Data documento
18/05/2023

Título
Avanços tecnológicos, conectividade e procrastinação

Autor(es)
Gustavo Varzim Mesquita

Palavras chave
internet - telas

Descrição
Orientador: Prof. Eduardo Marcelo Cândido

Data documento
14/05/2025

Título
Burnout na medicina: desafio para estudantes e profissionais

Autor(es)
Ana Julia Soler Favaleca

Palavras chave
Burnout

Descrição
Orientadora: Prof.ª Vânia Soares de Oliveira e Almeida Pinto

Data documento
03/02/2024

Título
Depressão: abordagens terapêuticas e suporte emocional

Autor(es)
Fabiane Ayumi

Palavras chave
transtorno mental - emocional

Descrição
Psicóloga Clínica CRP 06/179435

Data documento
01/11/2024

Título
Depressão: Um mal que vai além da mente

Autor(es)
Gabriel Martins Belentani

Palavras chave
transtorno mental - tristeza

Descrição
Orientadoras: Prof.ª Maria Luiza Nunes Mamede Rosa e Prof.ª Barbara Sgavioli Massucato

Data documento
06/05/2024

Título
Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets

Autor(es)
Marques R.F. - Moreno D.A. - da Silva L. - Leal L.F. - de Paula F.E. - Santana I. - Teixeira G. - Saggioro F. - Neder L. - Junior C.A. - Mançano B. - Reis R.M.

Palavras chave
immune checkpoints - immune profile - immunotherapy - medulloblastoma - nCounter mRNA expression assay

Resumo
Introduction: Medulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy. However, many patients do not respond to therapy, and most suffer severe side effects. Cancer immunotherapy targeting immune checkpoints (IC) (PD-1, PD-L1, and CTLA4) has been getting disappointing outcomes in brain tumors. Nevertheless, other less explored immune checkpoints may be promising candidates for medulloblastoma therapy. Objectives: In the present study, we aimed to characterize the expression profile of 19 immune checkpoints in medulloblastoma. Methods: We analyzed 88 formalin-fixed paraffin-embedded medulloblastomas previously classified for each molecular subgroup and three non-tumoral brain tissue. mRNA levels of 19 immune checkpoint-related genes were quantified using the nCounter (PanCancer Immune Profiling Panel) assay. Further in silico analysis was performed in two larger public microarray datasets, one of which enabled comparisons between tumoral and non-tumoral tissues. Immunohistochemistry of PD-L1 was performed in a subset of cases. Microsatellite instability was also molecularly analyzed. Results: We observed an absence of expression of the canonic ICs, namely PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, as well as CD80, CD86, BTLA, IDO1, CD48, TNFSF14, CD160, CEACAM1, and CD244. PD-L1 protein expression was also practically absent. We found higher mRNA levels of CD24, CD47, CD276 (B7-H3), and PVR, and lower mRNA levels of HAVCR2, LAG3, and TIGIT genes, with significant differences across the four molecular subgroups. Compared to the non-tumor tissues, the expression levels of CD276 in all subgroups and CD24 in SHH, Group 3, and Group 4 subgroups are significantly higher. The in silico analysis confirmed the expression profile found in the Brazilian cohort, including the lower/absent expression of the canonic ICs. Moreover, it confirmed the overexpression of CD24 and CD276 in medulloblastomas compared with the non-tumor tissue. Additionally, CD276 and CD24 high levels were associated with worse survival. Conclusion: These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.

Citação
Marques RF, Moreno DA, da Silva L, Leal LF, de Paula FE, Santana I, Teixeira G, Saggioro F, Neder L, Junior CA, Mançano B, Reis RM. Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets. Front Immunol. 2023 Feb 7;14:1062856. doi: 10.3389/fimmu.2023.1062856. PMID: 36825029; PMCID: PMC9941636.

Data documento
14/10/2024

Título
Esquizofrenia: entendendo a doença para por fim ao seu estigma

Autor(es)
Ana Júlia Soler Favaleça

Palavras chave
transtorno mental

Descrição
Orientadoras: Prof.ª Maria Luiza Mamede Rosa e Prof.ª Barbara Sgavioli Massucato

Data documento
06/05/2024

Título
Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood

Autor(es)
Zapaterini J.R. - Fonseca A.R.B. - Bidinotto L.T. - Colombelli K.T. - Rossi A.L.D. - Kass L. - Justulin L.A. - Barbisan L.F.

