Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.De...Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.Despite high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health Initiative.Subsequently,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes prolonged.Subsequent analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal women.Regarding cognitive function,the timing hypothesis is consistent with observations from basic and animal studies.There is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women.It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural tissues.In the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.展开更多
In recent years,many therapeutic advances have been made in the management of castration-resistant prostate cancer,with the development and approval of many new drugs.The androgen receptor(AR)is the main driver in pro...In recent years,many therapeutic advances have been made in the management of castration-resistant prostate cancer,with the development and approval of many new drugs.The androgen receptor(AR)is the main driver in prostate cancer growth and progression and the most effective therapeutic agents are still directed against this pathway.Among these,new generation hormonal agents(NHA)including enzalutamide,abiraterone acetate,apalutamide,and darolutamide have shown to improve overall survival and quality of life of prostate cancer patients.Unfortunately,despite the demonstrated benefit,not all patients respond to treatment and almost all are destined to develop a resistant phenotype.Although the resistance mechanisms are not fully understood,the most studied ones include the activation of both dependent and independent AR signalling pathways.Recent findings about multiple growth-promoting and survival pathways in advanced prostate cancer suggest the presence of alternative mechanisms involved in disease progression,and an interplay between these pathways and AR signalling.In this review we discuss the possible mechanisms of primary and acquired resistance to NHA with a focus on AR independent pathways.展开更多
文摘Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.Despite high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health Initiative.Subsequently,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes prolonged.Subsequent analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal women.Regarding cognitive function,the timing hypothesis is consistent with observations from basic and animal studies.There is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women.It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural tissues.In the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.
文摘In recent years,many therapeutic advances have been made in the management of castration-resistant prostate cancer,with the development and approval of many new drugs.The androgen receptor(AR)is the main driver in prostate cancer growth and progression and the most effective therapeutic agents are still directed against this pathway.Among these,new generation hormonal agents(NHA)including enzalutamide,abiraterone acetate,apalutamide,and darolutamide have shown to improve overall survival and quality of life of prostate cancer patients.Unfortunately,despite the demonstrated benefit,not all patients respond to treatment and almost all are destined to develop a resistant phenotype.Although the resistance mechanisms are not fully understood,the most studied ones include the activation of both dependent and independent AR signalling pathways.Recent findings about multiple growth-promoting and survival pathways in advanced prostate cancer suggest the presence of alternative mechanisms involved in disease progression,and an interplay between these pathways and AR signalling.In this review we discuss the possible mechanisms of primary and acquired resistance to NHA with a focus on AR independent pathways.
