ADAM12 promotes temozolomide resistance in glioblastoma by activating the TNF-α - NF-κB pathway.

Development of temozolomide (TMZ) resistance is a critical factor contributing to a poor prognosis in glioma patients. TMZ resistance is also closely associated with the phosphorylation level of NF-κB, yet targeted inhibition of NF-κB activity in glioma can be leveraged to overcome TMZ resistance. ADAM12, a protein significantly overexpressed in glioma cells, is implicated in the pathogenesis and progression of glioma, yet its role in the development of TMZ resistance is completely understood.

EPIC-1042 alleviates cerebral ischemic/reperfusion injury through TAX1BP1-induced mitophagy.

Post ischemia-reperfusion (I/R) injury, an upregulation in Polymerase I and transcript release factor (PTRF) expression is observed. PTRF is implicated in the regulation of various cellular processes within neuronal cells, thereby exacerbating the deleterious effects of I/R injury. EPIC-1042 is a small molecule pharmacological agent that exhibits specificity in binding to PTRF.

Identification of key genes and immune infiltration in peripheral blood biomarker analysis of delayed cerebral ischemia: Valproic acid as a potential therapeutic drug.

Background: Delayed cerebral ischemia (DCI) is a common and serious complication of subarachnoid hemorrhage (SAH). Its pathogenesis is not fully understood. Here, we developed a predictive model based on peripheral blood biomarkers and validated the model using several bioinformatic multi-analysis methods.

CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis/TMZ resistance in the mesenchymal subtype of glioblastoma.

The large-scale genomic analysis classifies glioblastoma (GBM) into three major subtypes, including classical (CL), proneural (PN), and mesenchymal (MES) subtypes. Each of these subtypes exhibits a varying degree of sensitivity to the temozolomide (TMZ) treatment, while the prognosis corresponds to the molecular and genetic characteristics of the tumor cell type. Tumors with MES features are predominantly characterized by the NF1 deletion/alteration, leading to sustained activation of the RAS and PI3K-AKT signaling pathways in GBM and tend to acquire drug resistance, resulting in the worst prognosis compared to other subtypes (PN and CL).

HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma.

Background: Hypoxia is a pathological hallmark in most cancers, including glioblastoma (GBM). Hypoxic signaling activation and post-translational modification (PTM) of oncogenic proteins are well-studied in cancers. Accumulating studies indicate glycolytic enzyme PGK1 plays a crucial role in tumorigenesis, yet the underlying mechanisms remain unknown.

Mechanisms underlying the therapeutic effects of cinobufagin in treating melanoma based on network pharmacology, single-cell RNA sequencing data, molecular docking, and molecular dynamics simulation.

Malignant melanoma is one of the most aggressive of cancers; if not treated early, it can metastasize rapidly. Therefore, drug therapy plays an important role in the treatment of melanoma. Cinobufagin, an active ingredient derived from Venenum bufonis, can inhibit the growth and development of melanoma.

EPIC-1042 as a potent PTRF/Cavin1-caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for glioblastoma.

Background: Temozolomide (TMZ) treatment efficacy in glioblastoma is determined by various mechanisms such as TMZ efflux, autophagy, base excision repair (BER) pathway, and the level of O6-methylguanine-DNA methyltransferase (MGMT). Here, we reported a novel small-molecular inhibitor (SMI) EPIC-1042 (C20H28N6) with the potential to decrease TMZ efflux and promote PARP1 degradation via autolysosomes in the early stage.

Methods: EPIC-1042 was obtained from receptor-based virtual screening.