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Grant number: 12/09778-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): February 29, 2016
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Debora Aparecida Pires de Campos Zuccari
Grantee:Camila Leonel da Silva
Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
Associated scholarship(s):12/25146-5 - Metastasis inhibition via epithelial-mesenchymal transition by metformin in mammary neoplasia, BE.EP.DR


The Epithelial-mesenchymal transition (EMT) is characterized by the change in mesenchymal to epithelial phenotype leads to loss or reduced expression of markers of epithelial cells such as E-cadherin and claudin, and increased expression of markers of mesenchymal cells such as n- cadherin and vimentin, as well as increased expression of the transcription factor twist. The EMT can be induced by extracellular matrix components and growth factors such as transforming growth factor beta (TGF-²), responsible for regulating cellular differentiation and proliferation, migration and apoptosis. The EMT starts with the transformation and differentiation of stem cells in breast cancer (BCSCs). Recent studies reproduced in vitro process of EMT in mammary epithelial cells generating cell BCSCs properties. In addition, a small subpopulation of tumor cells with the phenotype characteristic of stem cells (CD44 + / CD24-) are present in breast tumors. Currently, various tools of intervention have been employed to inhibit EMT and subsequent metastasis, such as the use of RNA interference (siRNA). For this purpose, recently emerged new research using metformin, a drug for type 2 diabetes, inhibiting the action of TGF-B in EMT and subsequent metastasis of breast cancer. The objective of this study is to identify markers associated with EMT, by immunofluorescence staining and RT-PCR, and prevent the process of metastasis of breast cancer through inhibition of TGF-² by siRNA technology and treatment with metformin in canine breast cancer cell lines and in animal model. The data obtained in this study will confirm the likely benefits of gene silencing and metformin as therapeutic agents in the treatment of breast cancer, reducing the occurrence of metastases and thus contributing to a better prognosis for patients with breast cancer.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Camila Leonel da. Inhibition of metastasis via epithelial-mesenchymal transition by shRNA, metformin and Y27632 in breast cancer. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.

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