Although the purely endoscopic supracerebellar infratentorial approach has been widely used for the resection of pineal region and posterior third ventricular tumors, its application in tumors extending across the tentorium is rarely reported. Here, we present a case of a supra-infratentorial tumor resected via a purely 3D-endoscopic supracerebellar infratentorial transtentorial (SCITTT) keyhole approach. Under a purely 3D endoscopic system, the SCITTT approach was performed through a paramedian keyhole craniotomy to resect a supra-infratentorial tumor. The tumor originated from the edge of right tentorium and extended both supra- and infratentorially. The infratentorial tumor was dissected and removed via the supracerebellar corridor. Subsequently, the tentorium was incised circumferentially around the tumor origin, followed by piecemeal resection of the supratentorial component. Using an approximately 2–3 cm keyhole craniotomy combined with the SCITTT approach and appropriate patient positioning, purely 3D-endoscopic surgery allows safe and minimally invasive resection of supra-infratentorial tumor without complications.

ObjectTo explore the prediction of the efficacy of bevacizumab (BEV) in treating peritumoral brain edema based on the radiomic features of T1-enhanced and T2-FLAIR MRI in patients with glioblastoma.MethodsA retrospective study was conducted on 321 glioblastoma patients who received bevacizumab treatment at The First Affiliated Hospital of Soochow University and The Second Affiliated Hospital of Soochow University from January 2020 to January 2025. The patients were randomly divided into a training set (n=224) and a validation set (n=97) at a ratio of 7:3. According to the Response Assessment in Neuro-Oncology (RANO) criteria, patients were classified into the remission group and non-remission group based on the reduction rate of peritumoral edema volume. Radiomic features were extracted from the glioma tumor and peritumoral edema regions on pretreatment baseline MRI using 3D-Slicer software. Features with significant intergroup differences were screened by univariate analysis and Lasso regression. Subsequently, three machine learning algorithms, namely logistic regression (LR), support vector machine (SVM), and random forest (RF), were used to construct radiomics prediction models. The efficacy of each model was compared using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The clinical practicability of the models was further evaluated by decision curve analysis.ResultsA total of 9 optimal radiomic features were finally screened out to construct the machine learning models. In the training set, the AUC values of the LR, SVM, and RF models were 0.832 (95% confidence interval [CI]: 0.690–0.973), 0.814 (95%CI: 0.730–0.897), and 0.796 (95%CI: 0.707–0.883), respectively. In the validation set, the corresponding AUC values were 0.883 (95%CI: 0.769–0.996), 0.800 (95%CI: 0.713–0.886), and 0.770 (95%CI: 0.604–0.934), respectively. For the LR model, decision curve analysis showed that the net benefit of the model was greater than 0 when the risk threshold ranged from 0.05 to 0.95.ConclusionThe LR, SVM, and RF models constructed based on MRI radiomic features all exhibit excellent predictive performance. Among them, the LR model has high clinical value and practicability with favorable net clinical benefit as confirmed by the clinical decision curve, and can be used to predict the therapeutic efficacy of bevacizumab for peritumoral brain edema in glioblastoma patients.

