Similar Datasets
Project description:Ahmed Scientific Advances 2023 data repository
| PRJNA944688 | ENA
Project description:Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, glioblastoma patients show dismal prognosis. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma and its inhibition imparts an anti-tumor effect. Even though Temozolomide (TMZ) is the standard chemotherapeutic agent in the treatment of glioblastoma, tumor cells invariably develop resistance to TMZ. However, the mechanistic role of PRMT5 in glioblastoma therapy resistance is unknown. Methods: Patient-derived primary glioblastoma neurospheres (GBMNS), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5 target-specific siRNA were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment. Results: We found that PRMT5 inhibition increased the cytotoxic effect and caspase 3/7 activity of TMZ in GBMNS suggesting that apoptosis is the potential mode of cell death in the combination treatment. PRMT5 inhibition abrogated the TMZ-induced G2/M cell cycle arrest. Unbiased transcriptomic studies indicate that PRMT5 inhibition negatively enriches DNA damage repair genes. Importantly, combination therapy increased DNA double-strand breaks (ɣH2AX foci) and enhanced the DNA damage (comet assay), suggesting that the combination treatment increases the TMZ-induced DNA damage. Specifically, the LLY-283 treatment blocked homologous recombination repair in GBMNS. In vivo, LLY-283 and TMZ combination significantly curbed the tumor growth and prolonged the survival of tumor-bearing mice. Conclusion: Concomitant treatment of LLY-283 and TMZ has significantly greater antitumor efficacy, suggesting that PRMT5 inhibition and TMZ combination could be a new therapeutic strategy for glioblastoma.
2026-05-27 | GSE286560 | GEO
Project description: Not available
| S-EPMC6630716 | biostudies-literature
Project description:Purpose: Gut microbiota is associated with the progression of brain tumor. However, the alterations in the gut microbiota during glioma growth and temozolomide (TMZ) therapy remains to be understood. Methods: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered by gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. Results: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased at the earlier stage of glioma development (T1), and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase and then a subsequent decrease. Twenty genera altered following TMZ treatment. The enrichment of Akkermansia and Bifidobacterium was observed only at the early stage following TMZ treatment (T2), but not at the later stage (T3). Additionally, the decrease of Anaerotruncus was slighter in TMZ group at T3 comparing to the vehicle group. The abundance of Intestinimonas increased constantly during the progression of glioma, but was unaffected by TMZ. Conclusions: Glioma development and progression resulted in altered gut microbiota. TMZ reversed the decrease of Anaerotruncus in glioma at T3, and increased the abundance of Bifidobacterium with no influence on the increase of Intestinimonas. Short-term and long-term effects of TMZ treatment on the bacterial communities may be differential. This study will improve understanding the role of gut microbiota in glioma, and help develop gut microbiota as a potential therapeutic target.
2021-04-28 | GSE171041 | GEO
Project description:Comparison of treatment sensitive GSC clones (TSGC) with treatment resistant GSC clones (TRGC). We used microarrays to identify molecular signatures of TRGC (upregulated genes). We used radiation treatment (RT) or RT plus TMZ to select treatment resistant GSC clones (TRGC)
2013-11-01 | E-GEOD-46531 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is the most common primary brain tumor in adults with a median survival of 11-12 months. Standard therapy consists of radiotherapy (RT) plus chemotherapy with Temozolomide (TMZ), and no alternative treatment is available. We assessed changes in tumor microenvironment (TME) after RT associated with TMZ and metformin (MET) in a syngenic murine GBM model using single-cell RNA-sequencing (scRNA-seq). RT induced an enrichment of GO annotation related with cell cycle, translation and ribosome biogenesis in all tumor clusters, except the radio resistant one where an increase in the inflammatory phenotype was observed. Resident GAM were reduced after RT alone and differentially modulated by RT-drug combinations. After RT alone, we detected an increase in GAM markers and a downregulation of glycolytic metabolism in both microglial and peripheral macrophage subclusters. Association of TMZ increased the pro-inflammatory phenotype of some GAM clusters in comparison to RT. A different signature was observed for the TMZ-MET association but limited to peripheral infiltrating GAM.
2025-06-18 | GSE256358 | GEO
Project description:Temozolomide (TMZ) resistance may contribute to the treatment failure in patients with glioblastoma (GBM). Hence, understanding the underlying mechanisms and developing effective strategies against TMZ resistance are highly desired in the clinic. long non-coding RNAs (lncRNAs) have emerged as new regulatory molecules with diverse functions in biological processes and been deregulated in many pathologies, involved in the therapeutic resistance. It is urgent to elucidate the underlying lncRNA-based mechanisms of TMZ resistance in GBM patients.
2019-04-12 | GSE113510 | GEO
Project description:The discovery of long non-coding RNAs (lncRNAs) has improved the understanding of development and progression in various cancer sub-types. However, the role of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remains largely undefined. In this present study, the differential expression of lncRNAs were identified between U87 and U87TR (TMZ-resistant) cells and to find potential therapeutic targets of GBM for improving the survival of patients.
2022-03-30 | GSE199689 | GEO
Project description:Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, with a median survival of less than two years despite standard therapy. Transglutaminase 2 (TGM2) contributes to tumor progression and poor clinical outcomes. This study evaluated the therapeutic potential of combining streptonigrin (SN), a TGM2 inhibitor, with temozolomide (TMZ), the standard chemotherapeutic agent for GBM. The combination of SN and TMZ significantly reduced cell viability and ATP levels and induced apoptosis more effectively than either agent alone. Moreover, the combination effectively reduced stemness and invasiveness in GBM TSs, along with the expression of related proteins and mRNAs. In vivo, combination therapy prolonged survival in mice and reduced expression of invasiveness-related protein, as shown by immunohistochemistry. These findings suggest that targeting TGM2 with SN enhances the therapeutic efficacy of TMZ in GBM. The combination of SN and TMZ holds promise as a novel treatment strategy for GBM.
2026-06-01 | GSE310591 | GEO