Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice
Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , |
| التنسيق: | article |
| منشور في: |
2006
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/2735 http://dx.doi.org/ 10.1158/1078-0432.CCR-06-2019 http://www.ncbi.nlm.nih.gov/pubmed/17189417 |
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إضافة وسم
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| _version_ | 1864513459123650560 |
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| author | Abi-Habib, Ralph J. |
| author2 | Singh, Ravibhushan Leppla, Stephen H. Greene, John J. Ding, Yan Berghuis, Bree Duesbery, Nicholas S. Frankel, Arthur E. |
| author2_role | author author author author author author author |
| author_facet | Abi-Habib, Ralph J. Singh, Ravibhushan Leppla, Stephen H. Greene, John J. Ding, Yan Berghuis, Bree Duesbery, Nicholas S. Frankel, Arthur E. |
| author_role | author |
| dc.creator.none.fl_str_mv | Abi-Habib, Ralph J. Singh, Ravibhushan Leppla, Stephen H. Greene, John J. Ding, Yan Berghuis, Bree Duesbery, Nicholas S. Frankel, Arthur E. |
| dc.date.none.fl_str_mv | 2006 2015-11-30T11:40:02Z 2015-11-30T11:40:02Z 2015-11-30 |
| dc.identifier.none.fl_str_mv | 1078-0432 http://hdl.handle.net/10725/2735 http://dx.doi.org/ 10.1158/1078-0432.CCR-06-2019 Abi-Habib, R. J., Singh, R., Leppla, S. H., Greene, J. J., Ding, Y., Berghuis, B., ... & Frankel, A. E. (2006). Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clinical cancer research: an official journal of the American Association for Cancer Research, 12(24), 7437 http://www.ncbi.nlm.nih.gov/pubmed/17189417 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Clinical cancer research |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx. Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses of LeTx. Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage. Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_ff32b57e7c72a65bcd091cd9e32be58a |
| identifier_str_mv | 1078-0432 Abi-Habib, R. J., Singh, R., Leppla, S. H., Greene, J. J., Ding, Y., Berghuis, B., ... & Frankel, A. E. (2006). Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clinical cancer research: an official journal of the American Association for Cancer Research, 12(24), 7437 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/2735 |
| publishDate | 2006 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude miceAbi-Habib, Ralph J.Singh, RavibhushanLeppla, Stephen H.Greene, John J.Ding, YanBerghuis, BreeDuesbery, Nicholas S.Frankel, Arthur E.Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx. Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses of LeTx. Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage. Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development.PublishedN/A2015-11-30T11:40:02Z2015-11-30T11:40:02Z20062015-11-30Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1078-0432http://hdl.handle.net/10725/2735http://dx.doi.org/ 10.1158/1078-0432.CCR-06-2019Abi-Habib, R. J., Singh, R., Leppla, S. H., Greene, J. J., Ding, Y., Berghuis, B., ... & Frankel, A. E. (2006). Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clinical cancer research: an official journal of the American Association for Cancer Research, 12(24), 7437http://www.ncbi.nlm.nih.gov/pubmed/17189417enClinical cancer researchinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/27352016-08-02T08:26:48Z |
| spellingShingle | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice Abi-Habib, Ralph J. |
| status_str | publishedVersion |
| title | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| title_full | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| title_fullStr | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| title_full_unstemmed | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| title_short | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| title_sort | Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice |
| url | http://hdl.handle.net/10725/2735 http://dx.doi.org/ 10.1158/1078-0432.CCR-06-2019 http://www.ncbi.nlm.nih.gov/pubmed/17189417 |