Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatoc...Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.展开更多
三阴性乳腺癌(triple negative breast cancer,TNBC)的恶性程度高,尤其在青年女性中发病率更高,易发生早期转移和化疗耐受,目前仍缺乏有效的临床治疗靶点,预后极差。研究发现,雄激素受体(androgen receptor,AR)在TNBC组织中高表达,与TNB...三阴性乳腺癌(triple negative breast cancer,TNBC)的恶性程度高,尤其在青年女性中发病率更高,易发生早期转移和化疗耐受,目前仍缺乏有效的临床治疗靶点,预后极差。研究发现,雄激素受体(androgen receptor,AR)在TNBC组织中高表达,与TNBC的预后紧密相关,并且AR能够促进TNBC细胞的生长和转移。当前,临床上单一采用抗雄激素药物治疗TNBC已显示出一定的敏感性,而AR抑制剂联合其他经典靶向治疗药物对于TNBC的治疗更具有潜在的价值。AR作为TNBC预后的一个重要参考指标,抗AR治疗在TNBC中的研究已引起一定的关注。本文就抗AR治疗在TNBC中可能的机制和临床研究进行综述。展开更多
Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is hi...Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.Methods:Immunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.Results:The median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).Conclusion:ANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.展开更多
文摘Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.
文摘三阴性乳腺癌(triple negative breast cancer,TNBC)的恶性程度高,尤其在青年女性中发病率更高,易发生早期转移和化疗耐受,目前仍缺乏有效的临床治疗靶点,预后极差。研究发现,雄激素受体(androgen receptor,AR)在TNBC组织中高表达,与TNBC的预后紧密相关,并且AR能够促进TNBC细胞的生长和转移。当前,临床上单一采用抗雄激素药物治疗TNBC已显示出一定的敏感性,而AR抑制剂联合其他经典靶向治疗药物对于TNBC的治疗更具有潜在的价值。AR作为TNBC预后的一个重要参考指标,抗AR治疗在TNBC中的研究已引起一定的关注。本文就抗AR治疗在TNBC中可能的机制和临床研究进行综述。
基金supported by funding from Takeda Science Foundation,and JSPS KAKENHI(grant numbers JP19H03793 to Obinata D,JP20K07350 to Takayama K,JP19K09740 to Takahashi S,JP20K07875 to Hara M,and JP20K21667 and JP21H04829 to Inoue S).
文摘Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.Methods:Immunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.Results:The median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).Conclusion:ANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.
