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Yuji Ikeda,Sho Sato,Akira Yabuno,Daisuke Shintani,Aiko Ogasawara,Maiko Miwa,Makda Zewde,Takashi Miyamoto,Keiichi Fujiwara,Yusuke Nakamura,Kosei Hasegawa 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.6
Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attentionas a therapeutic target in various types of cancers. In this study, we aimed to evaluate theprognostic significance of MELK expression in ovarian cancer using clinical samples, andassessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derivedovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed bywestern blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay. MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients byquantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluatedusing freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normalovaries (p<0.001), and high MELK mRNA expression was observed in patients with advancedstage, positive ascites cytology and residual tumor size. Patients with high MELK mRNAexpression showed shorter progression-free survival (p=0.001). Expression of MELK wasalso confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitoryconcentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167showed significant growth inhibitory effect against patient-derived ovarian cancer cells,regardless of their tumor locations, histologic subtypes and stages. Conclusions: We demonstrated MELK as both a prognostic marker and a therapeutic targetfor ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may bean effective approach to treat ovarian cancer patients.
Yu-Ichiro Ohnishi,Nobuhiko Nakajima,Sho Fujiwara,Takashi Moriwaki,Hideyuki Arita,Haruhiko Kishima 대한척추신경외과학회 2020 Neurospine Vol.17 No.2
Care should be taken regarding surrounding anatomic structures during access to deepseated extracranial schwannomas in the craniocervical junction (CCJ). Herein, we present surgical tips for extracranial schwannomas in the CCJ using the anterolateral approach. A retrospective review was performed of 3 cases of surgical treatment of extracranial schwannomas in the CCJ by the anterolateral approach, which is a presternomastoid retrojugular route to the CCJ. The combination of neck rotation and reflection of the sternocleidomastoid muscle presented a sufficient, shallow surgical field for the CCJ. We could identify tumors along the accessory nerves and internal jugular veins, and had sufficient rostrocaudal working space to resect the tumors. Two cases were enucleated total resection and 1 was subtotal resection. Two patients experienced transient postoperative vocal cord partial paralysis and 1 had transient dysphagia. These neurological complications improved within 1 month. The anterolateral approach can provide a shallow and sufficient rostral and caudal surgical window.