7 results on '"Leonardo Vinícius Barbosa"'
Search Results
2. Polymorphisms in Pathways in Pediatric Astrocytomas
- Author
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Eduardo Morais de Castro, Leonardo Vinícius Barbosa, Aline Simoneti Fonseca, Seigo Nagashima, Caroline Busatta Vaz de Paula, Rafaela Zeni, Letícia Arianne Panini do Carmo, Luciane Regina Cavalli, Luiz Fernando Bleggi Torres, Andrea Senff Ribeiro, Lucia de Noronha, and Cleber Machado-Souza
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 ( TPT1 ) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR , MDM2 , TP53 , and CDKN1A , correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas ( p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared ( p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma ( p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.
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- 2023
- Full Text
- View/download PDF
3. Parkin and its molecular associations in gliomas – a systematic review
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Eduardo Morais de Castro, Leonardo Vinícius Barbosa, João Vitor Alves Ferreira, Diancarlos Pereira de Andrade, Rosiane Guetter Mello, Luiz Fernando Bleggi Torres, Lucia de Noronha, and Cleber Machado-Souza
- Subjects
Parkin ,PRKN ,Gliomas ,GBM ,Systematic reviews ,Surgery ,RD1-811 ,Pathology ,RB1-214 - Abstract
Abstract Parkin, a protein encoded by PRKN, discovered in the context of Parkinson’s disease, controls proteasomal degradation by protein ubiquitination and acts on cell cycle control and mitochondrial homeostasis, among other cellular processes. Parkin has been also implicated in several carcinomas, melanoma and leukemia. In the neoplastic setting, reduced parkin level usually indicates poorer prognosis. Some authors have described the associations between parkin and gliomas. Gliomas are a heterogeneous group of tumors that arise in the central nervous system, astrocytomas being the most common. The aim of this systematic review is to evaluate how parkin behaves in gliomas and the molecular pathways associated in this interaction. A search was conducted in PubMed, EBSCO and Scopus and 8 published articles were identified as eligible studies. The studies were categorized in three groups, according to their main emphasis: PRKN mutation patterns detected in gliomas, parkin effects on tumor growth and survival rates, and molecular interactions between parkin and other proteins. The studies showed higher PRKN mutation rates and lower parkin expression in high grade gliomas. Patients with higher parkin expression had better overall survival. Besides, different molecular pathways associated with parkin were described, some of them regarded as potential therapeutic targets.
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- 2021
- Full Text
- View/download PDF
4. Pediatric Astrocytomas and Their Association With Polymorphisms in Embryonic Stem Cell Marker Genes
- Author
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Eduardo Morais de Castro, Leonardo Vinícius Barbosa, Aline Simoneti Fonseca, Seigo Nagashima, Caroline Busatta Vaz de Paula, Rafaela Zeni, Luciane R. Cavalli, Luiz Fernando Bleggi Torres, Lucia de Noronha, and Cleber Machado-Souza
- Subjects
SOXB1 Transcription Factors ,Pediatrics, Perinatology and Child Health ,Humans ,Nanog Homeobox Protein ,Neurology (clinical) ,Astrocytoma ,Child ,Embryonic Stem Cells - Abstract
Background Embryonic stem cell markers, such as SOX2, NANOG, and OCT4, are transcription factors expressed in pluripotent stem cells, involved in the mediation of pluripotency and self-renewal. Especially after the discovery of cancer stem cells, these proteins have been associated with several types of neoplasia, including astrocytomas. In the pediatric population, astrocytomas are the most common solid neoplasia and present the highest mortality rates. Methods Our study evaluated 5 polymorphisms in SOX2, NANOG, and POU5F1 genes in 101 pediatric astrocytoma samples. Results We describe the associations between wild and polymorphic alleles in astrocytomas. Conclusions In our results, the intronic polymorphic G allele in SOX2 rs77677339 [G/A] had a borderline association with low-grade astrocytomas, and the intronic polymorphic T allele in NANOG rs10845877 [C/T] showed a higher frequency in grade 2, compared to grade 1 astrocytomas, thus showing promising results. Impact Our study is relevant because it shows a potential correlation between polymorphic embryonic stem cell marker genes and pediatric astrocytomas.
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- 2022
5. Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas
- Author
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Eduardo Morais de Castro, Leonardo Vinícius Barbosa, Aline Simoneti Fonseca, Seigo Nagashima, Caroline Busatta Vaz de Paula, Rafaela Zeni, Letícia Arianne Panini do Carmo, Luciane Regina Cavalli, Luiz Fernando Bleggi Torres, Andrea Senff Ribeiro, Lucia de Noronha, and Cleber Machado-Souza
- Subjects
General Neuroscience ,Neurology (clinical) - Abstract
Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 ( TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas ( p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared ( p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma ( p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.
