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ニューロサイエンスの旅 Vol.42

富山に赴任してから開始している脳腫瘍グリオーマの基礎+臨床研究の論文が新たに出版されました。
本研究では、精巣や胎児組織以外では正常組織に発現していないものの、数多くの悪性腫瘍に発現していることが判明しつつあるT-LAK cell originated protein kinase (TOPK)について検証しました。
その結果、①TOPKがグリオーマにも発現していること、②TOPKの発現量がグリオーマの悪性度と相関していること、③TOPKの発現が最も悪性度の高い多形性膠芽腫(グリオブラストーマ)の予後(PFS/OS)と有意に相関することが判明しました。

A Voyage to Depth of Neuroscience Vol. 42

Hayashi T, Hayakawa Y, Koh M, Tomita T, Nagai S, Kashiwazaki D, Sugimori M, Origasa H, Kuroda S:
Impact of a novel marker, T-LAK cell originating protein kinase (TOPK) expression on outcome in malignant glioma. Neuropathology 21 DEC 2017 | DOI: 10.1111/neup.12446

Abstract
This study was aimed to evaluate the biological features of T-LAK cell originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in the patients with malignant glioma. TOPK protein level and TOPK mRNA level in six glioma-cell lines were examined using Western blot and RT-PCR, respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimen from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double fluorescence immunohistochemistry. Impacts of TOPK/Ki-67 expression on the overall survival (OS) and progression-free survival (PFS) in 32 patients with glioblastoma multiforme (GBM) were examined, using Kaplan-Meier and Cox proportion hazard model. Immunohistochemistry revealed that approximately 20 to 30% of glioma cells were positive for TOPK in vitro. TOPK mRNA was identified in all glioma cell lines on RT-PCR. The value of TOPK/GAPDH was 0.27±0.11. TOPK and Ki-67 expressions were significantly higher in GBM patients than in non-GBM patients. A majority of TOPK-positive cells were also positive for Ki-67 and vice versa. Multivariate analysis revealed that a low TOPK expression (≤12.7%) was an independent predictor of longer OS (P=0.0372), and that gross total removal and a low TOPK expression (≤12.7%) were independent predictors of longer PFS (P=0.0470 and P=0.0189, respectively). The findings strongly suggest biological and clinical importance of TOPK expression in gliomas, indicating a novel therapeutic potential of TOPK inhibitors to treat malignant gliomas.

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