Unilateral vestibular deafferentation (UVD) interrupts afferent signals from one side, resulting in an imbalance of the resting activity between bilateral vestibular nuclei. Vestibular compensation is the process of balancing the resting activity to reestablish homeostasis. Here, we investigated microRNAs (miRNAs) that regulate vestibular compensation using the Sprague–Dawley rat. After determining the progression of vestibular compensation following UVD, microarray analysis was performed and nine miRNAs were selected as candidates. Following validation by quantitative reverse transcription-PCR, three miRNAs remained. We assessed the effect of these miRNAs on vestibular compensation using miRNA oligomers. We compared the results of the rotarod test and 5-bromo-2′-deoxyuridine immunohistochemistry following UVD between the control group and the groups in which the candidate miRNA oligomers were administered. Administration of miR-218a-5p, 219a-5p, and 221-3p oligomers significantly affected vestibular compensation. Target pathway analysis of these miRNAs supported our results. Our findings suggest that the miRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation.
Hearing protection after systemic administration of steroids is more effective when continued for at least a week after CI. Similarly, this treatment approach was more effective in reducing the fibrosis that encapsulates the CI electrode. Reduced fibrosis seemed to be the most likely explanation for the hearing protection.
Objectives
The role of celecoxib in preventing and treating tumors has attracted broad attention in recent years because of its selective and specific inhibition of COX‐2 activity. We investigated the inhibitory effects and mechanisms of celecoxib combined with 5‐fluorouracil (5‐FU) on proliferation of squamous cell carcinoma cells in vivo and in vitro.
Study Design
Animal study and basic research.
Methods
SNU‐1041 and SNU‐1076 squamous cell lines and an orthotopic tongue cancer mouse model were used to study growth inhibition with 5‐FU enhanced by celecoxib. Sensitivity of cells to drug treatment was analyzed by the MTT assay, and generation of reactive oxygen species (ROS) was measured using dichlorofluorescein diacetate. Phosphorylation of AKT was detected by Western blotting. Survival analysis in the mouse model was assessed according to combination treatment with 5‐FU and celecoxib.
Results
Reactive oxygen species production in vitro was highest when celecoxib was administered 48 hours after 5‐FU treatment. 5‐FU–induced inhibition of cell proliferation was enhanced when combined with celecoxib, which was positively correlated with ROS production. Antioxidant treatment reversed 5‐FU–inhibited cell proliferation by up to 60%. Cotreatment with celecoxib and 5‐FU partially blocked AKT phosphorylation, although no significant changes in total AKT protein levels were detected. An increased survival time was observed in an orthotopic mouse model treated with a combination of celecoxib and 5‐FU compared to treatment with either agent alone.
Conclusion
Celecoxib may have an enhanced anticancer effect in combination with 5‐FU. Reactive oxygen species production may be a key mechanism in this combination therapy by inhibiting the AKT pathway.
Level of Evidence
N/A. Laryngoscope, 127:E117–E123, 2017
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