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This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co\u2010treating cancer cells with H\u20101PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H\u20101PV\/VPA co\u2010treatment strongly inhibits tumour growth promoting complete tumour remission in all co\u2010treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1\u2010mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H\u20101PV\/VPA co\u2010treatment against cervical and pancreatic ductal carcinomas.<\/jats:p>","DOI":"10.1002\/emmm.201302796","type":"journal-article","created":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T03:18:07Z","timestamp":1383707887000},"page":"1537-1555","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Synergistic combination of valproic acid and oncolytic parvovirus H\u20101PV as a potential therapy against cervical and pancreatic carcinomas"],"prefix":"10.1038","volume":"5","author":[{"given":"Junwei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Bonifati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi","family":"Hristov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Marttila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Valmary\u2010Degano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Stanzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schn\u00f6lzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Mougin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Aprahamian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana P.","family":"Grekova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahari","family":"Raykov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Rommelaere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Marchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,9,17]]},"reference":[{"key":"BFEMMM201302796_CR1","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1128\/JVI.06208-11","volume":"86","author":"X Allaume","year":"2012","unstructured":"Allaume X, El\u2010Andaloussi N, Leuchs B, Bonifati S, Kulkarni A, Marttila T, Kaufmann JK, Nettelbeck DM, Kleinschmidt J, Rommelaere J, et al (2012) Retargeting of rat parvovirus H\u20101PV to cancer cells through genetic engineering of the viral capsid. 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