This study developed and evaluated nnU-Net models for three-dimensional semantic segmentation of pituitary adenomas (PAs) from contrast-enhanced T1 (T1ce) images, with aims to train a deep learning-based model cost-effectively and apply it to clinical practice. Methods: This study was conducted in two phases. In phase one, two models were trained with nnUNet using distinct PA datasets. Model 1 was trained with 208 PAs in total, and model 2 was trained with 109 primary nonfunctional pituitary adenomas (NFPA). In phase two, the performances of the two models were investigated according to the Dice similarity coefficient (DSC) in the leave-out test dataset. Results: Both models performed well (DSC > 0.8) for PAs with volumes > 1000 mm³, but unsatisfactorily (DSC < 0.5) for PAs < 1000 mm³. Conclusions: Both nnU-Net models showed good segmentation performance for PAs > 1000 mm³ (75% of the dataset) and limited performance for PAs < 1000 mm³ (25% of the dataset). Model 2 trained with fewer samples was more cost-effective. We propose to combine the use of model-based segmentation for PA > 1000 mm³ and manual segmentation for PA < 1000 mm³ in clinical practice at the current stage.

Glioma stem-like cells (GSCs) are a subset of tumor cells that initiate malignant growth and promote the therapeutic resistance of glioblastoma, the most lethal primary brain tumor. Ribosome biogenesis is an essential cellular process to maintain cell growth, but its regulatory mechanism in GSCs remains largely unknown. Here, we show that WD repeat domain 12 (WDR12), a component of the Pes1-Bop1 complex (PeBoW), is required for ribosome biogenesis in GSCs. WDR12 is preferentially expressed in GSCs compared to non-stem tumor cells and normal brain cells. High levels of WDR12 are associated with glioblastoma progression and poor prognosis. Silencing WDR12 results in the degradation of PeBoW complex components and prevents the maturation of 28S rRNA, thereby inhibiting ribosome biogenesis in GSCs. Subsequently, WDR12 depletion compromises GSC proliferation, inhibits GSC-derived orthotopic tumor growth, and extends animal survival. Together, our results suggest that WDR12 is crucial for ribosome biogenesis in GSCs, and is thus a potential target for GSC-directed therapy of glioblastoma.

High-grade gliomas—particularly glioblastoma (GBM)—remain refractory to standard-of-care surgery followed by chemoradiation, with a median overall survival of ~15 months. Oncolytic viruses (OVs), which selectively infect and lyse tumor cells while engaging antitumor immunity, offer a mechanistically distinct therapeutic modality. This review synthesizes clinical progress of OVs in GBM, with emphasis on oncolytic herpes simplex virus (oHSV) and coverage of other vectors (adenovirus, reovirus, Newcastle disease virus, vaccinia virus) across phase I–III trials, focusing on efficacy and safety. Key observations include the encouraging clinical trajectory of oHSV exemplars—T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)—the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Emerging evidence indicates that oHSV therapy augments immune infiltration within the tumor microenvironment and alleviates immunosuppression, with synergy when combined with chemotherapy or immune checkpoint inhibitors. Persistent challenges include GBM’s inherently immunosuppressive milieu, limitations imposed by the blood–brain barrier, intrapatient viral delivery and biodistribution, and concerns about viral shedding. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit.

The infiltration of glioblastoma multiforme (GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1 (FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6 (HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.