去势后阻断自噬对大鼠前列腺细胞凋亡的影响

目的：探讨去势后阻断自噬对大鼠前列腺细胞凋亡的影响。方法 SD雄性大鼠72只随机分为3组：即假切对照组、去势组、去势＋硫酸羟氯喹处理组。各组大鼠分别于术后第1、3、7、10、14、21d随机抽取4只,完整取出前列腺组织。 HE染色观察大鼠前列腺组织形态学变化,电镜下观察前列腺微观结构、自噬和凋亡的变化,免疫组化SP法检测自噬受体蛋白P62和凋亡促进蛋白 Caspase－3在前列腺组织中表达。结果光镜下去势后大鼠前列腺体积逐渐缩小,腺上皮细胞逐渐萎缩,核染色加深,腺泡萎缩甚至闭塞,间质增生,加用羟氯喹处理后这一变化更加明显。电镜下观察去势后自噬小体的数量明显增加。免疫组化检测去势后自噬活性蛋白P62表达减弱,用羟氯喹处理后表达增强;凋亡促进蛋白 Caspase－3表达增强,用羟氯喹处理后表达进一步增强。结论去势后大鼠前列腺细胞自噬增加,自噬抑制剂羟氯喹可通过阻断细胞自噬增加大鼠细胞凋亡,自噬可能具有抗凋亡作用。     

细胞自噬在肿瘤中的作用

自噬为一种细胞的自我消耗过程,其具有潜在的抗肿瘤生物学活性,亦与肿瘤耐药有关。该文从自噬的调节机制入手,综述自噬参与肿瘤发生的机制,自噬在肿瘤治疗中的作用及应用,以期为自噬在临床上的应用提供依据。     

保留耻骨前列腺韧带在耻骨后根治性前列腺切除术控尿中的作用

目的 探讨耻骨后根治性前列腺切除术中保留耻骨前列腺韧带(PL)的控尿作用.方法前列腺癌患者74例.年龄52～73岁,平均65岁.术前实验室检查PSA 2.0～23.6 ng/ml,平均16.5 ng/ml.其中64例行经直肠超声引导下前列腺系统穿刺活检,病理证实为前列腺癌;10例行TURP后病理发现前列腺癌.74例均行盆腔MRI及全身骨扫描未见前列腺外转移病灶.A期6例、B期68例.手术方法:常规行双侧盆腔淋巴结清扫,锐性切开盆内筋膜至PL侧缘,50例保留PL,在尿道前方紧贴前列腺尖部的弧形缘放置集束血管钳,控制耻骨后血管复合体(包括PL与背静脉复合体);对照组24例紧贴耻骨切断PL,在尿道前方紧贴前列腺尖部的弧形缘放置集束血管钳,控制背静脉复合体.在集束钳下方用1-0可吸收线分别贯穿缝扎集束血管钳控制的组织,沿前列腺的弧形切断该束组织达前列腺尖部与尿道连接处.离断尿道.采用"网球拍"式的膀胱颈重建.整形后的膀胱颈与尿道黏膜对黏膜于2、5、7和10点分别吻合4针,将保留在复合体上的1-0缝线于重建膀胱颈的12点、距吻合缘0.5～1.0 cm处浆肌层贯穿缝扎,将其与复合体结扎固定.术后保留尿管2周.结果 74例手术均顺利.随访3～12个月.保留PL组及切断PL组年龄分别为(61.3±2.4)和(60.8±2.1)岁,实验室检查PSA分别为(14.3±1.2)和(14.7±1.3)ng/ml,手术时间为(110.5±10.4)和(109.7±10.6)min,术中出血量为(250.5±23.4)和(253.4±22.3)ml,切缘阳性率为6%(3/50)和8%(2/24);2组比较差异均无统计学意义(P>0.05).保留PL组与切断PL组术后拔除尿管不同时间的控尿率分别为:即刻26%(13/50)和0%(0/24),1个月时为50%(25/50)和12%(3/24),3个月时为80%(40/50)和42%(10/24),6个月时为96%(48/50)和67%(16/24),12个月时为100%(50/50)和75%(18/24);2组比较差异均有统计学意义(P<0.05). 结论 PL在耻骨后根治性前列腺切除术后控尿中发挥较大作用,术中应积极保留.     

雄激素受体在去势抵抗性前列腺癌细胞铁死亡中的作用研究

目的 探讨雄激素受体(AR)在去势抵抗性前列腺癌(CRPC)细胞铁死亡中的作用.方法 将CRPC细胞系22Rv1和VCaP设置对照组、erastin(10μM)组和erastin+Lip(1μM)组,噻唑蓝(MTT)检测细胞活力,流式细胞仪测定可变铁池(LIP),生化法检测谷胱甘肽(GSH)和丙二醛(MDA)水平,蛋白...     

