The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At...The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.展开更多
目的:评价TCu220C宫内节育器(IUD)因症终止情况以及不同产地、实施地区、放置时期对其影响,为安全避孕提供科学依据。方法:检索PubMed、EMBASE、中国知网、万方等9个数据库和相关网站,根据纳入和排除标准收集筛选自数据库收录至2014年5...目的:评价TCu220C宫内节育器(IUD)因症终止情况以及不同产地、实施地区、放置时期对其影响,为安全避孕提供科学依据。方法:检索PubMed、EMBASE、中国知网、万方等9个数据库和相关网站,根据纳入和排除标准收集筛选自数据库收录至2014年5月31日国内外发表的中英文文献进行质量评价。数据提取后使用Open meta analyst对纳入文献进行分析。检索结果:纳入28个涉及TCu220CIUD因症终止结局的RCT和准RCT研究共31篇文献、43239例观察对象,其中TCu220C组15794例。结果:国外产TCu220C的因症终止率远高于国产TCu220C;发达国家的因症终止率远高于发展中国家;哺乳期放置TCu220C的因症终止率高于月经间期和其他时期放置。结论:TCu220CIUD的因症终止率随着随访时间呈上升趋势,使用12年时高达24.3%,且国内外存在明显的地区间差异,哺乳期放置IUD的因症终止风险升高。提示医务人员应关注TCu220CIUD使用的风险人群(如哺乳期放置),减少因症终止,促进避孕安全。展开更多
基金funded by the Ministry of Science and Higher Education of the Russian Federation(Grant No.075-15-2020-795 of 29.09.2020,unique project ID:RF-190220X0027).
文摘The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.
文摘目的:评价TCu220C宫内节育器(IUD)因症终止情况以及不同产地、实施地区、放置时期对其影响,为安全避孕提供科学依据。方法:检索PubMed、EMBASE、中国知网、万方等9个数据库和相关网站,根据纳入和排除标准收集筛选自数据库收录至2014年5月31日国内外发表的中英文文献进行质量评价。数据提取后使用Open meta analyst对纳入文献进行分析。检索结果:纳入28个涉及TCu220CIUD因症终止结局的RCT和准RCT研究共31篇文献、43239例观察对象,其中TCu220C组15794例。结果:国外产TCu220C的因症终止率远高于国产TCu220C;发达国家的因症终止率远高于发展中国家;哺乳期放置TCu220C的因症终止率高于月经间期和其他时期放置。结论:TCu220CIUD的因症终止率随着随访时间呈上升趋势,使用12年时高达24.3%,且国内外存在明显的地区间差异,哺乳期放置IUD的因症终止风险升高。提示医务人员应关注TCu220CIUD使用的风险人群(如哺乳期放置),减少因症终止,促进避孕安全。
