{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:57:08Z","timestamp":1789192628792,"version":"build-2803163510"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2013,6,28]],"date-time":"2013-06-28T00:00:00Z","timestamp":1372377600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0067330","type":"journal-article","created":{"date-parts":[[2013,6,28]],"date-time":"2013-06-28T21:27:01Z","timestamp":1372454821000},"page":"e67330","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Anti-Tumour Efficacy of Capecitabine in a Genetically Engineered Mouse Model of Pancreatic Cancer"],"prefix":"10.1371","volume":"8","author":[{"given":"Aur\u00e9lie","family":"Courtin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tashinga E.","family":"Bapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo L.","family":"Bramhall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Neesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben-Fillippo","family":"Krippendorff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Tuveson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan I.","family":"Jodrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,6,28]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3322\/caac.20006","article-title":"Cancer statistics, 2009","volume":"59","author":"A Jemal","year":"2009","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1471-2407-8-82","article-title":"Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer","volume":"8","author":"V Heinemann","year":"2008","journal-title":"BMC Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1124\/jpet.104.081265","article-title":"Hydrolysis of capecitabine to 5&apos;-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide","volume":"313","author":"SK Quinney","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2165\/00003088-200140020-00002","article-title":"Clinical pharmacokinetics of capecitabine","volume":"40","author":"B Reigner","year":"2001","journal-title":"Clin Pharmacokinet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S0959-8049(98)00058-6","article-title":"Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue","volume":"34","author":"M Miwa","year":"1998","journal-title":"Eur J Cancer"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0006-2952(97)00682-5","article-title":"Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts","volume":"55","author":"T Ishikawa","year":"1998","journal-title":"Biochem Pharmacol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1023\/A:1006497231579","article-title":"Capecitabine: preclinical pharmacology studies","volume":"18","author":"H Ishitsuka","year":"2000","journal-title":"Invest New Drugs"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"8773","DOI":"10.1158\/1078-0432.CCR-05-0627","article-title":"Antitumor efficacy of capecitabine and celecoxib in irradiated and lead-shielded, contralateral human BxPC-3 pancreatic cancer xenografts: clinical implications of abscopal effects","volume":"11","author":"C Blanquicett","year":"2005","journal-title":"Clin Cancer Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1056\/NEJMoa032295","article-title":"A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer","volume":"350","author":"JP Neoptolemos","year":"2004","journal-title":"N Engl J Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1001\/jama.2010.1275","article-title":"Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial","volume":"304","author":"JP Neoptolemos","year":"2010","journal-title":"JAMA"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/MPA.0b013e31826c6aee","article-title":"Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer","volume":"42","author":"RA Hubner","year":"2013","journal-title":"Pancreas"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"SR Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1158\/0008-5472.CAN-05-2168","article-title":"Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations","volume":"66","author":"RH Hruban","year":"2006","journal-title":"Cancer Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1200\/JCO.2009.24.4491","article-title":"Cytidine deaminase residual activity in serum is a predictive marker of early severe toxicities in adults after gemcitabine-based chemotherapies","volume":"28","author":"J Ciccolini","year":"2010","journal-title":"J Clin Oncol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00280-008-0889-1","article-title":"Early severe toxicities after capecitabine intake: possible implication of a cytidine deaminase extensive metabolizer profile","volume":"63","author":"C Mercier","year":"2009","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1200\/JCO.1991.9.3.491","article-title":"A phase I clinical, plasma, and cellular pharmacology study of gemcitabine","volume":"9","author":"JL Abbruzzese","year":"1991","journal-title":"J Clin Oncol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"v7","DOI":"10.1093\/annonc\/mdj941","article-title":"Cellular pharmacology of gemcitabine","volume":"17","author":"E Mini","year":"2006","journal-title":"Ann Oncol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1126\/science.1171362","article-title":"Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer","volume":"324","author":"KP Olive","year":"2009","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/sj.bjc.6605642","article-title":"Guidelines for the welfare and use of animals in cancer research","volume":"102","author":"P Workman","year":"2010","journal-title":"Br J Cancer"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1053\/j.gastro.2004.03.058","article-title":"Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene","volume":"127","author":"FS