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Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma
Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333928/ https://www.ncbi.nlm.nih.gov/pubmed/37441092 http://dx.doi.org/10.3389/ftox.2023.1200650 |
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author | Farahmand, Pooyeh Gyuraszova, Katarina Rooney, Claire Raffo-Iraolagoitia, Ximena L. Jayasekera, Geeshath Hedley, Ann Johnson, Emma Chernova, Tatyana Malviya, Gaurav Hall, Holly Monteverde, Tiziana Blyth, Kevin Duffin, Rodger Carlin, Leo M. Lewis, David Le Quesne, John MacFarlane, Marion Murphy, Daniel J. |
author_facet | Farahmand, Pooyeh Gyuraszova, Katarina Rooney, Claire Raffo-Iraolagoitia, Ximena L. Jayasekera, Geeshath Hedley, Ann Johnson, Emma Chernova, Tatyana Malviya, Gaurav Hall, Holly Monteverde, Tiziana Blyth, Kevin Duffin, Rodger Carlin, Leo M. Lewis, David Le Quesne, John MacFarlane, Marion Murphy, Daniel J. |
author_sort | Farahmand, Pooyeh |
collection | PubMed |
description | Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit. |
format | Online Article Text |
id | pubmed-10333928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103339282023-07-12 Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma Farahmand, Pooyeh Gyuraszova, Katarina Rooney, Claire Raffo-Iraolagoitia, Ximena L. Jayasekera, Geeshath Hedley, Ann Johnson, Emma Chernova, Tatyana Malviya, Gaurav Hall, Holly Monteverde, Tiziana Blyth, Kevin Duffin, Rodger Carlin, Leo M. Lewis, David Le Quesne, John MacFarlane, Marion Murphy, Daniel J. Front Toxicol Toxicology Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit. Frontiers Media S.A. 2023-06-27 /pmc/articles/PMC10333928/ /pubmed/37441092 http://dx.doi.org/10.3389/ftox.2023.1200650 Text en Copyright © 2023 Farahmand, Gyuraszova, Rooney, Raffo-Iraolagoitia, Jayasekera, Hedley, Johnson, Chernova, Malviya, Hall, Monteverde, Blyth, Duffin, Carlin, Lewis, Le Quesne, MacFarlane and Murphy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Toxicology Farahmand, Pooyeh Gyuraszova, Katarina Rooney, Claire Raffo-Iraolagoitia, Ximena L. Jayasekera, Geeshath Hedley, Ann Johnson, Emma Chernova, Tatyana Malviya, Gaurav Hall, Holly Monteverde, Tiziana Blyth, Kevin Duffin, Rodger Carlin, Leo M. Lewis, David Le Quesne, John MacFarlane, Marion Murphy, Daniel J. Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title | Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title_full | Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title_fullStr | Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title_full_unstemmed | Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title_short | Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
title_sort | asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma |
topic | Toxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333928/ https://www.ncbi.nlm.nih.gov/pubmed/37441092 http://dx.doi.org/10.3389/ftox.2023.1200650 |
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