- Published
- 2023
6. Immune Response Gaps Linked to SARS-CoV-2 Infection: Cellular Exhaustion, Senescence, or Both?
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Leonardo Vinicius Barbosa, Daniele Margarita Marani Prá, Seigo Nagashima, Marcos Roberto Curcio Pereira, Rebecca Benicio Stocco, Francys de Luca Fernandes da Silva, Milena Rueda Cruz, Djessyka Dallagassa, Thiago João Stupak, George Willian Xavier da Rosa Götz, Georgia Garofani Nasimoto, Luiz Augusto Fanhani Cracco, Isabela Busto Silva, Karen Fernandes de Moura, Marina de Castro Deus, Ana Paula Camargo Martins, Beatriz Akemi Kondo Van Spitzenbergen, Andréa Novais Moreno Amaral, Caroline Busatta Vaz de Paula, Cleber Machado-Souza, and Lucia de Noronha
- Subjects
SARS-CoV-2 ,inflammation ,pathogenesis ,cellular exhaustion ,senescence ,CD8 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The COVID-19 pandemic, promoted by the SARS-CoV-2 respiratory virus, has resulted in widespread global morbidity and mortality. The immune response against this pathogen has shown a thin line between protective effects and pathological reactions resulting from the massive release of cytokines and poor viral clearance. The latter is possibly caused by exhaustion, senescence, or both of TCD8+ cells and reduced activity of natural killer (NK) cells. The imbalance between innate and adaptive responses during the early stages of infection caused by SARS-CoV-2 contributes to the ineffective control of viral spread. The present study evaluated the tissue immunoexpression of the tissue biomarkers (Arginase-1, CCR4, CD3, CD4, CD8, CD20, CD57, CD68, CD138, IL-4, INF-α, INF-γ, iNOS, PD-1, Perforin and Sphingosine-1) to understand the cellular immune response triggered in patients who died of COVID-19. We evaluated twenty-four paraffin-embedded lung tissue samples from patients who died of COVID-19 (COVID-19 group) and compared them with ten lung tissue samples from patients who died of H1N1pdm09 (H1N1 group) with the immunohistochemical markers mentioned above. In addition, polymorphisms in the Perforin gene were genotyped through Real-Time PCR. Significantly increased tissue immunoexpression of Arginase, CD4, CD68, CD138, Perforin, Sphingosine-1, and IL-4 markers were observed in the COVID-19 group. A significantly lower immunoexpression of CD8 and CD57 was also found in this group. It is suggested that patients who died from COVID-19 had a poor cellular response concerning viral clearance and adaptive response going through tissue repair.
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- 2022
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7. Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19
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Aline Cristina Zanchettin, Leonardo Vinicius Barbosa, Anderson Azevedo Dutra, Daniele Margarita Marani Prá, Marcos Roberto Curcio Pereira, Rebecca Benicio Stocco, Ana Paula Camargo Martins, Caroline Busatta Vaz de Paula, Seigo Nagashima, Lucia de Noronha, and Cleber Machado-Souza
- Subjects
SARS-CoV-2 ,secondary hemophagocytic lymphohistiocytosis ,macrophage ,immunohistochemistry ,polymorphisms ,Microbiology ,QR1-502 - Abstract
COVID-19 is a viral disease associated with an intense inflammatory response. Macrophage Activation Syndrome (MAS), the complication present in secondary hemophagocytic lymphohistiocytosis (sHLH), shares many clinical aspects observed in COVID-19 patients, and investigating the cytolytic function of the responsible cells for the first line of the immune response is important. Formalin-fixed paraffin-embedded lung tissue samples obtained by post mortem necropsy were accessed for three groups (COVID-19, H1N1, and CONTROL). Polymorphisms in MAS cytolytic pathway (PRF1; STX11; STXBP2; UNC13D and GZMB) were selected and genotyping by TaqMan® assays (Thermo Fisher Scientific, MA, USA) using Real-Time PCR (Applied Biosystems, MA USA). Moreover, immunohistochemistry staining was performed with a monoclonal antibody against perforin, CD8+ and CD57+ proteins. Histopathological analysis showed high perforin tissue expression in the COVID-19 group; CD8+ was high in the H1N1 group and CD57+ in the CONTROL group. An association could be observed in two genes related to the cytolytic pathway (PRF1 rs885822 G/A and STXBP2 rs2303115 G/A). Furthermore, PRF1 rs350947132 was associated with increased immune tissue expression for perforin in the COVID-19 group. The genotype approach could help identify patients that are more susceptible, and for this reason, our results showed that perforin and SNPs in the PRF1 gene can be involved in this critical pathway in the context of COVID-19.
- Published
- 2022
- Full Text
- View/download PDF
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