{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:25:16Z","timestamp":1773296716323,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T00:00:00Z","timestamp":1358985600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"DOI":"10.1038\/cddis.2012.200","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T15:05:39Z","timestamp":1359039939000},"page":"e471-e471","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms"],"prefix":"10.1038","volume":"4","author":[{"given":"N","family":"Charette","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"De Saeger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Horsmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Leclercq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"St\u00e4rkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,1,24]]},"reference":[{"key":"BFcddis2012200_CR1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","volume":"365","author":"HB El-Serag","year":"2011","unstructured":"El-Serag HB . Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118\u20131127.","journal-title":"N Engl J Med"},{"key":"BFcddis2012200_CR2","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA . Hallmarks of cancer: the next generation. Cell 2011; 144: 646\u2013674.","journal-title":"Cell"},{"key":"BFcddis2012200_CR3","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3748\/wjg.15.513","volume":"15","author":"I Fabregat","year":"2009","unstructured":"Fabregat I . Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol 2009; 15: 513\u2013520.","journal-title":"World J Gastroenterol"},{"key":"BFcddis2012200_CR4","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1172\/JCI34359","volume":"118","author":"A Ashkenazi","year":"2008","unstructured":"Ashkenazi A, Herbst RS . To kill a tumor cell: the potential of proapoptotic receptor agonists. J Clin Invest 2008; 118: 1979\u20131990.","journal-title":"J Clin Invest"},{"issue":"Suppl 1","key":"BFcddis2012200_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1440-1746.2010.06582.x","volume":"26","author":"JM Schattenberg","year":"2011","unstructured":"Schattenberg JM, Schuchmann M, Galle PR . Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling pathways. J Gastroenterol Hepatol 2011; 26 (Suppl 1): 213\u2013219.","journal-title":"J Gastroenterol Hepatol"},{"key":"BFcddis2012200_CR6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/sj.cgt.7700792","volume":"12","author":"L Zhang","year":"2005","unstructured":"Zhang L, Fang B . Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 2005; 12: 228\u2013237.","journal-title":"Cancer Gene Ther"},{"key":"BFcddis2012200_CR7","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.1172\/JCI31457","volume":"117","author":"DF Calvisi","year":"2007","unstructured":"Calvisi DF, Ladu S, Gorden A, Farina M, Lee JS, Conner EA et al. Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest 2007; 117: 2713\u20132722.","journal-title":"J Clin Invest"},{"key":"BFcddis2012200_CR8","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1053\/j.gastro.2008.08.008","volume":"135","author":"A Villanueva","year":"2008","unstructured":"Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135: 1972\u20131983 1983.","journal-title":"Gastroenterology"},{"key":"BFcddis2012200_CR9","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1053\/j.gastro.2006.01.006","volume":"130","author":"DF Calvisi","year":"2006","unstructured":"Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS et al. Ubiquitous activation of Ras and Jak\/Stat pathways in human HCC. Gastroenterology 2006; 130: 1117\u20131128.","journal-title":"Gastroenterology"},{"key":"BFcddis2012200_CR10","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.canlet.2008.08.018","volume":"273","author":"KH Tam","year":"2009","unstructured":"Tam KH, Yang ZF, Lau CK, Lam CT, Pang RW, Poon RT . Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma. Cancer Lett 2009; 273: 201\u2013209.","journal-title":"Cancer Lett"},{"key":"BFcddis2012200_CR11","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s00280-010-1463-1","volume":"67","author":"RP Sahu","year":"2011","unstructured":"Sahu RP, Batra S, Kandala PK, Brown TL, Srivastava SK . The role of K-ras gene mutation in TRAIL-induced apoptosis in pancreatic and lung cancer cell lines. Cancer Chemother Pharmacol 2011; 67: 481\u2013487.","journal-title":"Cancer Chemother Pharmacol"},{"key":"BFcddis2012200_CR12","doi-asserted-by":"publisher","first-page":"22263","DOI":"10.1074\/jbc.270.38.22263","volume":"270","author":"M Marom","year":"1995","unstructured":"Marom M, Haklai R, Ben-Baruch G, Marciano D, Egozi Y, Kloog Y . Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid. J Biol Chem 1995; 270: 22263\u201322270.","journal-title":"J Biol Chem"},{"key":"BFcddis2012200_CR13","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00280-009-1027-4","volume":"65","author":"AM Tsimberidou","year":"2010","unstructured":"Tsimberidou AM, Rudek MA, Hong D, Ng CS, Blair J, Goldsweig H et al. Phase 1 first-in-human clinical study of S-trans,trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors. Cancer Chemother Pharmacol 2010; 65: 235\u2013241.","journal-title":"Cancer Chemother Pharmacol"},{"key":"BFcddis2012200_CR14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1042\/CS20070152","volume":"114","author":"MA da Silva","year":"2008","unstructured":"da Silva MA, Saliez A, Leclercq I, Horsmans Y, Starkel P . Inhibition of the Ras oncoprotein reduces proliferation of hepatocytes in vitro and in vivo in rats. Clin Sci (Lond) 2008; 114: 73\u201383.","journal-title":"Clin Sci (Lond)"},{"key":"BFcddis2012200_CR15","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.ejca.2009.04.014","volume":"45","author":"T Schneider-Merck","year":"2009","unstructured":"Schneider-Merck T, Borbath I, Charette N, De SC, Abarca J, Leclercq I et al. The Ras inhibitor farnesylthiosalicyclic acid (FTS) prevents nodule formation and development of preneoplastic foci of altered hepatocytes in rats. Eur J Cancer 2009; 45: 2050\u20132060.","journal-title":"Eur J Cancer"},{"key":"BFcddis2012200_CR16","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1002\/mc.20849","volume":"51","author":"P Starkel","year":"2012","unstructured":"Starkel P, Charette N, Borbath I, Schneider-Merck T, De Saeger C, Abarca J et al. Ras inhibition in hepatocarcinoma by S-trans-trans-farnesylthiosalicyclic acid: Association of its tumor preventive effect with cell proliferation, cell cycle events, and angiogenesis. Mol Carcinog 2012; 51: 816\u2013825.","journal-title":"Mol Carcinog"},{"key":"BFcddis2012200_CR17","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/1476-4598-9-256","volume":"9","author":"N Charette","year":"2010","unstructured":"Charette N, De SC, Lannoy V, Horsmans Y, Leclercq I, Starkel P . Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition. Mol Cancer 2010; 9: 256.","journal-title":"Mol Cancer"},{"key":"BFcddis2012200_CR18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1471-2210-8-8","volume":"8","author":"SK Bopp","year":"2008","unstructured":"Bopp SK, Lettieri T . Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line. BMC Pharmacol 2008; 8: 8.","journal-title":"BMC Pharmacol"},{"key":"BFcddis2012200_CR19","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1158\/1535-7163.MCT-06-0193","volume":"5","author":"R Blum","year":"2006","unstructured":"Blum R, Jacob-Hirsch J, Rechavi G, Kloog Y . Suppression of survivin expression in glioblastoma cells by the Ras inhibitor farnesylthiosalicylic acid promotes caspase-dependent apoptosis. Mol Cancer Ther 2006; 5: 2337\u20132347.","journal-title":"Mol Cancer Ther"},{"key":"BFcddis2012200_CR20","doi-asserted-by":"publisher","first-page":"3872","DOI":"10.1158\/1078-0432.CCR-08-1946","volume":"15","author":"T Satoh","year":"2009","unstructured":"Satoh T, Okamoto I, Miyazaki M, Morinaga R, Tsuya A, Hasegawa Y et al. Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors. Clin Cancer Res 2009; 15: 3872\u20133880.","journal-title":"Clin Cancer Res"},{"key":"BFcddis2012200_CR21","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1074\/jbc.M410660200","volume":"280","author":"RF Kelley","year":"2005","unstructured":"Kelley RF, Totpal K, Lindstrom SH, Mathieu M, Billeci K, Deforge L et al. Receptor-selective mutants of apoptosis-inducing ligand 2\/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling. J Biol Chem 2005; 280: 2205\u20132212.","journal-title":"J Biol Chem"},{"key":"BFcddis2012200_CR22","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1158\/1078-0432.CCR-07-1416","volume":"14","author":"SJ Hotte","year":"2008","unstructured":"Hotte SJ, Hirte HW, Chen EX, Siu LL, Le LH, Corey A et al. A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin Cancer Res 2008; 14: 3450\u20133455.","journal-title":"Clin Cancer Res"},{"key":"BFcddis2012200_CR23","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1093\/annonc\/mdp292","volume":"21","author":"HA Wakelee","year":"2010","unstructured":"Wakelee HA, Patnaik A, Sikic BI, Mita M, Fox NL, Miceli R et al. Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol 2010; 21: 376\u2013381.","journal-title":"Ann Oncol"},{"key":"BFcddis2012200_CR24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1365-2567.2009.03058.x","volume":"127","author":"C Falschlehner","year":"2009","unstructured":"Falschlehner C, Schaefer U, Walczak H . Following TRAIL's path in the immune system. Immunology 2009; 127: 145\u2013154.","journal-title":"Immunology"},{"key":"BFcddis2012200_CR25","doi-asserted-by":"publisher","first-page":"5000","DOI":"10.1158\/1078-0432.CCR-08-0746","volume":"14","author":"AC Mita","year":"2008","unstructured":"Mita AC, Mita MM, Nawrocki ST, Giles FJ . Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res 2008; 14: 5000\u20135005.","journal-title":"Clin Cancer Res"},{"key":"BFcddis2012200_CR26","doi-asserted-by":"publisher","first-page":"6264","DOI":"10.3748\/wjg.v13.i46.6264","volume":"13","author":"CP Ye","year":"2007","unstructured":"Ye CP, Qiu CZ, Huang ZX, Su QC, Zhuang W, Wu RL et al. Relationship between survivin expression and recurrence, and prognosis in hepatocellular carcinoma. World J Gastroenterol 2007; 13: 6264\u20136268.","journal-title":"World J Gastroenterol"},{"key":"BFcddis2012200_CR27","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3748\/wjg.v11.i2.193","volume":"11","author":"DJ Dai","year":"2005","unstructured":"Dai DJ, Lu CD, Lai RY, Guo JM, Meng H, Chen WS et al. Survivin antisense compound inhibits proliferation and promotes apoptosis in liver cancer cells. World J Gastroenterol 2005; 11: 193\u2013199.","journal-title":"World J Gastroenterol"},{"key":"BFcddis2012200_CR28","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/ijc.25367","volume":"128","author":"A Biran","year":"2011","unstructured":"Biran A, Brownstein M, Haklai R, Kloog Y . Downregulation of survivin and aurora A by histone deacetylase and RAS inhibitors: a new drug combination for cancer therapy. Int J Cancer 2011; 128: 691\u2013701.","journal-title":"Int J Cancer"},{"key":"BFcddis2012200_CR29","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.drudis.2011.04.001","volume":"16","author":"JR Kanwar","year":"2011","unstructured":"Kanwar JR, Kamalapuram SK, Kanwar RK . Targeting survivin in cancer: the cell-signalling perspective. Drug Discov Today 2011; 16: 485\u2013494.","journal-title":"Drug Discov Today"},{"key":"BFcddis2012200_CR30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1158\/1535-7163.MCT-06-0560","volume":"6","author":"AV Sarthy","year":"2007","unstructured":"Sarthy AV, Morgan-Lappe SE, Zakula D, Vernetti L, Schurdak M, Packer JC et al. Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells. Mol Cancer Ther 2007; 6: 269\u2013276.","journal-title":"Mol Cancer Ther"},{"key":"BFcddis2012200_CR31","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1158\/0008-5472.CAN-06-4287","volume":"67","author":"R Blum","year":"2007","unstructured":"Blum R, Elkon R, Yaari S, Zundelevich A, Jacob-Hirsch J, Rechavi G et al. Gene expression signature of human cancer cell lines treated with the ras inhibitor salirasib (S-farnesylthiosalicylic acid). Cancer Res 2007; 67: 3320\u20133328.","journal-title":"Cancer Res"},{"key":"BFcddis2012200_CR32","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.1038\/cddis.2012.24","volume":"3","author":"L Goldberg","year":"2012","unstructured":"Goldberg L, Israeli R, Kloog Y . FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice. Cell Death Dis 2012; 3: e284.","journal-title":"Cell Death Dis"},{"key":"BFcddis2012200_CR33","doi-asserted-by":"publisher","first-page":"5189","DOI":"10.1158\/1078-0432.CCR-09-3389","volume":"16","author":"KF Chen","year":"2010","unstructured":"Chen KF, Tai WT, Liu TH, Huang HP, Lin YC, Shiau CW et al. Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3. Clin Cancer Res 2010; 16: 5189\u20135199.","journal-title":"Clin Cancer Res"},{"key":"BFcddis2012200_CR34","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402\u2013408.","journal-title":"Methods"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cddis2012200.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cddis2012200","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2012200.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T23:56:48Z","timestamp":1672963008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2012200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,24]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,1]]}},"alternative-id":["BFcddis2012200"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2012.200","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,24]]},"assertion":[{"value":"8 October 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2013","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"}}]}}