{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T03:12:17Z","timestamp":1770433937388,"version":"3.49.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1939-1676.2011.0743.x","type":"journal-article","created":{"date-parts":[[2011,6,20]],"date-time":"2011-06-20T09:58:49Z","timestamp":1308563929000},"page":"838-845","source":"Crossref","is-referenced-by-count":46,"title":["Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU-Induced Hepatopathy in Tumor-Bearing Dogs"],"prefix":"10.1093","volume":"25","author":[{"given":"K.A.","family":"Skorupski","sequence":"first","affiliation":[{"name":"University of California, Davis Department of Surgical and Radiological Sciences, , Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.M.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Veterinary Medical Teaching Hospital, University of California, Davis , Davis, CA"},{"name":"VCA Sacramento Veterinary Referral Center , Sacramento, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.M.","family":"Irish","sequence":"additional","affiliation":[{"name":"Veterinary Medical Teaching Hospital, University of California, Davis , Davis, CA"},{"name":"VCA Veterinary Referral Associates , Gaithersburg, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.S.","family":"Kent","sequence":"additional","affiliation":[{"name":"University of California, Davis Department of Surgical and Radiological Sciences, , Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.A.","family":"Guerrero","sequence":"additional","affiliation":[{"name":"University of California, Davis Department of Surgical and Radiological Sciences, , Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.O.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Veterinary Medical Teaching Hospital, University of California, Davis , Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.W.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Nutramax Laboratories Inc , Edgewood, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"2026020303465153900_b1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1939-1676.1999.tb01452.x","article-title":"Lomustine (CCNU) for the treatment of resistant lymphoma in dogs","volume":"13","author":"Moore","year":"1999","journal-title":"J Vet Intern Med"},{"key":"2026020303465153900_b2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1939-1676.2006.tb02833.x","article-title":"CCNU in the treatment of canine epitheliotropic lymphoma","volume":"20","author":"Williams","year":"2006","journal-title":"J Vet Intern Med"},{"key":"2026020303465153900_b3","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1892\/0891-6640(2006)20[1389:ROCCEL]2.0.CO;2","article-title":"Response of canine cutaneous epitheliotropic lymphoma to lomustine (CCNU): A retrospective study of 46 cases (1999\u20132004)","volume":"20","author":"Risbon","year":"2006","journal-title":"J Vet Intern Med"},{"key":"2026020303465153900_b4","doi-asserted-by":"crossref","first-page":"6010","DOI":"10.1111\/j.1939-1676.1999.tb02217.x","article-title":"Treatment of canine mast cell tumors with CCNU (lomustine)","volume":"13","author":"Rassnick","year":"1999","journal-title":"J Vet Intern Med"},{"key":"2026020303465153900_b5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1939-1676.2007.tb02937.x","article-title":"CCNU for the treatment of dogs with histiocytic sarcoma","volume":"21","author":"Skorupski","year":"2007","journal-title":"J Vet Intern Med"},{"key":"2026020303465153900_b6","first-page":"40","article-title":"Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat","volume":"34","author":"Viotte","year":"1986","journal-title":"Pathol Biol (Paris)"},{"key":"2026020303465153900_b7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00254560","article-title":"Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity II. 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