Androgen deprivation therapy(ADT)has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer(PCa).However,this approach is rarely curative.Recent clinical trials have demonstrat...Androgen deprivation therapy(ADT)has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer(PCa).However,this approach is rarely curative.Recent clinical trials have demonstrated that ADT combined with other agents,notably docetaxel and abiraterone,lead to improved survival.The mechanisms surrounding this improved cancer outcomes are incompletely defined.The response of cancer cells to ADT includes apoptosis and cell death,but a significant fraction remains viable.Our laboratory has demonstrated both in vitro and in vivo that cellular senescence occurs in a subset of these cells.Cellular senescence is a phenotype characterized by cell cycle arrest,senescenceassociated b-galactosidase(SA-b-gal),and a hypermetabolic state.Positive features of cellular senescence include growth arrest and immune stimulation,although persistence may release cytokines and growth factors that are detrimental.Senescent tumor cells generate a catabolic state with increased glycolysis,protein turnover and other metabolic changes that represent targets for drugs,like metformin,to be applied in a synthetic lethal approach.This review examines the response to ADT and the putative role of cellular senescence as a biomarker and therapeutic target in this context.展开更多
The USMTArray was completed on June 27,2024,comprising a network of 1779 transportable long-period magnetotelluric(MT)stations(Fig.1)with nominal 70-km grid spacing spanning the conterminous United States,an area of 8...The USMTArray was completed on June 27,2024,comprising a network of 1779 transportable long-period magnetotelluric(MT)stations(Fig.1)with nominal 70-km grid spacing spanning the conterminous United States,an area of 8.1×10^(6)km^(2).Each station operated for weeksto-months,as required to meet data quality standards over the period band of 10–10000 s.The USMTArray shares similarities with the planned SinoProbe-II MT Array,with its 1-degree station spacing(~111 km in the latitudinal direction)spanning an area of 9.6×10^(6)km^(2).展开更多
基金The study was supported by DOD Prostate Cancer Research Program PC150221,R.Stephenson Family Fund.
文摘Androgen deprivation therapy(ADT)has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer(PCa).However,this approach is rarely curative.Recent clinical trials have demonstrated that ADT combined with other agents,notably docetaxel and abiraterone,lead to improved survival.The mechanisms surrounding this improved cancer outcomes are incompletely defined.The response of cancer cells to ADT includes apoptosis and cell death,but a significant fraction remains viable.Our laboratory has demonstrated both in vitro and in vivo that cellular senescence occurs in a subset of these cells.Cellular senescence is a phenotype characterized by cell cycle arrest,senescenceassociated b-galactosidase(SA-b-gal),and a hypermetabolic state.Positive features of cellular senescence include growth arrest and immune stimulation,although persistence may release cytokines and growth factors that are detrimental.Senescent tumor cells generate a catabolic state with increased glycolysis,protein turnover and other metabolic changes that represent targets for drugs,like metformin,to be applied in a synthetic lethal approach.This review examines the response to ADT and the putative role of cellular senescence as a biomarker and therapeutic target in this context.
文摘The USMTArray was completed on June 27,2024,comprising a network of 1779 transportable long-period magnetotelluric(MT)stations(Fig.1)with nominal 70-km grid spacing spanning the conterminous United States,an area of 8.1×10^(6)km^(2).Each station operated for weeksto-months,as required to meet data quality standards over the period band of 10–10000 s.The USMTArray shares similarities with the planned SinoProbe-II MT Array,with its 1-degree station spacing(~111 km in the latitudinal direction)spanning an area of 9.6×10^(6)km^(2).
