Publications by authors named "Silvia Brandalise"

Pediatric adrenocortical tumors (ACTs), rare conditions with uncertain prognoses, have high incidence in southern and southeastern Brazil. Pediatric ACTs are highly heterogeneous, so establishing prognostic markers for these tumors is challenging. We have conducted transcriptomic analysis on 14 pediatric ACT samples and compared cases with favorable and unfavorable clinical outcomes to identify prognostically significant genes.

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Objective: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.

Methods: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.

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Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. The gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs.

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Background: Invasive Aspergillosis (IA) is a disease of significant clinical relevance, especially among immunosuppressed patients, and is associated with high mortality rates. In this study, we evaluated the epidemiological features and clinical outcomes in children and adults with IA.

Methods: This was an observational, multicentre, prospective surveillance study of inpatients with IA at two different hospitals in Campinas, Brazil, between 2018 and 2021.

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Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs.

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Increased glycolytic metabolism plays an important role in B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL). We previously showed that IGFBP7 exerts mitogenic and prosuvival effects in ALL by promoting IGF1 receptor (IGF1R) permanence on the cell surface, thus prolonging Akt activation upon IGFs/insulin stimulation. Here, we show that sustained activation of the IGF1R-PI3K-Akt axis concurs with GLUT1 upregulation, which enhances energy metabolism and increases glycolytic metabolism in BCP-ALL.

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Members of the HDAC family are predictive biomarkers and regulate the tumorigenesis in several cancers. However, the role of these genes in the biology of intracranial ependymomas (EPNs) remains unexplored. Here, an analysis of eighteen HDACs genes in an EPN transcriptomic dataset, revealed significantly higher levels of HDAC4 in supratentorial ZFTA fusion (ST-ZFTA) compared with ST-YAP1 fusion and posterior fossa EPNs, while HDAC7 and SIRT2 were downregulated in ST-ZFTA.

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Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 "classical" ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis.

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Introduction: Methotrexate (MTX), a folic acid antagonist and nucleotide synthesis inhibitor, is a cornerstone drug used against acute lymphoblastic leukemia (ALL), but its mechanism of action and resistance continues to be unraveled even after decades of clinical use.

Methods: To better understand the mechanisms of this drug, we accessed the intracellular metabolic content of 13 ALL cell lines treated with MTX by 1H-NMR, and correlated metabolome data with cell proliferation and gene expression. Further, we validated these findings by inhibiting the cellular antioxidant system of the cells in vitro and in vivo in the presence of MTX.

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Pediatric adrenocortical tumor (ACT) is a rare and aggressive neoplasm, with incidence in southern and southeastern Brazil 10-15 times higher than worldwide. Although microRNAs (miRNAs) have been reported to act as tumor suppressors or oncogenes in several cancers, the role of miR-149-3p in ACT remains unknown. In this study, we evaluated the expression of miR-149-3p in 67 pediatric ACT samples and 19 non-neoplastic adrenal tissues.

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Children diagnosed with pediatric adrenocortical tumors (pACT) have variable outcomes, and, to date, the disease lacks robust prognostic biomarkers. The prognostic potential of tumor methylation has been demonstrated in several cancers. We aimed to evaluate the pACT methylation profile and its association with disease presentation and survival.

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Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis.

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Article Synopsis
  • Pediatric adrenocortical tumors (pACT) show complex genomic profiles and lack clear prognostic markers and treatment options, prompting research into the Vitamin D3 receptor (VDR) for potential insights.
  • A study involving 108 pediatric patients found that most pACT had low VDR expression and high methylation, particularly in more aggressive carcinomas, suggesting a link between VDR status and disease severity.
  • The findings indicate that VDR hypermethylation and underexpression could serve as important predictive and prognostic biomarkers for pACT, affecting patient outcomes.
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Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer.

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The Group 3 Medulloblastoma (Grp3-MB) is an aggressive molecular subtype with a high incidence of metastasis and deaths. In this study, were used an RNA sequencing data (RNA-Seq) from a Brazilian cohort of MBs to identify hub genes associated with the metastatic risk. Data validation were performed by using multiple large datasets from MBs (GSE85217, GSE37418, and EGAS00001001953).

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Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well.

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Among the treatment-related acute toxic effects, risks for bloodstream infections (BSIs) are associated with several variables. The authors carried out a retrospective cohort study with 259 children and adolescents with ALL, treated with the GBTLI-LLA 2009 protocol, in order to assess the incidence of BSIs in the induction phase; to determine the risk factors for these BSIs; and to identify the related microorganisms and sensitivity profile of the microorganisms related to these infections. BSIs were documented in 19.

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Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system and, despite the standard therapy; the patients' prognoses remain dismal. The miRNA expression profiles have been associated with patient prognosis, suggesting that they may be helpful for tumor diagnosis and classification as well as predictive of tumor response to treatment. We described the microRNA expression profile of 29 primary GBM samples (9 pediatric GBMs) and 11 non-neoplastic white matter samples as controls (WM) by microarray analysis and we performed functional in vitro assays on these 2 most differentially expressed miRNAs.

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Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.

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Background: Ependymoma (EPN) is the third most common childhood cancer of the central nervous system. RELA fusion-positive EPN accounts for approximately 70% of all childhood supratentorial tumors and shows the worst prognosis among the supratentorial EPNs. TP53 mutation is infrequent in RELA fusions EPNs.

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Introduction: Acute promyelocytic leukemia (APL) is currently considered a highly curable disease. However, an early death (ED) remains one of the main causes of APL treatment failure.

Patients And Methods: In this retrospective study, we aimed to analyze the clinical characteristics of 91 children and adolescents with APL, who were consecutively registered at the (name of institution removed) Children's Center from January 1, 1998 to December 31, 2017.

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Purposes: Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development.

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