MicroRNAs (miRNAs) could be potential biomarkers for glioblastoma multiforme (GBM) prognosis and response to therapeutic agents. We previously demonstrated that the cancer stem cell marker Musashi-1 (MSI1) is an RNA binding protein that promotes radioresistance by increasing downstream RNA stability. To identify that MSI1 interacts with miRNAs and attenuates their function, we also get candidate miRNAs from the mRNA seq by predicting with TargetScan software. miR-671-5p in GBM cells interacts with MSI1 by intersecting the precipitated miRNAs with the predicted miRNAs. Notably, overexpression of MSI1 reversed the inhibitory effect of miR-671-5p. The phenotype of miR-671-5p in GBM cells could affect radiosensitivity by modulating the posttranscriptional activity of STAT3. In addition, miR-671-5p could attenuate tumor migration and cancer stem cell (CSC) characteristics by repressing the posttranscriptional activity of TRAF2. MSI1 may regulate GBM radioresistance, CSCs and tumor motility through miR-671-5p inhibition to increasing STAT3 and TRAF2 presentation. In vivo, the GBM tumor size was inversely correlated with miR-671-5p expression, but tumorigenesis was promoted by STAT3 and TRAF2 activation in the miR-671-5p-positive GBM population. miR-671-5p could be activated as a novel therapeutic target for GBM and has potential application as a predictive biomarker of glioblastoma prognosis.

In recurrent glioblastoma, Gliadel wafer implantation after surgery has been shown to result in incomplete chemical removal of residual tumor and development of brain edema. Furthermore, temozolomide (TMZ) resistance caused by O⁶-methylguanine-DNA-methyltransferase (MGMT) activation and programmed cell death-ligand 1 (PD-L1) expression leads to immune-cold lesions that result in poorer prognosis. Cerebraca wafer, a biodegradable polymer containing (Z)-n-butylidenephthalide (BP), is designed to eliminate residual tumor after glioma resection. An open-label, one-arm study with four dose cohorts, involving a traditional 3 + 3 dose escalation clinical trial, of the Cerebraca wafer combined with TMZ on patients with recurrent high-grade glioma, was conducted. Of the 12 patients who receive implantation of Cerebraca wafer, there were no drug-related adverse events (AEs) or serious AEs (SAEs). The median overall survival (OS) of patients receiving low-dose Cerebraca wafer was 12 months in the group with >25% wafer coverage of the resected tumor, which is longer than OS duration in previously published studies (Gliadel wafer, 6.4 months). Patients who received high-dose Cerebraca wafer treatment had not yet died at the data cut-off date; a 100% progression-free survival (PFS) rate at six month was achieved, indicating the median OS of cohort IV was more than 17.4 months. In vitro study of the primary cells collected from the patients revealed that the IC₅₀ of BP against tumor stem cells was four times lower than that of bis-chloroethylnitrosourea (BCNU). A synergistic effect between BP and TMZ was demonstrated by a reduction in MGMT expression. Furthermore, BP inhibited PD-L1 expression, thereby activating T-cell cytotoxicity and increasing interferon-gamma (IFN-γ) secretion. The better therapeutic effect of Cerebraca wafer on recurrent high-grade glioma could occur through re-sensitization of TMZ and reduction of PD-L1.

Primary brain malignancy is a rare tumor with a global incidence of less than 10 per 100,000 people. Hence, there is limited power for identifying risk loci in individual studies, especially for Han Chinese. We performed a genome-wide association study (GWAS) in Taiwan, including 195 cases and 195 controls. We identified five new genes for malignant neoplasms of the brain: EDARADD (rs645507, 1p31.3, p = 7.71 × 10⁻⁵, odds ratio (OR) = 1.893), RBFOX1 (rs8044700, p = 2.35 × 10⁻⁵, OR = 2.36), LMF1 (rs3751667, p = 7.24 × 10⁻⁷, OR = 2.17), DPP6 (rs67433368, p = 8.32 × 10⁻⁵, OR = 3.94), and NDUFB9 (rs7827791, p = 9.73 × 10⁻⁶, OR = 4.42). These data support that genetic susceptibility toward GBM or non-GBM tumors is highly distinct, likely reflecting different etiologies. Combined with signaling analysis, we found that RNA modification may be related to major risk factors in primary malignant neoplasms of the brain.

Neurosurgeons require considerable expertise and practical experience to deal with the critical situations commonly encountered in complex surgical operations such as cerebral cancer; however, trainees in neurosurgery seldom have the opportunity to develop these skills in the operating room. Physical simulators can give trainees the experience they require. In this study, we adopted advanced molding and replication techniques in the fabrication of a physical simulator for use in practicing the removal of cerebral tumors. Our combination of additive manufacturing and molding technology with elastic material casting made it possible to create a simulator that realistically mimics the skull, brain stem, soft brain lobes, and cerebral cancer with cerebral tumors located precisely where they are likely to appear. Multiple and systematic experiments were conducted to prove that the elastic material used herein was appropriated for building professional medical physical simulator. One neurosurgical trainee reported that under the guidance of a senior neurosurgeon, the physical simulator helped to elucidate the overall process of cerebral cancer removal and provided a realistic impression of the tactile feelings involved in craniotomy. The trainee also learned how to make decisions when facing the infiltration of a cerebral tumor into normal brain lobes. Our results demonstrate the efficacy of the proposed physical simulator in preparing trainees for the rigors involved in performing highly delicate surgical operations.

Background: Radiotherapy (RT) provides a modern treatment to enhance the malignant glioma control rate. The purpose of our study was to determine the effect of tumor coverage on disease prognosis and to predict optimal RT plans to achieve a lower normal tissue complication probability (NTCP). Methods: Ten malignant-glioma patients with tumors adjacent to organs at risk (OARs) were collected. The patients were divided into two groups according to adequate coverage or not, and prognosis was analyzed. Then, using intensity-modulated radiation therapy (IMRT), volume-modulated arc therapy (VMAT), and helical tomotherapy (TOMO) to simulate new treatment plans for 10 patients, the advantages of these planning systems were revealed for subsequent prediction of NTCP. Results: The results of clinical analysis indicated that overall survival (p = 0.078) between the adequate and inadequate groups showed no differences, while the adequate group had better recurrence-free survival (p = 0.018) and progression-free survival (p = 0.009). TOMO had better CI (p < 0.001) and also predicted a lower total-irradiated dose to the normal brain (p = 0.001) and a lower NTCP (p = 0.027). Conclusions: The TOMO system provided optimal therapeutic planning, reducing NTCP and achieving better coverage. Combined with the clinical results, our findings suggest that TOMO can make malignant glioma patients close to OARs achieve better disease control.