated with the lack of protein expression. Non-responders to","abstract_html":"Gliomas are among the most difficult of tumours to treat. Their highly invasive nature leads to recurrence even after aggressive therapy including surgery, radiotherapy and chemotherapy. A promising target for new therapies are tyrosine kinases, because they regulate a large range of proteins involved in growth, metabolism and differentiation. The receptor tyrosine kinases, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR) and C-Kit, as well as the non-receptor tyrosine kinase C-Abl are often amplified, overexpressed, and/or mutated in gliomas and play an important role in glioma development. A number of tyrosine kinase inhibitors (TKIs) have been developed and tested in clinical trials with mixed results. In collaboration with Beaumont hospital 31 glioma cell cultures were established to identify molecular markers indicative of responsiveness to EGFR and PDGFR blockade. Each culture was characterised with regard to their protein expression profile, their proliferative and invasive behaviour and their responsiveness to three TKIs, erlotinib, gefitinib and imatinib, and two chemotherapy drugs, docetaxel and temozolomide. All data of 26 high-grade gliomas (20 primary glioblastomas, 2 secondary glioblastomas, and 4 grade III astrocytomas including medical history of the patients were analysed using hierarchical clustering analysis (HCA) and principal component analysis (PCA) employing multivariate statistics. Two distinct clusters of samples were found, which separated by the expression of PTEN and PDGFR-a in cluster 1 and predominately PDGFR-b, EGFR, phosphorylated C-Kit (p-C-Kit) and phosphorylated C-Abl (p-C-Abl) expression in cluster 2. Principal components analysis of the culture data captured 55% of the variance in the dataset showing PTEN, PGDFR-a and PGDFR-� loading vectors in approximately the same direction. Imatinib responsiveness was strongly correlated with high expression levels of PTEN and PDGFR-a. Responsiveness to erlotinib was correlated with the lack of expression of all proteins tested, while non-responders showed higher expression of PTEN and PDGFR-a. Responders to gefitinib fit into two groups, the majority (group 1) were influenced by the expression of the proteins tested, while the second smaller group correlated with the lack of protein expression. Non-responders to","abstract_has_math":false,"creators":["Kinsella, Paula"],"institution":"Dublin City University","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01","date_published":"2011-01","updated_at":"2026-07-24T06:26:27Z","subjects":["Neuroscience","Cell biology","Molecular biology"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Cancer Research Ireland"]},{"key":"dc:creator","label":"Author","values":["Kinsella, Paula"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-01"]},{"key":"dc:date.issued","label":"Date","values":["2011-01"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["Dublin City University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://doras.dcu.ie/16061/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neuroscience","Cell biology","Molecular biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://doras.dcu.ie/16061/1/The_Investigation_of_Targets_for_Therapy_in_Brain_Tumours.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Gliomas are among the most difficult of tumours to treat. Their highly invasive nature leads to recurrence even after aggressive therapy including surgery, radiotherapy and chemotherapy. A promising target for new therapies are tyrosine kinases, because they regulate a large range of proteins involved in growth, metabolism and differentiation. The receptor tyrosine kinases, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR) and C-Kit, as well as the non-receptor tyrosine kinase C-Abl are often amplified, overexpressed, and/or mutated in gliomas and play an important role in glioma development. A number of tyrosine kinase inhibitors (TKIs) have been developed and tested in clinical trials with mixed results. In collaboration with Beaumont hospital 31 glioma cell cultures were established to identify molecular markers indicative of responsiveness to EGFR and PDGFR blockade. Each culture was characterised with regard to their protein expression profile, their proliferative and invasive behaviour and their responsiveness to three TKIs, erlotinib, gefitinib and imatinib, and two chemotherapy drugs, docetaxel and temozolomide. All data of 26 high-grade gliomas (20 primary glioblastomas, 2 secondary glioblastomas, and 4 grade III astrocytomas including medical history of the patients were analysed using hierarchical clustering analysis (HCA) and principal component analysis (PCA) employing multivariate statistics. Two distinct clusters of samples were found, which separated by the expression of PTEN and PDGFR-a in cluster 1 and predominately PDGFR-b, EGFR, phosphorylated C-Kit (p-C-Kit) and phosphorylated C-Abl (p-C-Abl) expression in cluster 2. Principal components analysis of the culture data captured 55% of the variance in the dataset showing PTEN, PGDFR-a and PGDFR-� loading vectors in approximately the same direction. Imatinib responsiveness was strongly correlated with high expression levels of PTEN and PDGFR-a. Responsiveness to erlotinib was correlated with the lack of expression of all proteins tested, while non-responders showed higher expression of PTEN and PDGFR-a. Responders to gefitinib fit into two groups, the majority (group 1) were influenced by the expression of the proteins tested, while the second smaller group correlated with the lack of protein expression. Non-responders to"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Investigation of Targets for Therapy in Brain Tumours"]}]}],"canonical_facts":{"dc:contributor.sponsor":["Cancer Research Ireland"],"dc:creator":["Kinsella, Paula"],"dc:date":["2011-01"],"dc:date.issued":["2011-01"],"dc:description.abstract":["Gliomas are among the most difficult of tumours to treat. Their highly invasive nature leads to recurrence even after aggressive therapy including surgery, radiotherapy and chemotherapy. A promising target for new therapies are tyrosine kinases, because they regulate a large range of proteins involved in growth, metabolism and differentiation. The receptor tyrosine kinases, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR) and C-Kit, as well as the non-receptor tyrosine kinase C-Abl are often amplified, overexpressed, and/or mutated in gliomas and play an important role in glioma development. A number of tyrosine kinase inhibitors (TKIs) have been developed and tested in clinical trials with mixed results. In collaboration with Beaumont hospital 31 glioma cell cultures were established to identify molecular markers indicative of responsiveness to EGFR and PDGFR blockade. Each culture was characterised with regard to their protein expression profile, their proliferative and invasive behaviour and their responsiveness to three TKIs, erlotinib, gefitinib and imatinib, and two chemotherapy drugs, docetaxel and temozolomide. All data of 26 high-grade gliomas (20 primary glioblastomas, 2 secondary glioblastomas, and 4 grade III astrocytomas including medical history of the patients were analysed using hierarchical clustering analysis (HCA) and principal component analysis (PCA) employing multivariate statistics. Two distinct clusters of samples were found, which separated by the expression of PTEN and PDGFR-a in cluster 1 and predominately PDGFR-b, EGFR, phosphorylated C-Kit (p-C-Kit) and phosphorylated C-Abl (p-C-Abl) expression in cluster 2. Principal components analysis of the culture data captured 55% of the variance in the dataset showing PTEN, PGDFR-a and PGDFR-� loading vectors in approximately the same direction. Imatinib responsiveness was strongly correlated with high expression levels of PTEN and PDGFR-a. Responsiveness to erlotinib was correlated with the lack of expression of all proteins tested, while non-responders showed higher expression of PTEN and PDGFR-a. Responders to gefitinib fit into two groups, the majority (group 1) were influenced by the expression of the proteins tested, while the second smaller group correlated with the lack of protein expression. Non-responders to"],"dc:format":["application/pdf"],"dc:identifier.uri":["https://doras.dcu.ie/16061/1/The_Investigation_of_Targets_for_Therapy_in_Brain_Tumours.pdf"],"dc:language":["en"],"dc:publisher.institution":["Dublin City University"],"dc:relation.isreferencedby":["https://doras.dcu.ie/16061/"],"dc:subject":["Neuroscience","Cell biology","Molecular biology"],"dc:title":["The Investigation of Targets for Therapy in Brain Tumours"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T06:26:27Z"}