MGMT expression

These data provide high resolution insight on how O6-MeG formation and repair are impacted by genome structure and nucleotide sequence. Further, O6-MeG-seq is expected to enable future studies of DNA modification signatures as diagnostic markers for addressing drug resistance and preventing secondary cancers.

MGMT promotor status by IHC may be a clinically useful indicator that predicts improved OS for NENs treated with CAPTEM, but IHC does not reliably correlate with the findings of MGMT promoter methylation by pyrosequencing.

In our cohort, MGMT expression seems helpful as a biomarker of good prognosis (low-grade and absence of muscle invasion). A heterogeneous methylation pattern in the MGMT gene requires additional investigation to elucidate its potential implications.

This meta-analysis highlights that Lev use may prolong survival in IDH wild-type GB patients. Further randomized trials are needed to confirm these findings and identify subgroups benefiting most from Lev treatment.

Targeting higher isoform Var2 of hnRNPA1 specifically induces chemosensitization in MGMT expressed Temozolomide resistant U87MG as well as in MGMT non-expressed LN229 TMZ resistant cells.

AP-2α activation by gene overexpression or RA treatment reveals the suppressive effects on glioma relapse, providing a novel therapeutic strategy against malignant refractory gliomas.

Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.

MiRNA is a promising epigenetic modulator that might be utilized in HGG management. A better understanding on the role of miRNA in HGG patients might be able to improve clinical outcome.

This study serves as a proof of concept for the utilization of CRISPR-based gene suppression to overcome TMZ resistance and enhance the lethal effect of TMZ in glioblastoma tumor cells.

In resistant SF763 mouse tumor xenografts, LND plus ACNU significantly inhibited tumor growth with fewer side effects than ACNU alone. Finally, we proposed a new "HMAGOMR" chemo-sensitizing mechanism through which LND may act as a potential chemo-sensitizer to reverse ACNU resistance in glioblastoma: moderate inhibition of hexokinase (HK) activity (H); mitochondrial dysfunction (M); suppressing adenosine triphosphate (ATP)-dependent drug efflux (A); changing redox homeostasis to inhibit GSH-mediated drug inactivation (G) and increasing intracellular oxidative stress (O); downregulating MGMT expression through intracellular acidification (M); and partial inhibition of energy-dependent DNA repair (R).

We first demonstrated that muscone suppressed TOP2A expression through the EGFR/Integrin β1/FAK pathway, hence restoring anoikis sensitivity in TMZ-resistant GBM cells. These data suggest that muscone may be a promising co-therapeutic agent for enhancing GBM treatment, particularly in cases of TMZ-resistant GBM with elevated TOP2A expression.

GBM 101.8 is a reliable model for further investigation due to its similarity to high-grade human GBMs, while GBM 11-9-2 and GBM 14-4-5 correspond to Grade 2-3 gliomas.