{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:09:12Z","timestamp":1761822552360,"version":"3.37.3"},"reference-count":36,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2003,6]]},"DOI":"10.1124\/jpet.103.049379","type":"journal-article","created":{"date-parts":[[2003,5,20]],"date-time":"2003-05-20T00:36:50Z","timestamp":1053391010000},"page":"1098-1103","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"title":["Melphalan Antitumor Efficacy and Hepatotoxicity: The Effect of Variable Infusion Duration in the Hepatic Artery"],"prefix":"10.1016","volume":"305","author":[{"given":"Joost","family":"Rothbarth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruud A.","family":"Woutersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf W.","family":"Sparidans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis J.H.","family":"van de Velde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard J.","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"doi-asserted-by":"crossref","unstructured":"Aigner KR, Walther H, and Link KH (1988) Isolated liver perfusion with MMC\/5-FU: surgical technique, pharmacokinetics, clinical results. Contr Oncol 29: 229-246.","key":"10.1124\/jpet.103.049379_bib1","DOI":"10.1159\/000415979"},{"unstructured":"Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, and Bachenheimer LC (2000) A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res 6: 3062-3070.","key":"10.1124\/jpet.103.049379_bib2"},{"doi-asserted-by":"crossref","unstructured":"Alexander HR Jr, Bartlett DL, Libutti SK, Fraker DL, Moser T, and Rosenberg SA (1998) Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver. J Clin Oncol 16: 1479-1489.","key":"10.1124\/jpet.103.049379_bib3","DOI":"10.1200\/JCO.1998.16.4.1479"},{"doi-asserted-by":"crossref","unstructured":"Bartlett DL, Libutti SK, Figg WD, Fraker DL, and Alexander HR (2001) Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer. Surgery 129: 176-187.","key":"10.1124\/jpet.103.049379_bib4","DOI":"10.1067\/msy.2001.110365"},{"unstructured":"Breedis C and Young G (1954) The blood supply of neoplasms in the liver. Am J Pathol 30: 969-985.","key":"10.1124\/jpet.103.049379_bib5"},{"doi-asserted-by":"crossref","unstructured":"Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, and Steinberg SM (1987) A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 206: 685-693.","key":"10.1124\/jpet.103.049379_bib6","DOI":"10.1097\/00000658-198712000-00001"},{"doi-asserted-by":"crossref","unstructured":"Cho KJ and Lunderquist A (1983) The peribiliary vascular plexus: the microvascular architecture of the bile duct in the rabbit and in clinical cases. Radiology 147: 357-364.","key":"10.1124\/jpet.103.049379_bib7","DOI":"10.1148\/radiology.147.2.6836115"},{"doi-asserted-by":"crossref","unstructured":"Daemen MJ, Thijssen HH, van Essen H, Vervoort-Peters HT, Prinzen FW, Struyker Boudier HA, and Smits JF (1989) Liver blood flow measurement in the rat. The electromagnetic versus the microsphere and the clearance methods. J Pharmacol Methods 21: 287-297.","key":"10.1124\/jpet.103.049379_bib8","DOI":"10.1016\/0160-5402(89)90066-1"},{"doi-asserted-by":"crossref","unstructured":"Frank AJ, Proctor SJ, and Tilby MJ (1996) Detection and quantification of melphalan-DNA adducts at the single cell level in hematopoietic tumor cells. Blood 88: 977-984.","key":"10.1124\/jpet.103.049379_bib9","DOI":"10.1182\/blood.V88.3.977.977"},{"unstructured":"Goodman DG, Maronpot RR, Newberne PM, Popp JA, and Squire RA (1994) Proliferative and selected other lesions in the liver of rats, in Standardized System of Nomenclature and Diagnostic Criteria, Guides for Toxicologic Pathology, STP\/ARP\/AFIP, The Armed Forces Institute of Pathology, The American Registry of Pathology and the Society of Toxicologic Pathology, Washington, DC","key":"10.1124\/jpet.103.049379_bib10"},{"unstructured":"Hansson J, Lewensohn R, Ringborg U, and Nilsson B (1987) Formation and removal of DNA cross-links induced by melphalan and nitrogen mustard in relation to drug-induced cytotoxicity in human melanoma cells. Cancer Res 47: 2631-2637.","key":"10.1124\/jpet.103.049379_bib11"},{"doi-asserted-by":"crossref","unstructured":"Hohn D, Melnick J, Stagg R, Altman D, Friedman