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Investigation of the effect of combined treatment with pharmacological inhibitors of JAK2 and IRS2 or mTOR in JAK2 V617F cells

Grant number: 15/09324-9
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2015
Effective date (End): April 30, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fabíola Traina
Grantee:Bruna Alves Fenerich
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The identification of the JAK2V617F mutation as a molecular marker for myeloproliferative neoplasms represents a milestone in the progress in the diagnosis of these diseases as well as for the development of JAK2 pharmacological inhibitors. However, the isolated treatment with JAK2 inhibitors, such as ruxolitinib, is not specific for the mutated JAK2 and does not result in significant better overall survival. Thus, new therapeutic approaches using Ruxolitinib in combination with other drugs that inhibit others proteins in JAK/STAT pathway has been tested and proved to be promising. This study aims to evaluate the effect of combined treatment of ruxolitinib with IRS2 or mTOR inhibitors in JAK2V617F cells and standardize a xenograft model of leukemogenesis induced by HEL JAK2V617F cells for further treatment in vivo. Cells submitted to the treatment with pharmacological inhibitors, isolated and in combination, will be submitted to functional tests for viability, proliferation, apoptosis and cell cycle, and western blot analysis for protein expression and activation. (AU)

Scientific publications
(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)
FENERICH, BRUNA ALVES; FERNANDES, JAQUELINE CRISTINA; RODRIGUES ALVES, ANA PAULA NUNES; COELHO-SILVA, JUAN LUIZ; SCOPIM-RIBEIRO, RENATA; SCHEUCHER, PRISCILA SANTOS; EIDE, CHRISTOPHER A.; TOGNON, CRISTINA E.; DRUKER, BRIAN J.; REGO, EDUARDO MAGALHAES; MACHADO-NETO, JOAO AGOSTINHO; TRAINA, FABIOLA. NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2(V617F)-positive myeloproliferative neoplasm cells. SIGNAL TRANSDUCTION AND TARGETED THERAPY, v. 5, n. 1 JAN 24 2020. Web of Science Citations: 0.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FENERICH, Bruna Alves. Pharmacological inhibition of insulin receptor substrates in myeloproliferative neoplasm JAK2V617F. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.