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HDAC2 and HR23B expression in the primary tumor and modulation of histone acetylation status in peripheral mononuclear cells in patients with oral and oropharyngeal squamous cell carcinoma under chemoradiation and valproic acid

Grant number: 15/01584-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2015
Effective date (End): July 31, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Gilberto de Castro Junior
Grantee:Alex Vitorio Amadio
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality in cancer patients worldwide. Most patients with HNSCC are diagnosed with locally advanced disease, and treated with cisplatin-based chemoradiation, but long-term disease control is still a challenge. The incorporation of epigenetic regulation into standard treatment could improve results of definitive platinum-based chemoradiation in such patients. Valproic acid is a known histone deacetylase inhibitor, available in the daily clinical practice as an anticonvulsive agent. Histone amino terminal domain has a critical role in the regulation of gene transcription in breast cancer and other malignancies. In this study we aim to evaluate the acetylation status of H3 and H4 histones in peripheral blood mononuclear cells (PBMC), the expression of HDAC2 and HR23B in the primary tumor, and the modulation of H3 and H4 histones in PBMC, in those patients diagnosed with oropharyngeal and oral cavity squamous cell carcinoma under cisplatin-based concurrent chemoradiation, and valproic acid. If positive, we hope to document some modulation of histone acetylation in PBMC, and to infer that changes in the epigenetic regulation of gene expression in the malignant cell does occur, in order to improve the outcomes of these patients treated with chemoradiation.