001     127676
005     20240228135031.0
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024 7 _ |a 1554-6578
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037 _ _ |a DKFZ-2017-03699
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Koschny, Ronald
|b 0
245 _ _ |a Bortezomib sensitizes primary meningioma cells to TRAIL-induced apoptosis by enhancing formation of the death-inducing signaling complex.
260 _ _ |a Oxford
|c 2014
|b Oxford University Press
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a A meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without different sensitizing protocols, and apoptotic cell death was then quantified. Mechanisms of TRAIL sensitization were determined by a combination of Western blotting, flow cytometry, receptor complex immunoprecipitation, and siRNA-mediated knockdown experiments. Tumor necrosis factor-related apoptosis-inducing ligand receptor expression was analyzed using immunohistochemistry and quantified by an automated software-based algorithm. Primary tumor cells from 11 (29.7%) tumor samples were sensitive to TRAIL-induced apoptosis, 12 (32.4%) were intermediate TRAIL resistant, and 14 (37.8%) were completely TRAIL resistant. We tested synergistic apoptosis-inducing cotreatment strategies and determined that only the proteasome inhibitor bortezomib potently enhanced expression of the TRAIL receptors TRAIL-R1 and/or TRAIL-R2, the formation of the TRAIL death-inducing signaling complex, and activation of caspases; this treatment resulted in sensitization of all TRAIL-resistant meningioma samples to TRAIL-induced apoptosis. Bortezomib pretreatment induced NOXA expression and downregulated c-FLIP, neither of which caused the TRAIL-sensitizing effect. Native TRAIL receptor expression could not predict primary TRAIL sensitivity. This first report on TRAIL sensitivity of primary meningioma cells demonstrates that TRAIL/bortezomib cotreatment may represent a novel therapeutic option for meningiomas.
536 _ _ |a 314 - Tumor immunology (POF3-314)
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650 _ 7 |a Antineoplastic Agents
|2 NLM Chemicals
650 _ 7 |a Boronic Acids
|2 NLM Chemicals
650 _ 7 |a GRAMD4 protein, human
|2 NLM Chemicals
650 _ 7 |a Mitochondrial Proteins
|2 NLM Chemicals
650 _ 7 |a Pyrazines
|2 NLM Chemicals
650 _ 7 |a TNF-Related Apoptosis-Inducing Ligand
|2 NLM Chemicals
650 _ 7 |a TNFSF10 protein, human
|2 NLM Chemicals
650 _ 7 |a Bortezomib
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700 1 _ |a Boehm, Christina
|b 1
700 1 _ |a Sprick, Martin R
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Haas, Tobias L
|b 3
700 1 _ |a Holland, Heidrun
|b 4
700 1 _ |a Xu, Li-Xin
|b 5
700 1 _ |a Krupp, Wolfgang
|b 6
700 1 _ |a Mueller, Wolf C
|b 7
700 1 _ |a Bauer, Manfred
|b 8
700 1 _ |a Koschny, Thomas
|b 9
700 1 _ |a Keller, Marius
|b 10
700 1 _ |a Sinn, Peter
|b 11
700 1 _ |a Meixensberger, Juergen
|b 12
700 1 _ |a Walczak, Henning
|0 P:(DE-HGF)0
|b 13
700 1 _ |a Ganten, Tom M
|b 14
773 _ _ |a 10.1097/NEN.0000000000000129
|g Vol. 73, no. 11, p. 1034 - 1046
|0 PERI:(DE-600)2033048-0
|n 11
|p 1034 - 1046
|t Journal of neuropathology and experimental neurology
|v 73
|y 2014
|x 1554-6578
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910 1 _ |a Deutsches Krebsforschungszentrum
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