前列腺癌去雄激素治疗不良反应的预防和处理

目的观察去雄激素治疗前列腺癌的不良反应,并探讨其预防和治疗。方法回顾性分析1998年7月-2006年1月112例去雄激素治疗晚期前列腺癌的临床资料。结果112例患者中,97例完成了不良反应的调查。随访3-36月,去雄激素治疗后潮热、性功能障碍、病理性骨折发生率分别为46％、75％、4％;患者潮热、精神疲乏、四肢乏力、纳差症状明显加重(P<0．05);性功能明显减退(P<0．05)。12例潮热症状严重者使用抗抑郁药博乐欣(25mg,tid)1-2周症状减轻。7例有骨转移性疼痛或严重骨质疏松患者,应用唑来膦酸4mg静脉滴注,每45d一次,骨痛症状缓解。结论去雄激素对前列腺癌患者生活质量有一定影响。博乐欣可减轻患者潮热症状,唑来膦酸可预防和治疗去雄激素相关的骨质疏松并发症。     

Combined androgen blockade in the management of advanced prostate cancer: A sensible or ostensible approach

BACKGROUND: To compare the efficacy of orchiectomy alone and orchiectomy plus flutamide in treating patients with advanced carcinoma prostate. MATERIALS AND METHODS: The study was initiated on 1 July 1997 and closed after enrolling 100 patients on 30 June 2000. Patients were prospectively randomized to orchiectomy alone (O) and orchiectomy plus flutamide (OF). A complete response (CR) was defined as the normalization of bone scans and serum prostate-specific antigen (PSA) levels returning to normal (< 4 ng/mL). A partial response (PR) was defined as a 50% reduction in metastasis mass compared to the initial study or a decrease in the PSA level of 50% of the initial value. Progressive disease (PD) was defined as the development of any new hot spot on bone scan or any increase in previously existing PSA level by 25%. RESULTS: A total of 100 patients were entered in the study. The maximum percentage change in PSA levels in both groups was found in the first 3 months after orchiectomy, that is, 95% and 97% for the O and OF groups, respectively. In more than 80% of the patients this decrease in PSA was maintained for 3 years. The mean percentage change at 3 years in the O and OF groups was 70% and 75% (P = 0.95), respectively, and the overall response rate (CR + PR) was 88.50% and 86.53% in the two groups, respectively (P = 0.85). The follow-up period ranged between 3 and 5 years (mean, 3.5 years). The mean time to progression was 27 and 29 months in the O and OF groups, respectively. The overall survival rate at 3 and 5 years in two treatment groups was 45.83% and 48.07%, 20.83% and 23.07% in the O and OF groups, respectively (P = 0.75). CONCLUSIONS: Maximum percentage decrease in PSA is seen within the first 3 months of therapy. Orchiectomy alone is as effective as combination therapy in decreasing serum PSA. Overall survival at 3 and 5 years in the orchiectomy only group was as good as that of combination therapy. These data suggest that the routine addition of flutamide to orchiectomy is not advisable.     

Light microscopic morphometric analysis of castration effects in the different lobes of the rat prostate

The morphologic effects of androgen deprivation in the different lobes of the rat prostate were examined by light microscopic morphometry. The prostates of Wistar male rats (260-340 g) were fixed in situ by glutaraldehyde perfusion in castrated animals 1 week after gonadectomy and in intact animals. The ventral (VP), dorsal (DP), and lateral (LP) lobes as well as the coagulating gland (CG) were dissected out, weighed, and processed for light microscopy. Using stereologic methods the following parameters were estimated for each lobe: volume fraction of connective tissue, epithelium and glandular lumina, average epithelial height, average epithelial cell volume, and total number of epithelial cells. Castration leads to a 58-76% reduction of the wet weight of all prostatic lobes. The decrease of glandular tissue is greater in VP than in LP, DP, and CG. In VP and LP, there is a 39-45% reduction of the epithelial height, and this effect is less pronounced in DP and CG. For all lobes, the shrinkage of average epithelial cell volume is in the same range (25-30%). Moreover, in VP and LP, there is a 70% reduction of the total number of cells, whereas the reduction is less in DP and CG. It thus seems that the reduction of prostatic epithelial tissue mass upon castration is due to a reduction of the number of cells as well as a reduction of the volume of individual cells. VP and LP appear to be more androgen-dependent than DP and CG.     

结直肠癌中雄激素受体及其与临床病理学特征关系的研究

应用放射性配基结合分析法，检测了４０例结直肠癌及部分癌旁正常粘膜组织中的雄激素受体（ＡｎｄｒｏｇｅｎＲｅｃｅｐｔｏｒ，ＡＲ），同时分析了ＡＲ水平与临床病理学变化的关系。证实结直肠癌ＡＲ数目（３３．７±２３．３ｆｍｏｌ／ｍｇ蛋白）明显低于癌旁５ｃｍ以外粘膜（５３．９±３２．４ｆｍｏｌ／ｍｇ蛋白），Ｐ＜０．０１，而其亲和力则无变化；结直肠癌时ＡＲ数目变化与女性、直肠癌、高分化癌及早期癌关系密切。提示ＡＲ与结直肠癌关系密切，本实验为临床上结直肠癌的诊断及内分泌治疗提供了初步资料。     

