Source:http://linkedlifedata.com/resource/pubmed/id/19469019
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-5-22
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| pubmed:abstractText |
Primary effusion lymphoma (PEL) is a refractory malignancy caused by human herpes virus 8 (HHV-8) in immunocompromised individuals. The tumor cells of PEL are characterized by constitutive NF-kappaB activation. Dehydroxymethylepoxyquinomicin (DHMEQ) is a new NF-kappaB inhibitor and is effective on various tumor cells with constitutively activated NF-kappaB. Thus, in search for a new therapeutic modality of PEL, we examined the effect of DHMEQ on PEL cells. We confirmed constitutive activation of NF-kappaB with subcomponents of p50 and p65 in PEL cell lines. DHMEQ quickly and transiently abrogated NF-kappaB activation and reduced the cell viability in dose- and time-dependent manners, inducing apoptosis through activation of both mitochondrial and membrane pathways. Array analysis revealed that DHMEQ down-regulated expression levels of NF-kappaB target genes, such as interleukin-6 (IL6), Myc, chemokine (C-C motif) receptor 5 (CCR5) and NF-kappaB1, whereas it up-regulated expression levels of some genes involved in apoptosis, and cell cycle arrest. DHMEQ did not reactivate HHV-8 lytic genes, indicating that NF-kappaB inhibition by DHMEQ did not induce virus replication. DHEMQ rescued CB-17 SCID mice xenografted with PEL cells, reducing the gross appearance of effusion. Thus, DHMEQ transiently abrogated the NF-kappaB activation, irreversibly triggering the apoptosis cascade without HHV-8 reactivation. In addition, DHMEQ could rescue the PEL-xenograft mice. Therefore, we suggest DHMEQ as a promising candidate for molecular target therapy of the PEL.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanones,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/dehydroxymethylepoxyquinomicin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1349-7006
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
100
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
737-46
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| pubmed:meshHeading |
pubmed-meshheading:19469019-Antineoplastic Agents,
pubmed-meshheading:19469019-Apoptosis,
pubmed-meshheading:19469019-Benzamides,
pubmed-meshheading:19469019-Caspase 3,
pubmed-meshheading:19469019-Caspase 8,
pubmed-meshheading:19469019-Caspase 9,
pubmed-meshheading:19469019-Cell Death,
pubmed-meshheading:19469019-Cell Line, Tumor,
pubmed-meshheading:19469019-Cell Survival,
pubmed-meshheading:19469019-Cyclohexanones,
pubmed-meshheading:19469019-Dose-Response Relationship, Drug,
pubmed-meshheading:19469019-Enzyme Activation,
pubmed-meshheading:19469019-HeLa Cells,
pubmed-meshheading:19469019-Herpesvirus 8, Human,
pubmed-meshheading:19469019-Humans,
pubmed-meshheading:19469019-In Situ Nick-End Labeling,
pubmed-meshheading:19469019-Jurkat Cells,
pubmed-meshheading:19469019-K562 Cells,
pubmed-meshheading:19469019-Lymphoma, Primary Effusion,
pubmed-meshheading:19469019-NF-kappa B,
pubmed-meshheading:19469019-Time Factors
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| pubmed:year |
2009
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| pubmed:articleTitle |
Transient inhibition of NF-kappaB by DHMEQ induces cell death of primary effusion lymphoma without HHV-8 reactivation.
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| pubmed:affiliation |
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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