Vestibular Schwannoma (Acoustic Neuroma)

Vestibular schwannomas (VSs), also known as acoustic neuromas, are intracranial tumors that typically arise from the vestibular nerves and cause hearing loss and tinnitus. We aim to understand mechanisms of this hearing loss, which will inform the development of future therapies to prevent and treat this hearing loss. By focusing on VS-secreted molecules, we discovered that TNFa, a pro-inflammatory molecule, is an ototoxic and FGF2 an otoprotective molecule secreted by VSs (Dilwali, Landegger et al, 2015). We further revealed that VS cells secrete extracellular vesicles that can damage cochlear cells (Soares et al, 2016). We discovered that anti-inflammatory medications that signal through NFkB (Dilwali, Briet et al, 2015) or COX-2 (Dilwali, Kao et al, 2015) reduce VS cell proliferation in vitro, in line with our finding that aspirin intake correlates with reduced growth of VS in vivo (Kandathil et al, 2014). Taken together, our findings have motivated the ongoing prospective, randomized, placebo-controlled phase II clinical trial of aspirin for vestibular schwannoma.

Publications

Sagers JE, Brown AS, Vasilijic S, Lewis R, Sahin MI, Landegger LD, Perlis RH, Kohane IS, Patel CJ, Stankovic KM. Computational Repositioning and Preclinical Validation of Mifepristone for Human Vestibular Schwannoma. Scientific Reports 8, 5437 (2018).

Buch K, Cunnane MB, Julianno A, Stankovic KM, Curtin H. Utility of Using a Constructive Interference in Steady State Sequence (CISS) Alone for the Follow-up Evaluation of Vestibular Schwannomas. Journal of Neurosurgery2018. Accepted.

Ren Y, Stankovic KM. The Role of Tumor Necrosis Factor Alpha in Hearing Loss and Vestibular Schwannomas. Current Otorhinolaryngology Reports, 2018. In press.

Zhao Y, Zhao F, Zhang N, Chen J, Landegger LD, Fujita T, Stemmer-Rachamimov A, Zhang J, Shang Y, Ferraro G, Liu H, Muzikansky A, Liu P, Plotkin S, Stankovic K, Jain R, Xu L. Targeting the cMET Pathway Augments Radiation Response without Adverse Effect on Hearing in NF2 Schwannoma Models. Proceedings of the National Academy of Sciences, 2018. [Epub ahead of print].  

Ren Y, Sagers JE, Landegger LD, Bhatia S, Stankovic KM. Tumor-penetrating Delivery of siRNA against TNFa to Human Vestibular Schwannomas. Scientific Reports 7, 12922 (2017).

Landegger LD, Lee JD, Linthicum FH, Stankovic KM. Cochlear Dysfunction is Not Common in Human Meningioma of the Internal Auditory Canal. Otology and Neurotology (2017).

Landegger LD*, Sagers JE*, Dilwali S, Fujita T, Sahin MI, Stankovic KM. A Unified Methodological Framework for Vestibular Schwannoma Research. Journal of Visualized Experiments (JoVE) 124, e55827 (2017). (*= equal contribution)

Kim BG, Fujita T, Stankovic KM, Welling DB,  Moon IS, Choi JY, Yun J, Kang JS, Lee JD. Sulforaphane, a Natural Component of Broccoli, Inhibits Vestibular Schwannoma Growth in vitro and in vivo. Scientific Reports. 2016 Nov 2; 6:36215.

Kandathil CK, Cunnane ME, McKenna MJ, Curtin H, Stankovic KM. Correlation Between Aspirin Intake and Reduced Growth of Human Vestibular Schwannoma: Volumetric Analysis. Otology and Neurotology 2016: 37:1428–1434.

Soares VYR, Atai NA, Fujita T, Dilwali S, Sivaraman S, Landegger LD, Hochberg FH, Oliveira CAPC, Bahmad F, Breakefield XO, Stankovic KM. Extracellular Vesicles Derived from Human Vestibular Schwannomas Associated with Poor Hearing Damage Cochlear Cells. Neuro-Oncology 2016. May 18. pii: now099.

Dilwali S*, Landegger LD*, Soares VY, Deschler DG, Stankovic KM. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage. Scientific Reports 2015;5:18599 (* = equal contribution).

Dilwali S, Briët MC, Kao SY, Fujita T, Landegger LD, Platt MP, Stankovic KM. Preclinical Validation of Anti-Nuclear Factor-kappa B Therapy to Inhibit Human Vestibular Schwannoma Growth. Molecular Oncology 2015;9(7):1359-70.

Dilwali S, Kao SY, Fujita T, Landegger LD, Stankovic KM. Non-Steroidal Anti-Inflammatory Medications are Cytostatic Against Human Vestibular Schwannomas. Translational Research 2015;166(1):1-11

  • Featured on Harvard Medical School's website.

Dilwali S, Roberts D, Stankovic KM. Interplay Between VEGF-A and c-MET Signaling in Human Vestibular Schwannomas and Schwann Cells. Cancer Biology and Therapy. 2015;16(1):170-5.

Dilwali S, Patel P, Roberts DS, Basinsky GM, Harris GJ, Emerick KS, Stankovic KM. Primary Culture of Human Schwann and Schwannoma Cells: Improved and Simplified Protocol. Hearing Research 2014; 315C:25-33.

Kandathil C, Dilwali S, Wu CC, Ibrahimov M, McKenna M, Lee H, Stankovic KM. Aspirin Intake Correlates with Halted Growth of Sporadic Vestibular Schwannoma in vivo. Otology and Neurotology 2014; 35(2):353-7.

  • Paper was highlighted on the MEE and HMS web sites, and has received international media coverage.

Dilwali S, Lysaght A, Roberts D, Barker FG, McKenna MJ, Stankovic KM. Sporadic Vestibular Schwannomas Associated with Good Hearing Secrete Higher Levels of Fibroblast Growth Factor 2 than Those Associated with Poor Hearing Irrespective of Tumor Size. Otology and Neurotology 2013; 34(4):748-54.

Gómez-Casati ME, Murtie JC, Rio C, Stankovic K, Liberman MC, Corfas G. Nonneuronal Cells Regulate Synapse Formation in the Vestibular Sensory Epithelium via ErbB-Dependent BDNF Expression.  Proceeding of the National Academy of Sciences U S A. 2010;107(39):17005-10.

Stankovic KM, Mrugala MM, Martuza, RL, Silver M, Betensky RA, Nadol, JB Jr., Stemmer-Rachamimov AO. Genetic Determinants of Hearing Loss Associated with Vestibular Schwannomas. Otology and Neurotology 2009; 30(5): 661-7.

  • Voted by The Hearing Journal as one of the best papers of 2009 in the Vestibular Schwannoma category.