Published papers

We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery. In this single-center retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (≥1 μg/mL) before surgery and on postoperative day (POD) 3 or 7. Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 μg/mL (sensitivity [0.636] and specificity [0.750]). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 μg/mL. The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 μg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 μg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.

Background: Intraosseous schwannomas are extremely rare and they have not yet been reported to occur in the clivus. We report a schwannoma in the clivus mimicking chordoma and review intraosseous schwannomas of the skull. Case Description: A 62-year-old man presented with gradually worsening hoarseness with dysphagia and atrophy of the left tongue, trapezius muscle, and sternocleidomastoid muscle. Magnetic resonance imaging showed that the tumor was mainly located in the clivus, and a computed tomography (CT) scan revealed an osteolytic lesion with expansion of the clivus and preservation of the bony cortex. Endoscopic endonasal surgery was performed to diagnose and treat symptoms. The tumor was subtotally removed without any complications. The histopathological findings revealed typical schwannoma, which showed Antoni A and Antoni B patterns positive for S100 protein. Based on the preoperative imaging, intraoperative and histopathological findings, the tumor was considered to be an intraosseous schwannoma in the clivus, and no recurrence was observed after 1 year of postoperative follow-up. Conclusion: Even though the intraosseous schwannoma in the clivus is uncommon, it should be considered as a differential diagnosis if an expansive lesion without destruction of the cortical bone is shown on CT as well as iso-hyperintensity on T2-weighted magnetic resonance imaging.

Meningiomas are the most frequent brain tumors, typically benign and curable by surgery. However, some patients experience repeated recurrences from residual tumors. To address such cases, the development of novel therapeutic options is crucial. For this purpose, the availability of cell lines that possess the characteristics of benign meningiomas is essential. Here, we established a benign meningioma cell line under 3% O2 hypoxic conditions without the induction of immortalization genes. This cell line, named TKB-MEN2, has been stably grown for over two years with more than 20 passages. There were no hotspot telomerase reverse transcriptase (TERT) promoter mutations or cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) homozygous deletions, which are genetic features typical of malignant meningiomas. Cultured under hypoxic conditions, this cell line showed fewer characteristics of cellular senescence, such as morphological changes, IL-6 secretion, and lower senescence-associated b-galactosidase activity, compared to the same cell line cultured under 20% O2 conditions. This immortalized non-transgenic cell line appears to reflect the characteristics of a genuine benign meningioma, potentially allowing the identification of new therapeutic targets and the development of novel therapies for benign meningiomas.

Purpose: Malignant meningiomas are characterized by high recurrence rates and limited therapeutic options beyond surgery and radiation. This study aimed to develop a novel nucleic acid-based therapeutic approach for malignant meningiomas and to evaluate its efficacy both in vitro and in vivo. Methods: IOMM-Lee and HKBMM cell lines were used as models of malignant meningioma. Inhibitory effects of hemagglutinating virus of Japan envelope (HVJ-E) and microRNA-34a-5p (miR-34a-5p) were assessed using cell viability assays, apoptosis assays, RT-qPCR, and western blotting. Finally, the tumor suppressive effect of HVJ-E encapsulating miR-34a-5p was evaluated using a subcutaneous xenograft model in nude mice. Result: HVJ-E significantly reduced viability of malignant meningioma cells. Furthermore, HVJ-E encapsulating miR-34a-5p demonstrated enhanced anti-tumor activity by inducing apoptosis through downregulation of survivin expression. This tumor-suppressive effect was also confirmed in a subcutaneous mouse model. Conclusion: Our findings indicate that HVJ-E encapsulating miR-34a-5p effectively inhibits the growth of malignant meningioma cells both in vitro and in vivo. This novel combination therapy holds promise as a potential treatment strategy for malignant meningiomas.

Insoluble iron deposits often exist as iron oxide nanoparticles in protein aggregates, impaired ferritin, or activated microglia and have been implicated as major causes of neuroinflammation in Alzheimer’s disease. However, no crucial evidence has been reported to support the therapeutic effects of current iron chelators on the deposition of various molecular forms of insoluble iron. We investigated the therapeutic effect of carbon ion stimulation (CIS) via a transmission beam on insoluble iron deposits, iron inclusion bodies, and the associated biological response in 5xFAD AD mouse brains. Compared with no treatment, CIS dose-dependently induced a 33–60% reduction in the amount of ferrous-containing iron species and associated inclusion bodies in the brains of AD mice. CIS induced considerable neuroinflammation downregulation and, conversely, anti-inflammatory upregulation, which was associated with improved memory and enhanced hippocampal neurogenesis. In conclusion, our results suggest that the effective degradation of insoluble iron deposits in combination with pathogenic inclusion bodies promotes AD-modifying properties and offers a potential CIS treatment option for AD.

Treatment of WHO grade Ⅱ and Ⅲ meningiomas is challenging, and the number of grade Ⅱ meningi-omas has increased after the recent revision of the WHO classification. In terms of surgical treatment, the benefit of gross total resection（GTR）to subtotal resection（STR）for grade Ⅱ meningiomas is well estab-lished, but it has not been established for grade Ⅲ meningiomas. In terms of postoperative radiotherapy （PORT）, PORT is effective after STR but not after GTR for grade Ⅱ meningiomas. However, PORT benefits after GTR for grade Ⅱ meningiomas have been recently reported and these techniques are currently being investigated in ongoing phase Ⅲ clinical trials. There have also been reports that high‒dose irradiation and particle beam irradiation, including boron neutron capture therapy, can benefit conventional radio-therapy, and their effectiveness is also being investigated in ongoing clinical trials. Despite poor prognoses, there have been reports about the benefits of radiotherapy for grade Ⅲ meningioma. The use of systemic therapy should only be considered for refractory tumors as salvage therapy because its effectiveness has been shown to be limited in clinical trials.