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Background: MGMT is a DNA repair protein that removes the cytotoxic O6-methylguanine (O6MG) DNA lesions generated by TMZ; thereby, MGMT expression is mechanistically linked to TMZ resistance. However, thus far, there is no effective treatment for these patients with MGMT promoter unmethylated. Therefore, a new treatment for GBM patients with MGMT expression is urgently needed. To this end, we examined the tumor microenvironment in GBM with or without MGMT expression. Methods: Based on The Cancer Genome Atlas (TCGA) primary GBM cohort, the tumor-infiltrating lymphocytes (TILs) expression level was calculated using the CIBERSORTx algorithms and the single-sample Gene Set Enrichment Analysis (ssGSEA) method. Furthermore, the differential expression gene analysis was conducted and pathway analysis was performed using Ingenuity Pathway Analysis (IPA). The results were validated using the GBM cohort from the Chinese Glioma Genome Atlas (CGGA) database. In addition, TILs were isolated from 13 surgically removed primary GBM tumors in our institution. Their responses to autologous tumors were evaluated by IFNγ ELISA. Results: T cells CD8 score by CIBERSORTx was significantly higher in the MGMT-high tumor. Similarly, ssGSEA scores for activated CD8 T cell, Macrophage, activated B cell, and Type 1 T helper cell were significantly higher in the MGMT-high tumor. Conversely, T cells CD4 naive was significantly higher in the MGMT-low tumor. Consistently, tumor-reactive TILs were detected in the MGMT-high tumor. Pathway analysis showed that Rictor was highly enriched in the MGMT-high tumor and Rictor inhibited lymphocyte activation. Coclusion: In this study, we demonstrated that macrophage was highly activated in the MGMT-high tumors. Thus, CSF-1R inhibitor can be combined with immunotherapy in these MGMT-high tumors to enhance anti-tumor immune responses. In addition, TMZ + mTOR2 inhibitors + PD-1 inhibitors may be effective against the MGMT-L group.

Objective: To improve the safety of carotid artery stenting (CAS), reducing the risk of perioperative ischemic complications is mandatory. To achieve this, embolic protection devices (EPD) are being used in the majority of the procedure. With the GuardWire Temporary Occlusion and Aspiration System EPD, complete evacuation of the plaque debris before deflating the occlusion balloon is important to avoid cerebral thromboembolism. We report a novel method to stain the debris on the filter device to enhance the visualization of the retrieved debris so as to facilitate complete removal of the thromboembolic source. Case Presentations:The filter devices were immersed with 0.5 ml of 1% pyoktanin solution for 5 s and irrigated with saline during the CAS procedure. The pre-stained and stained filters were compared for the visibility of the debris. The pyoktanin staining enhanced the visualization of minute debris captured on the filter that was not well recognized before the staining. Conclusion:This simple technique was effective in improving the visualization of the evacuated plaque debris and may decrease distal embolism caused by previously unrecognized debris.

Purpose Though prolonging survival is often the focus of brain tumor therapy, evaluation of health-related quality of life (HRQoL) is important in postoperative follow-up since treatment-induced side effects or tumor-induced functional impairment could affect HRQoL.In glioma treatment, we investigated the relationship between patient-reported HRQoL assessment from 1 month preoperatively to 6 months postoperatively and overall health status at 1 year and 1.5years postoperatively. Methods Thirty-one glioma patients who underwent surgical treatment at our hospital and the National Cancer Center Hospital from May 2011 to August 2022 were included in this study. HRQoL and KPS were evaluated at 1 month before surgery, 6 months, 1 year and 1.5 years after surgery, respectively. The median age was 47 years, 15 (48%) were men and 16 (52%) were women. Pathological results were GBM in 19 (61%), AA in 4 (13%), AO in 2 (6%), and others in 6 (19%). The EORTC QLQ-C30/BN20 was used as a measure of HRQoL, and eligible patients answered each of the 50 questions on a 4-point scale, with scores calculated for 26 QoL status items. Bivariate analysis (Wilcoxon test) was performed on the 26 HRQoL items and KPS. Results/Consideration High KPS(≥70)was seen in patients who perceived themselves at 6 months postoperatively, to be “good” in the following 10 items “Physical functioning,” “Role functioning,” “Cognitive functioning,” “Global health status,” “Fatigue,” “Constipation,” “Motor dysfunction,” Communication deficit,” “Itchy skin” and “Weakness of legs. “In addition, patients who perceived their HRQoL conditions of” Sleep disturbance,”“ Future Uncertain,”and “ Bladder control”to be “good” after 6 months had a KPS of 70 or higher at 1.5 years. Conclusions The results suggest that long-term systemic status can also be monitored by assessing HRQoL in the first six months after surgery. Patient evaluation including sequential HRQoL is important in the treatment of glioma.

BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.