Background: Vestibular schwannomas (VS) frequently express high levels of activated AKT. Small-molecule inhibitors of AKT signalling may have therapeutic potential in suppressing the growth of benign VS and malignant schwannomas.Method: Primary VS and Schwann cells, human malignant schwannoma HMS-97 cells and mouse Nf(2-/-) Schwann cells and schwannoma cells were prepared to investigate the growth inhibitory and anti-tumour activities of OSU-03012, a celecoxib-derived small-molecule inhibitor of phosphoinositide-dependent kinase-1. Cell proliferation assays, apoptosis, Western blot, in vivo xenograft analysis using SCID mice and immunohistochemistry were performed.Results: OSU-03012 inhibited cell proliferation more effectively in both VS and HMS-97 cells than in normal human Schwann cells. The IC50 of OSU-03012 at 48 h was approximately 3.1 mu M for VS cells and 2.6 mu M for HMS-97 cells, compared with the IC50 of greater than 12 mu M for human Schwann cells. Similarly, mouse Nf2(-/-) schwannoma and Nf2(-/-) Schwann cells were more sensitive to growth inhibition by OSU-03012 than wild-type mouse Schwann cells and mouse schwannoma cells established from transgenic mice carrying the NF2 promoter-driven SV40 T-antigen gene. Like VS cells, malignant schwannoma HMS-97 cells expressed high levels of activated AKT. OSU-03012 induced apoptosis in both VS and HMS-97 cells and caused a marked reduction of AKT phosphorylation at both the Ser-308 and Thr-473 sites in a dose-dependent manner. In vivo xenograft analysis showed that OSU-03012 was well tolerated and inhibited the growth of HMS-97 schwannoma xenografts by 55% after 9 weeks of oral treatment. The anti-tumour activity correlated with reduced AKT phosphorylation.Conclusion: OSU-03012 is a potential chemotherapeutic agent for VS and malignant schwannomas. (C) 2009 Elsevier Ltd. All rights reserved.

INTRODUCTION:Methods for surgical education and training have changed little over the years. Recent calls to improve surgical efficiency and safety impose additional pressures that have an impact on surgical education and training. USE OF SIMULATION: Integration of data from advanced imaging technologies and computer technologies are creating simulation environments of unprecedented realism. Surgical education and training are poised to exploit low-cost simulation technologies to mitigate these pressures that are having an adverse impact on curricula. To become effective, simulation needs to undergo rigorous validation studies.INTERVENTION:With funding from that National Institute on Deafness and Other Communicative Disorders, we have embarked on a research design project to develop, disseminate, and validate a surgical system for use in otologic resident training and assessment and present key steps from this process.DISCUSSION:We discuss limiting factors related to technology and conducting multi-institutional studies, along with current developments to integrate curricula, as well as training and assessment capabilities in surgical education using simulation.

Purpose of review To summarize advances in understanding the molecular biology of vestibular schwannomas over the past year. Recent findings The role of the neurofibromatosis type 2 protein, denoted as merlin or schwannomin, in embryonic development, cellular adherence, and in cell proliferation has become better elucidated in the past year. Likewise, the role of merlin in Schwann cell–axon interaction has been studied. Additionally, two comprehensive analyses of the spectrum of human neurofibromatosis type 2 mutations have been compiled which make up a valuable resource in understanding critical regions of the neurofibromatosis type 2 gene. Neurofibromatosis type 2 screening guidelines for young patients with solitary vestibular schwannomas have been published. The role of electromagnetic radiation via cellular and portable telephones as a predisposing factor to vestibular schwannoma formation has also been the topic of several studies. Based on increased knowledge of the pathways in which merlin functions and the available transgenic and xenograft mouse models, preliminary data regarding directed pharmacotherapy are also summarized. Summary With increased knowledge of the pathologic mechanisms and interacting proteins associated with merlin, the research community is poised to begin trials of targeted interventions in vitro and in the current mouse models.