Glioblastoma multiforme (GBM) requires radiotherapy (RT) as a part of definitive management strategy. RT is highly effective, destroying cancer cells that may exist around the surgical tumor bed. However, GBM still has a poor prognosis and a high local recurrence rate after RT. Accumulating research indicates that GBM contains cancer stem-like cells (CSCs), which are radioresistant and result in therapeutic failure. Additionally, GBM cells can aggressively invade normal brain tissue, inducing therapeutic failure. Using clinical observations, we evaluated the effect of radiation on tumor control. We also explored the biomolecular pathways that connect radioresistance and CSC- and epithelial-mesenchymal transition (EMT)-associated phenotypes in patient-derived GBM cells. Transwell and microarray assay demonstrated that radioresistant GBM cells (GBM-R2I2) exhibit increased invasion and self-renewal abilities compared with parental GBM cells. Finally, to identify potential mechanisms underlying these observations, we used a PCR array to search for molecular markers of cell motility. Signal transducer and activator of transcription 3 (STAT3) directly bound to the Slug promoter in a chromatin immunoprecipitation assay. Reduced STAT3 decreased Slug expression and suppressed cell invasion in GBM-R2I2 cells while increasing Slug reversed these effects. In addition, STAT3 knockdown significantly inhibited CSC properties, synergistically increased the radiotherapeutic effect, and effectively increased the survival rate in vivo. We deciphered a new pathway of GBM radioresistance, invasion, and recurrence via the STAT3/Slug axis that could be a new target of GBM therapy.

Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem‐like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient‐derived malignant glioblastoma cells with the PTV₉₅ (PTV coverage of more than 95%) program (GBM‐MG1 cells) and the Non‐PTV₉₅ (poor PTV coverage of less than 95%) program (GBM‐MG2 cells). The clinical results of PTV₉₅ and Non‐PTV₉₅ showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM‐MG1 (PTV₉₅ program) cells exhibited higher radioresistance than GBM‐MG2 (Non‐PTV₉₅ program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM‐MG1 (PTV₉₅ program) cells. GBM patients receiving RT with the PTV₉₅ program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV₉₅ program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV₉₅ program.

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.

Neurosurgeons require considerable expertise and practical experience in dealing with the critical situations commonly encountered during difficult surgeries; however, neurosurgical trainees seldom have the opportunity to develop these skills in the operating room. Therefore, physical simulators are used to give trainees the experience they require. In this study, we created a physical simulator to assist in training neurosurgeons in aneurysm clipping and the handling of emergency situations during surgery. Our combination of additive manufacturing with molding technology, elastic material casting, and ultrasonication-assisted dissolution made it possible to create a simulator that realistically mimics the brain stem, soft brain lobes, cerebral arteries, and a hollow transparent Circle of Willis, in which the thickness of vascular walls can be controlled and aneurysms can be fabricated in locations where they are likely to appear. The proposed fabrication process also made it possible to limit the error in overall vascular wall thickness to just 2–5%, while achieving a Young’s Modulus closely matching the characteristics of blood vessels (~5%). One neurosurgical trainee reported that the physical simulator helped to elucidate the overall process of aneurysm clipping and provided a realistic impression of the tactile feelings involved in this delicate operation. The trainee also experienced shock and dismay at the appearance of leakage, which could not immediately be arrested using the clip. Overall, these results demonstrate the efficacy of the proposed physical simulator in preparing trainees for the rigors involved in performing highly delicate neurological surgical operations.

The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.

Simple hematoma evacuation is often performed in cases of chronic subdural hematoma (CSDH) associated with arachnoid cysts (ACs) on the same side after head injury. However, it is not clear which procedure is appropriate when ACs and CSDH are located on different sides. Here, we present a case of a 3-year-old boy with right frontal–temporal subdural hematoma and an AC over the left frontal–temporal region. Treatment involved craniotomy with hematoma evacuation, but no drainage of contralateral AC was applied. The patient was discharged 7 days after surgery without any neurologic deficits and no symptoms of headache or poor appetite. These results suggest that craniotomy and hematoma evacuation without intervention for the AC is adequate in patients with contralateral CSDH with a large AC.