Imunomarcação das histonas acetiladas H3 e H4 e das enzimas histonas desacetilases HDAC1, HDAC2 e HDAC6 em sarcomas de tecidos moles em cães
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Data
2019-12-10
Autores
de Sena, Bruna Voltolin [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A epigenética é caracterizada por uma série de mecanismos que agenciam a expressão de genes através de reações químicas. Portanto, tornou-se alvo de estudos recentes, tanto em relação à carcinogênese quanto à investigação de possíveis alvos terapêuticos. Existem muitas limitações acerca do tratamento do sarcoma de tecidos moles (STM) em cães, principalmente quando se trata de casos avançados, visto que apresentam baixa resposta à quimioterapia. Tornam-se, portanto, necessárias pesquisas sobre novas possibilidades terapêuticas. Objetivou-se com o presente estudo investigar a expressão das histonas acetiladas e enzimas responsáveis por sua desacetilação nos STM em cães e correlacionar com aspectos histológicos e clínicos. Foram avaliadas 15 amostras de STM em cães, que foram submetidas à imunohistoquímica para imunodetecção das histonas acetiladas (H3 e H4) e enzimas desacetiladoras (HDAC1, HDAC2 e HDAC6). detectou-se alta imunomarcação da histona acetilada H4 em comparação com a H3. Foi observada uma forte correlação positiva entre o score de intensidade de H3 e o número de mitoses (p=0,004 e r=0,7). Observouse alta imunomarcação de HDAC1, se comparado a expressão de HDAC2 e HDAC6 nos STM avaliados. Tal achado sugere que a HDAC1 possa ser um alvo terapêutico para os inibidores de HDACs em cães.
Epigenetics is characterized by a series of mechanisms that drive gene expression through chemical reactions. Therefore, it has become the target of recent studies, both regarding carcinogenesis and the investigation of possible therapeutic targets. There are many limitations regarding the treatment of soft tissue sarcoma (STS) in dogs, especially for advanced cases, besides the low chemotherapy´s low response. In view of this, researches on new treatments are needed. This study aimed to investigate the expression of acetylated histones and enzymes responsible for their deacetylation in canine´s STS. Fifteen samples of STS in dogs were evaluated and submitted to immunohistochemistry for immunodetection of acetylated histones (H3 and H4) and deacetylating enzymes (HDAC1, HDAC2 and HDAC6). A strong positive correlation was observed between the intensity of H3 and the number of mitoses (p = 0.004 and r = 0.7). High expression of HDAC1 was observed compared to HDAC2 and HDAC6 in the evaluated MTS. Those findings suggests a potential for HDAC1 as a therapeutic target for HDAC inhibitors.
Epigenetics is characterized by a series of mechanisms that drive gene expression through chemical reactions. Therefore, it has become the target of recent studies, both regarding carcinogenesis and the investigation of possible therapeutic targets. There are many limitations regarding the treatment of soft tissue sarcoma (STS) in dogs, especially for advanced cases, besides the low chemotherapy´s low response. In view of this, researches on new treatments are needed. This study aimed to investigate the expression of acetylated histones and enzymes responsible for their deacetylation in canine´s STS. Fifteen samples of STS in dogs were evaluated and submitted to immunohistochemistry for immunodetection of acetylated histones (H3 and H4) and deacetylating enzymes (HDAC1, HDAC2 and HDAC6). A strong positive correlation was observed between the intensity of H3 and the number of mitoses (p = 0.004 and r = 0.7). High expression of HDAC1 was observed compared to HDAC2 and HDAC6 in the evaluated MTS. Those findings suggests a potential for HDAC1 as a therapeutic target for HDAC inhibitors.
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Palavras-chave
Canino, Epigenética neoplasia, Mesenquimal, Mesenchymal neoplasia, Epigenetic, Canine