Palavras chave
DNA damage - DNA repair and replication - N-methyl-N-nitrosourea - female Sprague–Dawley - maternal low protein intake - perinatal programming - risk for mammary carcinogenesis

Resumo
Studies have shown that maternal malnutrition, especially a low-protein diet (LPD), plays a key role in the developmental mechanisms underlying mammary cancer programming in female offspring. However, the molecular pathways associated with this higher susceptibility are still poorly understood. Thus, this study investigated the adverse effects of gestational and lactational low protein intake on gene expression of key pathways involved in mammary tumor initiation after a single dose of N-methyl-N-nitrosourea (MNU) in female offspring rats. Pregnant Sprague-Dawley rats were fed a normal-protein diet (NPD) (17% protein) or LPD (6% protein) from gestational day 1 to postnatal day (PND) 21. After weaning (PND 21), female offspring (n = 5, each diet) were euthanized for histological analysis or received NPD (n = 56 each diet). At PND 28 or 35, female offspring received a single dose of MNU (25 mg/kg body weight) (n = 28 each diet/timepoint). After 24 h, some females (n = 10 each diet/timepoint) were euthanized for histological, immunohistochemical, and molecular analyses at PDN 29 or 36. The remaining animals (n = 18 each diet/timepoint) were euthanized when tumors reached ≥2 cm or at PND 250. Besides the mammary gland development delay observed in LPD 21 and 28 groups, the gene expression profile demonstrated that maternal LPD deregulated 21 genes related to DNA repair and DNA replication pathways in the mammary gland of LPD 35 group after MNU. We further confirmed an increased γ-H2AX (DNA damage biomarker) and in ER-α immunoreactivity in mammary epithelial cells in the LPD group at PND 36. Furthermore, these early postnatal events were followed by significantly higher mammary carcinogenesis susceptibility in offspring at adulthood. Thus, the results indicate that maternal LPD influenced the programming of chemically induced mammary carcinogenesis in female offspring through increase in DNA damage and deregulation of DNA repair and DNA replication pathways. Also, Cidea upregulation gene in the LPD 35 group may suggest that maternal LPD could deregulate genes possibly leading to increased risk of mammary cancer development and/or poor prognosis. These findings increase the body of evidence of early-transcriptional mammary gland changes influenced by maternal LPD, resulting in differential response to breast tumor initiation and susceptibility and may raise discussions about lifelong prevention of breast cancer risk.

Citação
Zapaterini JR, Fonseca ARB, Bidinotto LT, Colombelli KT, Rossi ALD, Kass L, Justulin LA, Barbisan LF. Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood. Front Cell Dev Biol. 2022 Feb 1;9:756616. doi: 10.3389/fcell.2021.756616. PMID: 35178394; PMCID: PMC8844450.

Data documento
17/07/2024

Título
Meu filho está com gripe, o que devo fazer?

Autor(es)
Marina Cantieri Rocha

Palavras chave
IVAS - vias aéreas superiores - inverno

Descrição
Orientadora: Prof.ª Ludmilla Pereira Barbosa dos Santos

Data documento
26/06/2023

Título
Meu filho está resfriado, e agora?

Autor(es)
Rafaela Grimberg Hamer

Palavras chave
inverno - IVAS - infecção de vias aéreas

Descrição
Orientador: Prof. Vitor Emanoel de Lemos Carvalho

Data documento
18/04/2024

Título
Microcefalia em recém-nascidos: entenda essa condição

Autor(es)
Arthur Henrique dos Santos Vieira

Palavras chave
RN - crânio

Descrição
Orientador: Prof. Lucas Tadeu Bidinotto

Data documento
04/07/2024

Título
Nutrindo o futuro com bancos de leite humano

Autor(es)
Sophia Renzzo

Palavras chave
leite materno - amamentação - BLH

Descrição
Orientadora: Prof.ª Lorena Costa Oliveira Aparício

Data documento
18/06/2024

Título
Pré-natal: base para gravidez tranquila e segura

Autor(es)
Maria Isabela Souza da Silva

Palavras chave
maternidade - gravidez

Descrição
Orientador: Prof. Luiz Augusto Martins

Data documento
27/04/2023

Título
Psicofobia: os estigmas sobre transtornos mentais

Autor(es)
Frederico Denadai dos Santos

Palavras chave
saúde mental - depressão - transtorno mental

Descrição
Orientadora: Prof.ª Barbara Sgavioli Massucato

Data documento
31/10/2023

Título
Quais sinais indicam necessidade de suporte psicológico?

Autor(es)
Eduardo Morelli Pastorelli

Palavras chave
transtorno mental - emoção

Descrição
Orientador: Prof. Daniel Moreira Pinto