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dc.contributor.authorTümmler, Conny
dc.contributor.authorDumitriu, Gianina
dc.contributor.authorWickström, Malin
dc.contributor.authorCoopman, Peter
dc.contributor.authorValkov, Andrey Yurjevich
dc.contributor.authorKogner, Per
dc.contributor.authorJohnsen, John Inge
dc.contributor.authorMoens, Ugo
dc.contributor.authorSveinbjørnsson, Baldur
dc.date.accessioned2019-03-19T10:33:05Z
dc.date.available2019-03-19T10:33:05Z
dc.date.issued2019-02-10
dc.description.abstractNeuroblastoma is a malignancy arising from the developing sympathetic nervous system and the most common and deadly cancer of infancy. New therapies are needed to improve the prognosis for high-risk patients and to reduce toxicity and late effects. Spleen tyrosine kinase (SYK) has previously been identified as a promising drug target in various inflammatory diseases and cancers but has so far not been extensively studied as a potential therapeutic target in neuroblastoma. In this study, we observed elevated <i>SYK</i> gene expression in neuroblastoma compared to neural crest and benign neurofibroma. While SYK protein was detected in the majority of examined neuroblastoma tissues it was less frequently observed in neuroblastoma cell lines. Depletion of SYK by siRNA and the use of small molecule SYK inhibitors significantly reduced the cell viability of neuroblastoma cell lines expressing SYK protein. Moreover, SYK inhibition decreased ERK1/2 and Akt phosphorylation. The SYK inhibitor BAY 61-3606 enhanced the effect of different chemotherapeutic drugs. Transient expression of a constitutive active SYK variant increased the viability of neuroblastoma cells independent of endogenous SYK levels. Collectively, our findings suggest that targeting SYK in combination with conventional chemotherapy should be further evaluated as a treatment option in neuroblastoma.en_US
dc.description.sponsorshipThe University of Tromsø The Norwegian Childhood Cancer Society Erna and Olav Aakre Foundation for Cancer Research, Tromsø, Norway The Swedish Childhood Cancer Foundation The Swedish Cancer Foundation The Swedish Research Council The Swedish Foundation for Strategic Research The Cancer Research Foundations of Radiumhemmet The Institut National du Cancer and Plan Canceren_US
dc.descriptionSource at <a href=https://doi.org/10.3390/cancers11020202> https://doi.org/10.3390/cancers11020202</a>.en_US
dc.identifier.citationTümmler, C., Dumitriu, G.A., Wickström, M., Coopman, P., Valkov, A., Kogner, P., ... Sveinbjørnsson, B. (2019). SYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells <i>in Vitro</i>. <i>Cancers, 11</i>(2), 202. https://doi.org/10.3390/cancers11020202en_US
dc.identifier.cristinIDFRIDAID 1675738
dc.identifier.issn2072-6694
dc.identifier.urihttps://hdl.handle.net/10037/15021
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.ispartofTümmler, C. (2019). Novel Inflammatory Mediators in Neuroblastoma Tumorigenesis. (Doctoral thesis). <a href=https://hdl.handle.net/10037/17068>https://hdl.handle.net/10037/17068</a>.
dc.relation.journalCancers
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectpediatric canceren_US
dc.subjectneuroblastomaen_US
dc.subjecttyrosine kinaseen_US
dc.subjectcombination therapyen_US
dc.titleSYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells in Vitroen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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