Doutorado em Biotecnologia

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Navegando Doutorado em Biotecnologia por Autor "Arantes, Lidia Maria Rebolho Batista"

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    Avaliação da expressão de microRNAs e proteínas como biomarcadores de diagnóstico em carcinoma epidermoide de língua
    (Universidade Federal do Espírito Santo, 2023-11-22) Có, Anna Clara Gregório; Camillo, Cláudia Malheiros Coutinho; https://orcid.org/0000-0001-9016-2668; http://lattes.cnpq.br/3184503163639480; Zeidler, Sandra Lúcia Ventorin von; https://orcid.org/0000-0002-8897-5747; http://lattes.cnpq.br/5785612863130498; https://orcid.org/0000-0002-7737-0371; http://lattes.cnpq.br/3678557620411441; Nunes, Fabio Daumas; https://orcid.org/0000-0002-7785-6785; http://lattes.cnpq.br/4909755821591847; Errera, Flavia Imbroisi Valle; https://orcid.org/0000-0002-8069-6372; http://lattes.cnpq.br/9337327437538048; Arantes, Lidia Maria Rebolho Batista; https://orcid.org/0000-0001-8230-1218; http://lattes.cnpq.br/2019308149950531; Paula, Flavia de; https://orcid.org/0000-0001-8679-2982; http://lattes.cnpq.br/7913201450663683
    Oral squamous cell carcinoma (OSCC) is the 16th most commonly diagnosed form of cancer globally, with a higher prevalence in the tongue compared to other areas of the oral cavity. However, the lack of effective biomarkers for diagnosis, especially for precancerous lesions, poses a limitation, as visual or histological examination cannot predict the progression of dysplastic lesions, making it difficult to determine whether they will develop into cancer or return to normal epithelium. In this context, the present research aims to investigate molecular targets that may indicate the irreversible transformation of these cells, to provide a basis for broader studies aimed at using these targets as biomarkers for early OSCC diagnosis. To achieve this goal, this experimental study addressed the evaluation of the expression of a panel of microRNAs and proteins in tumour tissues and adjacent tumour-adjacent epithelium obtained from patients with tongue squamous cell carcinoma and oral epithelium from healthy individuals. Additionally, the research explored the association between these biomarkers, seeking to determine their potential application as diagnostic biomarkers for tongue squamous cell carcinoma. A total of 75 cases of tongue squamous cell carcinoma and adjacent tumouradjacent epithelium were included in the study, and the expression of the proteins survivin, Bcl-2, PLK1, p16, p40, p63, EGFR, and cyclin D1 was analysed by immunohistochemistry. The analysis of the microRNA panel's expression involved 31 samples of tongue squamous cell carcinoma, 10 samples of healthy gingival tissue, and 10 samples of serum from healthy individuals, as well as 7 samples of serum from patients diagnosed with OSCC, using the RT-qPCR technique. In silico analysis by bioinformatics validated the findings related to the expression of differentially expressed microRNAs in the sample group. The results showed differences in the expression of miRNA-31-5p (p<0.001) and miRNA-21-5p (p=0.001) in tumour samples compared to control samples. Significant differences were not observed in the expression of miRNA-24-3p, while miRNA-542-3p and 196a-5p were not detected in the sample group. No significant difference was observed in the expression of miRNAs in serum samples. The assessment of the diagnostic potential of microRNAs included ROC curve analysis, which revealed that miR-21-5p had an area under the curve (AUC) of 0.803, while miR-31-5p obtained an AUC of 0.777. The results also identified differential expression among the proteins survivin, PLK1, and p63, all of which showed increased expression in tumour tissue. Additionally, a correlation was observed between the expression of miR-21-5p and the protein p40 (chi-square: p=0.047; Spearman correlation: r=0.402; p=0.023). In conclusion, the results suggest that miR-21-5p and miR-31-5p may be potential diagnostic biomarkers for tongue squamous cell carcinoma, providing a foundation for further exploration for large-scale studies to explore miRNA-protein correlations, considering the site specificity of miRNAs.
