Source:http://linkedlifedata.com/resource/pubmed/id/21506127
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2011-6-7
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| pubmed:abstractText |
NF-?B is frequently over-expressed in a variety of non-Hodgkin's lymphomas (NHLs) and has been implicated in lymphomagenesis; however, its role in diffuse large B cell lymphoma (DLBCL) as a prognostic biomarker has not been fully elucidated. Therefore, we investigated the role of NF-?B and its association with clinicopathological features in a tissue microarray cohort of 230 DLBCL patient samples. We then elucidated the role of NF-?B inhibition on cell viability and apoptosis in vitro, using DLBCL cell lines. Using immunohistochemistry, NF-?B was detected in 25.6% (52/203) DLBCL tumours, was associated with activated B cell (ABC) phenotype (p = 0.0054), Epstein-Barr virus (EBV; p = 0.0080) and over-expression of the anti-apoptotic marker XIAP (p = 0.0013). DLBCL cases with nuclear expression of NF-?B showed a significantly poorer overall survival as compared to those without NF-?B expression (p = 0.0236). In a multivariate analysis using a Cox proportional hazard model for IPI and NF-?B expression, the relative risk was 2.97 for high NF-?B expression (95% CI 1.27-6.94; p = 0.0113) and 7.55 for the high-IPI group (95% CI 3.34-18.35; p < 0.0001). In vitro, Bay 11-7085 inhibited constitutively active NF-?B expression in a dose-dependent manner and inhibition of NF-?B also down-regulated expression of the downstream target gene products Bcl-2, Bcl-XL (BCL2L1), XIAP and Survivin, leading to apoptosis via activation of the mitochondrial apoptotic pathway. NF-?B over-expression was found to be an independent prognostic marker for poor survival in DLBCL. Altogether, these results suggest that NF-?B may be a useful prognostic biomarker and a potential target for therapeutic intervention in DLBCL.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(4-methylphenylsulfonyl)-2-propene...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
1096-9896
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| pubmed:author |
pubmed-author:AbubakerJehadJ,
pubmed-author:AhmedMaqboolM,
pubmed-author:AjarimDahishD,
pubmed-author:Al-DayelFouadF,
pubmed-author:Al-KurayaKhawla SKS,
pubmed-author:BaldeValorieV,
pubmed-author:BaviPrashantP,
pubmed-author:BuRongR,
pubmed-author:HussainAzhar RAR,
pubmed-author:QadriZeeshanZ,
pubmed-author:UddinShahabS
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| pubmed:copyrightInfo |
Copyright © 2011 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 |
224
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
355-66
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| pubmed:meshHeading |
pubmed-meshheading:21506127-Aged,
pubmed-meshheading:21506127-Antineoplastic Agents,
pubmed-meshheading:21506127-Apoptosis,
pubmed-meshheading:21506127-B-Lymphocytes,
pubmed-meshheading:21506127-Caspases,
pubmed-meshheading:21506127-Dose-Response Relationship, Drug,
pubmed-meshheading:21506127-Down-Regulation,
pubmed-meshheading:21506127-Enzyme Activation,
pubmed-meshheading:21506127-Female,
pubmed-meshheading:21506127-Herpesvirus 4, Human,
pubmed-meshheading:21506127-Humans,
pubmed-meshheading:21506127-Immunophenotyping,
pubmed-meshheading:21506127-Lymphocyte Activation,
pubmed-meshheading:21506127-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:21506127-Male,
pubmed-meshheading:21506127-Middle Aged,
pubmed-meshheading:21506127-NF-kappa B,
pubmed-meshheading:21506127-Nitriles,
pubmed-meshheading:21506127-Prognosis,
pubmed-meshheading:21506127-Sulfones,
pubmed-meshheading:21506127-Survival Analysis,
pubmed-meshheading:21506127-Tumor Cells, Cultured,
pubmed-meshheading:21506127-Tumor Markers, Biological
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| pubmed:year |
2011
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| pubmed:articleTitle |
The biological and clinical impact of inhibition of NF-?B-initiated apoptosis in diffuse large B cell lymphoma (DLBCL).
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| pubmed:affiliation |
Human Cancer Genomic Research, Research Center, King Fahad National Center for Children's Cancer, Riyadh, Saudi Arabia.
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| pubmed:publicationType |
Journal Article
|