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Background: In assessing the clinical utility and safety of 3.0 T intraoperative magnetic resonance imaging (iMRI) combined with multimodality functional MRI (fMRI) guidance in the resection of functional area gliomas, we conducted a study., Method: Among 120 patients with newly diagnosed functional area gliomas who underwent surgical treatment, 60 were included in each group: the integrated group with iMRI and fMRI and the conventional navigation group. Between-group comparisons were made for the extent of resection (EOR), preoperative and postoperative activities of daily living based on the Karnofsky performance status, surgery duration, and postoperative intracranial infection rate., Results: Compared to the conventional navigation group, the integrated navigation group with iMRI and fMRI exhibited significant improvements in tumor resection (complete resection rate: 85.0% vs. 60.0%, P = 0.006) and postoperative life self-care ability scores (Karnofsky score) (median ± interquartile range: 90 ± 25 vs. 80 ± 30, P = 0.013). Additionally, although the integrated navigation group with iMRI and fMRI required significantly longer surgeries than the conventional navigation group (mean ± standard deviation: 411.42 ± 126.4 min vs. 295.97 ± 96.48 min, P<0.0001), there was no significant between-group difference in the overall incidence of postoperative intracranial infection (16.7% vs. 18.3%, P = 0.624)., Conclusion: The combination of 3.0 T iMRI with multimodal fMRI guidance enables effective tumor resection with minimal neurological damage., (© 2024. The Author(s).)

Introduction: Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is notorious for its aggressive growth and dismal prognosis. This study aimed to elucidate the molecular underpinnings of GBM, particularly focusing on the role of AGBL4 and its connection to inflammatory pathways, to discover viable therapeutic targets., Methods: Single-cell sequencing was utilized to examine the expression levels of AGBL4 and functional assays were performed to assess the effects of AGBL4 modulation., Results: Our findings identified the significant upregulation of AGBL4 in GBM, which correlated with adverse clinical outcomes. Functional assays demonstrated that AGBL4 knockdown inhibited GBM cell proliferation, migration, and invasion and influenced inflammatory response pathways, while AGBL4 overexpression promoted these activities. Further investigation revealed that AGBL4 exerted its oncogenic effects through modulation of MMP-1, establishing a novel regulatory axis critical for GBM progression and inflammation., Discussion: Both AGBL4 and MMP-1 may be pivotal molecular targets, offering new avenues for targeted therapy in GBM management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Cheng, Su, Qian, Wang, Chen, Li, Zhang, He, Mao, Wang and Chen.)

Background: Abnormal proliferation and migration of cells are hallmarks of cancer initiation and malignancy. Asparagine endopeptidase (AEP) has specific substrate cleavage ability and plays a pro-cancer role in a variety of cancers. However, the underlying mechanism of AEP in cancer proliferation and migration still remains unclear., Methods: Co-immunoprecipitation and following mass spectrometry were used to identify the substrate of AEP. Western blotting was applied to measure the expression of proteins. Single cell/nuclear-sequences were done to detect the heterogeneous expression of Tmod3 in tumor tissues. CCK-8 assay, flow cytometry assays, colony formation assay, Transwell assay and scratch wound-healing assay were performed as cellular functional experiments. Mouse intracranial xenograft tumors were studied in in vivo experiments., Results: Here we showed that AEP cleaved a ubiquitous cytoskeleton regulatory protein, tropomodulin-3 (Tmod3) at asparagine 157 (N157) and produced two functional truncations (tTmod3-N and tTmod3-C). Truncated Tmod3 was detected in diverse tumors and was found to be associated with poor prognosis of high-grade glioma. Functional studies showed that tTmod3-N and tTmod3-C enhanced cancer cell migration and proliferation, respectively. Animal models further revealed the tumor-promoting effects of AEP truncated Tmod3 in vivo. Mechanistically, tTmod3-N was enriched in the cell cortex and competitively inhibited the pointed-end capping effect of wild-type Tmod3 on filamentous actin (F-actin), leading to actin remodeling. tTmod3-C translocated to the nucleus, where it interacted with Staphylococcal Nuclease And Tudor Domain Containing 1 (SND1), facilitating the transcription of Ras Homolog Family Member A/Cyclin Dependent Kinases (RhoA/CDKs)., Conclusion: The newly identified AEP-Tmod3 protease signaling axis is a novel "dual-regulation" mechanism of tumor cell proliferation and migration. Our work provides new clues to the underlying mechanisms of cancer proliferation and invasive progression and evidence for targeting AEP or Tmod3 for therapy., (© 2022. The Author(s).)

Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally targeted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM., (Copyright © 2020. Published by Elsevier B.V.)

Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma., (© 2017 UICC.)

Background: Primary intracranial germinomas occurring in the cerebral hemisphere are extremely rare, with only a few reported cases in the literature. We describe an unusual case of a primary germinoma that developed in the insular lobe, with little involvement in the basal frontal lobe., Case Description: A 19-year-old man presented with headache and vomiting. Magnetic resonance imaging showed a solitary, ring-like enhanced lesion in the left hemisphere, and a preliminary diagnosis of glioma was made. Surgery was performed, and the diagnosis of germinoma was made based on the histopathologic results., Conclusions: The causes of ectopic germinomas of the midline structures of the brain are still unclear, but the theory of misplacement may partially clarify this phenomenon. Reflecting a lack of definitive management guidelines for atypical germinoma, the present patient was treated with focal radiotherapy around the lesion after surgery and achieved remission by 34 months postoperatively., (Copyright © 2016 Elsevier Inc. All rights reserved.)