{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:31:23Z","timestamp":1779309083923,"version":"3.51.4"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2010,10,28]],"date-time":"2010-10-28T00:00:00Z","timestamp":1288224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2011,8]]},"DOI":"10.1007\/s00280-010-1481-z","type":"journal-article","created":{"date-parts":[[2010,10,27]],"date-time":"2010-10-27T07:18:17Z","timestamp":1288163897000},"page":"379-388","source":"Crossref","is-referenced-by-count":24,"title":["Phase II trial of the ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehydethiosemicarbazone plus gemcitabine in patients with advanced biliary tract cancer"],"prefix":"10.1007","volume":"68","author":[{"given":"Allyson J.","family":"Ocean","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Christos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Sparano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Matulich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Kaubish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abby","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen M.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Espinoza-Delgado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Yen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen E.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,10,28]]},"reference":[{"key":"1481_CR1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3322\/caac.20006","volume":"59","author":"A Jemal","year":"2009","unstructured":"Jemal A, Siegel R, Ward E et al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225\u2013249","journal-title":"CA Cancer J Clin"},{"key":"1481_CR2","doi-asserted-by":"crossref","unstructured":"Choi BI, Han JK, Hong ST et al (2004) Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis. Clin Microbiol Rev 17:540\u201352 ( table of contents)","DOI":"10.1128\/CMR.17.3.540-552.2004"},{"key":"1481_CR3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.6004\/jnccn.2009.0030","volume":"7","author":"KY Chang","year":"2009","unstructured":"Chang KY, Chang JY, Yen Y (2009) Increasing incidence of intrahepatic cholangiocarcinoma and its relationship to chronic viral hepatitis. J Natl Compr Canc Netw 7:423\u2013427","journal-title":"J Natl Compr Canc Netw"},{"key":"1481_CR4","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1056\/NEJM199910283411807","volume":"341","author":"PC Groen de","year":"1999","unstructured":"de Groen PC, Gores GJ, LaRusso NF et al (1999) Biliary tract cancers. N Engl J Med 341:1368\u20131378","journal-title":"N Engl J Med"},{"key":"1481_CR5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/jjco\/hyi021","volume":"35","author":"JS Park","year":"2005","unstructured":"Park JS, Oh SY, Kim SH et al (2005) Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study. Jpn J Clin Oncol 35:68\u201373","journal-title":"Jpn J Clin Oncol"},{"key":"1481_CR6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/01.coc.0000135924.94955.16","volume":"27","author":"C Eng","year":"2004","unstructured":"Eng C, Ramanathan RK, Wong MK et al (2004) A phase II trial of fixed dose rate gemcitabine in patients with advanced biliary tree carcinoma. Am J Clin Oncol 27:565\u2013569","journal-title":"Am J Clin Oncol"},{"key":"1481_CR7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1023\/B:DRUG.0000011797.09549.53","volume":"22","author":"N Tsavaris","year":"2004","unstructured":"Tsavaris N, Kosmas C, Gouveris P et al (2004) Weekly gemcitabine for the treatment of biliary tract and gallbladder cancer. Invest New Drugs 22:193\u2013198","journal-title":"Invest New Drugs"},{"key":"1481_CR8","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1023\/A:1016209901417","volume":"20","author":"R Kuhn","year":"2002","unstructured":"Kuhn R, Hribaschek A, Eichelmann K et al (2002) Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and cholangio-carcinomas. Invest New Drugs 20:351\u2013356","journal-title":"Invest New Drugs"},{"key":"1481_CR9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/sj.bjc.6605211","volume":"101","author":"JW Valle","year":"2009","unstructured":"Valle JW, Wasan H, Johnson P et al (2009) Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study\u2014The UK ABC-01 Study. Br J Cancer 101:621\u2013627","journal-title":"Br J Cancer"},{"key":"1481_CR10","doi-asserted-by":"crossref","unstructured":"Valle J, Wasan H, Palmer DH et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362:1273\u201381","DOI":"10.1056\/NEJMoa0908721"},{"key":"1481_CR11","first-page":"257","volume":"53\u201354","author":"JG