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- W2017400354 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILMelanoma and malignant pheochromocytoma are known for high MYC expression. MYCN amplification and its over-expression are associated with the worst neuroblastoma disease outcome. Meta-iodo-benzylguanidine (MIBG) is a norepinephrine analogue and a mitochondrial respiration inhibitor. 131I-MIBG has been used for scintigraphic detection of neural crest derived tumors (neuroblastoma, pheochromocytoma and melanoma) that specifically uptake MIBG by norepinephrine transporters (NET). 131I-MIBG is also used for targeted radiotherapy of neuroblastoma and pheochromocytoma. Non-radiolabeled MIBG had been reported to be cytotoxic to neuroblastoma cells in vitro and in vivo. However, the molecular mechanism of its growth suppressive effect was not elucidated. Our previous studies showed that FCCP, a well-known mitochondrial respiration inhibitor, destabilized MYCN and MYC in neuroblastoma cells and caused growth suppression. In this study we confirmed that MIBG suppressed growth of neuroblastoma cell lines (SKNBE(2)C, IMR5, Nb69, and SKNAS), and its growth suppressive effect in each cell line correlated with NET expression in these cells. In addition, MIBG suppressed growth of neuroblastoma stem cells derived from SKNBE(2)C. MIBG treatment of SKNBE(2)C and SKNAS resulted in an increase expression of growth suppressive gene (GADD45B) and genes encoding for biomarkers of favorable neuroblastoma (CD44, EPHB6, EFNB2, EFNB3, NTRK1). Treatment of MYCN amplified (SKNBE(2)C, IMR5) and non-MYCN amplified (Nb69, SKNAS) neuroblastoma cells with MIBG resulted in marked reduction of MYCN and MYC expression, respectively in dose and time dependent fashions. Collectively, our studies suggest that MIBG not only targets neural crest derived tumors, but also is a MYCN/MYC destabilizing agent.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2875. doi:1538-7445.AM2012-2875" @default.
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- W2017400354 date "2012-04-15" @default.
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- W2017400354 title "Abstract 2875: Meta-iodo-benzylguanidine (MIBG) is a MYCN/MYC destabilizer that specifically targets neural crest derived tumors" @default.
- W2017400354 doi "https://doi.org/10.1158/1538-7445.am2012-2875" @default.
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