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FGF-2, FGFR-1, PI3K, Akt and COX-2 expression in Oral Leucoplakia, primary and metastatic Oral Squamous Cell Carcinoma

Grant number: 18/24715-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2019
Effective date (End): April 30, 2021
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Jacks Jorge Junior
Grantee:Bruno Augusto Linhares Almeida Mariz
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Oral Squamous Cell Carcinoma (OSCC) accounts for the great majority of the malignancies in the oral cavity, with 300,000 new cases for year, representing one of the sixth most common types of Cancer in the world. The prognostic perspectives for patients are cloudy, with a 5-years survival rate of only 50% after diagnosis, with small advances in the past three decades. Despite the advances in molecular pathology, no tumor biomarkers associated with oral Cancer progression and prognosis have been approved for clinical use, as occurs in other types of Cancer. Oral Leucoplakia (OL) is the most common Oral Potentially Malignant Disorder (OPMD), affecting 1% of the global population, with malignant transformation rates ranging from 2 to 5%. FGF-2 and FGFR-1 immunoexpression is correlated with worse prognosis and more invasive tumors in patients with OSCC. Changes in the FGF/FGFR pathway can activate a downstream signaling via PI3K/Akt. Akt is an inactive cytosolic protein, activated through phosphorylation via PI3K, blocking several apoptotic proteins. It has been proved that Akt directly regulates COX-2 gene and protein expression. Similarly, COX-2 overexpression is associated with more aggressiveness in different types of Cancer, including breast, colon, lung, and head and neck tumors. From all the evidence given above, the main objectives of this project are: (1) evaluate the immunoexpression of FGF-2, FGFR-1, PI3K, Akt, and COX-2 in oral leucoplakia, primary and metastatic OSCC; and (2) study how the FGFR-1 gene silencing affects the biological behavior of primary and metastatic OSCC cell lines in vitro and in vivo. (AU)

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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)
DINIZ, PRISCILLA BARBOSA; SENA-FILHO, MARCONDES; GRANER, KAREN MENDES; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; DOS REIS, LEONARDO AMARAL; DE ALMEIDA, OSLEI PAES; JORGE, JACKS. Comparison of the whole slide imaging and conventional light microscopy in the grading of oral epithelial dysplasia: a multi-institutional study. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 26, n. 1, p. E8-E13, JAN 2021. Web of Science Citations: 0.
LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; KOWALSKI, LUIZ PAULO; WILLIAM JR, WILLIAM NASSIB; DE CASTRO, GILBERTO; FREITAS CHAVES, ALINE LAUDA; SANTOS, MARCOS; DE OLIVEIRA, THIAGO BUENO; DAMACENO ARAUJO, ANNA LUIZA; COSTA NORMANDO, ANA GABRIELA; PRADO RIBEIRO, ANA CAROLINA; BRANDAO, THAIS BIANCA; VARGAS, PABLO AGUSTIN; LOPES, MARCIO AJUDARTE; SANTOS-SILVA, ALAN ROGER; GR, LATIN AMER COOPERATIVE ONCOLOGY; CANC, BRAZILIAN GRP HEAD NECK. Global prevalence of human papillomavirus-driven oropharyngeal squamous cell carcinoma following the ASCO guidelines: A systematic review and meta-analysis. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 156, DEC 2020. Web of Science Citations: 0.
MARIZ, BRUNO A. L. A.; SANCHEZ-ROMERO, CELESTE; ROMANACH, MARIO J.; DE ALMEIDA, OSLEI P.; CARLOS, ROMAN. Respiratory scleroma: A clinicopathologic study of 51 cases from Guatemala. ORAL DISEASES, v. 26, n. 3, p. 670-676, APR 2020. Web of Science Citations: 0.

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