Search

Your search keyword '"Sheppard, Freda"' showing total 6 results
Start Over Author "Sheppard, Freda"
6 results on '"Sheppard, Freda"'

6. Reversing Hypoxic Cell Chemoresistance in Vitro Using Genetic and Small Molecule Approaches Targeting Hypoxia Inducible Factor-1

Author

Brown, Louisa M., Cowen, Rachel L., Debray, Camille, Eustace, Amanda, Erler, Janine T., Sheppard, Freda C. D., Parker, Catriona A., Stratford, Ian J., and Williams, Kaye J.

Abstract

The resistance of hypoxic cells to conventional chemotherapy is well documented. Using both adenovirus-mediated gene delivery and small molecules targeting hypoxia-inducible factor-1 (HIF-1), we evaluated the impact of HIF-1 inhibition on the sensitivity of hypoxic tumor cells to etoposide. The genetic therapy exploited a truncated HIF-1α protein that acts as a dominant-negative HIF-1α (HIF-1α-no-TAD). Its functionality was validated in six human tumor cell lines using HIF-1 reporter assays. An EGFP-fused protein demonstrated that the dominant-negative HIF-1α was nucleus-localized and constitutively expressed irrespective of oxygen tension. The small molecules studied were quinocarmycin monocitrate (KW2152), its analog 7-cyanoquinocarcinol (DX-52-1), and topotecan. DX-52-1 and topotecan have been previously established as HIF-1 inhibitors. HT1080 and HCT116 cells were treated with either AdHIF-1α-no-TAD or nontoxic concentrations (0.1 µM;

Published
2006

Catalog

Books, media, physical & digital resources
See catalog results