Akt, COX-2, RUNX1 and MMPs expression in metastatic melanomas

• Grant number: 17/16102-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: November 30, 2019
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Jacks Jorge Junior
• Grantee: Jacks Jorge Junior
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Associated researchers: Ciro Dantas Soares ; Edgard Graner

Abstract

Melanoma is a neoplasm derived of melanocytes that is associated with aggressive clinical behavior and mainly by the high propensity for metastatic spread, which results in a poor prognosis. This tumor shows a heterogeneous clinical course. Patients with non-metastatic form of the disease (stage I and II) shows an overall survival rate of 97-53% in 5 years, however, in patients with metastatic melanoma (MM) this index ranges from 20-15% in the same period. Accumulating evidence in recent years about metastatic tumors focused great interest to determine molecular mechanisms underlying the ability of cancer cells to metastasize for development of new therapies with emphasis in patients with MM in advanced stage. Several molecules have been identified as having important roles to play in invasion and metastasis processes. Akt is associated with cell survival, metabolism regulation, migration and apoptosis. Recent studies reported that transcription factor RUNX1 activates the PI3K signaling pathway, resulting in phosphorylation of Akt, on the other hand, the cells showed inhibition of migration, apoptosis and invasion when Akt is silencing in vitro in many cells of different tumors. In cancer cells, Akt is also believed to be upregulated by the COX-2 pathway and is associated with a more aggressive phenotype in tumors, including by activation of metalloproteinases matrix, especially MMP-2 and MMP -9. Although the correlation of Akt and COX-2 has been related in several cancers and associated with metastases, their correlation in metastatic melanomas has not been widely reported. Thus, the project aims to study the relationship of signaling pathways (Akt, COX-2, RUNX1 and MMPs) in metastasis progression of melanoma model in vivo and in vitro. The slides will be scanned and analyzed using specific algorithms to quantify the expression intensity. Additionally, the biological role and effect of the Akt gene silencing in B16F10 cells will be investigated by in vitro assays: to determine the rate of cell death (necrosis and apoptosis), cell viability, proliferation, migration and invasion. Furthermore, B16F10 cells (silenced or not to Akt gene) will be injected in the tongue of C57BL/6 and chronological analysis of histological and biological events that occur during the metastatic process will be performed. (AU)

Scientific publications

(13)

(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)

SOARES, CIRO D.; MORAIS, THAYNA M. L.; CARLOS, ROMAN; JORGE, JACKS; DE ALMEIDA, OSLEI PAES; DE CARVALHO, MARIA G. F.; ALTEMANI, ALBINA M. M.. Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases. Histopathology, v. 73, n. 4, p. 585-592, OCT 2018. (17/16102-8, 15/25905-1)

FONSECA, FELIPE PAIVA; BENITES, BERNAR MONTEIRO; SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; DO AMARAL-SILVA, GLEYSON KLEBER; DE ALMEIDA, OSLEI PAES; SOARES, FERNANDO AUGUSTO; FREGNANI, EDUARDO RODRIGUES. Prognostic importance of FGF2 and FGFR1 expression for patients affected by ameloblastoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 47, n. 4, p. 417-424, APR 2018. (17/16102-8, 15/25905-1)

DE SOUZA, LUCAS LACERDA; DE LIMA MORAIS, THAYNA MELO; REBELO PONTES, HELDER ANTONIO; DE ALMEIDA, OSLEI PAES; FREIRE DE CARVALHO, MARIA GORETTI; SOARES, CIRO DANTAS. Rapidly ulcerated swelling in the hard palate of a HIV-positive pregnant woman. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 131, n. 3, p. 6-pg., 2021-02-12. (17/16102-8, 17/14880-3)

SOARES, CIRO DANTAS; DE CACERES, CINTHIA VERONICA BARDALEZ LOPEZ; RODRIGUES-FERNANDES, CARLA ISABELLY; DE LIMA MORAIS, THAYNA MELO; DE ALMEIDA, OSLEI PAES; DE CARVALHO, MARIA GORETTI FREIRE; FONSECA, FELIPE PAIVA. Prognostic importance of RUNX1 expression for head and neck adenoid cystic carcinoma. ORAL DISEASES, v. 27, n. 2, JUL 2020. (15/25905-1, 17/16102-8)

