The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer, which is frequently associated with the BRAFV600E mutation, remains unknown. This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1 was more frequently detected in BRAFV600E (+) PTC. In the thyroid cancer cell lines TPC-1 and HTH7, which do not have the BRAFV600E mutation, YAP1 was cytosolic and inactive at high cell densities. In contrast, YAP1 was retained in the nucleus and its target genes were expressed in the thyroid cancer cells 8505C and K1, which harbor the BRAFV600E mutation, regardless of cell density. Furthermore, the nuclear activation of YAP1 in 8505C was not inhibited by RAF or MEK inhibitor. In vitro experiments, YAP1 silencing or overexpression affected migratory capacities of 8505C and TPC-1 cells. YAP1 knockdown resulted in marked decrease of tumor volume, invasion and distant metastasis in orthotopic tumor xenograft mouse models using the 8505C thyroid cancer cell line. Taken together, YAP1 is involved in the tumor progression of thyroid cancer and YAP1-mediated effects might not be affected by the currently used RAF kinase inhibitors.

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Background: Topiramate shows excellent reduction in seizure rate and minimal adverse events. However, there is a significant difference about the optimal dose, duration of topiramate management. Thus, we conduct the multi-center retrospective survey to examine the practical using patterns of topiramate in the neurosurgical patients.Objective: This study is to investigate the actual using patterns and clinical effects of topiramate in patients with neurosurgical disease as antiepileptic drugs (AEDs) in 94 korean multi-centers. Patients and methods: A total of 7,152 patients who had taken topiramate for at least 3 months between August 2008 and February 2009 were eligible to participate in this study. We evaluated demographic data, primary diseases, duration of topiramate administration, initial and subsequent dosage adjustment, concomitant AEDs, the frequency of seizure reduction, and adverse events. Results: Topiramate was most commonly prescribed in stroke (38%), and the mean initial dosage was 65 mg/day, and the mean maintenance dosage was 105 mg/day. The mean duration of the initial dosage for topiramate administration was 24 days, and the mean duration of the maintenance dosage was 125 days, respectively. Among groups with prophylactic administration, 98% did not develop convulsion and among groups with therapeutic administration, 2% was ineffective to control seizure. After taking topiramate, 2% patients showed adverse events, that sensory aberration was the most common. Conclusion: These results suggest that topiramate prescribe widely in diverse neurosurgical disorders, and effective in reduction of seizure frequency, and does not cause serious adverse effects comparable with old AEDs.Abstracts / Journal of the Neurological Sciences 357 (2015) e142-e160 e150