{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:59:13Z","timestamp":1790258353862,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2002,10,3]],"date-time":"2002-10-03T00:00:00Z","timestamp":1033603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The P\u2010glyprotein (P\u2010gp), which is a membrane channel encoded by the <jats:italic>MDR1<\/jats:italic> gene, represents a possible explanation for multidrug resistance in human hepatoblastoma (HB). P\u2010gp shows up\u2010regulation in tumor cells after chemotherapy; however, to date, its exact role in HB has not been described. The authors investigated the role of the <jats:italic>MDR1<\/jats:italic> gene in the clinical course of patients with HB and in an in vivo model of HB. They also studied the effects of the <jats:italic>MDR1<\/jats:italic> antagonizer PSC 833 on chemotherapy in mice xenotransplanted with HB.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Resected tumor specimens, including both primary tumors and recurrent tumors, from a child suffering from HB were investigated histologically. Cell suspensions from the originally removed tumor were incorporated subcutaneously into nude mice. Animals were treated with cisplatin (CDDP) plus PSC 833. <jats:italic>MDR1<\/jats:italic> gene expression levels in the different resected tumors from the patient and in the xenotransplants after treatment were determined with polymerase chain reaction analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>MDR1<\/jats:italic> gene expression was increased in the patient's tumors after every course of chemotherapy from 30% to &gt; 190%. In the xenotransplants, <jats:italic>MDR1<\/jats:italic> gene expression was enhanced significantly after chemotherapy (<jats:italic>P<\/jats:italic><jats:sub>CDDP<\/jats:sub> = 0.008; <jats:italic>P<\/jats:italic><jats:sub>CDDP+PSC<\/jats:sub> = 0.002). Tumor volumes (<jats:italic>P<\/jats:italic> &lt; 0.001) and serum \u03b1\u2010fetoprotein levels (<jats:italic>P<\/jats:italic> = 0.0002) were significantly lower in the animals that were treated with CDDP + PSC compared with the animals that were treated with CDDP alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The current results suggest that <jats:italic>MDR1<\/jats:italic> gene expression and P\u2010gp are a potential mechanism of drug resistance in HB. The chemosensitizer PSC 833 significantly improved the effects of chemotherapy in animals xenotransplanted with HB. These data encourage further studies concerning the role of chemosensitizers in overcoming multidrug resistance in patients with HB. Cancer 2002;95:1795\u2013801. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10858<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10858","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T01:58:50Z","timestamp":1034128730000},"page":"1795-1801","source":"Crossref","is-referenced-by-count":36,"title":["The role of the <i>MDR1<\/i> gene in the development of multidrug resistance in human hepatoblastoma"],"prefix":"10.1002","volume":"95","author":[{"given":"Steven","family":"Warmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Hunger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Teichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peer","family":"Flemming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus Friedrich","family":"Gratz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,10,3]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(91)90677-L"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19971219)74:6<593::AID-IJC6>3.0.CO;2-P"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(95)90762-9"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)00095-6"},{"key":"e_1_2_5_6_2","first-page":"3127","article-title":"Altered expression of resistance associated genes in hepatoblastoma xenografts incorporated in mice following treatment with doxorubicin or cisplatin","volume":"18","author":"Bader P","year":"1998","journal-title":"Anticancer Res."},{"key":"e_1_2_5_7_2","first-page":"559","article-title":"Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines","volume":"15","author":"Minemura M","year":"1999","journal-title":"Int J Oncol."},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.2.116"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01008030"},{"key":"e_1_2_5_10_2","first-page":"426","article-title":"Expression of PKC isoenzyme and MDR\u2010associated genes in primary and relapsed state AML","volume":"10","author":"Beck J","year":"1996","journal-title":"Leukemia."},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00057-3"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00100-1"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00111-6"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00091-3"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.3109\/02841869509093961"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000101)85:1<131::AID-IJC23>3.0.CO;2-R"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1043805"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1995.tb03312.x"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(96)90242-0"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981201)83:11<2400::AID-CNCR21>3.0.CO;2-6"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1996.tb03157.x"},{"key":"e_1_2_5_22_2","unstructured":"Dawson\u2010SaundersB TrappRE.Basic and clinical biostatistics. 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