{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:05:04Z","timestamp":1792713904191,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T00:00:00Z","timestamp":1427760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non\u2010existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro\u2010inflammatory transcription factor nuclear factor\u2010kappa B (NF\u2010\u03baB) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF\u2010\u03baB complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS\u2010derived human cell line HEI\u2010193 were treated with specific NF\u2010\u03baB siRNAs, experimental NF\u2010\u03baB inhibitor BAY11\u20107082 (BAY11) and clinically relevant NF\u2010\u03baB inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI\u2010193 cells, with siRNA, 5\u00a0\u03bcM BAY11 and 50\u00a0\u03bcM curcumin reducing average proliferation (\u00b1standard error of mean) to 62.33%\u00a0\u00b1\u00a010.59%, 14.3\u00a0\u00b1\u00a09.7%, and 23.0\u00a0\u00b1\u00a020.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF\u2010\u03baB as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF\u2010\u03baB in VS.<\/jats:p>","DOI":"10.1016\/j.molonc.2015.03.009","type":"journal-article","created":{"date-parts":[[2015,4,5]],"date-time":"2015-04-05T19:35:21Z","timestamp":1428262521000},"page":"1359-1370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Preclinical validation of anti\u2010nuclear factor\u2010kappa B therapy to inhibit human vestibular schwannoma growth"],"prefix":"10.1002","volume":"9","author":[{"given":"Sonam","family":"Dilwali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn C.","family":"Bri\u00ebt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyan-Yuan","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas D.","family":"Landegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Platt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina M.","family":"Stankovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e3181ec7b71"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22709"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.587"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.12.008"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0243"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e3181e40e4f"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24748"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-004-5176-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24967"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e3181be6478"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e3181f20655"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e31827c9fbf"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20150"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.9.5286-5294.2003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2014.05.006"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/mao.0b013e31815d4429"},{"key":"e_1_2_10_18_1","unstructured":"2014 T. 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