Evaluation of chemotherapy, gene expression and proteins quantification in head and neck carcinoma

• Grant number: 10/12932-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2010
• End date: October 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eny Maria Goloni Bertollo
• Grantee: Ana Lívia Silva Galbiatti-Dias
• 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

Abstract

Chemotherapy with the methotrexate (MTX) and 5-fluorouracil (5-FU) antifolate drugs in head and neck carcinoma may present acute toxicity and side effects and some tumors may show resistance to these agents. Furthermore, the cytotoxic effect is dependent on a competitive interaction with folate metabolism and therefore the high or decreased expression of certain genes this pathway have an important role in the clinical toxicity modulating and efficacy of these drugs. The objectives of this study are to evaluate the efficacy in vitro of MTX and 5-FU chemotherapeutics on FaDu tumor cell line; quantify mRNA expression of proteins from genes DHFR, TS, MTHFR and RFC1 in cells treated with chemotherapies and to correlate with the gene expression. For this will be used FaDu cell line (squamous cell carcinoma of the pharynx Grade I), after which cell culture will be given three different doses of each chemotherapy (MTX: 0.25 mM, 25 mM and 75 mM and 5-FU: 10 ng / ml, 50 ng / ml and 100 ng / ml). After this procedure, mRNA and proteins will be extracted for analysis of DHFR, TS, MTHFR and RFC1 gene expression involved in folate metabolism, which will be quantified by quantitative real time PCR and Western blotting. It is expected, with the results of this proposal contribute to new therapeutic strategies for this disease, as prognostic factors with greater sensitivity and specificity can provide insight to new therapeutic strategies providing benefits to patients and new information regarding decision treatments. (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)

SILVA GALBIATTI, ANA LIVIA; CALDAS, HELOISA CRISTINA; MANIGLIA, JOSE VICTOR; PAVARINO, ERIKA CRISTINA; GOLONI-BERTOLLO, ENY MARIA. Gene expression profile of 5-fluorouracil metabolic enzymes in laryngeal cancer cell line: Predictive parameters for response to 5-fluorouracil-based chemotherapy. BIOMEDICINE & PHARMACOTHERAPY, v. 68, n. 5, p. 515-519, JUN 2014. (10/12930-4, 10/12932-7)

SILVA GALBIATTI, ANA LIVIA; CASTRO, RODRIGO; CALDAS, HELOISA CRISTINA; PADOVANI, JR., JOAO ARMANDO; PAVARINO, ERIKA CRISTINA; GOLONI-BERTOLLO, ENY MARIA. Alterations in the expression pattern of MTHFR, DHFR, TYMS, and SLC19A1 genes after treatment of laryngeal cancer cells with high and low doses of methotrexate. TUMOR BIOLOGY, v. 34, n. 6, p. 3765-3771, DEC 2013. (10/12930-4, 10/12932-7)