Author: Shapira, Assaf; Benhar, Itai
Title: Toxin-Based Therapeutic Approaches Document date: 2010_10_28
ID: 00cf294x_36
Snippet: Recently, Mizrahi et al [345] reported the use of transcriptional regulatory sequences of the H19 gene to drive the expression of DT-A specifically in ovarian tumor cells. H19 is a paternally imprinted, maternally expressed, oncofetal gene that encodes an RNA acting as "riboregulator" without a protein product. It is expressed at substantial levels in several different human tumor types, including epithelial ovarian cancer [390] , but is only mar.....
Document: Recently, Mizrahi et al [345] reported the use of transcriptional regulatory sequences of the H19 gene to drive the expression of DT-A specifically in ovarian tumor cells. H19 is a paternally imprinted, maternally expressed, oncofetal gene that encodes an RNA acting as "riboregulator" without a protein product. It is expressed at substantial levels in several different human tumor types, including epithelial ovarian cancer [390] , but is only marginally or not at all expressed in normal adult tissues [391] [392] [393] [394] [395] [396] [397] [398] [399] . Cationic polymer PEI based delivery of DTA-H19 plasmid, encoding the toxic DT-A transcriptionally controlled by regulatory sequences of the H19 gene, showed high killing potential in ovarian cancer cell lines and a significant tumor growth inhibition in animals [345] . In a later case study, DTA-H19 plasmid that was intraperitoneally injected into the peritoneum of a woman with advanced and recurrent ovarian carcinoma has been reported to yield a complete resolution of ascites following several infusions, with minimum adverse events [346] . Phase I/II study of DTA-H19 administered intraperitoneally in subjects with advanced stage ovarian cancer with evidence of symptomatic ascites is currently ongoing.
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