已收录 272983 条政策
 政策提纲
  • 暂无提纲
5-AZA-2’-deoxycytidine as a potential therapeutic option in the treatment of head and neck squamous cell carcinoma (HNSCC)
[摘要] Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Epigenetic mechanisms including changes in DNA methylation (5mC) and hydroxymethylation (5hmC) are major contributors to HNSCC progression and can be altered by the use of epigenetic therapies such as the DNA demethylating agent, 5-aza-2’-deoxycytidine (DAC). Here, the potential use of DAC in the treatment of HNSCC was investigated and a subset of HNSCC cell lines determined to respond to nanomolar concentrations of the drug. Furthermore, the efficacy of DAC was significantly increased by co-treatment with the common analgesic, paracetamol, providing an appealing new therapeutic option. Genome-wide sequencing methods were used to compare the distribution of 5mC and 5hmC between normal oral keratinocytes and an HNSCC cell line and investigate how this is altered by DAC. In addition to causing global DNA demethylation, DAC partially restores 5mC and 5hmC patterns to those of normal oral keratinocytes. In normal cells, 5mC and 5hmC mark clusters of Alu elements in gene rich regions; this is dramatically reduced in HNSCC. Treatment with DAC restores DNA modifications to Alu elements, leading to repression of Alu RNA. Furthermore, DAC caused demethylation and increased expression of endogenous retroviruses, prompting a viral mimicry response.
[发布日期]  [发布机构] University:University of Birmingham;Department:School of Dentistry
[效力级别]  [学科分类] 
[关键词] R Medicine;R Medicine (General) [时效性] 
   浏览次数:8      统一登录查看全文      激活码登录查看全文