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研究发现,雄激素受体与前列腺癌的发生存在密切关系。雄激素拮抗疗法成为临床治疗早期前列腺癌的有效手段,近20年来已有多个药物上市(如氟他胺、羟基氟他胺和比卡鲁胺等),但这些经典的药物在治疗中易产生抗雄激素撤除综合症等问题,因此其应用受到限制。目前,新近研发的非甾体类雄激素受体拮抗剂(如RD162、MDV3100和BMS-641988)活性更强,正进行临床试验,并有望解决过去雄激素受体拮抗剂存在的问题。查阅国内外相关文献,对已上市药物、当前临床研究的药物以及近年发现的小分子雄激素受体抑制剂的研究进展进行综述。 相似文献
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目的 对二代雄激素受体抑制剂治疗非转移性去势抵抗性前列腺癌(nmCRPC)的安全性、有效性和经济性进行初步评估,以满足决策者的需要。方法 系统检索计算机检索pubmed、embase、the cochrane library、NHS EED和CADTH等英文数据库,中国知网(CNKI)、万方数据库和重庆维普(VIP)等中文数据库,搜集达罗他胺(Darolutamide),恩扎卢胺(Enzalutamide),阿帕他胺(Apalutamide)治疗nmCRPC的系统评价/Meta分析、经济学研究以及HTA报告,由2名评价者根据纳入排除标准提取数据.对结果进行定性分析。结果 共纳入系统评价/Meta分析18篇,经济学评价1篇,恩扎卢胺和阿帕他胺与达罗他胺间接比较无转移生存期(MFS)较高;总生存期(OS)相近无显著差异;阿帕他胺提供最大无进展生存期(PSA-PFS)的可能性最高,其次是恩扎卢胺。在涉及不良事件(AEs)的情况下,达罗他胺是首选剂,经济性方面,达罗他胺相较于其他两种药物治疗nmCRPC,成本-效果更好。结论 三种二代雄激素受体抑制剂治疗非转移性去势抵抗性前列腺癌均有显著优势,... 相似文献
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目的探讨阿比特龙联合泼尼松治疗雄激素剥夺治疗失败后转移性去势抵抗性前列腺癌的可行性。方法选择我院2015年8月至2017年1月收治的148例雄激素剥夺治疗失败后转移性去势抵抗性前列腺癌患者作为研究对象,采用随机数字表法分为对照组(85例)和观察组(63例),对照组采取多西他赛联合泼尼松治疗,观察组采取阿比特龙联合泼尼松治疗。以总体生存期为主要研究终点指标,以前列腺特异性抗原(PSA)无进展生存期、影像学无进展生存期为次要研究终点指标。比较两组PSA反应率、骨痛缓解率、治疗前后的晚期前列腺癌患者生活质量量表(FACT-P)评分及不良反应发生情况。结果在入组患者中,对照组79例,观察组60例,均获得随访,随访6~38个月,中位随访时间17.0个月;观察组中位总体生存期、中位PSA无进展生存期、中位影像学无进展生存期均明显长于对照组,差异均有统计学意义(P<0.05);观察组PSA反应率、骨痛缓解率及治疗后的FACT-P评分均明显高于对照组,差异均有统计学意义(P<0.05);观察组Ⅲ~Ⅳ级不良反应发生率为6.67%,明显低于对照组的35.44%,差异有统计学意义(P<0.05)。结论阿比特龙联合泼尼松治疗能有效抑制雄激素剥夺治疗失败后转移性去势抵抗性前列腺癌的进展,使患者在延长总体生存期、降低PSA水平、缓解骨痛和改善生活质量上明显获益,且治疗耐受性良好,值得进一步研究应用。 相似文献
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作为全球男性第二大常见癌症,前列腺癌严重威胁着人类健康。在前列腺癌发病过程中,雄激素受体(androgen receptor,AR)起着关键作用,糖皮质激素受体(glucocorticoid receptor,GR)也参与调节部分AR通路下游基因,因此,阻断AR和GR信号通路是前列腺癌治疗的重要策略。综述从核受体AR和GR的结构特征和生物学功能出发,从药物化学角度系统介绍了近5年来靶向核受体的抗前列腺癌药物研发新进展,包括雄激素竞争性AR拮抗剂、雄激素非竞争性AR拮抗剂、AR降解剂、GR拮抗剂和AR/GR双重拮抗剂等,为去势抵抗性前列腺癌的治疗提供新思路。 相似文献
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雄激素剥夺疗法作为晚期前列腺癌的标准疗法迄今已有50余年。去势手术对多数患者起初有效,但最终会发展为去势抵抗性前列腺癌(CRPC),主要原因是前列腺癌的发生和发展与雄激素受体(AR)受到雄激素的持续刺激有关, 相似文献
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目的 观察放疗对前列腺癌细胞雄激素受体的影响.方法 培养人前列腺癌细胞株LNCap及CWR22R,每个细胞株各分为两组,即放疗组及非放疗组,培养第3天,每组3个培养皿分别加入75%乙醇1nm(EtoH组,作为阴性对照),比较放疗本身对细胞株ARmRA的影响);加入DHT(二氢睾酮)1 nm及10 nm,DHT分别相当去势及正常睾酮水平.培养至第5天,放疗组进行放射治疗,剂量为2.7 Gy/min,持续3 min,放疗后24 h收集细胞;非放疗组不作放射治疗,RT-PCR方法比较每个细胞株组雄激素受体(AR),PSA表达的改变,并重复试验3次.结果 放射治疗前后,EtoH组的ARmRNA,PSAmRNA差异无统计学意义,DHT1组ARmRNA,PSAmRNA显著下降(P〈0.01),而DHT10组ARmRNA表达则显著上升(P〈0.01),PSAmRNA轻度升高(P〉0.05).结论在睾酮达去势水平的前列腺癌细胞,放疗有效;而在正常睾酮水平的前列腺癌细胞,放疗效果不佳.AR下降可作为放疗有效性的较灵敏指标. 相似文献
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Testosterone and structurally related anabolic steroids have been used to treat hypogonadism, muscle wasting, osteoporosis, male contraception, cancer cachexia, anemia, and hormone replacement therapy in aging men or age-related frailty; while antiandrogens may be useful for treatment of conditions like acne, alopecia (male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH) and prostate cancer. However, the undesirable physicochemical and pharmacokinetic properties of steroidal androgen receptor (AR) ligands limited their clinical use. Nonsteroidal AR ligands with improved pharmacological and pharmacokinetic properties have been developed to overcome these problems. This review focuses on the pharmacokinetics, metabolism, and pharmacology of clinically used and emerging nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators. 相似文献
