Glioma, characterized by infiltrative growth and treatment resistance, is regarded as the most prevalent intracranial malignant tumor. Due to its poor prognosis, accumulating investigation has been performed for improvement of overall survival (OS) and progression-free survival (PFS) in glioma patients. Valproic acid (VPA), one of the most common histone deacetylase inhibitors (HDACIs), has been detected to directly or synergistically exert inhibitory effects on glioma in vitro and in vivo. In this review, we generalize the latest advances of VPA in treating glioma and its underlying mechanisms and clinical implications, providing a clearer profile for clinical application of VPA as a therapeutic agent for glioma.

Glioma is the most common type of intracranial malignant tumor, with a great recurrence rate due to its infiltrative growth, treatment resistance, intra- and intertumoral genetic heterogeneity. Recently, accumulating studies have illustrated that activated aerobic glycolysis participated in various cellular and clinical activities of glioma, thus influencing the efficacy of radiotherapy and chemotherapy. However, the glycolytic process is too complicated and ambiguous to serve as a novel therapy for glioma. In this review, we generalized the implication of key enzymes, glucose transporters (GLUTs), signalings and transcription factors in the glycolytic process of glioma. In addition, we summarized therapeutic interventions via the above aspects and discussed promising clinical applications for glioma.

Glioma is the most common malignant tumor in the central nervous system with a poor median survival. Valproic acid (VPA), a widely used antiepileptic drug, has been found to have antitumor effects on gliomas, but its role still has not been determined. In this study, we investigated VPA-induced apoptotic and autophagic effects on human U251 and SNB19 cells by cell counting kit-8 assay, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick end labeling staining, western blots, and immunofluorescence assay in vitro, and then we further explored the role of autophagy in apoptosis by using the selective antagonist MHY1485. The data showed that VPA inhibited U251 and SNB19 glioma cells viability in a dose-dependent and time-dependent manner and induced apoptosis through the mitochondria-dependent pathway in vitro. In addition, VPA activated the Akt/mTOR pathway by decreasing their protein phosphorylation to promote cellular apoptosis. Surprisingly, the mTOR agonist MHY1485, causing a strong elevation of mTOR activity, partially reduced apoptosis ratio, which supposing that the autophagy of VPA is involved in the regulation of apoptosis. These findings suggest that VPA enhanced apoptosis by promoting autophagy via Akt/mTOR signaling in glioma, which could be further evaluated as a reliable therapy for glioma.

Long non-coding RNAs (lncRNAs) have been potent regulators in the initiation and development of human cancers regarding their biological roles in the modulation of dosage compensation effect, epigenetics and cell differentiation. Recently, aberrant expression of lncRNA small nucleolar RNA host gene 5 (SNHG5) has been observed in various solid tumors, which was intently correlated with tumor range, metastasis, pathological stage and prognosis. Additional mechanical investigation disclosed that SNHG5 was involved in multiple cellular activities, including proliferation, migration, invasion, cell-cycle, apoptosis and autophagy, via targeting miRNAs, signaling pathways and other biological molecules or proteins. In this review, we summarized the latest advances made towards understanding the roles of SNHG5 in human cancers and further discussed potential methods that could be adopted for clinical interventions.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of cerebrovascular pathology. However, its treatment remains a matter of debate among neurosurgeons and neurologists. The study was to explore the efficacy of minimally invasive surgery (stereotactic catheter drainage, SCD) for patients with severe intracerebral hemorrhage (Glasgow Coma Scale, GCS) score ≤ 8 and hematoma volume ≥ 30 cm3) and to determine predisposing factors for good clinical outcome. A total of 75 patients with severe ICH were included in this retrospective study. Patients were assigned to the SCD group (n=38) or the conventional craniotomy group (n=37). Patients were followed up for 12 months postoperatively, and their clinical parameters were compared. During the operation, the SCD group exhibited a lower bleeding volume ( p<0.001) and shorter operating time ( p<0.001) than the conventional craniotomy group. For postoperative efficacy, the rates of pneumonia and tracheotomy were lower ( p=0.002 and p=0.027, respectively), and the duration of hospital and neurosurgery intensive care unit (NSICU) in days were significantly shorter in the SCD group ( p=0.046 and p=0.047, respectively). Furthermore, patients in the SCD group showed improved modified Rankin Scale (mRS) scores at discharge ( p<0.018) and at 12-month follow up ( p<0.001). Predisposing factors for good clinical outcomes were hematoma volume (<50 cm3, 95% confidence interval (CI): 1.043–1.956, p6, 95% CI: 3.248–187.466, p<0.001), hypertension (none, 95% CI: 1.440–2.922, p<0.001), and treatment modality (SCD, 95% CI: 1.422–3.226, p<0.001). Taken together, SCD surgery is safe and effective in patients with severe ICH and has fewer complications and better clinical outcomes than conventional craniotomy.