Accession Number : AD1020481


Title :   Preclinical Validation of Anti-Nuclear Factor Kappa B Therapy Against Vestibular Schwannoma and Neurofibromatosis Type II


Descriptive Note : Technical Report,15 May 2015,14 May 2016


Corporate Author : Massachusetts Eye and Ear Infirmary Boston United States


Personal Author(s) : Stankovic,Konstantina M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1020481.pdf


Report Date : 01 Jun 2016


Pagination or Media Count : 42


Abstract : Neurofibromatosis type 2 (NF2) is a genetic disorder that causes substantial suffering and debility due to many tumors that occur on the nerves within the skull and spine throughout a persons life. The hallmark ofNF2 is vestibular schwannomas (VSs), also known as acoustic neuromas, which occur on the vestibular nerves that connect the inner ear with the brain. Initially, VSs cause hearing loss. However, as they grow, they can compress the brainstem and cause death. Current treatment options are limited to surgical removal and radiation therapy, both of which carry substantial risks, including deafness and facial paralysis. Although drug therapies against NF2 are gaining momentum, more effective and better tolerated drugs are sorely needed. Because NF2 tumors are typically slowly growing and non-malignant, even therapies that simply reduce tumor volume and retard growth can be lifesaving. The most successful drug used today to treat NF2, bevacizumab, works in only about 50% of patients in halting tumor growth or causing tumor shrinkage. Bevacizumab is known to inhibit vascular endothelial growth factor (VEGF), but its precise mechanism of action in VSs is unknown. During the first year of DoD funding, we demonstrated that a specific inhibition of a pro-inflammatory transcription factor nuclear factor kappa B (NFB) can be cytotoxic for VS cells in vitro. We also demonstrated a cytostatic effect of non-steroidal anti-inflammatory drugs(NSAIDs) on VS cells in vitro, suggesting novel treatment options for VS and NF2.


Descriptors :   neoplasms , brain , Genetic diseases , hearing loss , therapeutics , drug therapy , mice , models , aspirin , ear


Distribution Statement : APPROVED FOR PUBLIC RELEASE