Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Systemic chemotherapy-induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine

Texto completo
Autor(es):
Pinto, Jorge L. F. [1, 2] ; Fonseca, Fernando L. A. [2] ; Marsicano, Sarah R. [2] ; Delgado, Pamela O. [2] ; Sant'Anna, Aleksandra V. L. [2] ; Coelho, Patricia G. [2] ; Maeda, Patrica [2] ; Del Giglio, Auro [1, 2, 3]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Sao Paulo - Brazil
[2] ABC Fdn Sch Med, Santo Andre - Brazil
[3] Albert Einstein Jewish Hosp, ABC Fdn, Sch Med, Dept Oncol, BR-01444000 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Journal of Pharmacy and Pharmacology; v. 62, n. 7, p. 931-934, JUL 2010.
Citações Web of Science: 6
Resumo

Objectives Microsatellite instability (MSI) induction by alkylating agent-based chemotherapy (ACHT) may underlie both tumor resistance to chemotherapy and secondary leukaemias in cancer patients. We investigated if ACHT could induce MSI in tumor-derived plasma-circulating DNA (pfDNA) and in normal peripheral blood mononuclear (PBMN) cells. We also evaluated if amifostine could interfere with this process in an in-vitro model. Methods MSI was determined in pfDNA, PBMN cells and urine cell-free DNA (ufDNA) of 33 breast cancer patients before and after ACHT. MCF-7 cells and PBMN from normal donors were exposed in vitro to melphalan, with or without amifostine. Results We observed at least one MSI event in PBMN cells, pfDNA or ufDNA of 87, 80 and 80% of patients, respectively. In vitro, melphalan induced MSI in both MCF-7 and normal PBMN cells. In PBMN cells, ACHT-induced MSI occurred together with a significant decrease in the expression of the DNA mismatch repair gene hMSH2. Amifostine decreased hMSH2 expression and also prevented MSI induction only in normal PBMN cells. Conclusions ACHT induced MSI in PBMN cells and in tumour-derived pfDNA. Because of its protective effect against ACHT induction of MSI in normal PBMN cells in vitro, amifostine may be a potential agent for preventing secondary leukaemias in patients exposed to ACHT. (AU)

Processo FAPESP: 05/00651-5 - DNA plasmático e urinário em pacientes com câncer de mama: possibilidade de um novo marcador de instabilidade genética tumoral induzida por quimioterapia
Beneficiário:Auro del Giglio
Linha de fomento: Auxílio à Pesquisa - Regular