BACKGROUND:Glioblastoma (GBM) is a highly aggressive brain malignancy driven by glioma stem cells (GSCs). TIGAR (TP53-induced glycolysis and apoptosis regulator) is primarily known as a metabolic regulator that supports cell survival. However, its non-metabolic functions in neuro-oncology remain largely unexplored. This study aims to investigate the structural role of TIGAR in maintaining mitotic spindle integrity and its potential interplay with the ubiquitin-proteasome system in GSCs. METHODS:The clinical relevance of TIGAR expression was evaluated using GEPIA2, TCGA, CGGA, GTEx, and PDX-based analyses. TIGAR function was investigated in human GSC lines (GSC464 and GSC23) using lentiviral shRNA knockdown. Cell cycle progression and spindle morphology were analyzed with flow cytometry and immunofluorescence. Protein-protein interactions and stability were assessed via immunoprecipitation, cycloheximide chase, ubiquitination assays, NAC rescue testing, and Parkin co-depletion rescue assays. In vivo effects of TIGAR depletion were evaluated using GSC-derived orthotopic xenografts in SCID mice and an HRas-driven, p53-deficient primary glioblastoma mouse model. RESULTS:TIGAR expression is significantly upregulated in human GBM, correlating with tumor malignancy, stemness features, and poor patient prognosis. Public transcriptomic analysis showed a positive association between TIGAR expression and a GSC-related stemness signature, and double immunofluorescence staining confirmed co-localization of TIGAR with SOX2 or CD133 in two PDX models. TIGAR ablation in GSCs induced G2/M arrest and severe spindle defects, and these effects were validated in an additional GSC line. Mechanistically, TIGAR localizes to the mitotic spindle and physically interacts with βII-tubulin, protecting it from Parkin-mediated polyubiquitination and subsequent proteasomal degradation. NAC failed to rescue βII-tubulin loss after TIGAR knockdown, whereas Parkin co-depletion restored βII-tubulin levels and partially normalized the G2/M fraction. In vivo, TIGAR knockdown inhibited GSC-driven tumor growth, reduced stemness marker expression, and significantly prolonged animal survival. CONCLUSIONS:The study reveals an essential non-metabolic function of TIGAR in GBM. The TIGAR-Parkin-βII-tubulin axis serves as a critical mechanism for maintaining mitotic stability and protecting the GSC cytoskeletal network. These findings highlight TIGAR as a structural stabilizer during mitosis and a promising therapeutic target for glioblastoma, independent of p53 mutational status.

Spatial transcriptomics is an innovative technology that enables high-throughput, genome-wide analysis of transcript expression and spatial localization within tissues. By preserving structural organization, it provides critical insights into tumor sub-regions, substructures, and the heterogeneity and plasticity of cancer, stromal, and immune cells, as well as cell-cell interactions. Spatial transcriptomics also offers an unprecedented understanding of the tumor microenvironment, including immune cell infiltration, activation and repression, and immune suppression mediated by stromal cells. Importantly, it deepens our understanding of malignant transformation from precancerous lesions, tumorigenesis, and immune escape. Furthermore, spatial transcriptomics is reshaping cancer subtype diagnosis and risk stratification, uncovering factors associated with drug resistance, predicting therapy responses, and informing the development of personalized cancer treatments and potentially prevention. In summary, spatial transcriptomics serves as a cornerstone of cancer research, transforming the research landscape and unlocking groundbreaking opportunities for precision cancer diagnosis, risk stratification, targeted therapy, and prevention.

Glioma surgery, while critical for tumor control, often disrupts brain network integrity, leading to postoperative neurological deficits. This study employed resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) to assess functional and structural connectivity changes in 28 patients with supratentorial gliomas before and after surgical resection. We observed widespread reductions in functional connectivity (FC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuations (ALFF) after surgery, primarily involving sensorimotor and language networks. DTI revealed significant decreases in white matter integrity (fractional anisotropy, FA) in tumor-adjacent tracts, with reduced structural connectivity between tumor-affected and contralateral regions. Notably, we identified compensatory FC enhancements in language- and cognitive-related regions, which positively correlated with postoperative Karnofsky Performance Status (KPS) scores. Inter-group comparisons revealed that high-grade gliomas caused more severe network damage than low-grade tumors, and baseline network impairments were already evident preoperatively. These findings advance our understanding of glioma surgery-induced brain network disruption and highlight the role of neural plasticity in functional preservation. They also have important clinical implications for surgical planning, rehabilitation, and prognosis assessment.

