中老年男性血清催乳素水平与良性前列腺增生的关系

目的　探讨中老年男性血清催乳素 (PRL)和睾酮 (T)的变化 ,研究PRL与良性前列腺增生的关系。　方法　将 84例健康中老年男性分为 4个年龄组 ,测定血清PRL和T水平 ,分析不同年龄组的数值变化。采用B超测定其中 38例的前列腺体积 ,与PRL进行相关性分析。　结果　 5 0、6 0、70和 80岁年龄组的T水平分别为 (2 5 .92± 2 .5 4)、(2 1.0 0± 1.92 )、(18.37± 2 .49)和 (14.75±2 .38)nmol/L ,不同年龄组之间T水平比较 ,差别有显著性意义 (F =3.44 ,P <0 .0 5 ) ;PRL水平分别为 (1.11± 0 .16 )、(0 .96± 0 .2 0 )、(0 .99± 0 .18)和 (0 .91± 0 .2 9)nmol/L ,组间比较差别无显著性意义(F =0 .12 ,P >0 .0 5 ) ;PRL水平与前列腺体积无显著相关性 (r =0 .2 5 ,P >0 .0 5 )。　结论　PRL通过雄激素在前列腺的生长过程中产生作用 ,但中老年男性雄激素水平不断降低 ,削弱了PRL在前列腺增生中的作用。     

锤头状核酶阻断雄激素受体基因表达的研究

目的　探讨核酶 (RZ)在细胞水平调节雄激素受体 (AR)基因表达的作用。方法　设计并合成针对AR的锤头状核酶序列 ,分子克隆技术构建活性核酶和无活性核酶表达载体 ,脂质体介导下转染雄激素受体表达阳性细胞株T47D。转染第 1～ 3天 ,应用免疫组织化学和逆转录 聚合酶链反应 (RT PCR)技术检测细胞内AR基因表达水平。结果　AR活性核酶表达载体转染后 ,T47D细胞ARmRNA水平降低 2 2 .4%～ 50 .7% (P <0 .0 5) ,AR蛋白阳性细胞减少 7.1 0 %～1 1 .90 % (P <0 .0 5)。而无活性核酶对细胞AR基因表达差异无显著性 (P >0 .0 5)。结论　成功构建AR锤头状核酶表达载体 ,能特异性切割ARmRNA ,阻断雄激素受体基因表达     

雌激素受体（ER）、雄激素受体（AR）与前列腺癌

近年研究显示，雌激素受体（ER）和雄激素受体（AR）在前列腺癌的发生发展中具有十分重要的作用。本文综述前列腺癌中雌激素受体，雌激素受体的表达活化，基因多态性及基因突变等研究进展。     

Efficacy of maximal androgen blockade versus castration alone in the treatment of advanced prostate cancer： a retrospective clinical experience from a Chinese medical centre

In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608 patients with advanced prostate cancer were included in the study. Patients were retrospectively divided into two groups according to different therapeutic regimens. Of the 608 patients, 300 patients were treated with MAB （castration plus nonsteroidal antiandrogens） and the remaining 308 were treated with castration alone. The 2- and 5-year overall survival rates of these patients were 73.7% and 56%, respectively. Multivariate analysis showed that, in patients with metastatic prostate cancer, MAB was associated with not only the improvement of progression-free survival （PFS） （increased by 10 months） but also a 20.6% reduction in mortality risk compared with castration alone. In contrast, the efficacy of MAB was not superior to castration alone for patients with nonmetastatic prostate cancer. Interestingly, among patients with MAB, those using bicalutamide had a longer PFS than those using flutamide; this was especially so in patients with metastatic prostate cancer. Almost all of the toxicities due to the hormone therapy were mild to moderate and manageable. To conclude, in China, hormone therapies, including MAB and castration alone, have been standard treatments for advanced prostate cancer. For patients with nonmetastatic prostate cancer, castration alone might be adequately practical and efficient. In patients with metastatic prostate cancer, however, MAB has superior efficacy over castration alone. It is clear that MAB should be considered the first-line standard treatment for patients with metastatic prostate cancer.     

