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Characterization of neurotoxicity induced by anticancer agents

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Titel Characterization of neurotoxicity induced by anticancer agents
Looptijd 01 / 2006 - onbekend
Status Afgesloten
Onderzoeknummer OND1326710
Leverancier gegevens Website V-ICI

Samenvatting (EN)

The aim of this study is to characterize the extend of drug induced neurotoxicity. Many antineoplastic drugs show neurotoxicity and this side effect might be dose-limiting or leading to the cessation of the treatment. Two different model systems (rat pheochromocytoma cell line PC12 and human neuroblastoma cell line SH-SY5Y) are used to determine wether different antineoplastic compounds (Oxaliplatin, EpothiloneB and Bortezomib) act differently or similarly in these model systems compared to tumor cells (U-87 Glioma cell line). PC12 cells were induced to neuronal differentiation using Nerve Growth Factor (NGF) while SH-SY5Y differentiate towards a mature neuronal phenotype with neurite elongation following the treatment with Retinoic Acid (RA). After treatment neuronal differentiation was evaluated using a morphological method requiring tracking and measuring of neurites. Differentiated cells were treated with IC50 drugs concentration showing a statistically significant decrease of neurite lenght with respect to control cells. Since quantification of neurite outgrowth is impractical on a large scale decreases in Cyclin B2 and BIRC5 can be used as model marker. The expression of these two genes is being evaluated with TaqMan RT-PCR.

Betrokken organisaties

Betrokken personen

Onderzoeker Dr. A.A. Geldof
Onderzoeker Prof.dr. G. Giaccone
Projectleider C. Ceresa
Projectleider Prof.dr. G.J. Peters

Classificatie

D23120 Kanker
D23230 Neurologie, KNO , oogheelkunde
D23340 Biofarmaceutische wetenschappen, toxicologie

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