Publications by authors named "M B Garcia-Fabiani"
Article Synopsis
- Mutant isocitrate dehydrogenase 1 (mIDH1) creates excess 2-hydroxyglutarate (2HG), leading to changes in gene expression and making mIDH1 gliomas more resilient to DNA damage and radiation.* -
- Research found mIDH1 glioma cells showed reduced mitochondrial metabolism and increased autophagy, which became their main energy source, indicating they rely heavily on autophagy for survival.* -
- Blocking autophagy weakened the growth of mIDH1 glioma cells and, when combined with radiation, enhanced treatment effectiveness, suggesting targeting autophagy could improve therapies for mIDH1 glioma patients.*
Pediatric high-grade gliomas (pHGGs) are diffuse and highly aggressive CNS tumors which remain incurable, with a 5-year overall survival of less than 20%. Within glioma, mutations in the genes encoding the histones H3.1 and H3.
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- * Research showed that these mutations lead to reduced DNA repair, making tumors more vulnerable to DNA damage, which activates immune responses through the cGAS/STING pathway.
- * Treatment combining radiotherapy and DNA damage response inhibitors improved survival rates in mice with H3.3-G34R pHGG, and adding a STING agonist further enhanced the effectiveness, promoting immune memory against the cancer.
Mutant isocitrate-dehydrogenase 1 () synthesizes the oncometabolite 2-hydroxyglutarate (2HG), which elicits epigenetic reprogramming of the glioma cells’ transcriptome by inhibiting DNA and histone demethylases. We show that the efficacy of immune-stimulatory gene therapy (TK/Flt3L) is enhanced in gliomas, due to the reprogramming of the myeloid cells’ compartment infiltrating the tumor microenvironment (TME). We uncovered that the immature myeloid cells infiltrating the TME are mainly nonsuppressive neutrophils and preneutrophils.
View Article and Find Full Text PDFHigh grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors.
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