Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 expression in these neurospheres. In addition, VPA induced morphological changes consistent with neuronal differentiation and the increased expression of differentiation marker genes TUBB3 and ENO2. The expression of stemness genes SOX2, NES, and PRTG was differentially affected by VPA in MB cells with different TP53 status. VPA increased H3K9 occupancy of the promoter region of TP53. Among the genes regulated by VPA, the stemness regulators MYC and NES showed an association with patient survival in specific MB subgroups. Our results indicate that VPA may exert antitumor effects in MB by influencing histone acetylation, which may result in the modulation of stemness, neuronal differentiation, and the expression of genes associated with patient prognosis in specific molecular subgroups. Importantly, the actions of VPA in MB cells and neurospheres include a reduction in the expression of MYC and an increase in TP53.

Introduction: Several bleaching introduced over the last years. of 22% carbamide peroxide on mucosal cells is uncertain. products and methods were However, the consequences the genetic material of oral Aim: This study investigated the genotoxic effect of 22% carbamide peroxide on oral mucosal cells using the Micronucleus (MN) technique. Materials and Methods: Sixteen volunteers participated in the study. At-home bleaching was performed for 2 hours per day for 21 days, Cells were collected by scraping the oral mucosa at four different evaluation times: Baseline (before treatment), 14 days, 21 days, and 52 days after the beginning of bleaching procedure. One thousand cells from each volunteer were examined and the frequencies of MN, binucleated cells, and metanuclear alterations were recorded. After preparing the slides, the microscopic fields were analysed from right to left, until a total of 1,000 cells were analysed. Data were analysed statistically using Kruskal Wallis test at 5% significance level. Results: There was a significant increase in the number of metanuclear alterations and binucleated cells between the baseline and day 21 (p<0.0001). The frequency of MN between the evaluation times was not significantly different (p=0.08). One month after bleaching, the alterations were similar to the baseline values. Conclusion: Although at-home bleaching using 22% carbamide peroxide can cause temporary effects on mucosa' cells, the alterations disappear one month after finishing the bleaching treatment.

Background: Although PSEN1 is best known for its role in Alzheimer's disease, it also regulates neural development and cerebellar morphogenesis. Medulloblastoma (MB) is the most common malignant paediatric brain tumour and arises from disrupted cerebellar developmental programmes. The clinical significance of PSEN1 in MB remains unknown. We investigated the prognostic value and transcriptional correlates of PSEN1 expression across molecular subgroups and subtypes of MB. Methods: Public bulk and single‐cell transcriptomic datasets were used to examine PSEN1 expression, associations with overall survival (OS) and transcriptional correlates in MB. The SHH α‐associated transcriptional pattern was evaluated in an independent cohort, and PSEN1 expression was further examined in the developing human cerebellum and across paediatric brain tumour types. Genes strongly correlated with PSEN1 in SHH α MB were subjected to gene ontology (GO) enrichment analysis. Results: High PSEN1 expression was consistently associated with significantly longer OS exclusively in SHH α MB. The PSEN1 ‐associated transcriptional pattern was reproduced in an independent SHH α cohort. PSEN1 was expressed across developing cerebellar cell populations and paediatric brain tumour types, with MB showing intermediate expression among the tumour entities examined. In SHH α MB, PSEN1 was associated with a coordinated transcriptional programme enriched for RNA homeostasis, intracellular membrane trafficking, protein quality control, lipid and calcium signalling and developmental pathways. Conclusions: High PSEN1 expression identifies a favourable‐prognosis subset of SHH α MB and is associated with a distinct transcriptional programme related to endomembrane organization and cellular homeostasis rather than canonical SHH signalling. These findings suggest that PSEN1 may mark a developmentally distinct tumour state and generate new hypotheses regarding subtype‐specific developmental programmes in MB.

From 1992 to 2018, cytogenetic analyses were successfully performed to explore the chromosomal abnormalities of 729 patients, who utilised a pioneering counselling service in the city of Passo Fundo in the northern part of the Brazilian state of Rio Grande do Sul. This city is characterised by a large conglomerate of private and public hospitals. A classical cytogenetic analysis and G-banding were performed using the patient samples. Although normal karyotypes were observed for 562 of the cases, 167 individuals evidenced chromosomal alterations. Among those, 110 exhibited numerical alterations (65.86%), 41 demonstrated structural modifications (24.55%), and 16 showed both numerical and structural chromosomal changes (9.58%). This study describes the diversity of the chromosomal alterations in this region, which have not been previously examined. After 26 years of study, we discuss our findings herein in a self-critical form.