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Concept of histone deacetylases in cancer:Reflections on esophageal carcinogenesis and treatment

World Journal of Gastroenterology 2018年第41期24卷 4635-4642页

作者： Dimitrios Schizas Aikaterini Mastoraki Leon Naar Eleftherios Spartalis Diamantis I Tsilimigras Georgia-Sofia Karachaliou George Bagias Dimitrios Moris 1^st Department of Surgery Laikon General HospitalNational and Kapodistrian University of AthensAthens 11527Greece 4^th Department of Surgery Attikon University HospitalNational and Kapodistrian University of AthensAthens 12462Greece Laboratory of Experimental Surgery and Surgical Research National and Kapodistrian University of AthensAthens 11527Greece Department of General Visceral and Transplant SurgeryUniversity Hospital EssenEssen 45141Germany Department of Surgery Duke University Medical CenterDurhamNC 27710United States

Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular *** addition,HDACs have also been associated with increased chemotherapy *** on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free *** aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.

关键词： Esophageal cancer Histone deacatylases Inhibitors Drugs

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