Favorable neuroblastoma genes and molecular therapeutics of neuroblastoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Xao X TangNaohiko Ikegaki

Abstract

Neuroblastoma (NB) is a common pediatric solid tumor that exhibits a striking clinical bipolarity: favorable and unfavorable. Favorable NB genes (EPHB6, EFNB2, EFNB3, NTRK1, and CD44) are genes whose high-level expression predicts favorable NB outcome, and forced expression of these genes inhibits growth of unfavorable NB cells. In this study, we investigated whether favorable NB gene expression could be augmented in unfavorable NB cells by chemical compounds and whether an increased expression of these genes was associated with suppression of NB growth and metastasis. We found that inhibitors of DNA methylation [5-aza-2'-deoxycytidine (5AdC)], histone deacetylase (HDAC) [4-phenylbutyrate (4PB)], and proteasome (MG262) enhanced the expression of favorable NB genes in NB cell lines and inhibited the growth of these cells in vitro (P < 0.0005). The growth-inhibitory effects of 5AdC and 4PB in vitro were in part due to caspase-dependent cell death and inhibition of DNA synthesis. Administration of 5AdC and/or 4PB also suppressed growth of subcutaneous NB xenografts in nude mice (P < 0.001), which was accompanied by enhanced favorable NB gene expression and an increase in apoptosis. Moreover, 4PB suppressed bone marrow and liver me...Continue Reading

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Citations

Mar 23, 2011·Cellular Oncology (Dordrecht)·Elena K SiapatiGeorge Vassilopoulos
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Naohiko IkegakiXao X Tang
Aug 31, 2006·Molecular and Cellular Biology·Gordin ZupkovitzChristian Seiser
Apr 2, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Luke Truitt, Andrew Freywald
Oct 26, 2011·BMC Bioinformatics·Sung Gon Yi, Taesung Park
Nov 6, 2013·International Journal of Molecular Medicine·Stephanie S WangXao X Tang
Sep 3, 2009·International Journal of Oncology·Bing KungNaohiko Ikegaki
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Nov 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jianqing FanYi Ren
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Oct 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Naohiko IkegakiXao X Tang
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