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• W1996400631 abstract "Abstract Purpose: Radioresistance may be caused by cancer stem cells (CSC). Because CSCs require telomerase to proliferate, a telomerase-specific oncolytic adenoviral vector carrying apoptotic tumor necrosis factor–related apoptosis-inducing ligand and E1A gene (Ad/TRAIL-E1) may preferentially target CSCs. Experimental Design: We established two pairs of parental and radioresistant (R) esophageal carcinoma cell lines (Seg-1, Seg-1R and TE-2, TE-2R) by fractionated irradiation. Stem cell markers were measured by Western blotting and flow cytometry. Serial sorting was used to enrich stem-like side population cells. Telomerase activity, transgene expression, antitumor activity, apoptosis induction, and viral replication were determined in vitro and/or in vivo. Results: Expression of the stem cell markers β-catenin, Oct3/4, and β1 integrin in Seg-1R cells was 29.4%, 27.5%, and 97.3%, respectively, compared with 4.8%, 14.9%, and 45.3% in Seg-1 cells (P &lt; 0.05). SP levels in Seg-1R and TE-2R cells were 14.6% and 2.7%, respectively, compared with 3.4% and 0.3% in Seg-1 and TE-2 cells. Serial sorting of Seg-1R SP cells showed enrichment of the SP cells. Telomerase activities in Seg-1R, Seg-1R SP, and TE-2R cells were significantly higher than in Seg-1, Seg-1R non-SP, and TE-2 cells, respectively (P &lt; 0.05). Seg-1R and TE-2R cells were more sensitive to Ad/TRAIL-E1 than parental cells. Increased Coxsackie-adenovirus receptor and elevated transgene expressions were found in the radioresistant cells. Ad/TRAIL-E1 resulted in significant tumor growth suppression and longer survival in Seg-1R–bearing mice (P &lt; 0.05) with no significant toxicity. Conclusion: Radioresistant cells established by fractionated irradiation display CSC-like cell properties. Ad/TRAIL-E1 preferentially targets radioresistant CSC-like cells." @default.
• W1996400631 created "2016-06-24" @default.
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• W1996400631 date "2008-05-01" @default.
• W1996400631 modified "2023-09-28" @default.
• W1996400631 title "Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus" @default.
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• W1996400631 doi "https://doi.org/10.1158/1078-0432.ccr-07-1528" @default.
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