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    FATORES DETERMINANTES DA DOR CRÔNICA E O PAPEL DA METILAÇÃO DO GENE NR3C1
    (Universidade Federal do Espírito Santo, 2021-08-30) Branco, Alexandre Lima Castelo; Louro, Iuri Drumond; https://orcid.org/0000000151609615; http://lattes.cnpq.br/3817361438227180; https://orcid.org/0000-0002-1704-9877; http://lattes.cnpq.br/7332472547330240; Guimarães, Marco Cesar Cunegundes; https://orcid.org/0000000321460180; http://lattes.cnpq.br/0261991057482057; Arantes, Lidia Maria Rebolho Batista; https://orcid.org/0000-0001-8230-1218; http://lattes.cnpq.br/2019308149950531; Carvalho, Marcos Brasilino de; https://orcid.org/0000-0001-6854-2680; http://lattes.cnpq.br/6208433886573740; Silva, Adriana Madeira Alvares da; https://orcid.org/0000000280780304; http://lattes.cnpq.br/6445492335035108
    Chronic pain is a multidimensional health condition with high prevalence in Brazil and its chronic condition may be related to depression and anxiety, diseases recognized as the most prevalent mental disorders in the world and major causes of functional incapacity, suffering and reduced quality of life. The relationship between depression, anxiety, pain, suffering and epigenetic alterations have already been described in the literature, but this relationship is not completely clear yet. Epigenetic alterations can affect gene expression and are related to the individual's adaptation to the environment in a relationship between genotype, phenotype and environment. The glucocorticoid receptor gene, NR3C1, is regulated by epigenetic mechanisms and acts to control the neuroendocrine axis via cortisol, which also links the gene to depression and other psychiatric illnesses. Thus, this research evaluated the determinants of chronic pain, biopsychosocial, biochemical and molecular factors in the epigenetic modifications of the NR3C1 gene in adults aged between 20 and 59 years, users of the Brazilian Unified Health System. The results of the biopsychosocial assessment in the sample showed a profile of people over 40 years old, with lower per capita income and education, low levels of cortisol, more reports of stress and anxiety, higher consumption of continuous medications, less physical activity and more prevalence of chronic pain. Pain was related to a statistical model that pointed out pain-related variables. Thus, the research showed indicators that point to a predominant profile of individuals with chronic pain, with determinant factors being: hypomethylation of the DNA of the NR3C1 gene in CpG 42, age over 40 years and low cortisol.
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    Potencial prognóstico de células inflamatórias e PD-L1 solúvel em carcinoma epidermoide de cabeça e pescoço
    (Universidade Federal do Espírito Santo, 2024-04-16) Daniel, Camila Batista; Co-orientador1; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador2; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador3; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador4; ID do co-orientador4; Lattes do co-orientador4; Zeidler, Sandra Lúcia Ventorin von ; https://orcid.org/0000-0002-8897-5747; http://lattes.cnpq.br/5785612863130498; Orientador2; https://orcid.org/; http://lattes.cnpq.br/; https://orcid.org/; http://lattes.cnpq.br/; Santos, Eldamária de Vargas Wolfgramm dos ; https://orcid.org/; http://lattes.cnpq.br/; Errera, Flavia Imbroisi Valle ; https://orcid.org/; http://lattes.cnpq.br/; Arantes, Lidia Maria Rebolho Batista ; https://orcid.org/; http://lattes.cnpq.br/; Mendonça, Elismauro Francisco de ; http://lattes.cnpq.br/; 5º membro da banca; https://orcid.org/; http://lattes.cnpq.br/; 6º membro da banca; https://orcid.org/; http://lattes.cnpq.br/; 7º membro da banca; https://orcid.org/; http://lattes.cnpq.br/
    Immunosuppression is recognized as a hallmark of cancer and has been associated with worse outcomes. In head and neck squamous cell carcinoma (HNSCC), immunosuppression is a hallmark of the tumour and may be mediated by immunosuppressive inflammatory cells and PD-L1 expression. Given their participation in this process, our study aimed to describe the prognostic impact of these elements in tumour tissue and peripheral blood HNSCC patients. We conducted a multicentre retrospective study with biological samples and clinical data from HNSCC patients recruited at two centres in Brazil and the United Kingdom and healthy individuals. To analyse the inflammatory infiltrate, we used tumour tissue slides stained with haematoxylin and eosin and immunohistochemistry for PD-L1 analysis and neutrophil quantification. Absolute leukocyte counts were retrieved from pretreatment blood counts available in medical records. To evaluate the prognostic value of PD-L1 in liquid biopsy, we used serum and plasma samples obtained from patients and healthy individuals for quantification of soluble PD-L1 (sPD-L1) by ELISA. Fresh tumour tissue samples were used to analyse CD274 gene expression levels using the RT-qPCR technique. Furthermore, we analysed PD-L1 expression by flow cytometry in HNSCC cell lines and quantified sPD-L1 levels in the supernatant. The tumour microenvironment analysis showed that low levels of lymphocytes are associated with worse overall survival and disease-free survival. However, we did not observe this relationship with tumour-associated neutrophils and tumour PD-L1. When analysed together in a scoring system, we demonstrated that low levels of lymphocytes, high expression of PD-L1 and high infiltration of neutrophils are associated with a worse outcome. In blood, a high ratio of neutrophils and lymphocytes (NLR) was also associated with worse survival but was not correlated with inflammatory components of the tumour. High levels of sPD-L1 protein were associated with reduced overall survival, however our study did not identify a relationship between sPD-L1 levels in the blood and PD-L1 expression in tumour tissue, determined by immunohistochemistry and RT-qPCR. In contrast, the in vitro study showed that the levels of sPD-L1 released 14 into the supernatant are strongly correlated with cytoplasmic and membrane expression. Our data further showed that sPD-L1 levels in patients were positively correlated with the number of leukocytes, neutrophils and monocytes in peripheral blood. Taken together, our results highlight the prognostic potential of markers of the tumour microenvironment analysed in a combined manner, in a scoring system, as a way of providing a more comprehensive overview of tumour behaviour, highlighting important events, such as immunosuppression. Our results highlight the prognostic potential of PD-L1 detected by liquid biopsy in HNSCC and indicate that the levels detected in the blood do not necessarily correspond to what is observed in the tumour. Therefore, it is believed that it should be analysed as an independent marker whose immunosuppressive role is carried out at a systemic level