Cory","year":"1983","unstructured":"Cory JG, Sato A (1983) Regulation of ribonucleotide reductase activity in mammalian cells. Mol Cell Biochem 53\u201354:257\u2013266","journal-title":"Mol Cell Biochem"},{"key":"1481_CR12","first-page":"1650","volume":"58","author":"H Fan","year":"1998","unstructured":"Fan H, Villegas C, Huang A et al (1998) The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation. Cancer Res 58:1650\u20131653","journal-title":"Cancer Res"},{"key":"1481_CR13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0006-2952(94)90105-8","volume":"48","author":"JG Cory","year":"1994","unstructured":"Cory JG, Cory AH, Rappa G et al (1994) Inhibitors of ribonucleotide reductase. Comparative effects of amino- and hydroxy-substituted pyridine-2-carboxaldehyde thiosemicarbazones. Biochem Pharmacol 48:335\u2212344","journal-title":"Biochem Pharmacol"},{"key":"1481_CR14","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1021\/jm9600454","volume":"39","author":"MC Liu","year":"1996","unstructured":"Liu MC, Lin TS, Cory JG et al (1996) Synthesis and biological activity of 3- and 5-amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone. J Med Chem 39:2586\u20132593","journal-title":"J Med Chem"},{"key":"1481_CR15","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.1016\/S0021-9258(18)62745-0","volume":"245","author":"HL Elford","year":"1970","unstructured":"Elford HL, Freese M, Passamani E et al (1970) Ribonucleotide reductase and cell proliferation. I. Variations of ribonucleotide reductase activity with tumor growth rate in a series of rat hepatomas. J Biol Chem 245:5228\u20135233","journal-title":"J Biol Chem"},{"key":"1481_CR16","first-page":"1369","volume":"22","author":"B Zhou","year":"2002","unstructured":"Zhou B, Mi S, Mo X et al (2002) Time and sequence dependence of hydroxyurea in combination with gemcitabine in human KB cells. Anticancer Res 22:1369\u221277","journal-title":"Anticancer Res"},{"key":"1481_CR17","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0006-2952(99)00419-0","volume":"59","author":"RA Finch","year":"2000","unstructured":"Finch RA, Liu M, Grill SP et al (2000) Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): a potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol 59:983\u2013991","journal-title":"Biochem Pharmacol"},{"key":"1481_CR18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0065-2571(98)00017-X","volume":"39","author":"RA Finch","year":"1999","unstructured":"Finch RA, Liu MC, Cory AH et al (1999) Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP): an inhibitor of ribonucleotide reductase with antineoplastic activity. Adv Enzyme Regul 39:3\u201312","journal-title":"Adv Enzyme Regul"},{"key":"1481_CR19","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.bcp.2007.01.025","volume":"73","author":"J Sigmond","year":"2007","unstructured":"Sigmond J, Kamphuis JA, Laan AC et al (2007) The synergistic interaction of gemcitabine and cytosine arabinoside with the ribonucleotide reductase inhibitor triapine is schedule dependent. Biochem Pharmacol 73:1548\u20131557","journal-title":"Biochem Pharmacol"},{"key":"1481_CR20","first-page":"331","volume":"54","author":"Y Yen","year":"2004","unstructured":"Yen Y, Margolin K, Doroshow J et al (2004) A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer. Cancer Chemother Pharmacol 54:331\u2013342","journal-title":"Cancer Chemother Pharmacol"},{"key":"1481_CR21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/ajh.20547","volume":"81","author":"LM Foltz","year":"2006","unstructured":"Foltz LM, Dalal BI, Wadsworth LD et al (2006) Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Am J Hematol 81:210\u2013211","journal-title":"Am J Hematol"},{"key":"1481_CR22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/jnci\/92.3.205","volume":"92","author":"P Therasse","year":"2000","unstructured":"Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205\u2013216","journal-title":"J Natl Cancer Inst"},{"key":"1481_CR23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1006\/abio.1998.2890","volume":"267","author":"S Wadler","year":"1999","unstructured":"Wadler S, Zhang H, Cammer M et al (1999) Quantification of ribonucleotide reductase expression in wild-type and hydroxyurea-resistant cell lines employing in situ reverse transcriptase polymerase chain reaction and a computerized image analysis system. Anal Biochem 267:24\u201329","journal-title":"Anal Biochem"},{"key":"1481_CR24","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10637-007-9044-9","volume":"25","author":"JJ Knox","year":"2007","unstructured":"Knox JJ, Hotte SJ, Kollmannsberger C et al (2007) Phase II study of Triapine in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161). Invest New Drugs 25:471\u2013477","journal-title":"Invest New Drugs"},{"key":"1481_CR25","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10637-008-9123-6","volume":"26","author":"S Attia","year":"2008","unstructured":"Attia S, Kolesar J, Mahoney MR et al (2008) A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas. Invest New Drugs 26:369\u2013379","journal-title":"Invest New Drugs"},{"key":"1481_CR26","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10637-007-9066-3","volume":"25","author":"MJ Mackenzie","year":"2007","unstructured":"Mackenzie MJ, Saltman D, Hirte H et al (2007) A Phase II study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and gemcitabine in advanced pancreatic carcinoma. A trial of the Princess Margaret hospital Phase II consortium. Invest New Drugs 25:553\u2013558","journal-title":"Invest New Drugs"},{"key":"1481_CR27","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10637-007-9085-0","volume":"26","author":"B Ma","year":"2008","unstructured":"Ma B, Goh BC, Tan EH et al (2008) A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. Invest New Drugs 26:169\u2013173","journal-title":"Invest New Drugs"},{"key":"1481_CR28","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.leukres.2005.12.013","volume":"30","author":"KW Yee","year":"2006","unstructured":"Yee KW, Cortes J, Ferrajoli A et al (2006) Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leuk Res 30:813\u2013822","journal-title":"Leuk Res"},{"key":"1481_CR29","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S0006-2952(97)00641-2","volume":"55","author":"S Wadler","year":"1998","unstructured":"Wadler S, Horowitz R, Zhang HY et al (1998) Effects of perturbations of pools of deoxyribonucleoside triphosphates on expression of ribonucleotide reductase, a G1\/S transition state enzyme, in p53-mutated cells. Biochem Pharmacol 55:1353\u20131360","journal-title":"Biochem Pharmacol"},{"key":"1481_CR30","doi-asserted-by":"crossref","first-page":"18085","DOI":"10.1074\/jbc.M109.003020","volume":"284","author":"YW Zhang","year":"2009","unstructured":"Zhang YW, Jones TL, Martin SE et al (2009) Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. J Biol Chem 284:18085\u201318095","journal-title":"J Biol Chem"},{"key":"1481_CR31","first-page":"8256","volume":"61","author":"T Yamaguchi","year":"2001","unstructured":"Yamaguchi T, Matsuda K, Sagiya Y et al (2001) p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res 61:8256\u20138262","journal-title":"Cancer Res"},{"key":"1481_CR32","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1158\/1541-7786.MCR-07-2027","volume":"6","author":"HL Devlin","year":"2008","unstructured":"Devlin HL, Mack PC, Burich RA et al (2008) Impairment of the DNA repair and growth arrest pathways by p53R2 silencing enhances DNA damage-induced apoptosis in a p53-dependent manner in prostate cancer cells. Mol Cancer Res 6:808\u2013818","journal-title":"Mol Cancer Res"},{"key":"1481_CR33","doi-asserted-by":"crossref","unstructured":"Mortazavi A, Dearn, D, Ling, Y, Harper EJ, Phelps MA, Espinoza-Delgado I, Monk JP, Otterson GA, Grever MR, Belkaii-Saab T (2010) A phase I study of prolonged infusion of triapine in combination with fixed-dose rate of gemcitabine in patients with advanced solid tumors. Proceedings of the American Society of Clinical Oncology Abstract 53259","DOI":"10.1200\/jco.2010.28.15_suppl.2602"},{"key":"1481_CR34","doi-asserted-by":"crossref","unstructured":"Kunos CA, Waggoner S, von Gruenigen V, et al (2010) Phase I trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced cervical cancer. Clin Cancer Res 16:1298\u20131306","DOI":"10.1158\/1078-0432.CCR-09-2469"}],"container-title":["Cancer Chemotherapy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-010-1481-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00280-010-1481-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-010-1481-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T18:59:19Z","timestamp":1636743559000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00280-010-1481-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,28]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["1481"],"URL":"https:\/\/doi.org\/10.1007\/s00280-010-1481-z","relation":{},"ISSN":["0344-5704","1432-0843"],"issn-type":[{"value":"0344-5704","type":"print"},{"value":"1432-0843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,28]]}}}