{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:36:20Z","timestamp":1789706180601,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T00:00:00Z","timestamp":1357776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100001755","name":"Mesothelioma Applied Research Foundation","doi-asserted-by":"crossref","award":["2009"],"award-info":[{"award-number":["2009"]}],"id":[{"id":"10.13039\/100001755","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione Buzzi Unicem and GIMe"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant Pleural Mesothelioma (<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>) is a rare but increasingly prevalent, highly aggressive cancer with poor prognosis. The aetiology of<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>is essentially a function of previous exposure to asbestos fibres, which are considered to be an early\u2010stage carcinogen. Asbestos is toxic to human mesothelial cells (<jats:styled-content style=\"fixed-case\">HMCs<\/jats:styled-content>), that activate the nuclear enzyme poly(<jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content>\u2010ribose) polymerase\u20101 (<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>) to repair<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. The targeting of<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>is showing considerable potential for delivering selective tumour cell kill while sparing normal cells, and offers a scientifically rational clinical application. We investigated<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>expression in normal mesothelial and<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>tissues samples. Immunohistochemical analysis revealed low<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>staining in peritumoural mesothelium. As opposite, a progressive increase in epithelioid and in the most aggressive sarcomatoid<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>tissues was evident. In<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>cell lines, we correlated increased<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>expression to sensitivity to its inhibitor<jats:styled-content style=\"fixed-case\"><jats:roman>CO<\/jats:roman><\/jats:styled-content>\u2010338 and demonstrated that<jats:styled-content style=\"fixed-case\"><jats:roman>CO<\/jats:roman><\/jats:styled-content>\u2010338 significantly reduced cell viability as single agent and was synergistic with cis\u2010platin. Interestingly, we described a new correlation between<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>and the<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>axis regulated by<jats:styled-content style=\"fixed-case\">SIRT1<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">SIRT1<\/jats:styled-content>has a role in the modulation of<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>activation and<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>has been described to be a gatekeeper for<jats:styled-content style=\"fixed-case\">SIRT1<\/jats:styled-content>activity by limiting<jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content>+ availability. Here, we firstly demonstrate an inverse correlation between<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>acetylation and phosphorylation modulated by<jats:styled-content style=\"fixed-case\">SIRT1<\/jats:styled-content>in<jats:styled-content style=\"fixed-case\">MMe<\/jats:styled-content>cells treated with<jats:styled-content style=\"fixed-case\"><jats:roman>CO<\/jats:roman><\/jats:styled-content>\u2010338. In conclusion, this study demonstrates that<jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>overexpression defines increased responsiveness to its inhibition, then these results imply that a substantial fraction of patients could be candidates for therapy with<jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>inhibitors.<\/jats:p>","DOI":"10.1111\/jcmm.12000","type":"journal-article","created":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T17:39:59Z","timestamp":1357839599000},"page":"233-241","source":"Crossref","is-referenced-by-count":34,"title":["PARP1 inhibition affects pleural mesothelioma cell viability and uncouples AKT\/mTOR axis via SIRT1"],"prefix":"10.1111","volume":"17","author":[{"given":"Giulia","family":"Pinton","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Piemonte Orientale A. Avogadro Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arcangela Gabriella","family":"Manente","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Piemonte Orientale A. Avogadro Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Murer","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Mestre Hospital Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"De Marino","sequence":"additional","affiliation":[{"name":"Department of Oncology and Medicine Vercelli Hospital Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Mutti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Medicine Vercelli Hospital Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Moro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Piemonte Orientale A. Avogadro Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604544103"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2005.03.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1272874"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-2665"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.912"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2008.02.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2068"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2006.08.002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006542107"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20085"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.02.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1139\/o05-038"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2812"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/S146239940500904X"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040776"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0128"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(00)00016-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0460OC"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-012-1252-8"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.01.008"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.5.1474"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-4975(94)90090-6"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1988.tb00806.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.104117"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0022-3565(24)29450-7","article-title":"Drug synergism: its detection and applications","volume":"298","author":"Tallarida RJ","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2009.11.072"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.004"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2001465"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-012-0197-3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806092105"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-3039"},{"key":"e_1_2_8_34_1","article-title":"Current status of poly(ADP\u2010ribose) polymerase inhibitors as novel therapeutic agents for triple\u2010negative breast cancer","volume":"829315","author":"Hiller DJ","year":"2012","journal-title":"Int J Breast Cancer"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/ger020"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.2007.00018.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.011"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009199"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46243"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709698200"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171301998"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.20.8809-8823.2005"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3979"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.12000","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.12000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.12000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T16:47:55Z","timestamp":1745945275000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.12000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,10]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/jcmm.12000"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.12000","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,10]]}}}