Carlos Alberto Scrideli

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is classified into four molecular groups: WNT, SHH, G3, and G4. G3 and G4 MBs are characterized by poor prognosis and high metastatic potential. Although USP2 (ubiquitin-specific peptidase 2) has been described as a prognostic biomarker and a promising therapeutic target in several cancer types, its role in the pathogenesis of G3 and G4 MBs remains unexplored. In this study, USP2 expression was investigated through in silico analyses, public datasets (GSE85217), and tumor samples from 54 pediatric MB patients. In addition, the effects of USP2 inhibition were evaluated in two G3/G4 MB cell lines (D283 Med and USP-13) using ML364, a selective USP2 inhibitor. USP2 was overexpressed in G3 and G4 MBs and was associated with metastasis and unfavorable clinical outcomes. Furthermore, ML364 treatment reduced USP2 protein expression level, as well as cell viability, migration, invasion, and colony-forming capacity in both cell lines. These findings indicate that USP2 is upregulated in pediatric G3 and G4 MBs and support its potential role as a biomarker of poor prognosis and a therapeutic target in these molecular subgroups.

Molecular subgroups of ependymomas are strongly associated with their primary anatomical compartments, namely the supratentorial region, posterior fossa and spine locations. Although it is generally accepted that posterior fossa ependymomas may arise from radial glia-like progenitor cells, the precise cellular origin of the distinct posterior fossa molecular subgroups remains to be determined. Given that DNA methylation profile strongly recapitulates developmental lineage and the cell of origin, the characterization of unexpectedly located molecular subgroups of ependymomas may provide insights into their cells of origin and potential migratory dynamics during embryogenesis and brain development. Herein, we describe two male school-aged pediatric patients with supratentorial tumors located in the third ventricle/pineal region that were classified as posterior fossa group B ependymomas based on DNA methylation profiling. To our knowledge, this represents the first reports of posterior fossa group B ependymomas identified outside the posterior fossa compartment.

Lymphomas are the third most frequent malignant neoplasm in pediatrics. Although polychemotherapy, with or without radiotherapy, is the first-line treatment, relapsed or refractory patients still represent a major challenge, with no established therapeutic consensus. In this context, immunotherapy has emerged as a promising strategy, with growing evidence of its efficacy in adults but limited data in pediatric patients. We report three male patients, aged 13 to 16 years of age, diagnosed with advanced-stage HL and T/NK-cell NHL, all refractory to multiple prior lines of treatment. The use of checkpoint inhibitors enabled disease rescue in two of the three cases, both achieving complete remission followed by consolidation with allogeneic hematopoietic stem cell transplantation. Immunotherapy demonstrated potential in selected pediatric cases of refractory lymphomas, allowing remission and subsequent hematopoietic stem cell transplantation in two patients. Despite the inherent limitations of a small case series, our findings contribute to real-world experience with immunotherapy in the pediatric setting and reinforce its emerging role in the management of these challenging clinical scenarios.

To investigate the involvement of regulators of pluripotency and self-renewal of embryonic stem cells in adrenocortical tumors (ACT). Clinicopathological data and tissues from 114 ACT patients (96 pediatric-pACT; 18 adults) were analyzed. Normal fetal (n = 33) and postnatal adrenals (n = 26) were used as controls. STAT3, NANOG, SOX2, and OCT4 expression was evaluated by qPCR and IHC. We evaluated intracellular NANOG localization by immunofluorescence and its interaction with beta-catenin after inhibiting the Wnt pathway in a beta-catenin-mutated ACT cell line (NCI-H295). IHC showed NANOG, OCT4, SOX2, and STAT3 expression in fetal adrenals until mid-pregnancy, disappearing thereafter. Positive OCT4 nuclear staining was found in 32% of pACT samples and was associated with metastasis (OR = 2.28; 95% CI:1.13-4.59; P < 0.05). ACTs presented lower SOX2 mRNA expression (P < 0.01). STAT3 mRNA levels were higher in cortisol-secreting ACT (P = 0.01) and in adult adenomas (P < 0.01). NANOG mRNA was higher in p.S45P CTNNB1 mutated ACT (P < 0.01). NCI-H295 cells exhibit nuclear NANOG expression, which was decreased by inhibiting the Wnt/beta-catenin pathway (P < 0.01). Markers of pluripotency and self-renewal of embryonic stem cells are expressed until mid-pregnancy, contributing to the adult adrenal stem cell niche. They are absent postnatally but are expressed in a subset of ACT. Specifically, pS45P beta-catenin-mutated ACTs express more NANOG. Increased OCT4 expression in pACT is associated with worse prognosis, and inhibiting the Wnt/beta-catenin pathway in these cells impairs NANOG expression.

Highlights ■ Immersive virtual reality reduced heart rate, pain, agitation, and crying during pediatric venipuncture. ■ This technology effectively reduced pain during repeated invasive procedures, including catheter punctures. ■ The serious game strategy is low-cost, easy to implement, and well-suited for pediatric oncology care. ABSTRACT Objective: To analyze the impact of a serious immersive virtual reality game on the physiological and behavioral aspects of pain during peripheral venous access or central catheter puncture in children and adolescents with cancer. Methods:

Introduction: Pain is a common adverse event of chemotherapy in pediatric oncology patients. Understanding pain’s impact on these patients is essential for improving their quality of life and treatment outcomes. This short communication aims to describe the characteristics of pain in children with Acute Lymphoblastic Leukemia (ALL) and to explore its interactions with hospitalization duration and relapse, considering variables such as age, gender, and risk level. Methods: This retrospective study analyzed data from 610 observations of pediatric patients with ALL treated under the Brazilian GBTLI-99 protocol. Pain was recorded according to CTCAE criteria. Statistical analyses, including Chi-square, Mann-Whitney, Poisson, and logistic regression models, were applied to explore associations between pain, hospitalization length, relapse, and other variables. Results: Our results indicated that patients who presented with pain experienced longer hospitalization lengths. No significant difference in the presence of pain in female or male pediatric patients was observed. Conclusion: This study is a first step towards treating pain as a limiting event that compromises the quality of life and response to treatment in Brazilian pediatric cancer patients.

The tumorigenesis of medulloblastoma (MB), the most frequent malignant brain tumor in children, is not completely known. MicroRNA (miRNA) expression profiles have been associated with human cancers; however, the role played by miRNAs in pediatric MB has been poorly explored. Global miRNA expression in MB and non-neoplastic cerebellum samples was evaluated by microarray assay. Nine miRNAs (miR-31-5p, -329, -383, -433, -485-3p, -485-5p, -491, -512-3p, and 539-5p) in 51 pediatric MB and 7 pediatric non-neoplastic cerebellum samples were chosen for validation by qRT-PCR. The validated miRNAs were less expressed in the MB samples than in the non-neoplastic controls. In our cohort of patients, higher miR-512-3p expression was associated with incomplete degree of resection, classification as high risk, classification as group 4, and poor overall survival. In silico analysis in an independent cohort of MB patients identified that some of the miR-512-3p target genes were also correlated with prognostic features. Our results have shown that miR-512-3p could be associated with poor clinical outcomes in pediatric MB, suggesting that miR-512-3p is a potential biomarker of prognosis.