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• W2125343208 abstract "Abstract Differential regulation of telomerase activity in normal and tumor cells provides a rationale for the design of new classes of telomerase inhibitors. The telomerase enzyme complex presents multiple potential sites for the development of inhibitors. GRN163L, a telomerase enzyme antagonist, is a lipid-modified 13-mer oligonucleotide N3′ → P5′-thio-phosphoramidate, complementary to the template region of telomerase RNA (hTR). We evaluated both the in vitro and in vivo effects of GRN163L using A549-luciferase (A549-Luc) human lung cancer cells expressing a luciferase reporter. GRN163L (1 μmol/L) effectively inhibits telomerase activity of A549-Luc cells, resulting in progressive telomere shortening. GRN163L treatment also reduces colony formation in soft agar assays. Surprisingly, after only 1 week of treatment with GRN163L, A549-Luc cells were unable to form robust colonies in the clonal efficiency assay, whereas the mismatch control compound had no effect. Finally, we show that in vivo treatment with GRN163L is effective in preventing lung metastases in xenograft animal models. These in vitro and in vivo data support the development of GRN163L as a therapeutic for the treatment of cancer." @default.
• W2125343208 created "2016-06-24" @default.
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• W2125343208 date "2005-09-01" @default.
• W2125343208 modified "2023-10-17" @default.
• W2125343208 title "<i>In vivo</i> Inhibition of Lung Cancer by GRN163L: A Novel Human Telomerase Inhibitor" @default.
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• W2125343208 doi "https://doi.org/10.1158/0008-5472.can-05-1215" @default.
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