The mitogen-activated protein kinase (MAPK) signaling pathway plays roles in cell proliferation, differentiation, and apoptosis, all crucial for cellular transformation. It’s no surprise that MAPK alterations are prevalent in numerous tumors. Several critical genes in the MAPK signaling pathway, including BRAF, FGFR, and NF1, are mutated in brain tumors. For example, FGFR1 mutation or rearrangement has been described in pilocytic astrocytoma, diffuse astrocytoma, and dysembryoplastic neuroepithelial tumor (DNT). These MAPK-activated brain tumors are benign and seldom progress to malignancies, with the mechanisms driving this rare transformation not yet fully understood. In this study, we present two cases of high-grade glioma characterized by a single activating mutation of FGFR1 and massive chromosome loss (near-haploid genome). Similar haploidy is found in 3 additional high-grade astrocytoma by literature review, all harbor a single gene mutation in the MAPK pathway. We propose that the massive chromosome loss might serve as a significant mechanism contributing to the unusual malignant transformation of benign brain tumors activated by the MAPK pathway.

Background Hypertension is widely acknowledged as a significant contributory factor to the heightened risk of intracranial aneurysm rupture. Nevertheless, the impact of hypertension management on the outcomes subsequent to aneurysmal subarachnoid haemorrhage (aSAH), particularly concerning the severity of aSAH, remains an underexplored area.Methods We conducted a retrospective analysis using data from a prospectively multicentre cohort of 4545 patients with aSAH in China. Premorbid hypertension status and the utilisation of antihypertensive medications prior to admission were set as key exposure factors. The primary outcomes encompassed unfavourable clinical grading scales observed on admission. Employing multivariable logistic regression, we explored the association between premorbid hypertension status, preadmission use of renin-angiotensin-aldosterone system (RAAS) inhibitors and unfavourable clinical grading scales.Results In comparison to patients with normal blood pressure, only uncontrolled hypertension demonstrated a significant and independent association with an elevated risk of poor outcomes on the Hunt-Hess scale (OR=1.799, 95% CI 1.413 to 2.291, p<0.001) and the World Federation of Neurological Surgeons (WFNS) scale (OR=1.721, 95% CI 1.425 to 2.079, p<0.001). Furthermore, the antecedent use of RAAS inhibitors before admission was markedly and independently linked to a diminished risk of adverse outcomes on the Hunt-Hess scale (OR=0.653, 95% CI 0.430 to 0.992, p=0.046) and the WFNS scale (OR=0.656, 95% CI 0.469 to 0.918, p=0.014).Conclusions Uncontrolled hypertension markedly elevates the risk of adverse clinical outcomes following an aSAH. Conversely, the preadmission utilisation of RAAS inhibitors demonstrates a noteworthy association with a favourable clinical outcome after aSAH.

[This corrects the article DOI: 10.3389/fonc.2025.1694881.].

Gliomas are the most common primary malignant tumors of the central nervous system and are characterized by their highly aggressive nature and poor prognosis. This study elucidates the oncogenic role of transmembrane protein TMEM165 in glioblastoma and its therapeutic potential. Bioinformatics analysis revealed that high expression of N-linked glycosylation regulatory proteins predicts poor prognosis in glioma patients, with TMEM165 first reported here demonstrating significant associations with shorter survival, higher tumor grade, and IDH wild-type status. Enrichment analysis indicated activation of the epithelial-mesenchymal transition (EMT) pathway in TMEM165-high groups and a positive correlation with temozolomide (TMZ) resistance. In vivo and in vitro experiments demonstrated that TMEM165 promotes glioblastoma proliferation, migration, and invasion by modulating EMT-related proteins, while reducing its sensitivity to TMZ. These findings identify TMEM165 as a novel therapeutic target for glioblastoma.

Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

IntroductionThe incidence of hemangioblastoma is low, constituting only 1-5% of all spinal cord tumors. Specifically, intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome represents an exceedingly rare condition.MethodsWe report the first documented case of cervical intradural extramedullary hemangioblastoma in China. A 53-year-old male patient presented with a 3-year history of mild right hemiplegia, segmental muscle strength and sensation impairment, and a positive pyramidal tract sign. MRI showed an abnormal oval signal focus in the intradural and extramedullary region at the C6-C7 vertebral level. Before surgery, angiography was performed to identify the supplying arteries and draining veins. Subsequent interventional therapy achieved over 90% occlusion of blood vessels, creating optimal conditions for complete resection of the spinal tumor.ResultsThe patient demonstrated satisfactory postoperative recovery with significant restoration of sensory and motor functions. Pathological examination showed a significant upregulation of CD31 in tumor cells and a substantial presence of the neuro-specific marker S100 in the tumor stroma, consistent with the diagnostic criteria for spinal hemangioblastoma.ConclusionThe rarity of cervical intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome was reaffirmed by a comprehensive review of the existing literature. Complete tumor resection remains the optimal approach for managing this uncommon condition, generally resulting in a favorable prognosis. Traditional open fenestration surgery is linked to elevated risks of bleeding and trauma. Meanwhile, endovascular injection of embolic agents may lead to residual lesions and an increased risk of recurrence. Therefore, we recommend a one-time combined treatment conducted in a hybrid operating room to achieve complete resection and effectively reduce intraoperative bleeding risk. Despite presenting challenges and requiring high proficiency, we still recommend this type of combined surgery as a suitable therapeutic option for such diseases.

Cancer is one of the intractable diseases of serious threat to human health,underscoring the urgent need for efficacious therapies in addition to conventional treatments including surgery,chemotherapy,and radiotherapy.Boron neutron capture therapy(BNCT)is regarded as one of the most cutting-edge techniques for cancer treatment with high precision and efficacy.BNCT is based on the 10B(n,α)7Li capture reaction between low-energy(0.025 eV)thermal neutrons and nonradioactive 10B isotope with a high neutron capture cross-section of 3840 barns,leading to the generation of α particles(4He)and recoiling 7Li nuclei with high linear energy transfer(LET)and very short path lengths of 5-9 μm.

BACKGROUND: Keyhole surgery has been widely used to clip various intracranial aneurysms. Here, the feasibility of microsurgical clipping of multiple intracranial aneurysms via the keyhole approach was further investigated. METHODS: The clinical data of 80 patients with multiple intracranial aneurysms treated with keyhole surgery were retrospectively analyzed. The patients included 25 males and 55 females, with an average age of 57.5 years. There were 13 patients with unruptured aneurysms, 67 patients with ruptured aneurysms (small aneurysms accounted for 52.2% of ruptured aneurysms), and a total of 198 aneurysms. A 4 cm incision and a bone hole of approximately 2.5 cm were used per craniotomy standards. Forty-eight cases were treated via the supraorbital keyhole approach, 45 cases via the pterional keyhole approach, and 3 cases via the interhemispheric keyhole approach. RESULTS: A bilateral and unilateral keyhole approach was applied in 18 and 62 cases, respectively. A total of 170 ipsilateral and 7 contralateral aneurysms were clipped. The complete clipping rate was 98.9%. During the followp period of 6-12 months after surgery, the Glasgow outcome scale score was 5 points in 74 cases, 4 points in 5 cases, and 3 points in 1 case. The prognosis was associated with the preoperative Hunt -Hess classification but not with the number of operative sides, the operation opportunity, or the number of clipped aneurysms. CONCLUSION: Early keyhole surgical clipping of multiple intracranial aneurysms is an effective treatment. Among ruptured aneurysms, small aneurysms are common and need attention and timely treatment.

The blood-brain barrier (BBB)/blood-tumor barrier (BTB) impedes brain entry of most brain-targeted drugs, whether they are water-soluble or hydrophobic. Endothelial WNT signaling and neoplastic pericytes maintain BTB low permeability by regulating tight junctions. Here, we proposed nitazoxanide (NTZ) and ibrutinib (IBR) co-loaded ICAM-1-targeting nanoparticles (NI@I-NPs) to disrupt the BTB in a time-dependent, reversible, and size-selective manner by targeting specific ICAM-1, inactivating WNT signaling and depleting pericytes in tumor-associated blood vessels in breast cancer brain metastases. At the optimal NTZ/IBR mass ratio (1:2), BTB opening reached the optimum effect at 48-72 h without any sign of intracranial edema and cognitive impairment. The combination of NI@I-NPs and chemotherapeutic drugs (doxorubicin and etoposide) extended the median survival of mice with breast cancer brain metastases. Targeting BTB endothelial WNT signaling and tumor pericytes via NI@I-NPs could open the BTB to improve chemotherapeutic efficiency against brain metastases.

