{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:00:58Z","timestamp":1791928858441,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE14-0013-01"],"award-info":[{"award-number":["ANR-17-CE14-0013-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-IDEX-0004-02"],"award-info":[{"award-number":["ANR-11-IDEX-0004-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["FRM SPF201809007054"],"award-info":[{"award-number":["FRM SPF201809007054"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Siric Curamus","award":["195741"],"award-info":[{"award-number":["195741"]}]},{"DOI":"10.13039\/501100006431","name":"CANCEROPOLE ILE DE FRANCE","doi-asserted-by":"publisher","award":["193602"],"award-info":[{"award-number":["193602"]}],"id":[{"id":"10.13039\/501100006431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"S\u00e9same Ile de France : PF2-ABIOMEDE","award":["16016309"],"award-info":[{"award-number":["16016309"]}]},{"DOI":"10.13039\/501100009516","name":"Universit\u00e9 Sorbonne Paris Cit\u00e9","doi-asserted-by":"publisher","award":["156815"],"award-info":[{"award-number":["156815"]}],"id":[{"id":"10.13039\/501100009516","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA in both an in vivo and in vitro context. In vivo, using subcutaneous xenografts into immunocompromised mice, CAP treatment of CCA induced DNA lesions and tumor cell apoptosis, as evaluated by 8-oxoguanine and cleaved caspase-3 immunohistochemistry, respectively. The analysis of the tumor microenvironment showed changes in markers related to macrophage polarization. In vitro, the incubation of CCA cells with CAP-treated culture media (i.e., plasma-activated media, PAM) led to a dose response decrease in cell survival. At molecular level, CAP treatment induced double-strand DNA breaks, followed by an increased phosphorylation and activation of the cell cycle master regulators CHK1 and p53, leading to cell cycle arrest and cell death by apoptosis. In conclusion, CAP is a novel therapeutic option to consider for CCA in the future.<\/jats:p>","DOI":"10.3390\/cancers12051280","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:37:38Z","timestamp":1589971058000},"page":"1280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-6962","authenticated-orcid":false,"given":"Javier","family":"Vaquero","sequence":"first","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"LPP (Laboratoire de physique des plasmas, UMR 7648), Sorbonne Universit\u00e9, Centre national de la recherche scientifique (CNRS), Ecole Polytechnique, 75005 Paris, France"},{"name":"TGF-\u03b2 and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain"},{"name":"Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Jud\u00e9e","sequence":"additional","affiliation":[{"name":"LPP (Laboratoire de physique des plasmas, UMR 7648), Sorbonne Universit\u00e9, Centre national de la recherche scientifique (CNRS), Ecole Polytechnique, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7967-7042","authenticated-orcid":false,"given":"Marie","family":"Vallette","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Decauchy","sequence":"additional","affiliation":[{"name":"LPP (Laboratoire de physique des plasmas, UMR 7648), Sorbonne Universit\u00e9, Centre national de la recherche scientifique (CNRS), Ecole Polytechnique, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ander","family":"Arbelaiz","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Aoudjehane","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Inserm, Institute of cardiometabolism and nutrition (ICAN), Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Scatton","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Inserm, Institute of cardiometabolism and nutrition (ICAN), Sorbonne Universit\u00e9, 75013 Paris, France"},{"name":"Department of Hepatobiliary Surgery and Liver Transplantation, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance publique-H\u00f4pitaux de Paris (AP-HP), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Gonzalez-Sanchez","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"TGF-\u03b2 and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain"},{"name":"Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Merabtene","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8194-0624","authenticated-orcid":false,"given":"J\u00e9r\u00e9my","family":"Augustin","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (Inserm), Centre de recherche 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