Roles of Histone Deacetylases and Inhibitors in Anticancer Therapy

Histones are the main structural proteins of eukaryotic chromatin. Histone acetylation/ deacetylation are the epigenetic mechanisms of the regulation of gene expression and are catalyzed by histone acetyltransferases (HAT) and histone deacetylases (HDAC). These epigenetic alterations of DNA structure influence the action of transcription factors which can induce or repress gene transcription. The HATs catalyze acetylation and the events related to gene transcription and are also responsible for transporting newly synthesized histones from the cytoplasm to the nucleus. The activity of HDACs is mainly involved in silencing gene expression and according to their specialized functions are divided into classes I, II, III and IV. The disturbance of the expression and mutations of HDAC genes causes the aberrant transcription of key genes regulating important cancer pathways such as cell proliferation, cell-cycle regulation and apoptosis. In view of their role in cancer pathways, HDACs are considered promising therapeutic targets and the development of HDAC inhibitors is a hot topic in the search for new anticancer drugs. The present review will focus on HDACs I, II and IV, the best known inhibitors and potential alternative inhibitors derived from natural and synthetic products which can be used to influence HDAC activity and the development of new cancer therapies

Social isolation stress facilitates chemically induced oral carcinogenesis.

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators

A experiência de cinco anos do projeto de extensão Atendimento aos pacientes do Centro de Oncologia Bucal da Faculdade de Odontologia de Araçatuba – UNESP

The Oral Oncology Center is a unit Simple Structure of Auxiliary of the Universidade Estadual Paulista "Julio de Mesquita Filho" - UNESP installed at the Faculty of Dentistry of Araçatuba Campus. The main activity carried out in this center is the interdisciplinary treatment of patients with malignant tumors of the head and neck. Develops activities in education, such as the Discipline of Oncology, which involves undergraduate and graduate; research activities with the development of scientific papers by graduate students, and especially the extension, through the care of patients with oral pathologies, including head and neck cancer. Among the registered extension projects in Oral Oncology Center, stands out the "Assistance to patients of Oral Oncology Center, Faculty of Dentistry of Araçatuba-UNESP," registered with the Dean of UNESP University Extension in 2010. The objective of this study is to present the activities and results of this 2010-2014 project.O Centro de Oncologia Bucal é uma Unidade Auxiliar de Estrutura Simples da Universidade Estadual Paulista “Júlio de Mesquita Filho”- UNESP instalado na Faculdade de Odontologia do Campus de Araçatuba. A principal atividade realizada nesse centro é o tratamento interdisciplinar de pacientes com tumores malignos de cabeça e pescoço. Desenvolve atividades na área do ensino, a exemplo da Disciplina de Oncologia, que envolve alunos de graduação e pós-graduação; atividades de pesquisa com o desenvolvimento de trabalhos científicos pelos alunos de pós-graduação e, principalmente, a extensão, por meio do atendimento de pacientes com patologias bucais, incluindo o câncer de cabeça e pescoço. Dentre os projetos de extensão cadastrados no Centro de Oncologia Bucal, destaca-se o “Atendimento aos pacientes do Centro de Oncologia Bucal da Faculdade de Odontologia de Araçatuba-UNESP,” registrado junto à Pró-Reitoria de Extensão Universitária da UNESP em 2010. O objetivo desse trabalho é apresentar as atividades realizadas e os resultados desse projeto de 2010 a 2014