Supplementary Figure S7. OTX015 and carfilzomib synergistically improve mouse survival in a PDX model of TERT-rearranged neuroblastoma.

The treatment of lumbar spinal synovial cysts (LSCs) which are relatively rare but can cause neurogenic dysfunction and intractable pain has been a controversial topic for many years. Surgical excision of LSCs is the standard treatment for patients in whom conservative treatment options fail. This meta-analysis was undertaken to compare clinical outcomes between minimally invasive approaches using tubular retractors (microscopic vs. endoscopic) and traditional percutaneous approaches for LSCs. Studies reporting surgical management of LSCs were searched in the Cochrane Library, PubMed and Web of Science database. This meta-analysis was reported following the PRISMA Statement, registered in Prospero (CRD42021288992). A total of 1833 patients were included from both the related relevant studies (41 studies, n = 1831) and the present series ( n = 2). Meta-analysis of minimally invasive tubular approaches revealed no statistically significant difference in pain improvement, dural tear, residual cyst, recurrence and operation time between minimal groups with traditional groups ( p > 0.05). Minimal groups had better Functional improvement of 100% (95% CI 1.00–1.00; p < 0.001, I 2 = 75.3%) and less reoperation rates of 0% (95% CI − 0.00–0.00; p = 0.007, I 2 = 47.1%). Postoperative length of hospital stay and intraoperative bleeding in minimal groups were also less than traditional groups ( p < 0.05). Subgroup analysis revealed endoscopic groups had less operation time ( p = 0.004), and there was no significant difference in the rest. For patients with LSCs but without obvious clinical and imaging evidence of vertebral instability, even when preoperative stable grade 1 spondylolisthesis is present, minimally invasive tubular approaches without fusion may provide the best outcome in surgical management.

Supplementary Figure S5. BET bromodomain inhibitors and proteasome inhibitors exert synergistic anticancer effects against TERT-rearranged neuroblastoma cells.

Boron neutron capture therapy (BNCT) has emerged as a treatment modality with high precision and efficacy of intractable tumors. At the core of effective tumor BNCT are 10B carriers with facile preparation as well as advantageous pharmacokinetic and therapeutic profiles. Herein, the design and preparation of sub‐10 nm 10B‐enriched hexagonal boron nitride nanoparticles grafted with poly(glycerol) (h‐10BN‐PG), and their application to cancer treatment by BNCT are reported. By virtue of their small particle size and outstanding stealth property, h‐10BN‐PG nanoparticles accumulate efficiently in murine CT26 colon tumors with a high intratumor 10B concentration of 8.8%ID g−1 or 102.1 µg g−1 at 12 h post‐injection. Moreover, h‐10BN‐PG nanoparticles penetrate into the inside of the tumor parenchyma and then are taken up by the tumor cells. BNCT comprising a single bolus injection of h‐10BN‐PG nanoparticles and subsequent one‐time neutron irradiation results in significant shrinkage of subcutaneous CT26 tumors. h‐10BN‐PG‐mediated BNCT not only causes direct DNA damage to the tumor cells, but also triggers pronounced inflammatory immune response in the tumor tissues, which contributes to long‐lasting tumor suppression after the neutron irradiation. Thus, the h‐10BN‐PG nanoparticles are promising BNCT agents to eradicate tumor through highly efficient 10B accumulation.

Supplementary Figure S2. BRD4 is required for TERT expression and cell proliferation in TERT-rearranged neuroblastoma cells.