Purpose: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. Experimental Design: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. Results: The probe screening identified proline-arginine–HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. Conclusions: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

In conducting medical research, a system which can objectively predict the future trends of the given research field is awaited. This study aims to establish a novel and versatile algorithm that predicts the latest trends in neuro-oncology. Seventy-nine neuro-oncological research fields were selected with computational sorting methods such as text-mining analyses. Thirty journals that represent the recent trends in neuro-oncology were also selected. As a novel concept, the annual impact (AI) of each year was calculated for each journal and field (number of articles published in the journal × impact factor of the journal). The AI index (AII) for the year was defined as the sum of the AIs of the 30 journals. The AII trends of the 79 fields from 2008 to 2017 were subjected to machine learning predicting analyses. The accuracy of the predictions was validated using actual past data. With this algorithm, the latest trends in neuro-oncology were predicted. As a result, the linear prediction model achieved relatively good accuracy. The predicted hottest fields in recent neuro-oncology included some interesting emerging fields such as microenvironment and anti-mitosis. This algorithm may be an effective and versatile tool for prediction of future trends in a particular medical field.

BACKGROUND: High-grade gliomas, particularly isocitrate dehydrogenase–wildtype glioblastomas (GBMs), are highly aggressive brain tumors with limited treatment options and poor outcomes. A subset of these tumors, including epithelioid GBM, can harbor the BRAF V600E mutation, which drives tumor growth via persistent activation of the RAS/MAPK signaling pathway. Recently, the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) has been approved for treating inoperable solid tumors with this mutation. OBSERVATIONS: The authors present the case of a 51-year-old man with epithelioid GBM harboring the BRAF V600E mutation who developed early leptomeningeal metastasis (LMM) following standard therapy with surgery, temozolomide, and radiotherapy. Owing to disease progression, he was treated with dabrafenib and trametinib. Remarkably, the patient showed rapid clinical and radiographic improvement within 2 weeks of treatment initiation. MR images demonstrated significant reduction in tumor-associated edema and contrast enhancement. At the 28-week follow-up, the patient achieved near-complete radiographic remission without notable adverse effects. LESSONS: This case highlights the potential of BRAF/MEK inhibitor therapy to significantly improve outcomes in patients with aggressive gliomas and LMM, conditions typically associated with extremely poor prognosis. Further studies are needed to validate the long-term efficacy and safety of this targeted therapeutic approach in similar cases. https://thejns.org/doi/10.3171/CASE25247

Trapped temporal horn (TTH) is a subtype of focal obstructive hydrocephalus. Although a ventriculoperitoneal shunt is a traditional treatment approach, it poses risks of shunt failure and infection. The emergence of neuroendoscopy has led to an increased interest in ventriculocisternostomy as an alternative. This study aimed to evaluate the efficacy and safety of endoscopic ventriculocisternostomy with stent placement (EVSP) for TTH. We collected data of TTH cases treated with EVSP at our institutions between September 2013 and September 2021 and evaluated baseline characteristics and outcomes. A ventricular stoma was created at the medial wall of the abnormally enlarged temporal horn using a neuroendoscope, and a ventricular stent tube with multiple side holes was placed through the stoma to maintain patency. The study included 10 patients (4 women and 6 men) with a mean age of 56.7 ± 19.7 years. The average follow-up period was 35.0 months (range, 1-96 months). The underlying pathologies were postoperative scarring (5 cases), intraventricular tumor (3 cases), and extraventricular tumor (2 cases). There were no procedural complications; however, one patient experienced recurrence and underwent additional cisternostomy. All patients exhibited partial or complete resolution of the preoperative symptoms and demonstrated shrinkage of the trapped ventricle, with a mean reduction rate of 84.5% ± 14.9%. EVSP is a safe and feasible option for the treatment of TTH and is a viable alternative to ventriculo-peritoneal shunt.

The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt ) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.