Valproic acid (VPA) has anticancer, anti-inflammatory, and epigenetic effects. The study aimed to determine the expression of carcinogenesis-related SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 in adult glioblastoma U87 MG and T98G cells and the effects of 0.5 mM, 0.75 mM, and 1.5 mM doses of VPA. RNA gene expression was determined by RT-PCR. GAPDH was used as a control. U87 and T98G control cells do not express SLC5A8 or CDH1. SLC12A5 was expressed in U87 control but not in T98G control cells. The SLC12A2 expression in the U87 control was significantly lower than in the T98G control. T98G control cells showed significantly higher CDH2 expression than U87 control cells. VPA treatment did not affect SLC12A2 expression in U87 cells, whereas treatment dose-dependently increased SLC12A2 expression in T98G cells. Treatment with 1.5 mM VPA induced SLC5A8 expression in U87 cells, while treatment of T98G cells with VPA did not affect SLC5A8 expression. Treatment of U87 cells with VPA significantly increased SLC12A5 expression. VPA increases CDH1 expression depending on the VPA dose. CDH2 expression was significantly increased only in the U87 1.5 mM VPA group. Tested VPA doses significantly increased CDH2 expression in T98G cells. When approaching treatment tactics, assessing the cell’s sensitivity to the agent is essential.
Background/Objectives: The ineffectiveness of current treatments for glioblastoma underscores the urgent need for effective alternatives. This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA–NaDCA) on formed patients’ primary cell tumors on the chick embryo chorioallantoic membrane (CAM). Methods: Glioblastoma tissue samples were obtained from three patients during tumor surgery. WHO grade IV, IDH wild-type, and a strong positive cytoplasmic GFAP reaction in tumor cells characterized the investigated glioblastoma cases. The tumor cells GBM2-2F, GBM2-3F, and GBM-4M from the patients were examined. Histological examination of tumor invasion into CAM, angiogenesis, and immunohistochemical expression of GFAP-, PCNA-, p53-, EZH2- and vimentin-positive cells were examined. Results: No difference in GFAP expression was observed between the patient’s GBM tumor tissue and the tumor formed on CAM from the same patient’s tumor cells. There were no significant differences in invasion or in the frequency of GFAP- and p53-positive cells among the study control groups. The expression of PCNA-, EZH2-, and vimentin-positive cells in control tumors varied significantly. Treatment significantly reduced the incidence of tumor invasion in GBM2-2F and GBM2-4M and did not affect GBM2-3F tumors; treatment also significantly reduced GFAP expression in GBM2-3F and GBM2-4M and did not affect GBM2-2F tumors. The treatment with NaVPA–NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. Conclusions: Data demonstrated an antitumor effect of NaVPA–NaDCA in an in vivo model of a patient’s primary glioblastoma cells.
The search for an effective treatment for adult high-grade glioblastoma (GBM) remains urgent. Background/Objectives: The study aimed to determine the expression of carcinogenesis-related genes, such as SLC12A2, SLC12A5, CDH1, CDH2, EZH2, and GFAP, in primary glioblastoma (WHO Grade IV; IDH-wild-type) cells from three adult women: GBM5-1, GBM5-2F, and GBM5-3F. Methods: The impact of the combination of sodium valproate and sodium dichloroacetate (2 mM NaVPA–3 mM NaDCA) on the expression of these genes was determined and compared with the effects of 50 µM temozolomide after 24 h of treatment. Results: 2 mM NaVPA–3 mM NaDCA, as well as temozolomide, had individual impacts on the SLC12A2, SLC12A5, CDH1, CDH2, EZH2, and GFAP expressions of tested GBM5-1, GBM5-2F, and GBM5-3F primary cells of female GBM patients. Conclusions: The combination of 2 mM NaVPA–3 mM NaDCA may have an advantage in antitumor activity and may be more effective than TMZ; however, the effect is individual.
Monitoring intracranial pressure (ICP) dynamics is critical for the management of traumatic brain injury, stroke, other neurosurgical conditions, and cerebral blood flow autoregulation; however, invasive ICP monitoring carries risks such as infection, hemorrhage, and sensor zero drift. Increasing evidence suggests that ICP waveform morphology provides clinically relevant information beyond mean ICP value alone. In this first-in-human prospective comparative clinical study, we evaluated the feasibility and accuracy of a novel, fully passive, non-invasive ICP pulse waveform monitoring system (Archimedes 02) based on the detection of eyeball mechanical movement. Fifteen intensive care unit patients (6 males, 9 females; mean age 57.1 ± 18.8 years) with clinically indicated invasive ICP monitoring or external ventricular drainage were enrolled. Three-minute monitoring sessions were performed to simultaneously acquire non-invasive ICP pulse waveforms, invasive ICP waveforms, and invasive radial artery blood pressure (ABP) waveforms. Averaged waveforms were derived for each patient and compared graphically and using correlation analysis. Non-invasive ICP pulse waves recorded with Archimedes 02 showed a strong correlation with invasive ICP waveforms ( = 0.965). In contrast, correlations between non-invasive ICP and ABP waveforms ( = 0.699), as well as between invasive ICP and ABP waveforms ( = 0.749), were lower. These findings indicate that the non-invasive signal primarily reflects ICP dynamics rather than arterial blood pressure. This novel non-invasive ICP monitoring approach has the potential to enhance neurocritical care, particularly in settings where invasive monitoring is impractical or unavailable. Further validation in larger and more diverse patient populations is warranted.