{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:48:35Z","timestamp":1775584115874,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T00:00:00Z","timestamp":1537833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL048546"],"award-info":[{"award-number":["P01 HL048546"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fanconi anemia is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Currently, no interventions to prevent or delay the formation of solid tumors are available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Two of the most important hallmarks of Fanconi anemia are inflammation and oxidative stress. In this study, we administrated the antioxidant atorvastatin and the anti\u2010inflammatory drug celecoxib to cohorts of <jats:italic>Fancd2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Trp53<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice, a model of Fanconi anemia. Treatment started at weaning and continued until the mice developed a palpable mass or suffered from\u00a0&gt;20% weight loss. Tumor samples and selected tissues were subjected to histopathological examination. \u03c7<jats:sup>2<\/jats:sup> test was performed to analyze tumor incidence, and Kaplan\u2013Meier survival curves were evaluated with log\u2010rank test. In addition, a small cohort of mice was monitored for the safety of the drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combined oral administration of both drugs significantly delayed tumor onset in <jats:italic>Fancd2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Trp53<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice. Specifically, the treatment delayed the onset of ovarian tumors in <jats:italic>Fancd2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Trp53<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice and increased the mean ovarian tumor\u2010free survival time by 17%, whereas this combinatorial drug regimen did not have a significant effect on other tumor types. In addition, no detrimental effects on hematopoiesis from the drug treatment were observed during a 12\u2010month safety monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The data presented here suggest that a combination of atorvastatin and celecoxib may be a good candidate for chemoprevention in Fanconi anemia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27460","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T04:11:17Z","timestamp":1537935077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Combination therapy with atorvastatin and celecoxib delays tumor formation in a Fanconi anemia mouse model"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-6053","authenticated-orcid":false,"given":"Qing\u2010shuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Oregon Stem Cell Center Department of Pediatrics Oregon Health and Science University  Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Deater","sequence":"additional","affiliation":[{"name":"Oregon Stem Cell Center Department of Pediatrics Oregon Health and Science University  Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngoc","family":"Phan","sequence":"additional","affiliation":[{"name":"Oregon Stem Cell Center Department of Pediatrics Oregon Health and Science University  Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Marcogliese","sequence":"additional","affiliation":[{"name":"Department of Pathology Baylor College of Medicine  Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Major","sequence":"additional","affiliation":[{"name":"Department of Pathology Baylor College of Medicine  Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva C.","family":"Guinan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts"},{"name":"Department of Radiation Oncology Harvard Medical School  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Grompe","sequence":"additional","affiliation":[{"name":"Oregon Stem Cell Center Department of Pediatrics Oregon Health and Science University  Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.07.043"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-099218"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2129"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.16.4478"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/290142a0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5186"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/2141-9248.157511"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.11.4092"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0114"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2013.09.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/hq0202.104081"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710790979980"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23315"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4619"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0242"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24766"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1103403"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.10.014"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-278226"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24780"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-683490"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1158\/0008-5472.85.65.1","article-title":"Heterozygosity for p53 (Trp53+\/\u2010) accelerates epithelial tumor formation in fanconi anemia complementation group D2 (Fancd2) knockout mice","volume":"65","author":"Houghtaling S","year":"2005","journal-title":"Cancer Res"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4428"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2013.12.014"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0222"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm852"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00111-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.01.015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.19.9590"},{"key":"e_1_2_8_31_1","first-page":"2478","article-title":"Atorvastatin exhibits anti\u2010tumorigenic and anti\u2010metastatic effects in ovarian cancer in vitro","volume":"7","author":"Jones HM","year":"2017","journal-title":"Am J Cancer Res."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767001-00007"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0394-0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21662"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"S761","DOI":"10.3928\/0147-7447-20000702-05","article-title":"COX\u20102 specific inhibitors offer improved advantages over traditional NSAIDs","volume":"23","author":"Urban MK","year":"2000","journal-title":"Orthopedics"},{"key":"e_1_2_8_36_1","first-page":"5040","article-title":"The cyclooxygenase\u20102 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis","volume":"60","author":"Jacoby RF","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2011.203"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-09-0059"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2009.06.005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-09-0243"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b17-00077"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.27460","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.27460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T16:38:05Z","timestamp":1694709485000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.27460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,25]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/pbc.27460"],"URL":"https:\/\/doi.org\/10.1002\/pbc.27460","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,25]]},"assertion":[{"value":"2018-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e27460"}}