{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:56:19Z","timestamp":1777503379813,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,1,13]],"date-time":"2009-01-13T00:00:00Z","timestamp":1231804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2009,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis C virus (HCV) infection is often associated with chronic liver disease, which is a major risk factor for the development of hepatocellular carcinoma (HCC). To study the HCV host\u2010cell relationship on the molecular level, HepG2 and Huh7 cells were stably transfected with an infectious cDNA clone of HCV or with empty vector. Evidence for HCV replication was obtained in both culture systems. HCV also stimulated growth <jats:italic>in vitro<\/jats:italic>. To identify genes whose altered expression by HCV are important to the pathogenesis of infection, RNAs were isolated from HepG2\u2010HCV and HepG2\u2010vector cells and subjected to microarray analysis. The results showed that arginase 1 mRNA and protein were elevated about threefold in HCV positive compared with negative cells (<jats:italic>p<\/jats:italic> &lt; 0.01). Arginase 1 expression was elevated in more than 75% of HCV infected liver samples compared with paired HCC from the same patients (&gt;33% positive) and to uninfected liver tissues (0% positive). Arginase 1 specific siRNA inhibited the ability of HCV to stimulate hepatocellular growth in culture by &gt;70%, suggesting that the metabolism of arginine to ornithine may contribute to HCV mediated stimulation of hepatocellular growth. Introduction of arginase specific siRNA also resulted in increased nitric oxide synthase (iNOS) (&gt;1.2\u2010fold), nitric oxide (NO) production (&gt;3\u2010fold) and increased cell death (&gt;2.5\u2010fold) in HCV positive compared with negative cells, suggesting that these molecules potentially contribute to hepatocellular damage. Hence, an important part of the mechanism whereby HCV regulates hepatocellular growth and survival may be through altering arginine metabolism. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24265","type":"journal-article","created":{"date-parts":[[2009,1,13]],"date-time":"2009-01-13T14:19:26Z","timestamp":1231856366000},"page":"2886-2892","source":"Crossref","is-referenced-by-count":27,"title":["Hepatitis C virus targets over\u2010expression of arginase I in hepatocarcinogenesis"],"prefix":"10.1002","volume":"124","author":[{"given":"Wenjun","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bill","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Feitelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Tur\u2010Kaspa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qishi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,27]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01652.x"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04669.x"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2006.07.002"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209562"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-7-1527"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/2053"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.1652"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5386.103"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20083"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-200410000-00002"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.2003.11605.x"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.5301\/JBM.2008.4541"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s102380200007"},{"key":"e_1_2_5_15_2","first-page":"511","article-title":"Usefulness of preoperative assasy of arginase in pancreatic cancer patients","volume":"15","author":"Porembska Z","year":"2003","journal-title":"Polski Merkuriusz Lekarski"},{"key":"e_1_2_5_16_2","first-page":"76","article-title":"Possible implications of arginase and diamine oxidase in prostatic carcinoma","volume":"25","author":"Keskinege A","year":"2001","journal-title":"Cancer Detect Prev"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-002-2563-2"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(92)90040-W"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2001.114543"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00202199"},{"key":"e_1_2_5_21_2","first-page":"619","article-title":"Arginase activity determination. A marker of large bowel mucosa proliferation","volume":"34","author":"Kocna P","year":"1996","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"e_1_2_5_22_2","first-page":"215","article-title":"Serum arginase activfity in patients with liver cirrhosis and hepatocellular carcinoma","volume":"60","author":"Chrzanowska A","year":"2007","journal-title":"Wiadomosci Lekarskie"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(01)00254-5"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300712"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2.4.589"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.2030"},{"key":"e_1_2_5_27_2","first-page":"363","article-title":"Transfection of HepG2 cells with infectious hepatitis C virus genome","volume":"151","author":"Dash S","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202470"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.25545"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2900"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890410410"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6533"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00236.x"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524043359944"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm762"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.24265","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.24265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T07:27:29Z","timestamp":1696836449000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.24265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,27]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,6,15]]}},"alternative-id":["10.1002\/ijc.24265"],"URL":"https:\/\/doi.org\/10.1002\/ijc.24265","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,27]]}}}