Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter
The nuclear factor-κB (NF-κB) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-κB-based reporter system (five tandem repeats of NF-κB re...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , |
| Format: | article |
| Published: |
2011
|
| Online Access: | http://hdl.handle.net/10725/4823 http://dx.doi.org/10.1038/gt.2010.1562 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.nature.com/gt/journal/v18/n5/abs/gt2010156a.html |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513464606654464 |
|---|---|
| author | Zalloua, P. A. |
| author2 | Tannous, B. A. Badr, C. E. Niers, J. M. Morse, D. Koelen, J. A. Vandertop, P. Noske, D. Wurdinger, T. |
| author2_role | author author author author author author author author |
| author_facet | Zalloua, P. A. Tannous, B. A. Badr, C. E. Niers, J. M. Morse, D. Koelen, J. A. Vandertop, P. Noske, D. Wurdinger, T. |
| author_role | author |
| dc.creator.none.fl_str_mv | Zalloua, P. A. Tannous, B. A. Badr, C. E. Niers, J. M. Morse, D. Koelen, J. A. Vandertop, P. Noske, D. Wurdinger, T. |
| dc.date.none.fl_str_mv | 2011 2016-11-16T13:43:36Z 2016-11-16T13:43:36Z 2016-11-16 |
| dc.identifier.none.fl_str_mv | 0969-7128 http://hdl.handle.net/10725/4823 http://dx.doi.org/10.1038/gt.2010.1562 Badr, C. E., Niers, J. M., Morse, D., Koelen, J. A., Vandertop, P., Noske, D., ... & Tannous, B. A. (2011). Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter. Gene therapy, 18(5), 445-451. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.nature.com/gt/journal/v18/n5/abs/gt2010156a.html |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Gene Therapy |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | The nuclear factor-κB (NF-κB) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-κB-based reporter system (five tandem repeats of NF-κB responsive genomic element (NF; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NF-CU-IGluc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-κB. When NF-κB was further activated by tumor necrosis factor-α in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_87377fa3efdcf6f43d4adf59e4f35dd6 |
| identifier_str_mv | 0969-7128 Badr, C. E., Niers, J. M., Morse, D., Koelen, J. A., Vandertop, P., Noske, D., ... & Tannous, B. A. (2011). Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter. Gene therapy, 18(5), 445-451. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/4823 |
| publishDate | 2011 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporterZalloua, P. A.Tannous, B. A.Badr, C. E.Niers, J. M.Morse, D.Koelen, J. A.Vandertop, P.Noske, D.Wurdinger, T.The nuclear factor-κB (NF-κB) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-κB-based reporter system (five tandem repeats of NF-κB responsive genomic element (NF; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NF-CU-IGluc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-κB. When NF-κB was further activated by tumor necrosis factor-α in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy.PublishedN/A2016-11-16T13:43:36Z2016-11-16T13:43:36Z20112016-11-16Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0969-7128http://hdl.handle.net/10725/4823http://dx.doi.org/10.1038/gt.2010.1562Badr, C. E., Niers, J. M., Morse, D., Koelen, J. A., Vandertop, P., Noske, D., ... & Tannous, B. A. (2011). Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter. Gene therapy, 18(5), 445-451.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://www.nature.com/gt/journal/v18/n5/abs/gt2010156a.htmlenGene Therapyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/48232021-03-19T10:00:51Z |
| spellingShingle | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter Zalloua, P. A. |
| status_str | publishedVersion |
| title | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| title_full | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| title_fullStr | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| title_full_unstemmed | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| title_short | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| title_sort | Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter |
| url | http://hdl.handle.net/10725/4823 http://dx.doi.org/10.1038/gt.2010.1562 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.nature.com/gt/journal/v18/n5/abs/gt2010156a.html |