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dc.contributor.authorAktas, Esin
dc.contributor.authorBonavıda, Benjamin
dc.contributor.authorUslu, Atilla
dc.contributor.authorOzdemır, Aysegul
dc.contributor.authorÖktem, Gülperi
dc.contributor.authorErguven, Mine
dc.contributor.authorBilir, Ayhan
dc.date.accessioned2020-08-13T07:41:43Z
dc.date.available2020-08-13T07:41:43Z
dc.date.issued2008
dc.identifier.citationBilir A., Erguven M., Öktem G., Ozdemır A., Uslu A., Aktas E., Bonavıda B., "Potentiation Of Cytotoxicity By Combination Of İmatinib And Chlorimipramine İn Glioma.", International Journal Of Oncology, Vol.32, Pp.829-39, 2008
dc.identifier.urihttp://hdl.handle.net/20.500.12627/653
dc.description.abstractRat C6 glioma is a chemo-resistant experimental brain tumor that is difficult to treat with various drug combinations. Previous studies suggested that imatinib mesylate (Gleevec) is effective in pre-clinical trials for glioblastoma. Also, chlorimipramine (Anafranil) is an anti-depressant drug in use in the clinic and shown to have anti-neoplastic activity. We hypothesized that treatment of resistant C6 glioma with combination of imatinib and chlorimipramine may potentiate cytotoxicity and reverse resistance. C6 glioma was examined both as monolayer and as spheroid cultures. Several experimental designs were examined all of which showed synergistic activity albeit at different time kinetics. Combination treatment resulted in inhibition of cell growth and enhanced cell death as determined by dye exclusion. Further, the combination treatment resulted in significant induction of apoptosis as determined by Annexin V-FITC and PI. Also, there was inhibition of DNA synthesis and cAMP. Altogether, these findings supported the antiproliferative and cytotoxic effects of the combination treatment. Morphological studies were also performed using transmission and scanning electron microscopy. Significant synergistic apoptosis was detected by the combination treatment in both the monolayers and spheroid cultures. There was also a synergistic effect in autophagy by the combination. Several altered morphological features were noted by both the individual compound and enhanced by the combination treatment. The present findings support our hypothesis and demonstrate the potentiation of cytotoxicity by the com-bination of imatinib and chlorimipramine in C6 glioma. Further, the findings suggest the potential clinical application of the combination in the treatment of drug-resistant glioma.
dc.language.isoeng
dc.subjectOncology
dc.titlePotentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma.
dc.typearticle
dc.contributor.departmentAziz Sancar Deneysel Tıp Araştırma Enstitüsü,İmmünoloji Ana Bilim Dalı; İstanbul Tıp Fakültesi,Temel Tıp Bilimleri Bölümü,Fizyoloji Ana Bilim Dalı; Eczacılık Fakültesi,Temel Eczacılık Bilimleri Bölümü,Biyokimya Ana Bilim Dalı; İstanbul Tıp Fakültesi,Temel Tıp Bilimleri Bölümü,Histoloji Ve Embriyoloji Ana Bilim Dalı
dc.contributor.authorID0000-0002-8078-2780; 0000-0003-1351-1072
dc.identifier.volume32
dc.identifier.startpage829
dc.identifier.endpage39


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