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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0079744,
umls-concept:C0164786,
umls-concept:C0185117,
umls-concept:C0220901,
umls-concept:C0237881,
umls-concept:C0750502,
umls-concept:C0812228,
umls-concept:C1280500,
umls-concept:C1337109,
umls-concept:C1710082,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2010-9-7
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pubmed:abstractText |
The inhibitor of apoptosis protein (IAP) family member X-linked inhibitor of apoptosis protein (XIAP) is essential for cell survival in lymphoma. However, the role of XIAP overexpression in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Therefore, we analysed the expression of XIAP protein and its clinicopathological correlation in a large cohort of DLBCLs by immunohistochemistry in a tissue micro-array format. XIAP was found to be overexpressed in 55% of DLBCLs and significantly associated with poor clinical outcome (p = 0.0421). To further elucidate the role of XIAP in DLBCL and the inter-relationship with PI3-kinase/AKT signalling, we conducted several in vitro studies using a panel of DLBCL cell lines. We found that pharmacological inhibition of XIAP led to caspase-dependent apoptosis in DLBCL cells. We also detected an inter-relationship between XIAP expression and activated AKT in DLBCL cells that may explain cellular resistance to PI3-kinase/AKT inhibition-mediated apoptosis. Finally, this anti-apoptotic effect was overcome by simultaneous pharmacological inhibition of XIAP and PI3-kinase/AKT signalling leading to a more potent synergistically induced apoptosis. In summary, our data suggest that XIAP expression is a poor prognostic factor in DLBCL and the XIAP-AKT relationship should be explored further as a potential therapeutic target in DLBCL.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/embelin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1096-9896
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pubmed:author |
pubmed-author:AbubakerJehadJ,
pubmed-author:AhmedMaqboolM,
pubmed-author:AhmedSaeeda OSO,
pubmed-author:AjarimDahishD,
pubmed-author:Al-DayelFouadF,
pubmed-author:Al-KurayaKhawla SKS,
pubmed-author:BaviPrashant PPP,
pubmed-author:BuRongR,
pubmed-author:HussainAzhar RAR,
pubmed-author:SultanaMeharM,
pubmed-author:UddinShahabS
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pubmed:copyrightInfo |
Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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pubmed:issnType |
Electronic
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pubmed:volume |
222
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
180-90
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20632385-Aged,
pubmed-meshheading:20632385-Antineoplastic Agents,
pubmed-meshheading:20632385-Apoptosis,
pubmed-meshheading:20632385-Benzoquinones,
pubmed-meshheading:20632385-Caspases,
pubmed-meshheading:20632385-Cell Division,
pubmed-meshheading:20632385-Chromones,
pubmed-meshheading:20632385-Drug Evaluation, Preclinical,
pubmed-meshheading:20632385-Drug Resistance, Neoplasm,
pubmed-meshheading:20632385-Enzyme Activation,
pubmed-meshheading:20632385-Enzyme Inhibitors,
pubmed-meshheading:20632385-Female,
pubmed-meshheading:20632385-Humans,
pubmed-meshheading:20632385-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:20632385-Male,
pubmed-meshheading:20632385-Middle Aged,
pubmed-meshheading:20632385-Morpholines,
pubmed-meshheading:20632385-Neoplasm Proteins,
pubmed-meshheading:20632385-Neoplasm Staging,
pubmed-meshheading:20632385-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20632385-Prognosis,
pubmed-meshheading:20632385-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20632385-Signal Transduction,
pubmed-meshheading:20632385-Survival Analysis,
pubmed-meshheading:20632385-Tumor Cells, Cultured,
pubmed-meshheading:20632385-Tumor Markers, Biological,
pubmed-meshheading:20632385-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2010
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pubmed:articleTitle |
Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling.
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pubmed:affiliation |
Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
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pubmed:publicationType |
Journal Article
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