Schreiber","year":"2004","journal-title":"Gastroenterology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nchembio817","article-title":"Systems biology and combination therapy in the quest for clinical efficacy","volume":"2","author":"JB Fitzgerald","year":"2006","journal-title":"Nat Chem Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrd1609","article-title":"Multicomponent therapeutics for networked systems","volume":"4","author":"CT Keith","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/bjc.2012.450","article-title":"Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells","volume":"107","author":"Y Lin","year":"2012","journal-title":"Br J Cancer"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0076-6879(07)00406-5","article-title":"K-Ras-driven pancreatic cancer mouse model for anticancer inhibitor analyses","volume":"439","author":"N Cook","year":"2008","journal-title":"Methods Enzymol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jchromb.2005.09.010","article-title":"Simultaneous determination of capecitabine and its metabolites by HPLC and mass spectrometry for preclinical and clinical studies","volume":"826","author":"SM Guichard","year":"2005","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"S Reagan-Shaw","year":"2008","journal-title":"FASEB J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ejca.2007.10.023","article-title":"Gene expression predicts differential capecitabine metabolism, impacting on both pharmacokinetics and antitumour activity","volume":"44","author":"SM Guichard","year":"2008","journal-title":"Eur J Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/ijc.20360","article-title":"Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum","volume":"112","author":"I Ninomiya","year":"2004","journal-title":"Int J Cancer"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1200\/JCO.20.1.160","article-title":"Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer","volume":"20","author":"TH Cartwright","year":"2002","journal-title":"J Clin Oncol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1200\/JCO.1997.15.6.2403","article-title":"Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial","volume":"15","author":"HA Burris 3rd","year":"1997","journal-title":"J Clin Oncol"},{"key":"ref31","first-page":"1505","article-title":"Effects of thymidylate synthase inhibition on thymidine kinase activity and nucleoside transporter expression","volume":"55","author":"J Pressacco","year":"1995","journal-title":"Cancer Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/bjc.1995.437","article-title":"Modulation of the equilibrative nucleoside transporter by inhibitors of DNA synthesis","volume":"72","author":"J Pressacco","year":"1995","journal-title":"Br J Cancer"},{"key":"ref33","first-page":"6075","article-title":"Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity","volume":"60","author":"DR Rauchwerger","year":"2000","journal-title":"Cancer Res"},{"key":"ref34","first-page":"4349","article-title":"Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines","volume":"58","author":"JR Mackey","year":"1998","journal-title":"Cancer Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1200\/JCO.2009.24.2446","article-title":"Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer","volume":"27","author":"D Cunningham","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1200\/JCO.2006.09.0886","article-title":"Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group","volume":"25","author":"R Herrmann","year":"2007","journal-title":"J Clin Oncol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1124\/dmd.110.034397","article-title":"Influence of cytidine deaminase on antitumor activity of 2&apos;-deoxycytidine analogs in vitro and in vivo","volume":"38","author":"T Yoshida","year":"2010","journal-title":"Drug Metab Dispos"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000074480","article-title":"Forced expression of cytidine deaminase confers sensitivity to capecitabine","volume":"65","author":"T Morita","year":"2003","journal-title":"Oncology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1158\/2159-8290.CD-11-0242","article-title":"nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer","volume":"2","author":"KK Frese","year":"2012","journal-title":"Cancer Discov"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bbrc.2007.05.088","article-title":"Drug resistance to 5-FU linked to reactive oxygen species modulator 1","volume":"359","author":"IT Hwang","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/nm1001-1111","article-title":"Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells","volume":"7","author":"PM Hwang","year":"2001","journal-title":"Nat Med"},{"key":"ref42","first-page":"3879","article-title":"5-fluorouracil-induced death of Jurkat T-cells\u2013a role for caspases and MCL-1","volume":"30","author":"DM Aresvik","year":"2010","journal-title":"Anticancer Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2131\/jts.36.411","article-title":"Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans\u2013toxicological implications","volume":"36","author":"H Shindoh","year":"2011","journal-title":"J Toxicol Sci"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0067330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T21:01:26Z","timestamp":1540242086000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0067330"}},"subtitle":[],"editor":[{"given":"Hana","family":"Alg\u00fcl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,6,28]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0067330","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,28]]}}}