Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas

Abstract

Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle. Significant clinical need exists for pharmacotherapies against VSs. Motivated by previous findings that immunohistochemical expression of cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was found to be aberrantly expressed in human VS and primary human VS cells in comparison to control human nerve specimens and primary Schwann cells (SCs), respectively. Further, levels of prostaglandin E2, the downstream enzymatic product of COX-2, correlated with primary VS culture proliferation rate. Because COX-2 inhibiting salicylates such as aspirin are well-tolerated and frequently clinically used, we assessed their repurposing for VS. Changes in proliferation, cell death and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate (NaSal) or 5-aminosalicylic acid (5-ASA). These drugs did not increase VS cell death nor affect healthy SCs. The cytostatic effect of aspirin in vitro was in concurrence with our previous clinical finding that VS patients taking aspirin demonstrate reduced tumor growth. Overall, this work suggests that COX-2 is a key modulator in VS cell proliferation and survival, and highlights salicylates as promising pharmacotherapies against VS.

Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

“…Notably, the study by Hunter et al also examined whether alternative NSAIDs, other than aspirin, were associated with reduced VS growth . This is important given that the COX‐2 pathway (rather than COX‐1) that is implicated in tumor growth control and aspirin is a poorly selective inhibitor of COX‐2 compared to some other NSAIDs . However, as with aspirin, NSAID use was not found to be associated with VS growth/stability.…”

“…High levels of COX‐2 expression in VS have been shown to correlate with high proliferation rates . COX‐2 expression has been shown to be higher in human VS cells in comparison with control human Schwann cells . The same study also showed that aspirin was selectively cytostatic against human VS cells but not Schwann cells .…”

“…COX‐2 expression has been shown to be higher in human VS cells in comparison with control human Schwann cells . The same study also showed that aspirin was selectively cytostatic against human VS cells but not Schwann cells . A single‐cohort, clinical observational study has suggested an association between aspirin intake and VS tumor stability; however, there were some limitation in the study design .…”

Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds

“…Several studies reveal the benefits of daily aspirin on multiple aspects of cancer chemoprevention, by reducing both incidence and mortality [63], and metastasis in patients already diagnosed with cancer [64]. Its antineoplastic effects are likely to result from different candidate mechanisms, such as cyclo-oxygenase (COX)-2 inhibition as described in vestibular schwannomas [65] or interference with NF-κB, AMP-activated protein kinase (AMPK), or PI3K/mTOR signaling [66]. Moreover, patients with cancer have a high risk of developing venous thromboembolism (VTE), which can significantly reduce their survival; interestingly, recent trials demonstrated the benefits of low-dose aspirin for VTE prophylaxis in patients with multiple myeloma treated with thalidomide or lenalidomide [67].…”

Current Concepts and Evaluation of Uro-Rectal Diseases by Transrectal Ultrasound: A Review

“…Prostate Cancer [107] Perianal Paget's Disease [108] Myxoid Liposarcoma [109] Malignant Fibrous Histiocytoma [110] Hemangiopericytoma [111] Cauda Equina Syndrome [112] Carcinoma of the Cervix [113] Carcinoma of the Vagina [114] Epidermoid Cysts [115] Prader-Willi Syndrome [116] Colorectal Carcinoma [117] Benign Prostate Hyperplasia [118] Microglandular Hyperplasia [119] Adenocarcinoma of Cervix [120] Adenoma Malignum [121] Adenosquamous Carcinoma of Cervix [122] Glassy Cell Carcinoma of Cervix [123] Adenoid Basal Carcinoma of Cervix [124] Adenomyosis [125] Uterine Fibroids [126] Endometrial Polyps [127] Hematoma [128] Fournier's Gangrene [129] Malakoplakia [130] Aneurysmal bone cyst [131] Ewing Sarcoma [132] Osteosarcoma [133] Chondrosarcoma [134] Neurofibroma [135] Neuroblastoma [136] Schwannoma [137] Chordoma [138] Malignant Schwannoma [139] Hemangioma [140] Myelolipoma [141] Leiomyoma [142] Villous Adenoma [143] Solitary Fibrous tumor [144] Castleman disease [145] Lymphoma [146] Gastrointestinal Stromal Tumor [147] Epithielial Malignancies …”