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Background: Isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM., Methods: In total, 34 recurrent IDHwt GBM patients who received a second surgery were included in the analysis (17 in the surgery group and 17 in the surgery + IORT group)., Results: The progression-free survival and overall survival after the second surgery were defined as PFS 2 and OS 2 , respectively. The median PFS 2 was 7.3 months (95% CI: 6.3-10.5) and 10.6 months (95% CI: 9.3-14.6) for those patients who received surgery and surgery + IORT, respectively. Patients in the surgery + IORT group also had a longer OS 2 (12.8 months, 95% CI: 11.4-17.2) than those in the surgery group (9.3 months, 95% CI: 8.9-12.9). The Kaplan-Meier survival curves, analyzed by log-rank test, revealed a statistically significant difference in PFS 2 and OS 2 between both groups, suggesting that IORT plays an active role in the observed benefits for PFS 2 and OS 2 . The effects of IORT on PFS 2 and OS 2 were further confirmed by multivariate Cox hazards regression analysis. Two patients in the surgery group developed distant glioma metastases, and no radiation-related complications were observed in the IORT group., Conclusions: This study suggests that low-dose IORT may improve the prognosis of recurrent IDHwt GBM patients. Future prospective large-scale studies are needed to validate the efficacy and safety of IORT., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increasing evidence indicates that glioma topographic location is linked to the cellular origin, molecular alterations and genetic profile. This research aims to (a) reveal the underlying mechanisms of tumor location predilection in glioblastoma multiforme (GBM) and lower-grade glioma (LGG) and (b) leverage glioma location features to predict prognosis. MRI images from 396 GBM and 190 LGG (115 astrocytoma and 75 oligodendroglioma) patients were standardized to construct frequency maps and analyzed by voxel-based lesion-symptom mapping. We then investigated the spatial correlation between glioma distribution with gene expression in healthy brains. We also evaluated transcriptomic differences in tumor tissue from predilection and nonpredilection sites. Furthermore, we quantitively characterized tumor anatomical localization and explored whether it was significantly related to overall survival. Finally, we employed a support vector machine to build a survival prediction model for GBM patients. GBMs exhibited a distinct location predilection from LGGs. GBMs were nearer to the subventricular zone and more likely to be localized to regions enriched with synaptic signaling, whereas astrocytoma and oligodendroglioma tended to occur in areas associated with the immune response. Synapse, neurotransmitters and calcium ion channel-related genes were all activated in GBM tissues coming from predilection regions. Furthermore, we characterized tumor location features in terms of a series of tumor-to-predilection distance metrics, which were able to predict GBM 1-year survival status with an accuracy of 0.71. These findings provide new perspectives on our understanding of tumor anatomic localization. The spatial features of glioma are of great value in individual therapy and prognosis prediction., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Accumulating evidence indicates long noncoding RNAs (lncRNA) play a vital role in tumor progression. However, the role of linc00645-induced accelerated malignant behavior in glioblastoma (GBM) remains unknown. In the present study, linc00645 expression was significantly upregulated in GBM tissues and cell lines. High level of linc00645 was associated with poor overall survival in GBM patients. Knockdown of linc00645 suppressed the proliferation, stemness, migration, invasion, and reversed transforming growth factor (TGF)-β-induced motility of glioma cell lines. Furthermore, linc00645 directly interacted with miR-205-3p and upregulated of miR-205-3p impeded efficiently the increase of ZEB1 induced by linc00645 overexpression. Moreover, knockdown of linc00645 significantly suppressed the progression of glioma cells in vivo. miR-205-3p was a target of linc00645 and linc00645 modulates TGF-β-induced glioma cell migration and invasion via miR-205-3p. Taken together, our findings identified the linc00645/miR-205-3p/ZEB1 signaling axis as a key player in EMT of glioma cells triggered by TGF-β. These data elucidated that linc00645 plays an oncogenic role in glioma and it may serve as a prognostic biomarker and a potential therapeutic target for the treatment of glioma in humans.

Background: Accumulating evidence demonstrates the oncogenic roles of lncRNA (long non-coding RNA) molecules in a wide variety of cancer types including glioma. Equally important, However, tumorigenic functions of lncRNA in glioma remain largely unclear. A recent study suggested lncRNA SNHG15 played a role for regulating angiogenesis in glioma but its role in the tumor microenvironment (TME) was not investigated., Methods: First, we showed that SNHG15 was upregulated in GBM cells and associated with a poor prognosis for the patients of GBM using public databases. Next, we collected temozolomide sensitive (TMZ-S) and resistant (TMZ-R) clinical samples and demonstrated that co-culturing TMZ-R cells with HMC3 (microglial) cells promoted M2-polarization of HMC3 and the secretion of pro-GBM cytokines TGF-β and IL-6., Results: Comparative qPCR analysis of TMZ-S and TMZ-R cells showed that a significantly higher level of SNHG15, coincidental with a higher level of Sox2, β-catenin, EGFR, and CDK6 in TMZ-R cells. Subsequently, using bioinformatics tool, a potential mechanistic route for SNHG15 to promote GBM tumorigenesis was by inhibiting tumor suppressor, miR-627-5p which leads to activation of CDK6. Gene-silencing technique was employed to demonstrate that suppression of SNHG15 indeed led to the suppression of GBM tumorigenesis, accompanied by an increase miR-627-5p and decreased its two oncogenic targets, CDK6 and SOX-2. In addition, SNHG15-silenced TMZ-R cells became significantly sensitive towards TMZ treatment and less capable of promoting M2-phenotype in the HMC3 microglial cells. We then evaluated the potential anti-GBM activity of CDK6 inhibitor, palbociclib, using TMZ-R PDX mouse models. Palbociclib treatment significantly reduced tumorigenesis in TMZ-R/HMC3 bearing mice and SNHG15 and CDK6 expression was significantly reduced while miR-627-5p level was increased. Additionally, palbociclib treatment appeared to overcome TMZ resistance as well as reduced M2 markers in HMC3 cells., Conclusion: Together, we provided evidence supporting the usage of CDK6 inhibitor for TMZ-resistant GBM cases. Further investigation is warranted for the consideration of clinical trials.