{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:49:47Z","timestamp":1780087787793,"version":"3.54.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T00:00:00Z","timestamp":1399507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T00:00:00Z","timestamp":1399507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"published-print":{"date-parts":[[2014,7]]},"DOI":"10.1038\/gt.2014.41","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T10:26:13Z","timestamp":1399544773000},"page":"673-681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Thymidine phosphorylase is both a therapeutic and a suicide gene in a murine model of mitochondrial neurogastrointestinal encephalomyopathy"],"prefix":"10.1038","volume":"21","author":[{"given":"S","family":"L\u00f3pez-Est\u00e9vez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Torres-Torronteras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Mansilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Casacuberta-Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Martorell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mart\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Barquinero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,8]]},"reference":[{"key":"BFgt201441_CR1","doi-asserted-by":"publisher","first-page":"e49","DOI":"10.1093\/nar\/gkn125","volume":"36","author":"GP Wang","year":"2008","unstructured":"Wang GP, Garrigue A, Ciuffi A, Ronen K, Leipzig J, Berry C et al. DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer. Nucleic Acids Res 2008; 36: e49.","journal-title":"Nucleic Acids Res"},{"key":"BFgt201441_CR2","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1093\/hmg\/ddn401","volume":"18","author":"LC Lopez","year":"2009","unstructured":"Lopez LC, Akman HO, Garcia-Cazorla A, Dorado B, Marti R, Nishino I et al. Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice. Hum Mol Genet 2009; 18: 714\u2013722.","journal-title":"Hum Mol Genet"},{"key":"BFgt201441_CR3","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/gt.2011.24","volume":"18","author":"J Torres-Torronteras","year":"2011","unstructured":"Torres-Torronteras J, Gomez A, Eixarch H, Palenzuela L, Pizzorno G, Hirano M et al. Hematopoietic gene therapy restores thymidine phosphorylase activity in a cell culture and a murine model of MNGIE. Gene Therapy 2011; 18: 795\u2013806.","journal-title":"Gene Therapy"},{"key":"BFgt201441_CR4","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1089\/hum.2012.116","volume":"23","author":"C Rivat","year":"2012","unstructured":"Rivat C, Santilli G, Gaspar HB, Thrasher AJ . Gene therapy for primary immunodeficiencies. Hum Gene Ther 2012; 23: 668\u2013675.","journal-title":"Hum Gene Ther"},{"key":"BFgt201441_CR5","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1046\/j.0960-7420.2001.00252.x","volume":"28","author":"E Simpson","year":"2001","unstructured":"Simpson E, Scott D, James E, Lombardi G, Cwynarski K, Dazzi F et al. Minor H antigens: genes and peptides. Eur J Immunogenet 2001; 28: 505\u2013513.","journal-title":"Eur J Immunogenet"},{"key":"BFgt201441_CR6","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.cct.2011.01.013","volume":"32","author":"M Lu","year":"2011","unstructured":"Lu M, Freytag SO, Stricker H, Kim JH, Barton K, Movsas B . Adaptive seamless design for an efficacy trial of replication-competent adenovirus-mediated suicide gene therapy and radiation in newly-diagnosed prostate cancer (ReCAP Trial). Contemp Clin Trials 2011; 32: 453\u2013460.","journal-title":"Contemp Clin Trials"},{"key":"BFgt201441_CR7","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1126\/science.276.5319.1719","volume":"276","author":"C Bonini","year":"1997","unstructured":"Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719\u20131724.","journal-title":"Science"},{"key":"BFgt201441_CR8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.clinthera.2005.01.005","volume":"27","author":"CM Walko","year":"2005","unstructured":"Walko CM, Lindley C . Capecitabine: a review. Clin Ther 2005; 27: 23\u201344.","journal-title":"Clin Ther"},{"key":"BFgt201441_CR9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/cncr.21986","volume":"107","author":"J Ajani","year":"2006","unstructured":"Ajani J . Review of capecitabine as oral treatment of gastric, gastroesophageal, and esophageal cancers. Cancer 2006; 107: 221\u2013231.","journal-title":"Cancer"},{"key":"BFgt201441_CR10","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrc1074","volume":"3","author":"DB Longley","year":"2003","unstructured":"Longley DB, Harkin DP, Johnston PG . 