M, Ignoffo R, Ferrell L, and Lewis B (1985) Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine. J Clin Oncol 3: 98-102.","key":"10.1124\/jpet.103.049379_bib12","DOI":"10.1200\/JCO.1985.3.1.98"},{"doi-asserted-by":"crossref","unstructured":"Hohn DC, Stagg RJ, Friedman MA, Hannigan JF Jr, Rayner A, Ignoffo RJ, Acord P, and Lewis BJ (1989) A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. J Clin Oncol 7: 1646-1654.","key":"10.1124\/jpet.103.049379_bib13","DOI":"10.1200\/JCO.1989.7.11.1646"},{"doi-asserted-by":"crossref","unstructured":"Kemeny N, Daly J, Reichman B, Geller N, Botet J, and Oderman P (1987) Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med 107: 459-465.","key":"10.1124\/jpet.103.049379_bib14","DOI":"10.7326\/0003-4819-107-4-459"},{"doi-asserted-by":"crossref","unstructured":"Kemeny N, Seiter K, Niedzwiecki D, Chapman D, Sigurdson E, Cohen A, Botet J, Oderman P, and Murray P (1992) A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. Cancer 69: 327-334.","key":"10.1124\/jpet.103.049379_bib15","DOI":"10.1002\/1097-0142(19920115)69:2<327::AID-CNCR2820690209>3.0.CO;2-U"},{"doi-asserted-by":"crossref","unstructured":"Kemeny NE (1995) Regional chemotherapy of colorectal cancer. Eur J Cancer 31A: 1271-1276.","key":"10.1124\/jpet.103.049379_bib16","DOI":"10.1016\/0959-8049(95)00162-C"},{"unstructured":"Kohn KW (1981) Molecular mechanisms of crosslinking of alkylating agents and latinum complexes., in Molecular Actions and Targets for Cancer Chemotherapeutic Agents (Sartorelli AC, Lazo JS, and Bertino JR eds) pp 3-16, Academic, San Diego.","key":"10.1124\/jpet.103.049379_bib17"},{"doi-asserted-by":"crossref","unstructured":"Lorenz M and Muller HH (2000) Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 18: 243-254.","key":"10.1124\/jpet.103.049379_bib18","DOI":"10.1200\/JCO.2000.18.2.243"},{"doi-asserted-by":"crossref","unstructured":"Lorenz M, Mueller HH, Mattes E, Gassel HJ, Junginger T, Saeger HD, Schramm H, Staib-Sebler E, Vetter G, Heinrich S, and Kohne CH (2001) Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5-fluorouracil and folinic acid for liver metastases from colorectal carcinomas. Ann Oncol 12: 321-325.","key":"10.1124\/jpet.103.049379_bib19","DOI":"10.1023\/A:1011181700258"},{"doi-asserted-by":"crossref","unstructured":"Marinelli A, van Dierendonck JH, van Brakel GM, Irth H, Kuppen PJ, Tjaden UR, and van de Velde CJ (1991) Increasing the effective concentration of melphalan in experimental rat liver tumours: comparison of isolated liver perfusion and hepatic artery infusion. Br J Cancer 64: 1069-1075.","key":"10.1124\/jpet.103.049379_bib20","DOI":"10.1038\/bjc.1991.466"},{"doi-asserted-by":"crossref","unstructured":"Marquet RL, Westbroek DL, and Jeekel J (1984) Interferon treatment of a transplantable rat colon adenocarcinoma: importance of tumor site. Int J Cancer 33: 689-692.","key":"10.1124\/jpet.103.049379_bib21","DOI":"10.1002\/ijc.2910330521"},{"doi-asserted-by":"crossref","unstructured":"Meta-Analysis Group in Cancer (1996) Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst 88: 252-258.","key":"10.1124\/jpet.103.049379_bib22","DOI":"10.1093\/jnci\/88.5.252"},{"unstructured":"Mitra SK (1966) The terminal distribution of the hepatic artery with special reference to arterio-portal anastomosis. J Anat 100: 651-663.","key":"10.1124\/jpet.103.049379_bib23"},{"doi-asserted-by":"crossref","unstructured":"Northover JM and Terblanche J (1979) A new look at the arterial supply of the bile duct in man and its surgical implications. Br J Surg 66: 379-384.","key":"10.1124\/jpet.103.049379_bib24","DOI":"10.1002\/bjs.1800660603"},{"doi-asserted-by":"crossref","unstructured":"Pang KS and Terrell JA (1981) Retrograde perfusion to probe the heterogeneous distribution of hepatic drug metabolizing enzymes in rats. J Pharmacol Exp Ther 216: 339-346.","key":"10.1124\/jpet.103.049379_bib25","DOI":"10.1016\/S0022-3565(25)32424-9"},{"unstructured":"Rappaport AM (1980) Hepatic blood flow: morphologic aspects and physiologic regulation. Int Rev Physiol 21: 1-63.","key":"10.1124\/jpet.103.049379_bib26"},{"doi-asserted-by":"crossref","unstructured":"Rothbarth J, Sparidans RW, Beijnen JH, Kool LJ, Putter H, van de Velde CJ, and Mulder GJ (2002a) Reduced Liver Uptake of Arterially Infused Melphalan during Retrograde Rat Liver Perfusion with Unaffected Liver Tumor Uptake. J Pharmacol Exp Ther 303: 736-740.","key":"10.1124\/jpet.103.049379_bib27","DOI":"10.1124\/jpet.102.037895"},{"doi-asserted-by":"crossref","unstructured":"Rothbarth J, Vahrmeijer AL, and Mulder GJ (2002b) Modulation of cytostatic efficacy of melphalan by glutathione: mechanisms and efficacy. Chem Biol Interact 140: 93-107.","key":"10.1124\/jpet.103.049379_bib28","DOI":"10.1016\/S0009-2797(02)00014-5"},{"doi-asserted-by":"crossref","unstructured":"Rougier P, Laplanche A, Huguier M, Hay JM, Ollivier JM, Escat J, Salmon R, Julien M, Roullet Audy JC, Gallot D, et al. (1992) Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol 10: 1112-1118.","key":"10.1124\/jpet.103.049379_bib29","DOI":"10.1200\/JCO.1992.10.7.1112"},{"doi-asserted-by":"crossref","unstructured":"Sigurdson ER, Ridge JA, Kemeny N, and Daly JM (1987) Tumor and liver drug uptake following hepatic artery and portal vein infusion. J Clin Oncol 5: 1836-1840.","key":"10.1124\/jpet.103.049379_bib30","DOI":"10.1200\/JCO.1987.5.11.1836"},{"doi-asserted-by":"crossref","unstructured":"Tanaka N, Tanaka K, Nagashima Y, Kondo M, and Sekihara H (1999) Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride-induced acute hepatic injury. Gastroenterology 117: 173-180.","key":"10.1124\/jpet.103.049379_bib31","DOI":"10.1016\/S0016-5085(99)70565-2"},{"doi-asserted-by":"crossref","unstructured":"Tilby MJ, Newell DR, Viner C, Selby PJ, and Dean CJ (1993) Application of a sensitive immunoassay to the study of DNA adducts formed in peripheral blood mononuclear cells of patients undergoing high-dose melphalan therapy. Eur J Cancer 29A: 681-686.","key":"10.1124\/jpet.103.049379_bib32","DOI":"10.1016\/S0959-8049(05)80346-6"},{"unstructured":"Vahrmeijer AL, van Dierendonck JH, Keizer HJ, Beijnen JH, Tollenaar RA, Pijl ME, Marinelli A, Kuppen PJ, van Bockel JH, Mulder GJ, and van de Velde CJ (2000) Increased local cytostatic drug exposure by isolated hepatic perfusion: a phase I clinical and pharmacologic evaluation of treatment with high dose melphalan in patients with colorectal cancer confined to the liver. Br J Cancer 82: 1539-1546.","key":"10.1124\/jpet.103.049379_bib33"},{"doi-asserted-by":"crossref","unstructured":"Vahrmeijer AL, van Dierendonck JH, and van de Velde CJ (1995) Treatment of colorectal cancer metastases confined to the liver. Eur J Cancer 31A: 1238-1242.","key":"10.1124\/jpet.103.049379_bib34","DOI":"10.1016\/0959-8049(95)00214-4"},{"doi-asserted-by":"crossref","unstructured":"Wang LQ, Persson BG, Bergqvist L, and Bengmark S (1994) Influence of dearterialization on distribution of absolute tumor blood flow between hepatic artery and portal vein. Cancer 74: 2454-2459.","key":"10.1124\/jpet.103.049379_bib35","DOI":"10.1002\/1097-0142(19941101)74:9<2454::AID-CNCR2820740911>3.0.CO;2-F"},{"doi-asserted-by":"crossref","unstructured":"Watanabe Y, Puschel GP, Gardemann A, and Jungermann K (1994) Presinusoidal and proximal intrasinusoidal confluence of hepatic artery and portal vein in rat liver: functional evidence by orthograde and retrograde bivascular perfusion. Hepatology 19: 1198-1207.","key":"10.1124\/jpet.103.049379_bib36","DOI":"10.1002\/hep.1840190518"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524307426?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524307426?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.103.049379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T14:25:22Z","timestamp":1739975122000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524307426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["S0022356524307426"],"URL":"https:\/\/doi.org\/10.1124\/jpet.103.049379","relation":{},"ISSN":["0022-3565"],"issn-type":[{"type":"print","value":"0022-3565"}],"subject":[],"published":{"date-parts":[[2003,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Melphalan Antitumor Efficacy and Hepatotoxicity: The Effect of Variable Infusion Duration in the Hepatic Artery","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.103.049379","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2003 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}