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dc.contributor.authorHefti, Martin-
dc.contributor.authorAlbert, Ina-
dc.contributor.authorLuginbühl, Vera-
dc.date.accessioned2018-11-16T12:37:30Z-
dc.date.available2018-11-16T12:37:30Z-
dc.date.issued2012-
dc.identifier.issn0167-594Xde_CH
dc.identifier.issn1573-7373de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/12923-
dc.description.abstractEpileptic seizures are among the presenting clinical signs of malignant glioma patients, frequently necessitating treatment with antiepileptic drugs (AEDs). The efficacy of 5-aminolevulinic acid (5-ALA)-based intraoperative fluorescence-guided surgery and photodynamic therapy (PDT) in glioblastoma multiforme (GBM) patients depends on the specific accumulation and total amount of intracellularly synthesized protoporphyrin IX (PpIX) in tumour cells. In this study, we investigated the effect of the AEDs phenytoin (PHY) and levetiracetam (LEVE) on 5-ALA-induced PpIX accumulation in two glioma cell lines (U373 MG and U-87 MG) and primary GBM cells isolated from a human biopsy. After treatment with PHY and LEVE for three days cells were incubated with 1 mM 5-ALA for 4 h and PpIX accumulation was determined by fluorescence measurement. We observed a decrease in PpIX synthesis of up to 55 ± 12% in primary GBM cells after incubation with phenytoin. This reduction was dose-dependent for all tested cell lines and primary GBM cells. LEVE on the other hand did not alter PpIX concentration in GBM cells. PDT was performed in vitro by irradiating the GBM cells with light doses from 0.5 to 10 J cm-2 at 627 nm after AED and 5-ALA treatment. Although less PpIX accumulated in PHY-treated cells, efficacy of PDT was not affected. We assume that damage to the mitochondrial membrane by PHY inhibits PpIX synthesis in vitro, because we showed mitochondrial dysfunction as a result of reduced mitochondrial membrane potential in PHY-treated cells. No change in glutathione status was observed. To evaluate further the effect of PHY on PpIX fluorescence, and to establish its significance in clinical practice, animal and clinical studies are required, because the results presented here imply PHY may reduce intracellular accumulation of PpIX in patients with highgrade gliomas.de_CH
dc.language.isodede_CH
dc.publisherSpringerde_CH
dc.relation.ispartofJournal of Neuro-Oncologyde_CH
dc.rightsLicence according to publishing contractde_CH
dc.subjectFluorescence-guided surgeryde_CH
dc.subjectPhotodynamic therapyde_CH
dc.subjectGlioblastoma multiformede_CH
dc.subject5-Aminolevulinic acidde_CH
dc.subjectBrain Tumorde_CH
dc.subject.ddc615: Pharmakologie und Therapeutikde_CH
dc.subject.ddc616: Innere Medizin und Krankheitende_CH
dc.titlePhenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cellsde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1007/s11060-012-0857-9de_CH
zhaw.funding.euNode_CH
zhaw.issue3de_CH
zhaw.originated.zhawYesde_CH
zhaw.pages.end450de_CH
zhaw.pages.start443de_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume108de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedPharmazeutische Technologiede_CH
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Hefti, M., Albert, I., & Luginbühl, V. (2012). Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells. Journal of Neuro-Oncology, 108(3), 443–450. https://doi.org/10.1007/s11060-012-0857-9
Hefti, M., Albert, I. and Luginbühl, V. (2012) ‘Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells’, Journal of Neuro-Oncology, 108(3), pp. 443–450. Available at: https://doi.org/10.1007/s11060-012-0857-9.
M. Hefti, I. Albert, and V. Luginbühl, “Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells,” Journal of Neuro-Oncology, vol. 108, no. 3, pp. 443–450, 2012, doi: 10.1007/s11060-012-0857-9.
HEFTI, Martin, Ina ALBERT und Vera LUGINBÜHL, 2012. Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells. Journal of Neuro-Oncology. 2012. Bd. 108, Nr. 3, S. 443–450. DOI 10.1007/s11060-012-0857-9
Hefti, Martin, Ina Albert, and Vera Luginbühl. 2012. “Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells.” Journal of Neuro-Oncology 108 (3): 443–50. https://doi.org/10.1007/s11060-012-0857-9.
Hefti, Martin, et al. “Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells.” Journal of Neuro-Oncology, vol. 108, no. 3, 2012, pp. 443–50, https://doi.org/10.1007/s11060-012-0857-9.


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