SOARES, CIRO DANTAS; DELGADO-AZANERO, WILSON; DE LIMA MORAIS, THAYNA MELO; DE ALMEIDA, OSLEI PAES; GHERSI MIRANDA, HUGO. Odontogenic Carcinosarcoma: Clinicopathologic Features of 2 Cases. INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY, v. 28, n. 4, DEC 2019. (17/16102-8, 15/25905-1)

SOARES, CIRO DANTAS; SANTANA, THALITA; DE SOUZA, LUCAS LACERDA; DE ALMEIDA, OSLEI PAES; SKALOVA, ALENA; ALTEMANI, ALBINA; SALES, ALEXANDRE DE OLIVEIRA. Intraductal carcinoma of the submandibular gland: A case report. Oral Oncology, v. 132, p. 3-pg., 2022-07-06. (17/16102-8, 15/25905-1)

SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; CARLOS, ROMAN; MARTINS, MANOELA DOMINGUES; DE ALMEIDA, OSLEI PAES; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA. Immunohistochemical expression of mammaglobin in salivary duct carcinomas de novo and salivary duct carcinoma ex pleomorphic adenoma. HUMAN PATHOLOGY, v. 92, p. 59-66, OCT 2019. (15/07304-0, 17/00831-0, 15/25905-1, 17/16102-8)

SOARES, CIRO DANTAS; ROCHA, BRENO AMARAL; RIBEIRO PARANAIBA, LIVIA MARIS; DE MELO-FILHO, MARIO RODRIGUES; JORGE, JACKS; FREIRE DE CARVALHO, MARIA GORETTI; DE ALMEIDA, OSLEI PAES. A challenging diagnosis: Case report of oral metastasis from gastric adenocarcinoma mimicking pyogenic granuloma. MEDICINE, v. 97, n. 13, MAR 2018. (15/25905-1, 17/16102-8)

MARIZ, BRUNO A. L. A.; SOARES, CIRO D.; DE CARVALHO, MARIA G. F.; JORGE-JUNIOR, JACKS. FGF-2 and FGFR-1 might be independent prognostic factors in oral tongue squamous cell carcinoma. Histopathology, v. 74, n. 2, p. 311-320, JAN 2019. (17/16102-8, 15/25905-1)

SOARES, CIRO D.; MORAIS, THAYNA M. L.; ARAUJO, ROBERTA M. F. G.; MEYER, PATRICIA F.; OLIVEIRA, ERIC A. F.; SILVA, V, RODRIGO M.; CARREIRO, ENEIDA M.; CARREIRO, EDVALDO P.; BELLOCO, VERONICA G.; MARIZ, BRUNO A. L. A.; et al. Effects of subcutaneous injection of ozone during wound healing in rats. GROWTH FACTORS, v. 37, n. 1-2, JULY 2019. (17/16102-8, 15/25905-1)

DE LIMA MORAIS, THAYNA MELO; SOARES, CIRO DANTAS; COSTA WANDERLEY, ARTHUR ERIC; ROSA DE OLIVEIRA, CATARINA RODRIGUES; BEDER RIBEIRO, CAMILA MARIA; DE ALMEIDA, OSLEI PAES; FREIRE DE CARVALHO, MARIA GORETTI; SOARES FERREIRA, SONIA MARIA. Oral melanomas in HIV-positive patients: Report of two cases and review of the literature. Oral Oncology, v. 101, FEB 2020. (17/16102-8, 15/25905-1)

SOARES, CIRO D.; CARLOS, ROMAN; MOTA, MARCELO V. B.; DE CARVALHO, MARIA G. F.; DE LIMA MORAIS, THAYNA M.; DE ALMEIDA, OSLEI P.; ALTEMANI, ALBINA. Bilateral multiple oncocytic cysts of the parotid gland in type 2 diabetes patients. Histopathology, v. 76, n. 4, p. 613-624, MAR 2020. (17/16102-8, 15/25905-1)

MARIZ, BRUNO A. L. A.; SOARES, CIRO D.; MORAIS, THAYNA M. L.; FONSECA, FELIPE P.; DE CARVALHO, MARIA G. F.; JORGE, JACKS. Expression of FGF-2/FGFR-1 in normal mucosa, salivary gland, preneoplastic, and neoplastic lesions of the oral cavity. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 47, n. 9, p. 816-822, OCT 2018. (17/16102-8, 15/25905-1)