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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-4-4
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pubmed:abstractText |
Proteasome inhibition results in proapoptotic changes in cancer cells, which may make them more sensitive to immune effector cells. We established a murine model to test whether the proteasome inhibitor bortezomib could sensitize established B16 melanoma tumors to dendritic cell (DC)-activated immune effector cells. Day 3-established s.c. B16 tumors had significantly decreased tumor outgrowth when treated with a combination of bortezomib and DC, regardless of whether the DC were loaded or not with a tumor Ag. In vivo Ab-depletion studies demonstrated that the effector cells were NK and CD8+ cells, but not CD4+ cells. NF-kappaB nuclear transcription factor assay and gene-expression profiling of B16 treated with bortezomib was consistent with inhibition of NF-kappaB target genes leading to a proapoptotic phenotype. In vitro lytic assays demonstrated that TNF-alpha, but not perforin, Fas-ligand, or TRAIL, was responsible for bortezomib-sensitized B16 cytotoxicity. In conclusion, the proteasome inhibitor bortezomib can pharmacologically sensitize tumor cells to the lytic effects of DC-activated immune effector cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:BonavidaBenjaminB,
pubmed-author:Comin-AnduixBegoñaB,
pubmed-author:DissetteVivian BVB,
pubmed-author:EconomouJames SJS,
pubmed-author:GarbanHermes JHJ,
pubmed-author:GlaspyJohn AJA,
pubmed-author:McBrideWilliam HWH,
pubmed-author:OwensSharla KSK,
pubmed-author:RibasAntoniA,
pubmed-author:SchumacherLana YLY,
pubmed-author:VoDan DDD
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
176
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pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
4757-65
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16585569-Animals,
pubmed-meshheading:16585569-Apoptosis,
pubmed-meshheading:16585569-Boronic Acids,
pubmed-meshheading:16585569-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16585569-Cell Line, Tumor,
pubmed-meshheading:16585569-Cytotoxicity, Immunologic,
pubmed-meshheading:16585569-Dendritic Cells,
pubmed-meshheading:16585569-Immunization,
pubmed-meshheading:16585569-Immunotherapy,
pubmed-meshheading:16585569-Killer Cells, Natural,
pubmed-meshheading:16585569-Melanoma, Experimental,
pubmed-meshheading:16585569-Mice,
pubmed-meshheading:16585569-Mice, Inbred C57BL,
pubmed-meshheading:16585569-Mice, Knockout,
pubmed-meshheading:16585569-Protease Inhibitors,
pubmed-meshheading:16585569-Pyrazines,
pubmed-meshheading:16585569-Tumor Necrosis Factor-alpha
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pubmed:year |
2006
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pubmed:articleTitle |
Immunosensitization of tumor cells to dendritic cell-activated immune responses with the proteasome inhibitor bortezomib (PS-341, Velcade).
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pubmed:affiliation |
Department of Surgery, Division of Surgical Oncology, University of California, Los Angeles 90095, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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