Regulated necrosis induced by photodynamic and sonodynamic therapies in oral epithelial dysplastic cells: in vitro and in vivo study

• Grant number: 23/11402-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• Status: Discontinued
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Luciana Corrêa
• Grantee: Saygo Tomo
• Host Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 25/02099-1 - Role of cancer-associated fibroblasts on modulating regulated cell death of oral dysplastic keratinocytes: an in vitro study, BE.EP.PD

Abstract

Oral epithelial dysplasias (OED) are potentially malignant lesions for which treatment is still debated, given the high rate of recurrence and the possibility of major tissue loss due to extensive surgical interventions. Photodynamic therapy (PDT) has been considered a promising non-surgical method for the treatment of OED, but the characterization of the mechanism of regulated necrosis (necroptsis, pyroptosis and ferroptosis) still needs to be described. Recently, sonodynamic therapy (SDT) has also emerged as an adjunctive treatment for malignant neoplasms, given its potential for high tissue penetration. The conjugation of PDT with SDT has been tested on some neoplastic cells in vitro and in tumor models in vivo, demonstrating a synergism between the two therapies that enhances the effectiveness of cell death, especially in the deeper tissue layers. This association has not yet been tested in OED, nor have the types of cell death induced by the combination of the two therapies been described in these lesions. The objective of this study is to verify the patterns of regulated necrosis present in dysplastic oral cells exposed to PDT, SDT and sono-photodynamic therapy (SPDT), mediated by 5-aminolevulinic acid. In the first phase of the study, the expression of necroptosis, pyroptosis and ferroptosis markers will be evaluated in three-dimensional cell cultures (organotypic) of dysplastic oral keratinpcytes, after exposure to PDT, SDT and SPDT. In the second stage, potentially malignant oral lesions will be chemically induced in Wistar Rat tongues, which will also be subjected to the same interventions and analyzes of regulated necrosis markers. The analysis of these markers will be done by biochemical assays and immunofluorescence. It is expected to elucidate the mechanism of cell death induced by PDT, SDT and SPDT in oral dysplastic lesions, contributing to the improvement of clinical protocols for the treatment of these lesions.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HEGUEDUSCH, DANIELE; CARVALHO, GIOVANNA LOPES; TOMO, SAYGO; AGUIAR, EMILIA MARIA GOMES; CUSTODIO, MARCOS; SIQUEIRA, JULIANA MOTA; MERCANTE, ANA MARIA DA CUNHA; CURY, PATRICIA MALUF; TAJARA, ELOIZA HELENA; DE CICCO, RAFAEL; et al. The Patterns of P53, E-Cadherin, β-Catenin, CXCR4 and Podoplanin Expression in Oral Squamous Cell Carcinoma Suggests a Hybrid Invasion Model: an Immunohistochemical Study on Tissue Microarrays. Head and Neck Pathology, v. 19, n. 1, p. 12-pg., 2025-01-07. (10/51168-0, 23/11402-4)

TOMO, SAYGO; LECHIEN, JEROME R.; BUENO, HUGO SOBRINHO; CANTIERI-DEBORTOLI, DANIELA FILIE; SIMONATO, LUCIANA ESTEVAM. Accuracy and consistency of ChatGPT-3.5 and-4 in providing differential diagnoses in oral and maxillofacial diseases: a comparative diagnostic performance analysis. CLINICAL ORAL INVESTIGATIONS, v. 28, n. 10, p. 11-pg., 2024-09-24. (23/11402-4)