Publications by authors named "Stefan Sweha"
Article Synopsis
- H3K27M diffuse midline gliomas (DMG) consist of two main types of cells: less-differentiated oligodendrocyte precursor-like stem cells and more differentiated astrocyte-like cells.
- Researchers created models representing these cell types and used various profiling techniques to understand their distinct metabolic programs, identifying specific weaknesses in each type.
- The study found that astrocyte-like cells are more prone to a type of cell death called ferroptosis, while oligodendrocyte precursor-like cells are sensitive to statins and inhibitors of mitochondrial function, suggesting targeted therapies could improve treatment outcomes for patients with these tumors.
Unlabelled: Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies.
View Article and Find Full Text PDFTargeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas.
Proc Natl Acad Sci U S A
May 2023
Article Synopsis
- Diffuse midline gliomas (DMGs), including DIPGs with H3K27M mutations, are aggressive childhood brain tumors characterized by altered histone modifications that impact gene expression.* -
- The study found that these mutations increase levels of specific SWI/SNF complex proteins, which help regulate chromatin structure and gene activation, making them potential targets for treatment.* -
- A targeted therapeutic approach using PROTAC compounds to degrade these proteins resulted in cell death in H3K27M mutant cells, suggesting a promising strategy for combating these lethal cancers.*
Article Synopsis
- Diffuse midline gliomas (DMG) are aggressive brain tumors with poor survival rates and an unclear mechanism of invasion, linked to increased levels of the ID1 protein due to specific genetic mutations.
- The study involved extensive genetic analyses and experiments to evaluate the role of ID1 in tumor growth and invasion, including tests with the compound cannabidiol (CBD).
- Findings indicate that high ID1 expression correlates with tumor characteristics and enhances migration, while targeting ID1 with CBD effectively reduces tumor cell growth and movement, suggesting a potential therapeutic strategy for treating DMG.
High-grade gliomas with arginine or valine substitutions of the histone H3.3 glycine-34 residue (H3.3G34R/V) carry a dismal prognosis, and current treatments, including radiotherapy and chemotherapy, are not curative.
View Article and Find Full Text PDFArticle Synopsis
- There are two types of childhood ependymomas: group A (PFAs) and group B (PFBs), and PFAs are harder to treat and have worse outcomes.
- PFAs have a special protein called EZHIP, which makes some important changes in the cells that help the cancer grow faster.
- Using a medicine called metformin, which is usually for diabetes, can help slow down the growth of these tumors by changing how the cancer cells use energy and by reducing the EZHIP protein.
Article Synopsis
- * Research indicates that these mutated cells undergo enhanced metabolic processes like glycolysis and glutaminolysis, leading to increased production of alpha-ketoglutarate (α-KG), which helps sustain the low H3K27me3 levels.
- * Disrupting the metabolic pathways that maintain this epigenetic state shows promising results in improving survival in animal models, highlighting potential new therapeutic strategies for treating H3K27M DIPGs.
Article Synopsis
- * Researchers found that female premutation carriers experience higher levels of obsessive-compulsive symptoms, anxiety, and depression, but do not show significant cognitive deficits compared to normal controls.
- * Despite some expected relationships between molecular markers and the CGG repeat number, the study concludes there are no strong correlations between these molecular measures and the reported clinical symptoms, indicating that other factors may be involved in the psychological profiles of these carriers.
Objectives: Several neurotransmitters involved in brain development are altered in fragile X syndrome (FXS), the most common monogenic cause of autism spectrum disorder (ASD). Serotonin plays a vital role in synaptogenesis and postnatal brain development. Deficits in serotonin synthesis and abnormal neurogenesis were shown in young children with autism, suggesting that treating within the first years of life with a selective serotonin reuptake inhibitor might be the most effective time.
View Article and Find Full Text PDFDistribution of AGG interruption patterns within nine world populations.
Intractable Rare Dis Res
November 2014
The CGG trinucleotide repeat within the FMR1 gene is associated with multiple clinical disorders, including fragile X-associated tremor/ataxia syndrome, fragile X-associated primary ovarian insufficiency, and fragile X syndrome. Differences in the distribution and prevalence of CGG repeat length and of AGG interruption patterns have been reported among different populations and ethnicities. In this study we characterized the AGG interruption patterns within 3,065 normal CGG repeat alleles from nine world populations including Australia, Chile, United Arab Emirates, Guatemala, Indonesia, Italy, Mexico, Spain, and United States.
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