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003; 3: 330\u2013338.","journal-title":"Nat Rev Cancer"},{"key":"BFgt201441_CR11","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/368198a0","volume":"368","author":"M Haraguchi","year":"1994","unstructured":"Haraguchi M, Miyadera K, Uemura K, Sumizawa T, Furukawa T, Yamada K et al. Angiogenic activity of enzymes. Nature 1994; 368: 198.","journal-title":"Nature"},{"key":"BFgt201441_CR12","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2174\/1568011043482089","volume":"4","author":"J Ciccolini","year":"2004","unstructured":"Ciccolini J, Evrard A, Cuq P . Thymidine phosphorylase and fluoropyrimidines efficacy: a Jekyll and Hyde story. Curr Med Chem Anticancer Agents 2004; 4: 71\u201381.","journal-title":"Curr Med Chem Anticancer Agents"},{"key":"BFgt201441_CR13","doi-asserted-by":"publisher","first-page":"19073","DOI":"10.1074\/jbc.270.32.19073","volume":"270","author":"EL Schwartz","year":"1995","unstructured":"Schwartz EL, Baptiste N, Wadler S, Makower D . Thymidine phosphorylase mediates the sensitivity of human colon carcinoma cells to 5-fluorouracil. J Biol Chem 1995; 270: 19073\u201319077.","journal-title":"J Biol Chem"},{"key":"BFgt201441_CR14","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/(SICI)1097-0215(19990129)80:3<465::AID-IJC21>3.0.CO;2-6","volume":"80","author":"A Evrard","year":"1999","unstructured":"Evrard A, Cuq P, Robert B, Vian L, Pelegrin A, Cano JP . Enhancement of 5-fluorouracil cytotoxicity by human thymidine-phosphorylase expression in cancer cells: in vitro and in vivo study. Int J Cancer 1999; 80: 465\u2013470.","journal-title":"Int J Cancer"},{"key":"BFgt201441_CR15","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/ijc.1212","volume":"92","author":"T Morita","year":"2001","unstructured":"Morita T, Matsuzaki A, Tokue A . Enhancement of sensitivity to capecitabine in human renal carcinoma cells transfected with thymidine phosphorylase cDNA. Int J Cancer 2001; 92: 451\u2013456.","journal-title":"Int J Cancer"},{"key":"BFgt201441_CR16","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1038\/sj.bjc.6690589","volume":"80","author":"A Evrard","year":"1999","unstructured":"Evrard A, Cuq P, Ciccolini J, Vian L, Cano JP . Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase. Br J Cancer 1999; 80: 1726\u20131733.","journal-title":"Br J Cancer"},{"key":"BFgt201441_CR17","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1172\/JCI35700","volume":"118","author":"S Hacein-Bey-Abina","year":"2008","unstructured":"Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118: 3132\u20133142.","journal-title":"J Clin Invest"},{"key":"BFgt201441_CR18","first-page":"112","volume":"71","author":"H Ishitsuka","year":"1980","unstructured":"Ishitsuka H, Miwa M, Takemoto K, Fukuoka K, Itoga A, Maruyama HB . Role of uridine phosphorylase for antitumor activity of 5\u2032-deoxy-5-fluorouridine. Gann 1980; 71: 112\u2013123.","journal-title":"Gann"},{"key":"BFgt201441_CR19","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1158\/1535-7163.MCT-11-0202","volume":"10","author":"D Cao","year":"2011","unstructured":"Cao D, Ziemba A, McCabe J, Yan R, Wan L, Kim B et al. Differential expression of uridine phosphorylase in tumors contributes to an improved fluoropyrimidine therapeutic activity. Mol Cancer Ther 2011; 10: 2330\u20132339.","journal-title":"Mol Cancer Ther"},{"key":"BFgt201441_CR20","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/annonc\/mdn592","volume":"20","author":"C Andreetta","year":"2009","unstructured":"Andreetta C, Puppin C, Minisini A, Valent F, Pegolo E, Damante G et al. Thymidine phosphorylase expression and benefit from capecitabine in patients with advanced breast cancer. Ann Oncol 2009; 20: 265\u2013271.","journal-title":"Ann Oncol"},{"key":"BFgt201441_CR21","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/BF00735915","volume":"32","author":"H Eda","year":"1993","unstructured":"Eda H, Fujimoto K, Watanabe S, Ura M, Hino A, Tanaka Y et al. Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5\u2032-deoxy-5-fluorouridine. Cancer Chemother Pharmacol 1993; 32: 333\u2013338.","journal-title":"Cancer Chemother Pharmacol"},{"key":"BFgt201441_CR22","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/0006-291X(92)91863-L","volume":"182","author":"EL Schwartz","year":"1992","unstructured":"Schwartz EL, Hoffman M, O'Connor CJ, Wadler S . Stimulation of 5-fluorouracil metabolic activation by interferon-alpha in human colon carcinoma cells. Biochem Biophys Res Commun 1992; 182: 1232\u20131239.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFgt201441_CR23","first-page":"1529","volume":"6","author":"J Ciccolini","year":"2000","unstructured":"Ciccolini J, Peillard L, Evrard A, Cuq P, Aubert C, Pelegrin A et al. Enhanced antitumor activity of 5-fluorouracil in combination with 2'-deoxyinosine in human colorectal cell lines and human colon tumor xenografts. Clin Cancer Res 2000; 6: 1529\u20131535.","journal-title":"Clin Cancer Res"},{"key":"BFgt201441_CR24","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/(SICI)1097-0215(19990924)83:1<127::AID-IJC22>3.0.CO;2-6","volume":"83","author":"M Endo","year":"1999","unstructured":"Endo M, Shinbori N, Fukase Y, Sawada N, Ishikawa T, Ishitsuka H et al. Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5\u2032-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int J Cancer 1999; 83: 127\u2013134.","journal-title":"Int J Cancer"},{"key":"BFgt201441_CR25","first-page":"172","volume":"10","author":"T Ma","year":"2004","unstructured":"Ma T, Zhu ZG, Ji YB, Zhang Y, Yu YY, Liu BY et al. Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2'-deoxyuridine. World J Gastroenterol 2004; 10: 172\u2013176.","journal-title":"World J Gastroenterol"},{"key":"BFgt201441_CR26","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3109\/07357907.2010.535060","volume":"29","author":"T Wang","year":"2011","unstructured":"Wang T, Wang L, Qian X, Yu L, Ding Y, Liu B . Relationship between gene expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in primary cancer cells isolated from malignant ascites. Cancer Invest 2011; 29: 130\u2013136.","journal-title":"Cancer Invest"},{"key":"BFgt201441_CR27","first-page":"330","volume":"40","author":"LJ Zhuo","year":"2011","unstructured":"Zhuo LJ, Gao MQ, Huang AM . [Improved sensitivity of gastric carcinoma cells to fluorouracil-related drugs by transfection of thymidine phosphorylase gene]. Zhonghua Bing Li Xue Za Zhi 2011; 40: 330\u2013333.","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"BFgt201441_CR28","first-page":"923","volume":"1","author":"J Ciccolini","year":"2002","unstructured":"Ciccolini J, Fina F, Bezulier K, Giacometti S, Roussel M, Evrard A et al. Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas. Mol Cancer Ther 2002; 1: 923\u2013927.","journal-title":"Mol Cancer Ther"},{"key":"BFgt201441_CR29","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1158\/0008-5472.CAN-09-3690","volume":"70","author":"J Vincent","year":"2010","unstructured":"Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 2010; 70: 3052\u20133061.","journal-title":"Cancer Res"},{"key":"BFgt201441_CR30","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248\u2013254.","journal-title":"Anal Biochem"},{"key":"BFgt201441_CR31","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1038\/mt.2009.198","volume":"17","author":"H Eixarch","year":"2009","unstructured":"Eixarch H, Gomez A, Kadar E, George M, Martinez N, Espejo C et al. Transgene expression levels determine the immunogenicity of transduced hematopoietic grafts in partially myeloablated mice. Mol Ther 2009; 17: 1904\u20131909.","journal-title":"Mol Ther"}],"container-title":["Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gt201441.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201441","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201441.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T12:08:56Z","timestamp":1648555736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gt201441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,8]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["BFgt201441"],"URL":"https:\/\/doi.org\/10.1038\/gt.2014.41","relation":{},"ISSN":["0969-7128","1476-5462"],"issn-type":[{"value":"0969-7128","type":"print"},{"value":"1476-5462","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,8]]},"assertion":[{"value":"6 September 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2014","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2014","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}