Cargando…
Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment
BACKGROUND: Paclitaxel is touted as an essential medicine due to its extensive use as a chemotherapeutic for various cancers and an antiproliferative agent for restenosis. Due to recent concerns related to long-term mortality, paclitaxel (PTX)-based endovascular therapy is now surrounded by controve...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915804/ https://www.ncbi.nlm.nih.gov/pubmed/36778300 http://dx.doi.org/10.21203/rs.3.rs-2487922/v1 |
_version_ | 1784885975525097472 |
---|---|
author | Zhang, Mengwei Lotfollahzadeh, Saran Elzinad, Nagla Yang, Xiaosheng Elsadawi, Murad Gower, Adam Belghasem, Mostafa Shazly, Tarek Kolachalama, Vijaya B. Chitalia, Vipul |
author_facet | Zhang, Mengwei Lotfollahzadeh, Saran Elzinad, Nagla Yang, Xiaosheng Elsadawi, Murad Gower, Adam Belghasem, Mostafa Shazly, Tarek Kolachalama, Vijaya B. Chitalia, Vipul |
author_sort | Zhang, Mengwei |
collection | PubMed |
description | BACKGROUND: Paclitaxel is touted as an essential medicine due to its extensive use as a chemotherapeutic for various cancers and an antiproliferative agent for restenosis. Due to recent concerns related to long-term mortality, paclitaxel (PTX)-based endovascular therapy is now surrounded by controversies. OBJECTIVE: Examine the inflammatory mediators driven by the systemic administration of PTX and explore the means to suppress these effects. METHODS: RNAseq analysis, cell and mouse models. RESULTS: RNAseq analysis of primary human endothelial cells (ECs) treated with PTX demonstrated transcriptional perturbations of a set of pro-inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1) and CD137, which were validated in EC lysates. These perturbations were abrogated with dexamethasone, a prototypic anti-inflammatory compound. The media of ECs pre-treated with PTX showed a significant increase in MCP-1 levels, which were reverted to baseline levels with DEX treatment. A group of mice harvested at different time points after PTX injection were analyzed for immediate and delayed effects of PTX. A 3-fold increase in MCP-1 was noted in blood and aortic ECs after 12 hours of PTX treatment. Similar changes in CD137 and downstream mediators such as tissue factor, VCAM-1 and E-selectin were noted in aortic ECs. CONCLUSIONS: Our study shows that systemic PTX exposure upregulates atherothrombotic markers, and co-delivery of DEX can subdue the untoward toxic effects. Long-term studies are needed to probe the mechanisms driving systemic complications of PTX-based therapies and evaluate the clinical potential of DEX to mitigate risk. |
format | Online Article Text |
id | pubmed-9915804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-99158042023-02-11 Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment Zhang, Mengwei Lotfollahzadeh, Saran Elzinad, Nagla Yang, Xiaosheng Elsadawi, Murad Gower, Adam Belghasem, Mostafa Shazly, Tarek Kolachalama, Vijaya B. Chitalia, Vipul Res Sq Article BACKGROUND: Paclitaxel is touted as an essential medicine due to its extensive use as a chemotherapeutic for various cancers and an antiproliferative agent for restenosis. Due to recent concerns related to long-term mortality, paclitaxel (PTX)-based endovascular therapy is now surrounded by controversies. OBJECTIVE: Examine the inflammatory mediators driven by the systemic administration of PTX and explore the means to suppress these effects. METHODS: RNAseq analysis, cell and mouse models. RESULTS: RNAseq analysis of primary human endothelial cells (ECs) treated with PTX demonstrated transcriptional perturbations of a set of pro-inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1) and CD137, which were validated in EC lysates. These perturbations were abrogated with dexamethasone, a prototypic anti-inflammatory compound. The media of ECs pre-treated with PTX showed a significant increase in MCP-1 levels, which were reverted to baseline levels with DEX treatment. A group of mice harvested at different time points after PTX injection were analyzed for immediate and delayed effects of PTX. A 3-fold increase in MCP-1 was noted in blood and aortic ECs after 12 hours of PTX treatment. Similar changes in CD137 and downstream mediators such as tissue factor, VCAM-1 and E-selectin were noted in aortic ECs. CONCLUSIONS: Our study shows that systemic PTX exposure upregulates atherothrombotic markers, and co-delivery of DEX can subdue the untoward toxic effects. Long-term studies are needed to probe the mechanisms driving systemic complications of PTX-based therapies and evaluate the clinical potential of DEX to mitigate risk. American Journal Experts 2023-01-30 /pmc/articles/PMC9915804/ /pubmed/36778300 http://dx.doi.org/10.21203/rs.3.rs-2487922/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Zhang, Mengwei Lotfollahzadeh, Saran Elzinad, Nagla Yang, Xiaosheng Elsadawi, Murad Gower, Adam Belghasem, Mostafa Shazly, Tarek Kolachalama, Vijaya B. Chitalia, Vipul Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title | Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title_full | Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title_fullStr | Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title_full_unstemmed | Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title_short | Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
title_sort | alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915804/ https://www.ncbi.nlm.nih.gov/pubmed/36778300 http://dx.doi.org/10.21203/rs.3.rs-2487922/v1 |
work_keys_str_mv | AT zhangmengwei alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT lotfollahzadehsaran alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT elzinadnagla alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT yangxiaosheng alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT elsadawimurad alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT goweradam alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT belghasemmostafa alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT shazlytarek alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT kolachalamavijayab alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment AT chitaliavipul alleviatingiatrogeniceffectsofpaclitaxelviaantiinflammatorytreatment |