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Epigenetically modulated genes may constitute therapeutic targets in patients with gastric cancer?

Grant number: 16/19953-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2017
Effective date (End): April 30, 2019
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Marilia de Arruda Cardoso Smith
Grantee:Fernanda Wisnieski
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Gastric cancer is the third leading cause of cancer death worldwide. The continuous study of new strategies for early diagnosis and identification of new therapeutic methods is of great interest in this disease. Hypermethylation of the promoters of tumor suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. Our research group previously identified by microarray analysis 83 differentially expressed genes in 5-aza-2'-deoxycytidine-treated gastric cancer cell lines compared with non-treated cells. Among the upregulated genes identified in this analysis, NRN1 and TNFAIP3 were selected for further studies. Therefore, the purpose of this project is to evaluate and compare the expression and methylation levels of NRN1 and TNFAIP3, as well as histone methylation levels associated with these genes in paired neoplastic and adjacent non-neoplastic gastric tissue samples. For this, these samples will be collected from 100 patients diagnosed with primary gastric adenocarcinoma that underwent gastrectomy. For the analysis of NRN1 and TNFAIP3 promoter regions and histone methylation, the next generation sequencing and the Chromatin Immunoprecipitation will be performed in all tissue samples, respectively. The present study has the potential to identify new therapeutic targets in gastric cancer, once DNA and histone methylation are reversible alterations. (AU)

Scientific publications (4)
(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)
ANAUATE, ANA CAROLINA; LEAL, MARIANA FERREIRA; QUEIROZ CALCAGNO, DANIELLE; GIGEK, CAROLINA OLIVEIRA; REAL KARIA, BRUNO TAKAO; WISNIESKI, FERNANDA; DOS SANTOS, LEONARDO CAIRES; CHEN, ELIZABETH SUCHI; BURBANO, ROMMEL RODRIGUEZ; CARDOSO SMITH, MARILIA ARRUDA. The Complex Network between MYC Oncogene and microRNAs in Gastric Cancer: An Overview. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 5 MAR 2020. Web of Science Citations: 0.
ANAUATE, ANA C.; LEAL, MARIANA F.; WISNIESKI, FERNANDA; SANTOS, LEONARDO C.; GIGEK, CAROLINA O.; CHEN, ELIZABETH S.; CALCAGNO, DANIELLE Q.; ASSUMPCAO, PAULO P.; DEMACHKI, SAMIA; ARASAKI, CARLOS H.; ARTIGIANI, RICARDO; RASMUSSEN, LUCAS T.; PAYAO, SPENCER M.; BURBANO, ROMMEL R.; SMITH, MARILIA A. C. Analysis of 8q24.21 miRNA cluster expression and copy number variation in gastric cancer. Future Medicinal Chemistry, v. 11, n. 9, p. 947-958, MAY 2019. Web of Science Citations: 3.
CALCAGNO, DANIELLE Q.; WISNIESKI, FERNANDA; DA SILVA MOTA, ELIZANGELA R.; MAIA DE SOUSA, STEFANIE B.; COSTA DA SILVA, JESSICA M.; LEAL, MARIANA F.; GIGEK, CAROLINA O.; SANTOS, LEONARDO C.; RASMUSSEN, LUCAS T.; ASSUMPCAO, PAULO P.; BURBANO, ROMMEL R.; SMITH, MARILIA A. C. Role of histone acetylation in gastric cancer: implications of dietetic compounds and clinical perspectives. Epigenomics, v. 11, n. 3, p. 349-362, FEB 2019. Web of Science Citations: 2.
GIGEK, CAROLINA OLIVEIRA; CALCAGNO, DANIELLE QUEIROZ; RASMUSSEN, LUCAS TREVIZANI; SANTOS, LEONARDO CAIRES; LEAL, MARIANA FERREIRA; WISNIESKI, FERNANDA; BURBANO, ROMMEL RODRIGUEZ; LOURENCO, LAERCIO GOMES; LOPES-FILHO, GASPAR JESUS; CARDOSO SMITH, MARILIA ARRUDA. Genetic variants in gastric cancer: Risks and clinical implications. Experimental and Molecular Pathology, v. 103, n. 1, p. 101-111, AUG 2017. Web of Science Citations: 14.

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