Prostate cancer is the most common male malignant neoplasm.Androgens and the androgen receptor(AR)play a key role in the onset and progression of prostate cancer.The expression of the AR is still preserved in the majo...Prostate cancer is the most common male malignant neoplasm.Androgens and the androgen receptor(AR)play a key role in the onset and progression of prostate cancer.The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer(CRPC).CRPC is considered to be induced by the following mechanisms:(1)sustained AR activation by enhancing intracellular conversion of adrenal androgens to dehydrotestosterone via a de novo route;(2)AR hypersensitivity;(3)promiscuous activation of AR signaling;and(4)outlaw pathways.Recent advances in the treatment of CRPC include novel medicinestargeting AR signaling pathways.In addition,functional molecular studies have shown that some of the ARregulated genes and AR coregulators are prognostic markers and potential therapeutic targets for prostate cancer,particularly in the castration-resistant state.Therefore,identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.展开更多
Background: Although various studies have been conducted on the effects of radiation therapy for prostate cancer, rectal toxicity after radiation therapy for prostate cancer, which is an important late adverse event ...Background: Although various studies have been conducted on the effects of radiation therapy for prostate cancer, rectal toxicity after radiation therapy for prostate cancer, which is an important late adverse event associated with radiation therapy, has not been sufficiently examined. This study aimed to assess the associations of late rectal disorder (LRD) with dosimetric, anatomic, and clinical factors in patients with prostate cancer who underwent three-dimensional conformal radiation therapy (3D-CRT). Methods: We retrospectively analyzed 104 patients undergoing 3D-CRT between January 2009 and October 2011. Thirty patients were administered anticoagulation/antiplatelet (AC/AP) agents. The standard dose was 74 Gy. Uni- and multi-va,iate analyses we,e performed to identify factors predictive of LRD after 3D-CRT. Results: The median follow-up period was 66 (range: 14 87) months. LRD occurred in 10.6% (11/104) of patients. The median time fi'om RT to LRD was 15 months (range: 7MI months). Sixty-four percent of those with LRD (7/11 patients) had been given AC/AP agents. Fitly-five (6/11 ) patients had severe internal iliac artery calcification. By univariate analysis, significant predictors of LRD were internal iliac artery calcification, administration of AC/AP agents, and age. Being very elderly was the significant predictor identified by multivariate analysis (P = 0.0276). For patients receiving AC/AP agents and those with severe internal iliac artery calcification, the LRD incidences were 23.3% (7/30 patients) and 23.1% (6/26 patients), respectively, and being 75 years of age or older was a significant predictor in these subsets. Conclusions: Our results suggest advanced age, administration of AC/AP agents, and severe internal iliac artery calcification to be risk factors tbr LRD in patients undergoing standard RT. Therefore, it is necessary to administer radiation with particular caution in the very elderly, especially those receiving AC/AP agents and/or with severe internal iliac artery calcification.展开更多
文摘Prostate cancer is the most common male malignant neoplasm.Androgens and the androgen receptor(AR)play a key role in the onset and progression of prostate cancer.The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer(CRPC).CRPC is considered to be induced by the following mechanisms:(1)sustained AR activation by enhancing intracellular conversion of adrenal androgens to dehydrotestosterone via a de novo route;(2)AR hypersensitivity;(3)promiscuous activation of AR signaling;and(4)outlaw pathways.Recent advances in the treatment of CRPC include novel medicinestargeting AR signaling pathways.In addition,functional molecular studies have shown that some of the ARregulated genes and AR coregulators are prognostic markers and potential therapeutic targets for prostate cancer,particularly in the castration-resistant state.Therefore,identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.
文摘Background: Although various studies have been conducted on the effects of radiation therapy for prostate cancer, rectal toxicity after radiation therapy for prostate cancer, which is an important late adverse event associated with radiation therapy, has not been sufficiently examined. This study aimed to assess the associations of late rectal disorder (LRD) with dosimetric, anatomic, and clinical factors in patients with prostate cancer who underwent three-dimensional conformal radiation therapy (3D-CRT). Methods: We retrospectively analyzed 104 patients undergoing 3D-CRT between January 2009 and October 2011. Thirty patients were administered anticoagulation/antiplatelet (AC/AP) agents. The standard dose was 74 Gy. Uni- and multi-va,iate analyses we,e performed to identify factors predictive of LRD after 3D-CRT. Results: The median follow-up period was 66 (range: 14 87) months. LRD occurred in 10.6% (11/104) of patients. The median time fi'om RT to LRD was 15 months (range: 7MI months). Sixty-four percent of those with LRD (7/11 patients) had been given AC/AP agents. Fitly-five (6/11 ) patients had severe internal iliac artery calcification. By univariate analysis, significant predictors of LRD were internal iliac artery calcification, administration of AC/AP agents, and age. Being very elderly was the significant predictor identified by multivariate analysis (P = 0.0276). For patients receiving AC/AP agents and those with severe internal iliac artery calcification, the LRD incidences were 23.3% (7/30 patients) and 23.1% (6/26 patients), respectively, and being 75 years of age or older was a significant predictor in these subsets. Conclusions: Our results suggest advanced age, administration of AC/AP agents, and severe internal iliac artery calcification to be risk factors tbr LRD in patients undergoing standard RT. Therefore, it is necessary to administer radiation with particular caution in the very elderly, especially those receiving AC/AP agents and/or with severe internal iliac artery calcification.