检索结果-南通市图书馆

methylthioadenosine (MTA) Rescues methylthioadenosine Phosphorylase (MTAP)-Deficient Tumors from Purine Synthesis Inhibition <i>in Vivo</i>via Non-Autonomous Adenine Supply

引用

Journal of Cancer Therapy 2011年第4期2卷 523-534页

作者： Astrid Ruefli-Brasse Doreen Sakamoto Jessica Orf Minqing Rong Jianxia Shi Tim Carlson Kim Quon Alexander Kamb Dineli Wickramasinghe 不详

methylthioadenosine phosphorylase, (MTAP) is a key enzyme in the adenine and methionine salvage pathways. MTAP is encoded on human chromosome 9p21 in close proximity to the p16INK4a and p14ARF tumor suppressor genes and is frequently co-deleted with p16INK4a in many cancers. Deletion of MTAP has been reported to create a reliance of MTAP–/– tumors on de novo purine synthesis to maintain adequate pools of AMP, leading to increased sensitivity to purine synthesis inhibitors, such as L-alanosine. The ‘Achilles heel’ created by the loss of MTAP in cancer cells provides a unique therapeutic opportunity whereby MTAP–/– tumors could be selectively targeted with purine synthesis inhibitors and normal tissues could be preferentially rescued with MTAP substrates, such as MTA. We demonstrate that, in contrast to published literature, MTAP–/– cells are not more sensitive to inhibition of de novo purine synthesis than MTAP+/+ cells. Although MTA can preferentially rescue MTAP+/+ cells from purine-synthesis inhibitor toxicity in vitro, MTA protects cells of both genotypes from L-alanosine equivalently in vivo. Our data demonstrate that in vivo, adenine salvaged from plasma and adjacent tissues is sufficient to protect MTAP–/– tumors from the effects of purine synthesis inhibitors. These results suggest targeting MTAP–/– tumors with de novo purine synthesis inhibitors is unlikely to provide significant benefit over other therapeutic strategies and may explain, at least in part, the lack of efficacy of L-alanosine in clinical trials.

关键词： methylthioadenosine Phosphorylase Purine Metabolism L-Alanosine Adenine Salvage

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Synthesis and Biological Evaluation of a Highly Constrained Analogue of methylthioadenosine (MTA)

引用

International Journal of Organic Chemistry 2012年第4期2卷 398-403页

作者： Gustavo Senra G. de Carvalho Rafael Mafra de P. Dias Jean-Louis Fourrey Vania L. Silva Cláudio G. Diniz Adilson D. da Silva Departamento de Parasitologia Microbiologia e Imunologia Instituto de Ciências Biológicas (ICB) Universidade Federal de Juiz de Fora Juiz de Fora-MG Brasil Departamento de Química Instituto de Ciências Exatas (ICE) Universidade Federal de Juiz de Fora Juiz de Fora-MG Brasil Institut de Chimie des Substances Naturelles Gif-sur-Yvette Cedex France

We describe the synthesis and the antibacterial evaluation 2’,N3-cyclonucleoside 3 analogue of MTA that is characterized by the presence of an additional linkage between the heterocyclic ring and the sugar moiety.

关键词： Synthesis Biological Evaluation Antibacterial Analogue methylthioadenosine

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：