{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:08:54Z","timestamp":1788790134885,"version":"build-2803163510"},"reference-count":102,"publisher":"Portland Press Ltd.","issue":"19","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["APP1124125"],"award-info":[{"award-number":["APP1124125"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary liver cancer is an increasing problem worldwide and is associated with significant mortality. A popular method of modeling liver cancer in mice is plasmid hydrodynamic tail vein injection (HTVI). However, plasmid-HTVI models rarely recapitulate the chronic liver injury which precedes the development of most human liver cancer. We sought to investigate how liver injury using thioacetamide contributes to the pathogenesis and progression of liver cancer in two oncogenic plasmid-HTVI-induced mouse liver cancer models. Fourteen-week-old male mice received double-oncogene plasmid-HTVI (SB\/AKT\/c-Met and SB\/AKT\/NRas) and then twice-weekly intraperitoneal injections of thioacetamide for 6 weeks. Liver tissue was examined for histopathological changes, including fibrosis and steatosis. Further characterization of fibrosis and inflammation was performed with immunostaining and real-time quantitative PCR. RNA sequencing with pathway analysis was used to explore novel pathways altered in the cancer models. Hepatocellular and cholangiocellular tumors were observed in mice injected with double-oncogene plasmid-HTVI models (SB\/AKT\/c-Met and SB\/AKT\/NRas). Thioacetamide induced mild fibrosis and increased alpha smooth muscle actin-expressing cells. However, the combination of plasmids and thioacetamide did not significantly increase tumor size, but increased multiplicity of small neoplastic lesions. Cancer and\/or liver injury up-regulated profibrotic and proinflammatory genes while metabolic pathway genes were mostly down-regulated. We conclude that the liver injury microenvironment can interact with liver cancer and alter its presentation. However, the effects on cancer development vary depending on the genetic drivers with differing active oncogenic pathways. Therefore, the choice of plasmid-HTVI model and injury agent may influence the extent to which injury promotes liver cancer development.<\/jats:p>","DOI":"10.1042\/cs20240560","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T13:40:58Z","timestamp":1725975658000},"page":"1227-1248","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model"],"prefix":"10.1042","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9374-9173","authenticated-orcid":false,"given":"Vincent","family":"Chiu","sequence":"first","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Yee","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Main","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Stevanovski","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Watt","sequence":"additional","affiliation":[{"name":"3School of Biomedical Sciences, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Wilson","sequence":"additional","affiliation":[{"name":"4Hudson Institute of Medical Research, Monash University, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Angus","sequence":"additional","affiliation":[{"name":"5Department of Gastroenterology and Hepatology, Austin Health, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Roberts","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"6School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Shackel","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-8531","authenticated-orcid":false,"given":"Chandana","family":"Herath","sequence":"additional","affiliation":[{"name":"1Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia"},{"name":"2South Western Sydney Clinical School, UNSW Sydney, Liverpool, New South Wales, Australia"},{"name":"7Department of Medicine, Austin Health, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2024092606062069400_B1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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