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Akt, COX-2, RUNX1 and MMPs expression in metastatic melanomas and biotechnology prospection of molecules with antineoplastic activity

Grant number: 15/25905-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2016
Effective date (End): March 31, 2020
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Jacks Jorge Junior
Grantee:Ciro Dantas Soares
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Associated research grant(s):17/14905-6 - Prognostic significance of cyclooxygenase 2 (COX-2) and p-Akt1 overexpression in primary non-metastatic and metastatic cutaneous melanomas, PUB.ART
Associated scholarship(s):17/18134-4 - Investigative project for microbiome characterization and immune response in primary and metastatic melanoma and their correlation with survival outcomes, BE.EP.DR

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. 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. Bioactive compounds derived from natural products are studied for their potential antitumour, and biotechnological prospecting of plant extracts are promising options for cancer treatment. Thus, the project aims to: (1) study the relationship of signaling pathways (Akt, COX-2, RUNX1 and MMPs) in metastasis progression of melanoma model in vivo and in vitro, and (2) evaluate the effect of the extracts, fractions and bioproducts of Croton cajucara Benth in microemulsion systems in melanoma cells. In vitro and in vivo studies shall be proposed. In vitro model will be evaluated the expression of proteins in human melanoma cell lines treated or not. In the in vivo model, mice will be submitted to the application of B16F10 cells in tongue for metastasis induction and treated with Croton cajucara. Histological analysis will be performed, immunohistochemistry and WB to assess antineoplastic and antimetastatic effects of bioactive compounds.

Scientific publications (14)
(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 DANTAS; CARLOS, ROMAN; DIAZ MOLINA, JUAN PABLO; DE LIMA MORAIS, THAYNA MELO; DE ALMEIDA, OSLEI PAES. Laryngeal Epstein-Barr Virus-Associated Smooth Muscle Tumor in an Undernourished Child. Head and Neck Pathology, v. 13, n. 4, p. 722-726, DEC 2019. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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.; JORGE-JUNIOR, JACKS. Effects of subcutaneous injection of ozone during wound healing in rats. GROWTH FACTORS, v. 37, n. 1-2 JULY 2019. Web of Science Citations: 0.
SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA; CORREA, MARCELO BRUM; DIAS DOS REIS, RODRIGO RIBAS; AMORIM, LUCIANA SCHULTZ; SOARES FERREIRA, SONIA MARIA; DE ALMEIDA, OSLEI PAES; CARLOS, ROMAN; JORGE, JACKS. Expression of mitochondrial dynamics markers during melanoma progression: Comparative study of head and neck cutaneous and mucosal melanomas. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 48, n. 5, p. 373-381, MAY 2019. Web of Science Citations: 0.
DE LIMA MORAIS, THAYNA MELO; MEYER, PATRICIA FROES; DE VASCONCELLOS, LILIANE SANTOS; COSTA E SILVA, JULIO; FERREIRA E ANDRADE, ITO; FREIRE DE FARIAS, VINICIUS ALVES; DA SILVA, IGOR CANDIDO; FALCO GONDIM ARAUJO, ROBERTA MARINHO; VALENTIM DA SILVA, RODRIGO MARCEL; PACHECO, ESTEBAN FORTUNY; SOARES, CIRO DANTAS. Effects of the extracorporeal shock wave therapy on the skin: an experimental study. Lasers in Medical Science, v. 34, n. 2, p. 389-396, MAR 2019. Web of Science Citations: 2.
SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; CARLOS, ROMAN; DE ALMEIDA, OSLEI PAES; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA; FREIRE DE CARVALHO, MARIA GORETTI; CORREA, MARCELO BRUM; DIAS DOS REIS, RODRIGO RIBAS; AMORIM, LUCIANA SCHULTZ; JORGE, JACKS. Prognostic importance of mitochondrial. markers in mucosal and cutaneous head and neck melanomas. HUMAN PATHOLOGY, v. 85, p. 279-289, MAR 2019. Web of Science Citations: 2.
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. Web of Science Citations: 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. Web of Science Citations: 0.
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. Web of Science Citations: 2.
SOARES, CIRO DANTAS; CARLOS, ROMAN; DE LIMA MORAIS, THAYNA MELO; DE ALMEIDA, OSLEI PAES. Giant dentinogenic ghost cell tumor: A case report. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 126, n. 4, p. E215-E219, OCT 2018. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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. Web of Science Citations: 0.
MEYER, PATRICIA FROES; DE OLIVEIRA, PATRICIA; SILVA, FLAVIA K. B. A.; DA COSTA, ANA C. S.; PEREIRA, CALINE R. A.; CASENAVE, SEBASTIAN; VALENTIM SILVA, RODRIGO MARCEL; ARAUJO-NETO, LUIS GONZAGA; SANTOS-FILHO, SEBASTIAO DAVID; AIZAMAQUE, ERIC; ARAUJO, HENNES GENTIL; BERNARDO-FILHO, MARIO; FREIRE CARVALHO, MARIA GORETTI; SOARES, CIRO DANTAS. Radiofrequency treatment induces fibroblast growth factor 2 expression and subsequently promotes neocollagenesis and neoangiogenesis in the skin tissue. Lasers in Medical Science, v. 32, n. 8, p. 1727-1736, NOV 2017. Web of Science Citations: 4.
SOARES, CIRO D.; BORGES, CAMILLA F.; SENA-FILHO, MARCONDES; DE ALMEIDA, OSLEI P.; STELINI, RAFAEL F.; CINTRA, MARIA L.; GRANER, EDGARD; ZECCHIN, KARINA G.; JORGE, JACKS. Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas. Melanoma Research, v. 27, n. 5, p. 448-456, OCT 2017. Web of Science Citations: 9.

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