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rdf:type |
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lifeskim:mentions |
umls-concept:C0002199,
umls-concept:C0009429,
umls-concept:C0016360,
umls-concept:C0105770,
umls-concept:C0205263,
umls-concept:C0556895,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1710082,
umls-concept:C1879547,
umls-concept:C2239176
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pubmed:issue |
10
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pubmed:dateCreated |
2009-5-13
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pubmed:abstractText |
Type I IFN receptor type 2 (IFNAR2) expression correlates significantly with clinical response to interferon (IFN)-alpha/5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). However, some IFNAR2-positive patients show no response to the therapy. This result suggests the possibility of other factors, which would be responsible for resistance to IFN-alpha/5-FU therapy. The aim of this study was to examine the mechanism of anti-proliferative effects of IFN-alpha/5-FU therapy and search for a biological marker of chemoresistance to such therapy. Gene expression profiling and molecular network analysis were used in the analysis of non-responders and responders with IFNAR2-positive HCC. The Wnt/beta-catenin signalling pathway contributed to resistance to IFN-alpha/5-FU therapy. Immunohistochemical analysis showed positive epithelial cell adhesion molecule (Ep-CAM) expression, the target molecule of Wnt/beta-catenin signalling, only in non-responders. In vitro studies showed that activation of Wnt/beta-catenin signalling by glycogen synthesis kinase-3 inhibitor (6-bromoindirubin-3'-oxime (BIO)) induced chemoresistance to IFN-alpha/5-FU. BrdU-based cell proliferation ELISA and cell cycle analysis showed that concurrent addition of BIO and IFN-alpha/5-FU significantly to hepatoma cell cultures reduced the inhibitory effects of the latter two on DNA synthesis and accumulation of cells in the S-phase. The results indicate that activation of Wnt/beta-catenin signalling pathway induces chemoresistance to IFN-alpha/5-FU therapy and suggest that Ep-CAM is a potentially useful marker for resistance to such therapy, especially in IFNAR2-positive cases.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-10632332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-10914738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-11130529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-11197059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-11809704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-11900229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-14702635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-14768007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15288478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15306667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15372092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15389810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15447987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15585621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15645432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15709199,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15829953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15920528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-15994935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16106266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16136080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16364680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16391861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16452319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16565970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16628664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-16831544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17045692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17139285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17300701,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17419255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17602782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17764107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17786339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-17941012,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-18006828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-18202759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-18337085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-18432252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-18519688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-6767674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-7165009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-7526796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-7691392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19401692-8163559
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/EPCAM protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/IFNAR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Interferon alpha-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1532-1827
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pubmed:author |
pubmed-author:DokiYY,
pubmed-author:DoniAA,
pubmed-author:KobayashiSS,
pubmed-author:MarubashiSS,
pubmed-author:MatsubaraKK,
pubmed-author:MatsuuraNN,
pubmed-author:MondenMM,
pubmed-author:MoriMM,
pubmed-author:MurakamiMM,
pubmed-author:NaganoHH,
pubmed-author:NodaTT,
pubmed-author:TakedaYY,
pubmed-author:TakemasaII,
pubmed-author:UmeshitaKK,
pubmed-author:WadaHH,
pubmed-author:YoshiokaSS
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1647-58
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pubmed:dateRevised |
2011-10-28
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pubmed:meshHeading |
|