新型雄激素受体种系错义突变与非裔男性家族性前列腺癌

种族、家族史和年龄是众所周知的前列腺癌危险因素。雄激素受体依赖性信号传送是前列腺癌变和肿瘤转移的重要基础。非裔男性的前列腺癌发病率、死亡率高于白人,且临床恶性程度高。本实验探究了非裔男性家族性前列腺癌与雄激素受体（AR）基因突变之间的关系。实验中我们对参与路易斯安那州立大学健康科学中心前列腺癌遗传连锁研究的30个高危黑人和白人家庭的60名前列腺癌患者的基因组HDNA序列进行了检测。应用外显子特异性聚合酶链反应,双向自动测序和限制性内切酶基因分型分析AR基因编码区突变,结果在一个有早发前列腺癌家族史黑人家庭的3名成员中发现了种系AR－A1675T（T559S）替换突变,突变位于DNA结合区。本研究首次在患家族性前列腺癌的黑人男性中发现了种系雄激素受体突变,该突变可能会改变受体与DNA结合亲和力和／或对雄激素、非雄性类固醇或雄激素拈抗剂的反应。今后的研究应当探索AR（A1675T）序列对黑人早发和／或家族性前列腺癌的影响和影响频率。     

The biochemical efficacy of primary cryoablation combined with prolonged total androgen suppression compared with radiotherapy on high-risk prostate cancer： a 3-year pilot study

To gain beneficial effects in the management of high-risk prostate cancer, an integrated approach that combines local therapy and androgen deprivation therapy （ADT） was used. We compared biochemical responses between primary cryosurgical ablation of the prostate （CSAP） combined with prolonged ADT and radiation combined with ADT, which is the established modality in high-risk disease. A total of 33 high-risk patients received CSAP combined with ADT for 3 months before and up to 24 months after treatment. This patient group was matched with another 33 patients who had undergone three-dimensional conformal radiation therapy （3D-CRT） with the same protocol for ADT. Biochemical recurrence （BCR） was assessed by the American Society for Therapeutic Radiation Oncology （ASTRO） definition, the Phoenix definition and a prostate-specific antigen （PSA） cutoff of 0.5 ng mL^-1. Median follow-up was 61.0 ± 11.9 months for the CSAP ＋ ADT group and 86.0±15.8 months for the 3D-CRT ＋ ADT group. In the CSAP group, major complications including rectourethral fistula and incontinence were not noted. In the CSAP ＋ ADT group, 57.0% had BCR using the ASTRO definition, 21.2% using the Phoenix definition and 54.5% using a PSA cutoff of 0.5 ng mL^-1. In the 3D-CRT ＋ ADT group, 54.5%, 21.2% and 54.5% had BCR using the ASTRO, Phoenix and PSA definition, respectively. In the CSAP ＋ ADT group, the BCR-free survival （BRFS） was 54 ± 10 months using the ASTRO definition, 65 ± 5 months using the Phoenix definition and 51 ± 4 months using a PSA cutoff of 0.5 ng mL-1. In the 3D-CRT ＋ ADT group, the BRFS was 68 ± 12, 93 ± 19 and 70 ± 18 months using the ASTRO, Phoenix and PSA definition, respectively. By the log-rank test, the BRFS values for each group were not statistically different. This intermediate-term result indicated that primary CSAP combined with prolonged ADT offers a parallel biochemical response compared with radiotherapy in high-risk prostate cancer.     

