{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:46:19Z","timestamp":1761929179003,"version":"3.30.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4536,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Hepatitis B virus (HBV) transgenic mice (official designation, Tg [Alb\u20131 HBV] Bri 44) invariably develop macroscopically evident tumors within the 20th month of life. Sustained proliferative activity seems to play an important role in the development of these lesions. We previously showed that ursodeoxycholate (UDC) stimulates hepatocyte proliferation in various experimental settings. Herein, we tested the assumption that biological factors able to further increase liver cell proliferation, such as UDC, could accelerate tumor development in this animal model. For this study, 22 eight\u2013week\u2013old male transgenic mice were divided into 2 groups; 11 animals received a standard diet, and 11 received a UDC\u2013enriched diet. The 2 groups were further divided into 2 subgroups of 5 and 6 animals each and were sacrificed at 3 and 15 months of age, respectively. These different times were chosen to exclude diet\u2013related toxicity (in 3\u2013month\u2013old mice) and evaluate tumor growth (in 15\u2013month\u2013old mice). In addition, hepatocyte proliferation was assessed in all animals. In 3\u2013month\u2013old mice receiving UDC, cholestatic and cytolytic indices as well as liver histology were comparable to those in controls. At 15 months, all UDC\u2013treated mice showed large multinodular tumors whereas only 33% of controls developed smaller uninodular neoplasms. Hepatocyte proliferation was increased in all animals receiving UDC compared with controls. In conclusion, the increase in serum UDC (undetectable in mice fed a standard diet), in the absence of any toxic effect on the liver, suggests the involvement of this bile salt in the stimulation of hepatocyte proliferation and tumor growth. (Hepatology 2003;37:880\u2013886.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50175","type":"journal-article","created":{"date-parts":[[2003,4,7]],"date-time":"2003-04-07T20:06:02Z","timestamp":1049745962000},"page":"880-886","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Influence of Ursodeoxycholate\u2013Enriched Diet on Liver Tumor Growth in Hbv Transgenic Mice"],"prefix":"10.1097","volume":"37","author":[{"given":"Michele","family":"Barone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Maiorano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Ladisa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Cuomo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Pece","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Berloco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lucia","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Valentini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Francavilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Di Leo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enzo","family":"Ierardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2003.50175-BIB1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1126\/science.3865369","volume":"230","author":"Chisari","year":"1985","journal-title":"Science"},{"key":"10.1053\/jhep.2003.50175-BIB2","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1073\/pnas.84.19.6909","volume":"84","author":"Chisari","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2003.50175-BIB3","first-page":"3400","volume":"50","author":"Dunsford","year":"1990","journal-title":"Cancer Res"},{"key":"10.1053\/jhep.2003.50175-BIB4","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/hep.1840200510","volume":"20","author":"Toshkov","year":"1994","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50175-BIB5","first-page":"620","volume":"21","author":"Huang","year":"1995","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50175-BIB6","first-page":"2823","volume":"52","author":"Pasquinelli","year":"1992","journal-title":"Cancer Res"},{"key":"10.1053\/jhep.2003.50175-BIB7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/jso.2930530504","volume":"3","author":"Barone","year":"1993","journal-title":"J Surg Oncol"},{"key":"10.1053\/jhep.2003.50175-BIB8","first-page":"1159","volume":"23","author":"Barone","year":"1996","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50175-BIB9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0016-5085(99)70242-8","volume":"116","author":"Alpini","year":"1999","journal-title":"Gastroenterology"},{"key":"10.1053\/jhep.2003.50175-BIB10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/003655202753387419","volume":"7","author":"Barone","year":"2002","journal-title":"Scand J Gastroenterol"},{"key":"10.1053\/jhep.2003.50175-BIB11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1053\/jhep.2001.26820","volume":"34","author":"Donato","year":"2001","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50175-BIB12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0002-9610(05)80547-1","volume":"160","author":"Lam","year":"1990","journal-title":"Am J Surg"},{"key":"10.1053\/jhep.2003.50175-BIB13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1365-2184.1995.tb00084.x","volume":"28","author":"Bauman","year":"1995","journal-title":"Cell Prolif"},{"key":"10.1053\/jhep.2003.50175-BIB14","first-page":"47","volume-title":"Immunocytochemistry: Modern Methods and Applications","author":"van Noorden","year":"1986","unstructured":"Tissue preparation and immunostaining techniques for light microscopy. 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