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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2019
• End date: April 30, 2021
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Jacks Jorge Junior
• Grantee: Bruno Augusto Linhares Almeida Mariz
• Host 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)

Scientific publications

(11)

(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)

SALES DE SA, RAISA; MIRANDA GALVIS, MARISOL; MARIZ, BRUNO AUGUSTO LINHARES ALMEIDA; LEITE, AMANDA ALMEIDA; SCHULTZ, LUCIANA; ALMEIDA, OSLEI PAES; SANTOS-SILVA, ALAN ROGER; PINTO, CLOVIS ANTONIO LOPES; VARGAS, PABLO AGUSTIN; GOLLOB, KENNETH JOHN; et al. Increased Tumor Immune Microenvironment CD3+and CD20+Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 8, FEB 18 2021. (18/24715-2)

MARIZ, BRUNO AUGUSTO LINHARES ALMEIDA; DE SA, RAISA SALES; ARAUJO, ANNA LUIZA DAMACENO; FERNANDES, CARLA ISABELLY RODRIGUES; MARIANO, FERNANDA VIVIANE; SANTOS-SILVA, ALAN ROGER; LOPES, MARCIO AJUDARTE; VARGAS, PABLO AGUSTIN; DE ALMEIDA, OSLEI PAES; KOWALSKI, LUIZ PAULO; et al. FGFR1 is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 52, n. 2, p. 8-pg., 2023-01-04. (18/24715-2)

DO AMARAL-SILVA, GLEYSON KLEBER; DIAS, LARYSSA MOURA; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; FONSECA, FELIPE PAIVA; CARRINHO AYROZA RANGEL, ANA LUCIA; ZANELLA, VIRGILIO GONZALES; CASTILHO, ROGERIO MORAES; MARTINS, MANOELA DOMINGUES; VARGAS, PABLO AGUSTIN; WAGNER, VIVIAN PETERSEN. MutS alpha expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 27, n. 2, p. 10-pg., 2022-03-01. (09/53839-2, 17/08995-2, 18/12435-5, 15/21520-8, 16/21785-4, 18/24715-2)

LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; MIGLIORATI, CESAR AUGUSTO; ALVES, FABIO DE ABREU; PENTEADO, FABIANA DE MORAES; CARVALHO FILHO, NEVICOLINO PEREIRA; SANTOS-SILVA, ALAN ROGER; ROCHA, ANDRE CAROLI. Successful denosumab treatment for central giant cell granuloma in a 9-year-old child. SPECIAL CARE IN DENTISTRY, v. 41, n. 4, p. 7-pg., 2021-03-24. (18/24715-2)

LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; MIGLIORATI, CESAR AUGUSTO; ALVES, FABIO DE ABREU; PENTEADO, FABIANA DE MORAES; CARVALHO FILHO, NEVICOLINO PEREIRA; SANTOS-SILVA, ALAN ROGER; ROCHA, ANDRE CAROLI. Successful denosumab treatment for central giant cell granuloma in a 9-year-old child. SPECIAL CARE IN DENTISTRY, MAR 2021. (18/24715-2)

MARIZ, B. A. L. A.; BRANDAO, T. B.; RIBEIRO, A. C. P.; LOPES, M. A.; SANTOS-SILVA, A. R.. New Insights for the Pathogenesis of COVID-19-Related Dysgeusia. JOURNAL OF DENTAL RESEARCH, v. 99, n. 10, JUN 2020. (18/24715-2, 18/02233-6)

SCARINI, JOAO FIGURIRA; ALMEIDA MARIZ, BRUNO AUGESTO LINHARES; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; TINCANI, ALFIO JOSE; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVANE. Spindle cell carcinoma of the lip: An immunohistochemical study of a challenging case. Oral Oncology, v. 125, p. 3-pg., 2022-02-01. (19/06809-2, 15/07304-0, 19/09419-0, 18/24715-2)

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. (18/24715-2)

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; et al. 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. (18/24715-2)

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. (18/24715-2)

MARIZ, BRUNO AUGUSTO LINHARES ALMEIDA; TAGER, ELENA MARIA JOSE ROMAN; FERNANDEZ, CARLOS CORDON; DE ALMEIDA, OSLEI PAES; CARLOS, ROMAN. Palatal Soft Tissue Myxoma in a Patient with Carney Complex. Head and Neck Pathology, v. 15, n. 3, p. 8-pg., 2020-10-21. (18/24715-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARIZ, Bruno Augusto Linhares Almeida. FGFR1 protein expression and gene amplification in tongue squamous cell carcinoma and oral leukoplakia. 2021. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.