Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is incr...Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is increasing.The introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mCRPC)has resulted in modestly increased survival advantages as demonstrated by initial clinical trials.However,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen signaling.Combination therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of mCRPC.In this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and enzalutamide.We discuss observational data that point to mechanisms of resistance that emerged from these studies.We further present and discuss recent experimental studies that address the mechanisms of resistance to these treatments.Finally,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mCRPC.展开更多
Background and aim:Colorectal cancer(CRC)is the third leading cause of cancer mortality worldwide and laparoscopic colectomy has been established as equivalent to the open approach in terms of oncological results and ...Background and aim:Colorectal cancer(CRC)is the third leading cause of cancer mortality worldwide and laparoscopic colectomy has been established as equivalent to the open approach in terms of oncological results and patients’safety.Survival benefits have been reported in favor of laparoscopic colectomy(LC)in stage III CRC patients.Different immune responses after surgery,in terms of innate and cellular immunity,may potentially explain some of the reported differences.This review summarizes the literature on differences in immune response after the laparoscopic and the open approach for CRC.Materials and Methods:A literature search of electronic databases was conducted and all studies published on‘colorectal cancer’,‘laparoscopic and open colectomy’‘immune response’and‘surgical stress laparoscopy versus open’were collected.Among these,the ones referring to CRC and those that had any clinical relevance offering information on perioperative parameters were used.Results:Despite the heterogeneity of studies,they support the view that innate immune response is activated to a greater degree in open colectomy(OC),which may be related to the more extensive trauma and surgical stress.On the other hand,cellular immunity is better preserved after LC.These differences are more pronounced in the immediate postoperative period.Conclusions:LC has been related to decreased up-regulation of innate immunity and better-preserved cellular immunity.The latter may be related to better anti-tumor activity and may be beneficial in terms of oncological survival in a subgroup of LC patients.展开更多
基金supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant,5 P30 CA16672the Department of Epidemiology,Second Military Medical University,Shanghai,China.
文摘Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is increasing.The introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mCRPC)has resulted in modestly increased survival advantages as demonstrated by initial clinical trials.However,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen signaling.Combination therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of mCRPC.In this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and enzalutamide.We discuss observational data that point to mechanisms of resistance that emerged from these studies.We further present and discuss recent experimental studies that address the mechanisms of resistance to these treatments.Finally,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mCRPC.
文摘Background and aim:Colorectal cancer(CRC)is the third leading cause of cancer mortality worldwide and laparoscopic colectomy has been established as equivalent to the open approach in terms of oncological results and patients’safety.Survival benefits have been reported in favor of laparoscopic colectomy(LC)in stage III CRC patients.Different immune responses after surgery,in terms of innate and cellular immunity,may potentially explain some of the reported differences.This review summarizes the literature on differences in immune response after the laparoscopic and the open approach for CRC.Materials and Methods:A literature search of electronic databases was conducted and all studies published on‘colorectal cancer’,‘laparoscopic and open colectomy’‘immune response’and‘surgical stress laparoscopy versus open’were collected.Among these,the ones referring to CRC and those that had any clinical relevance offering information on perioperative parameters were used.Results:Despite the heterogeneity of studies,they support the view that innate immune response is activated to a greater degree in open colectomy(OC),which may be related to the more extensive trauma and surgical stress.On the other hand,cellular immunity is better preserved after LC.These differences are more pronounced in the immediate postoperative period.Conclusions:LC has been related to decreased up-regulation of innate immunity and better-preserved cellular immunity.The latter may be related to better anti-tumor activity and may be beneficial in terms of oncological survival in a subgroup of LC patients.