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Zhe Wang Hyo-Jeong Lee Lei Wang Cheng Jiang Nam-In Baek Sung-Hoon Kim Junxuan Lü 《Pharmaceutical research》2009,26(5):1140-1148
Purpose Novel agents that target multiple aspects of androgen receptor (AR) signaling are desirable for chemoprevention and treatment
of prostate cancer (PCa). We aimed to identify compounds isolated from medicinal herbs as such drug candidates.
Methods In the LNCaP human androgen sensitive PCa cell model, we tested five compounds purified from Lindera fruticosa Hemsley in the range of 10–50 μM for growth inhibition and AR-prostate specific antigen (PSA) suppressing potency. We determined
the relationship between these activities and P53 tumor suppressor protein activation and apoptotic cleavage of PARP. We compared
these compounds to the anti-androgen drug Casodex/bicalutamide to identify mechanistic novelty.
Results Among 3 sucrose compounds, beta-D-(3,4-di-sinapoyl)fructofuranosyl-alpha-D-(6-sinapoyl)glucopyranoside decreased AR and PSA
mRNA and protein levels in LNCaP cells and inhibited androgen-stimulated AR translocation from the cytosol to the nucleus.
This compound also increased P53 Ser15 phosphorylation and PARP cleavage in LNCaP cells, but required higher dosage than for suppressing AR-PSA. Interestingly,
this compound did not inhibit the growth of RWPE-1 non-transformed prostate epithelial cells. The benzophenone compound 2-methoxy-3,4-(methylenedioxy)benzophenone
suppressed PSA and AR in LNCaP cells without apoptosis.
Conclusions Our data support novel anti-AR actions of these herbal compounds distinct from Casodex and merit further investigation as
drug candidates. 相似文献
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Aaron Balog Richard Rampulla GregoryS. Martin Stanley R. Krystek Ricardo Attar Janet Dell-John John D. DiMarco David Fairfax Jack Gougoutas Christian L. Holst Andrew Nation Cheryl Rizzo Lana M. Rossiter Liang Schweizer Weifang Shan Steven Spergel Thomas Spires Georgia Cornelius Marco Gottardis George Trainor Gregory D. Vite Mark E. Salvati 《ACS medicinal chemistry letters》2015,6(8):908-912
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Antiandrogens in Prostate Cancer 总被引:6,自引:0,他引:6
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《Expert opinion on pharmacotherapy》2013,14(1):91-96
Tacrolimus is an immunosuppressive drug that has been used widely in organ transplantation and topically for atopic dermatitis. Tacrolimus exerts its immunosuppressive effects by the inhibition of calcineurin, leading to interference with T-cell activation. As T-cell activation plays a major role in the pathogenesis of rheumatoid arthritis, there has been an interest in the use of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological properties of tacrolimus have the potential of suppressing the production of inflammatory cytokines, improvement of joint inflammation, improvement of bone and cartilage destruction, improvement of functional status and relief from arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics, clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid arthritis. 相似文献