Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964.

This study was aimed to analyze the outer diameter of the involved arteries in moyamoya disease, using three-dimensional (3D) constructive interference in steady state (CISS) and direct surgical inspection. Radiological evaluation was performed in 64 patients with moyamoya disease. As the controls, six patients with severe middle cerebral artery (MCA) stenosis and 17 healthy subjects were also recruited. On 3D-CISS, the outer diameter was quantified in the supraclinoid portion of internal carotid artery (C1), the horizontal portions of MCA (M1) and anterior cerebral artery (A1), and basilar artery. The involved carotid fork was directly observed during surgery in another series of three adult patients with moyamoya disease. In 53 adult patients with moyamoya disease, the outer diameters of C1, M1, and A1 segments were 2.3 ± 0.7 mm, 1.3 ± 0.5 mm, and 1.0 ± 0.4 mm in the involved side (n = 91), being significantly smaller than the control (n = 17), severe M1 stenosis (n = 6), and non-involved side in moyamoya disease (n = 15, P < 0.01). There were significant correlations between Suzuki’s angiographical stage and the outer diameters of C1, M1, and A1 (P < 0.001). The laterality ratio of C1 and M1 was significantly smaller in unilateral moyamoya disease (n = 20) than the controls and severe MCA stenosis (P < 0.01). Direct observations revealed a marked decrease in the outer diameter of the carotid fork (n = 3). These findings strongly suggest specific shrinkage of the involved arteries in moyamoya disease, which may provide essential information to distinguish moyamoya disease from other intracranial arterial stenosis and shed light on the etiology and novel diagnosis cue of moyamoya disease.

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Background: Writer's cramp is a specific movement disorder with hand muscle cramps in writing, being classified into focal and action-specific dystonia. Stereotactic surgery, such as thalamotomy and deep brain stimulation (DBS), has been reported for writer's cramp; however, the number of reported cases is still scarce and surgical procedures are also controversial. Objectives: In this study, therefore, we present 2 patients who underwent thalamotomy for writer's cramp and systematically review the literature on stereotactic surgery for writer's cramp. Methods: Case reports and literature review are presented. Results: Both patients underwent ventral oral nucleus (Vo) thalamotomy safely. Their symptoms completely disappeared after surgery and did not recur during follow-up periods. In the literature, a total of 31 cases were surgically treated for writer's cramp. Stereotactic surgery included thalamotomy in 25 cases and DBS in 6. The target included the Vo in 17 cases, the ventral intermediate nucleus (Vim) in 3, and both Vo and Vim in 7. Both procedures markedly improved or resolved the symptoms. Transient neurological deficits were observed in 16.0% of patients after thalamotomy. Conclusions: The Vo may be the most effective target to treat writer's cramp. Both thalamotomy and DBS are feasible and effective, but thalamotomy would be a better option, especially in younger or high-risk patients.

This study aimed to evaluate the biological features of T-lymphokine-activated killer cell-originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in patients with malignant glioma. TOPK protein level and TOPK mRNA and protein levels in six glioma cell lines were examined using Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimens from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double immunofluorescence 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 models. Immunohistochemistry revealed that approximately 20-30% 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.