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Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454. We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ.
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http://dx.doi.org/10.1038/s41419-023-06392-w | DOI Listing |
Acta Neuropathol
September 2025
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Exp Neurobiol
August 2025
Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Korea.
Neural tumors represent diverse malignancies with distinct molecular profiles and present particular challenges due to the blood-brain barrier, heterogeneous molecular etiology including epigenetic dysregulation, and the affected organ's critical nature. KCC-07, a selective and blood-brain barrier penetrable MBD2 (methyl CpG binding domain protein 2) inhibitor, can suppress tumor development by inducing p53 signaling, proven only in medulloblastoma. Here we demonstrate KCC-07 treatment's application to other neural tumors.
View Article and Find Full Text PDFJ Natl Cancer Inst
September 2025
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States.
Background: Among childhood cancer survivors, germline rare variants in autosomal dominant cancer susceptibility genes (AD CSGs) could increase subsequent neoplasm (SNs) risks, but risks for rarer SNs and by age at onset are not well understood.
Methods: We pooled the Childhood Cancer Survivor Study and St Jude Lifetime Cohort (median follow-up = 29.7 years, range 7.
ACS Appl Mater Interfaces
September 2025
Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, Kraków 30-387, Poland.
The multifunctional systems presented here introduce an innovative and deeply thought-out approach to the more effective and safer use of temozolomide (TMZ) in treating glioma. The developed hydrogel-based flakes were designed to address the issues of local GBL therapy, bacterial neuroinfections, and the bleeding control needed during tumor resection. The materials obtained comprise TMZ and vancomycin (VANC) loaded into cyclodextrin/polymeric capsules and embedded into gelatin/hyaluronic acid/chitosan-based hydrogel films cross-linked with genipin.
View Article and Find Full Text PDFJ Neurooncol
September 2025
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Purpose: Glioblastoma (GBM) remains one of the most aggressive primary brain tumors with poor survival outcomes and a lack of approved therapies. A promising novel approach for GBM is the application of photodynamic therapy (PDT), a localized, light-activated treatment using tumor-selective photosensitizers. This narrative review describes the mechanisms, delivery systems, photosensitizers, and available evidence regarding the potential of PDT as a novel therapeutic approach for GBM.
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