Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.
Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.
复制标题
石棉在恶性胸膜间皮瘤的遗传模型中加速了疾病的发作。
DOI：
10.3389/ftox.2023.1200650
复制
发表时间：
2023
影响因子：
--
通讯作者：
Murphy, Daniel J.
中科院分区：
文献类型：
--
作者：
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.
假设：石棉驱动的炎症有助于恶性胸膜间皮瘤超越收购限速突变。 研究方法：用表达Cre重组酶的慢病毒载体在胸膜内注射和不注射石棉的情况下诱导先前显示在不暴露于石棉的情况下发展间皮瘤的遗传修饰的条件等位基因小鼠，并监测直至症状需要安乐死。对所得肿瘤进行组织学检查，并通过免疫组化检测谱系标志物的表达和免疫细胞浸润。 结果：注射石棉显著加速疾病的发病和终末期肿瘤负荷。在石棉存在下发生的肿瘤显示巨噬细胞浸润增加。药理学抑制巨噬细胞在小鼠与建立肿瘤未能延长生存期或提高对化疗的反应。 结论：石棉驱动的炎症导致间皮瘤的严重程度超出了限速突变的获得，然而，在已建立的上皮样间皮瘤中靶向抑制巨噬细胞没有显示出治疗益处。
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.
登录
查看更多内容
影响因子：
50.3
作者：
Jongsma, Johan;van Montfort, Erwin;Berns, Anton
通讯作者：
Berns, Anton
影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
11.2
作者：
Kadariya Y;Cheung M;Xu J;Pei J;Sementino E;Menges CW;Cai KQ;Rauscher FJ;Klein-Szanto AJ;Testa JR
通讯作者：
Testa JR
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W