前列腺癌细胞系LNCaP中的新型雄激素调节基因Prosaposin

雄激素调节基因（ARG）在正常前列腺和前列腺肿瘤中起着调节细胞生长的作用。近来，作者报道了在雄激素非依赖性或转移前列腺癌细胞／组织中对先前已知的神经营养因子prosaposin的基因组扩增和／或过表达。正如多效生长因子一样，prosaposin及它的活性分子微生物（如saposin C）的功能更侧重于前列腺癌细胞的恶性表型。另外，在LNcaP细胞中prosaposin或saposin C上调雄激素受体（AR）和AR靶基因的表达和激活（如PSA等）。在该项研究中，作者检测了雄激素调节基因prosaposin，在DHT双氢睾酮干预的LNCaP细胞中，prosaposin的表达上调。另外，研究揭示了prosaposin启动子的雄激素反应性因为雄激素受体的激素反应元件位于prosaposin启动子近侧区。此研究首次证实了prosaposin是一种雄激素调节基因。此项观察及prosaposin的多效生长因子活性一起揭示了此种分子在雄激素受体依赖的前列腺肿瘤进展中的作用。     

Kennedy病一家系的临床和分子遗传学

目的报道国内首例Kennedy病大家系，探讨其临床特征和分子机制。方法根据先证者的叙述对该家系4代74名个体进行家系调查，进行神经系统体检，常规检测神经电生理、肌电图、血清肌酸磷酸激酶（CPK）等。并经家族成员知情同意后抽取静脉血5ml，标准法抽取基因组DNA，聚合酶链反应（PCR）检测连接素基因（Cx32），证实无基因突变后再检测雄激素受体（AR）基因第一外显子CAG重复片段。结果经临床方法检出家系中另外3例患者，经AR基因检测，其CAG重复数均为50次；而先证者CAG重复数为51次；4例患者肌电图均显示感觉、运动神经受累及，血清CPK均增高；AR基因检测还发现1例症状前个体，其CAG重复数为50次。结论临床上Kennedy病多被误诊为多发性肌炎、肢带型肌营养不良，甚至Charcot-Marie-Tooth病等，AR基因检测是诊断本病最可靠的方法。     

多激素分泌性垂体泌乳素腺瘤的激素分泌谱及克隆分析

目的 对多激素分泌性垂体泌乳素腺瘤的克隆状态以及激素分泌谱进行分析。方法 对26例女性垂体泌乳素腺瘤患者（单激素分泌性PRL腺瘤7例，多激素分泌性PRL腺瘤19例）进行肿瘤标本的免疫组化分析，并且提取DNA行HUMARA分析。结果免疫组化分析提示本组多激素分泌性垂体PRL腺瘤具有10种不同的激素分泌谱，现代分子生物学HUMARA克隆分析提示11／13例（85％）多激素分泌性垂体PRL腺瘤为单克隆起源。结论 结果提示垂体泌乳素腺瘤除了分泌泌乳素外，还可以分泌多种垂体激素，而且绝大多数多激素分泌性垂体腺瘤的起源是单克隆性的。     

抗雄激素药物联合应用治疗女性中重度迟发型痤疮的临床疗效评价

目的：探讨抗雄激素药物联合应用治疗女性中重度迟发型痤疮的最佳方案和疗效。方法：将112例患者按完全随机设计法分成三组：治疗Ⅰ组采用达英-35联合小剂量甲泼尼龙口服,治疗Ⅱ组采用螺内酯联合小剂量甲泼尼龙口服,对照组采用维胺酯口服,4周为1个疗程,连续治疗12周后观察疗效及不良反应,治疗前后检测三组患者血清睾酮（T）、雌二醇（E2）。结果：12周后,治疗Ⅰ组有效率为73.7%,与对照组比较差异无统计学意义（P〉0.05）;治疗Ⅱ组有效率为41.2%,与对照组比较差异有统计学意义（P〈0.05）;治疗Ⅰ、Ⅱ组治疗前后血清T差异有统计学意义（P〈0.05）,E2差异无统计学意义（P〉0.05）;对照组治疗前后T、E2差异均无统计学意义（P〉0.05）。结论：达英-35联合小剂量甲泼尼龙可有效治疗女性迟发型中重度痤疮。