Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Treatment of Ewing's Sarcoma Using an Antisense Oligodeoxynucleotide to Regulate the Cell Cycle
Satoru AsamiMotoaki ChinHiroyuki ShichinoYukihiro YoshidaNorimichi NemotoHideo MugishimaTakashi Suzuki
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2008 Volume 31 Issue 3 Pages 391-394

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Abstract

Ewing's sarcoma (ES) is one of the most malignant tumors of bone and soft tissue in children and young adults. ES belongs to a group of small round cell tumors (SRCTs) that also includes neuroblastoma, rhabdomyosarcoma, and malignant lymphoma. However, ES exhibits several specific chimeric genes (EWSFLI1, EWSERG, EWSETV1, EWSE1AF, and EWSFEV) caused by chromosomal translocations that are not shared by other SRCTs. These chimeric genes regulate the expression of various other genes; that is, they activate inhibitors of DNA binding 2 (Id2) gene expression or they suppress transforming growth factor β II (TβRII) receptor gene expression. The regulation of these chimeric genes may affect critical cell signal transductions, such as signals involved in cell cycle and apoptosis in ES tumor cells. Using an antisense oligodeoxynucleotide against a sequence containing the ATG initiation codon of the EWSFLI1 chimeric gene that specifically reacts with the EWSFLI1 and EWSERG chimeric genes, we were able to regulate the cell cycle through the down-regulation of Id2. Here, we report that treatment with an antisense oligodeoxynucleotide against this chimeric gene was very useful for inducing the regression of ES tumor growth; thus, this chimeric gene may be an important target for the treatment of ES patients.

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© 2008 The Pharmaceutical Society of Japan
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