Show simple item record

dc.contributor.authorAl-Saffar, NMS
dc.contributor.authorAgliano, A
dc.contributor.authorMarshall, LV
dc.contributor.authorJackson, LE
dc.contributor.authorBalarajah, G
dc.contributor.authorSidhu, J
dc.contributor.authorClarke, PA
dc.contributor.authorJones, C
dc.contributor.authorWorkman, P
dc.contributor.authorPearson, ADJ
dc.contributor.authorLeach, MO
dc.date.accessioned2018-02-19T12:42:27Z
dc.date.issued2017-01
dc.identifier.citationPloS one, 2017, 12 (7), pp. e0180263 - ?
dc.identifier.issn1932-6203
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1292
dc.identifier.eissn1932-6203
dc.identifier.doi10.1371/journal.pone.0180263
dc.description.abstractRecent experimental data showed that the PI3K pathway contributes to resistance to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess whether this combination results in metabolic changes that are detectable by nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic biomarkers for PI3K inhibition and TMZ combination treatment. Using two genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels (P<0.02) relative to control. In contrast, treatment with TMZ caused an increase in glycerolphosphocholine (GPC) levels (P≤0.05). Combination of PI-103 with TMZ showed metabolic effects of both agents including a decrease in the levels of lactate and PC (P<0.02) while an increase in GPC (P<0.05). We also report a decrease in the protein expression levels of HK2, LDHA and CHKA providing likely mechanisms for the depletion of lactate and PC, respectively. Our results show that our in vitro NMR-detected changes in lactate and choline metabolites may have potential as non-invasive biomarkers for monitoring response to combination of PI3K/mTOR inhibitors with TMZ during clinical trials in children with glioblastoma, subject to further in vivo validation.
dc.formatElectronic-eCollection
dc.format.extente0180263 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectGlioblastoma
dc.subjectBrain Neoplasms
dc.subjectPhosphorylcholine
dc.subjectLactic Acid
dc.subjectDacarbazine
dc.subjectFurans
dc.subjectPyridines
dc.subjectPyrimidines
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Outcome
dc.subjectCell Proliferation
dc.subjectChild
dc.subjectProton Magnetic Resonance Spectroscopy
dc.subjectBiomarkers, Tumor
dc.subjectTemozolomide
dc.titleIn vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the combination of temozolomide with PI3K inhibition in paediatric glioblastoma cells.
dc.typeJournal Article
dcterms.dateAccepted2017-06-13
rioxxterms.versionofrecord10.1371/journal.pone.0180263
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPloS one
pubs.issue7
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume12
pubs.embargo.termsNot known
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
icr.researchteamGlioma Teamen_US
icr.researchteamMagnetic Resonanceen_US
dc.contributor.icrauthorLeach, Martinen
dc.contributor.icrauthorClarke, Paulen
dc.contributor.icrauthorWorkman, Paulen
dc.contributor.icrauthorJones, Chrisen
dc.contributor.icrauthorAl-Saffar, Nadaen
dc.contributor.icrauthorMarsden,en


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0