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My line of research became the investigation of malignant tumors since my postdoctoral period and my main area of interest as a researcher is tumor biology, especially related to Oral Squamous Cell Carcinoma (OSCC). This tumor is relevant in Brazil because it is associated with high mortality and low quality of life for the patients affected. There is still well-established adjuvant chemotherapeutic therapy for this tumor, especially because of the lack of knowledge of the tumor biology of the OSCC.
We have focused our studies on the participation of the Hedgehog pathway (HH) in Oral Squamous Cell Carcinoma (OSCC). Our team pioneered the reactivation of this pathway in OSCC (Cavicchioli Buim ME, Gurgel CA, 2011) in scientific literature and in this study, I divided the first authorship with another postdoctoral student. In this study, we demonstrated activation of the HH pathway in human OSCC samples and we observed a correlation between the expression of the main transcription factor of the HH pathway (GLI1) with grade III (more advanced) tumors. Already as a professor of the Post-Graduation Program in Human Pathology, we continued this line of research and, our question was whether the HH pathway could be activated at a pre-malignant stage of the disease (Oral Epithelial Dysplasia). In this study, I did the experimental design, participated as a guide and corresponding author of the article (Dias et al., 2016). We focused the analyzes on the epithelial compartment of oral epithelial dysplasias and compared this disease with other reactive lesions that occurred in the same anatomical location (jugal mucosa, tongue, etc). We observed that the HH pathway was already activated at a pre-malignant stage of the OSCC and therefore could have a role in the initiation of oral cancer. These findings were important to expand my team 's work with the main objective of understanding the role of HH signaling in the context of tumor biology, with emphasis on cell proliferation, angiogenesis and invasion.
We outlined the strategies of the investigations related to the HH cascade participation in OSCC angiogenesis in 2014. Some functional assays are under way, but we obtained interesting results when we evaluated the expression of VEGFA mRNA levels in margins and tumors. From these observations, I oriented the work of Sales et al. (2016), whose results indicated a more relevant pro-angiogenic activity in the non-tumor margins adjacent to the primary tumor. In this work, I also participated as a counselor and corresponding author.
Through the analysis of the OSCC cases studied by the team, we observed that components of the tumor microenvironment also had the HH cascade activated. In the study by Valverde et al. (2016), in which I also participated as guide and corresponding author, demonstrated this through the presence of the nuclear GLI1 protein in endothelial cells of newly formed vessels (CD105 +) and the ligands of the HH pathway in CD163 + macrophages. These results demonstrated that the HH pathway participates in tumor angiogenesis and that, in OSCC, HH activation can occur through endocrine, paracrine and paracrine-reverse mechanisms. These are the areas of research that our laboratory is currently pursuing. Because of our results (some of which have yet to be published in the process of being completed), we have expanded our research to assess the therapeutic potential of the HH signaling pathway in OSCC and, as of 2016, I have consolidated my collaborative research networks, especially in the area of screening for new anti-cancer drugs focusing on mechanisms related to antitumoral activity. The Dias et al. (2018) work was the first article overseen by me, related to this field of research.
Research Interests
Papers共 79 篇Author StatisticsCo-AuthorSimilar Experts
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Cancer Researchno. 5_Supplement (2023): P6-13
Leonardo de Araujo Melo, Dandara Andrade de Santana,Caroline Brandi Schlaepfer Sales, Braulio Carneiro Jr,Marilia Trierveiler Martins,Valeria Souza Freitas,Flavia Calo Aquino Xavier,Patricia Ramos Cury,Clarissa Araujo Silva Gurgel,Jean Nunes dos Santos
Journal of Oral Diagnosisno. 1 (2019): 1-6
Rafael Rodrigues Dos Santos,Águida Cristina Gomes Henriques,Clarissa Araújo Silva Gurgel,Jean Nunes dos Santos,Leonardo De Araújo Melo
Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiologyno. 3 (2018)
Ernesto Santos Sousa-Neto,Maria Cristina Teixeira Cangussu,Clarissa Araújo Gurgel, Vanessa Sousa Guimarães,Eduardo Antônio Gonçalves Ramos,Flávia Caló Aquino Xavier,Patrícia Ramos Cury,Braúlio Carneiro Júnior,Rosalia Leonardi,Jean Nunes Dos Santos
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