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Effects of erlotinib and gefitinib therapy in combination with all-trans retinoic acid and arsenic trioxide in Acute Promyelocytic Leukemia: in vitro, ex vivo and murine experimental model studies

Grant number: 16/02713-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2016
Effective date (End): April 21, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Eduardo Magalhães Rego
Grantee:Luciana Yamamoto de Almeida
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The epidermal growth factor receptor (EGFR) is an important regulator of cell proliferation and differentiation. Changes in EGFR expression are associated with tumor growth and metastasis in solid tumors. On the other hand, there is scarce information in the literature about the participation of the EGFR pathway in hematological malignancies, including acute myeloid leukemia (AML). A previous study conducted in our laboratory showed that EGF (epidermal growth factor), EGFR ligand, showed prognostic value in patients with acute promyelocytic leukemia (APL), M3 subtype of AML, treated according to the International Consortium on LPA protocol. Interestingly, patients with non-small cell lung cancer (NSCLC) and synchronous AML treated with erlotinib, EGFR inhibitor used in the treatment of NSCLC, had regression of both neoplasias. However, it is important to note that the myeloblasts these patients did not express EGFR. Accordingly, another study showed that gefitinib, also inhibitor of EGFR, acted synergistically when combined with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in myeloid differentiation of LPA cell lines negative for EGFR. Until now, the mechanism by which erlotinib and gefitinib interact with hematopoietic progenitors are not well known. Moreover, it is necessary to determine if these drugs induce cell differentiation of APL-derived cells in vivo. Therefore, in this study, we intend to evaluate the effects of erlotinib and gefitinib isolated or in combination with ATRA and ATO in APL cell lines, primary blasts and murine experimental model as well as elucidate the molecular targets of these drugs.

Scientific publications (7)
(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)
DA MOTTA, RAPHAEL J. G.; ALMEIDA, LUCIANA YAMAMOTO; VILLAFUERTE, KELLY R. V.; RIBEIRO-SILVA, ALFREDO; LEON, JORGE E.; TIRAPELLI, CAMILA. FOXP3+and CD25+cells are reduced in patients with stage IV, grade C periodontitis: A comparative clinical study. JOURNAL OF PERIODONTAL RESEARCH, DEC 2019. Web of Science Citations: 0.
TEIXEIRA, LUCAS R.; ALMEIDA, LUCIANA Y.; SILVA, RODRIGO N.; MESQUITA, ANA T. M.; COLTURATO, CARLA B. N.; SILVEIRA, HEITOR A.; DUARTE, ANDRESSA; RIBEIRO-SILVA, ALFREDO; LEON, JORGE E. Young and elderly oral squamous cell carcinoma patients present similar angiogenic profile and predominance of M2 macrophages: Comparative immunohistochemical study. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 41, n. 12, p. 4111-4120, DEC 2019. Web of Science Citations: 0.
NEVES-SILVA, RODRIGO; ALMEIDA, LUCIANA Y.; SILVEIRA, HEITOR A.; COLTURATO, CARLA B. N.; DUARTE, ANDRESSA; FERRISSE, TULIO M.; SILVA, V, EVANIO; VANZOLIN, BARBARA F.; BUFALINO, ANDREIA; RIBEIRO-SILVA, ALFREDO; LEON, JORGE E. SMARCB1 (INI-1) and NUT immunoexpression in a large series of head and neck carcinomas in a Brazilian reference center. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 42, n. 3 NOV 2019. Web of Science Citations: 0.
FERRISSE, TULIO M.; ALMEIDA, LUCIANA Y.; SILVEIRA, HEITOR A.; DE OLIVEIRA, ANALU B.; BUFALINO, ANDREIA; LEON, JORGE E. Benign atypical intralymphatic CD30+lymphoid proliferation with activated regulatory T-cell phenotype in the oral cavity. JOURNAL OF CUTANEOUS PATHOLOGY, v. 46, n. 11 JULY 2019. Web of Science Citations: 0.
TAKAHAMA JR, ADEMAR; DE LIMA, HELITON GUSTAVO; ITO, FABIO AUGUSTO; RIBEIRO-SILVA, ALFREDO; LEON, JORGE ESQUICHE. Epstein-Barr Virus-Positive Mucocutaneous Ulcer Mimicking Peri-Implantitis in a Patient With Systemic Lupus Erythematosus. JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, v. 77, n. 5, p. 977-984, MAY 2019. Web of Science Citations: 0.
RODRIGO N. SILVA; HEITOR A. SILVEIRA; LUCIANA Y. ALMEIDA; CARLA N. B. COLTURATO; ALEXANDRE ELIAS TRIVELLATO; CASSIO E. SVERZUT; JORGE E. LEÓN. Gingival carcinoma cuniculatum mimicking a reactive/inflammatory process. Jornal Brasileiro de Patologia e Medicina Laboratorial, v. 55, n. 5, p. 498-505, Out. 2019.
LANGE, A. P.; ALMEIDA, L. Y.; ARAUJO SILVA, C. L.; SCHEUCHER, P. S.; CHAHUD, F.; KRAUSE, A.; BOHLANDER, S. K.; REGO, E. M. CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice. Brazilian Journal of Medical and Biological Research, v. 52, n. 6 2019. Web of Science Citations: 0.

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