RNAi抑制前列腺癌雄激素受体表达的实验研究

目的:利用RNA干扰(RNAi)效应抑制雄激素受体(AR)的表达,观察RNAi在人前列腺癌PC3细胞中的干扰效应,寻找高效率的干扰片断。方法:设计5个针对AR的不同的siRNA(siRNA1、siRNA2、siRNA3、siRNA4和siRNA5)为实验组,构建表达载体并瞬时转染PC3细胞,提取总RNA和总蛋白,分别行荧光定量PCR和Western印迹检测AR mRNA和蛋白的表达,另设一无意义RNA表达载体为阴性对照组,比较实验组与对照组间的差异。结果:各实验组的AR mRNA的表达较对照组均不同程度下降,统计学分析差异有显著性(P(0.05),以siRNA1、siRNA4和siRNA5抑制效率最高,对比其余实验组差异有显著性(P(0.05),AR蛋白检测显示相同结果。结论:RNAi技术可有效地抑制前列腺癌细胞AR的表达,找到了具有较高抑制效率的siRNA并合成了其表达载体,为下一步的体内实验和药物研制奠定了基础。     

间歇性雄激素阻断治疗晚期前列腺癌效果观察

目的 评价间歇性雄激素阻断治疗晚期前列腺癌的可行性及优点.方法 选取晚期前列腺癌患者59例,随机分为2组.给予间歇性雄激素阻断治疗30例(A组),给予持续雄激素阻断治疗29例(B组),观察两组患者的疾病进展及治疗期间副反应的发生情况,比较两种方法的治疗效果.结果 A组患者平均随访26个月,B组患者平均随访27个月,两组患者疾病进展情况未见明显差异.A组患者副反应低于B组患者且能在治疗间歇期得到缓解.结论 间歇性雄激素阻断治疗方法可行,能够减少患者治疗的副反应,提高患者生活质量.     

经尿道前列腺电汽化切除加雄激素阻断治疗晚期前列腺癌

目的探讨经尿道前列腺电汽化切除加雄激素阻断治疗晚期前列腺癌的临床疗效。方法对31例前列腺癌晚期(D)患者采用经尿道前列腺电汽化切除及睾丸切除术,术后3~5d口服氟他胺做全雄激素阻断以及氟他胺加达菲林的药物去势治疗。结果随访3~42个月,生存者29例,2例患者生存超过5年,20例超过1年。其中7例骨转移病灶减少,6例骨痛患者治疗后疼痛消失。前列腺特异性抗原(PSA)从术前的75.37μg/L降至1.34μg/L(术后1个月),3个月后降为0.27μg/L。B超、胸片、骨扫描未见新的转移灶。结论经尿道前列腺癌电汽化切除加全雄激素阻断治疗晚期前列腺癌具有较好的临床疗效。     

Mutations in the androgen receptor gene of seven Chinese patients with complete androgen insensitivity syndromes

Androgenplaysanimportantroleinthenormaldevelopmentofmalephenotypeandtheregulationofvirilization.Theseactionsofandrogenaremediatedbytheintracellularandrogenreceptor(AR)containingN--terminal,DNAuandsteroidbindingdomains.MutationsintheARgenecancausevariousdegreesofandrogenInsensitivitysyndromes(AlS)inpatientswith46,XYkaryotype.ThephenotypeofpatientswithAlSrangesfromcompletefemaleexternalgenitalia(completeAlS,CAIS)overgenitalambiguity(partialAlS,PAlS)totheinfertilewithnormalmaleornearlys…     

Androgen receptors in the cytosolic fraction of malignant prostatic tumors and their clinical significance

The occurrence and mean content of androgen receptors in the cytosolic fraction of prostatic adenocarcinoma depend on the age of patients, stage of tumor anaplasia, tumor differentiation, type of therapy, and the concentration of androgen receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 432–436, October, 1996     

Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells

BACKGROUND: The present study was conducted to investigate the effect of androstenedione, insulin and LH on human granulosa cell oestrogen and progesterone production. We postulated that elevated concentrations of androstenedione, insulin and LH may be important modulators of granulosa cell steroidogenesis. METHODS: Granulosa cells obtained in connection with IVF procedures were cultured for a total of 4 days in serum-free medium containing androstenedione (10(-6) mol/l). We tested the effect of androstenedione (10(-5) mol/l) on insulin (0-800 microIU/ml), LH (1-10 ng/ml) as well as on insulin + LH-stimulated oestrogen and progesterone production. RESULTS: Insulin increased the basal secretion of steroid hormones, and furthermore augmented LH-stimulated oestrogen and progesterone accumulation in granulosa cell cultures. Androstenedione (10(-5) mol/l) stimulated basal oestrogen production, but significantly reduced (32-58%) insulin + LH-stimulated oestrogen and progesterone secretion (P < 0.05). CONCLUSION: These results suggest that high androstenedione concentrations may act directly to impair insulin augmentation of LH-stimulated oestradiol and progesterone production in cultured human granulosa luteal cells. This is compatible with the hypothesis that high androgen levels may inhibit oestrogen production in polycystic ovary follicles, and as such may contribute to anovulation and infertility in women with polycystic ovary syndrome.