Bcl-2在细胞自噬中的作用

细胞凋亡是一种生理性细胞死亡机制,它是由基因控制的细胞自主的有序的死亡过程.细胞自噬是一种自我消化过程,通过包裹细胞内成分,再与溶酶体溶合,进而降解细胞成分.细胞自噬与凋亡之间存在复杂联系,在一定条件下自噬是细胞对应激适应性反应从而避免发生死亡,而在其他环境中,自噬是细胞死亡的替代途径.Bel-2家族成员在细胞凋亡与自噬过程中发挥着交叉性作用.本综述主要总结Bcl-2家族成员在细胞自噬中研究进展.     

前列腺动脉结扎在前列腺切除术中的止血作用

本文对20例前列腺增生症（BPH）病人在预先结扎前列腺动脉的基础上施行耻骨上经膀胱前列腺切除术,疗效满意,现报告如下。1资料与方法1．1临床资料本组20例,年龄57～82（平均68．5）岁。病程为8个月～15年,平均3．5年。Ⅰ度增生4例,Ⅱ度增生11例,Ⅲ度增生5例。急性尿潴留4例,残余尿50～200ml15例,膀胱结石5例,膀胱肿瘤2例,肉眼血尿3例。1,2手术方法硬膜外麻醉,消毒铺巾后,插入F16－18导尿管,向膀胱注水300～500ml以充盈膀胱,拔出导尿管。作下腹中线切口,推开腹膜襞褶,切开膀胱。辨认双侧输尿管开口。用大圆针、2个"0"肠线…     

前列腺摘除术与去势术前后雄激素变化的研究

目的探讨和研究前列腺摘除术与去势术对血清中雄激素(T、FT、DHT)的变化。方法39例研究对象,其中23例前列腺摘除术,16例去势术在手术前后分别采集血清样本,用放射免疫法测定血清中T、FT、DHT浓度。结果 前列腺摘除术后血清中T、FT、DHT分别较术前下降34.45％,33.53％,50.41％;去势术后血清中T、FT、DHT分别较术前下降92.27％,92.26％,58.36％。两种手术前后血清中T、FT、DHT的变化都有显著的统计学意义(P<0.001)。结论 前列腺摘除术后血清中雄激素会发生明显的变化,以DHT改变为显著。而去势术能够去除绝大部分T、FT,而DHT仅下降58.36%,在雄激素依赖的前列腺癌病例应当继续使用雄激素受体竞争剂,阻止残存的雄激素作用。     

细胞自噬及其在肾脏疾病中的作用

自噬（autophagy）是保持细胞内物质合成与分解代谢平衡,维持细胞器更新的重要生物学过程.近十年来随着自噬相关基因和相关标志蛋白的发现以及检测手段的进步,自噬的研究不断取得新的突破.细胞自噬不仅在细胞分化、生长、发育、老化等生理过程中有重要作用,在应激和疾病中,如内质网（ER）应激、氧化应激和自由氧离子（ROS）产生、神经元退行性疾病、微生物感染、肿瘤、肾病中同样起了重要作用.     

Water imbibition in the rat prostate during castration-induced regression

The present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70 degrees C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%-84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr-EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr-EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration-induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.     

The magnitude of early castration-induced primary tumour regression in prostate cancer does not predict clinical outcome

INTRODUCTION: This study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease. PATIENTS AND METHODS: Biopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome. RESULTS: Decreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1 ng/ml predicted a longer cancer-specific survival after castration therapy. CONCLUSION: Castration therapy causes primary tumour regression in most patients with advanced prostate cancer, but these primary tumour effects are not predictive for systemic disease control. Studies of early changes in metastases during hormonal therapy will probably give more predictive information for clinical outcome than further studies in primary tumours.     

自噬在雄激素抵抗型前列腺癌中的作用

正前列腺癌(prostate cancer,PCa)是美国等西方国家男性最常见的恶性肿瘤之一,病死率居男性各种癌症第2位~([1])。我国近年来前列腺癌的死亡率也逐渐上升,1998～2008年中国男性前列腺癌死亡率的年均增长率为8.44%~([2])。晚期PCa的治疗大多依赖于去除雄激素的方法。然而,经历18～24个月的去势治疗后,绝大多数患者均会由雄激素依赖型前列腺癌转变为非雄激素依赖型前列腺癌,即雄激素抵抗型前列腺癌(castrate resistant prostate cancer,CRPC),导致对传统的去势治疗反应效果较差~([3])。相关研究已经初步证明自噬在CRPC的进     

Inhibition of the epidermal growth factor receptor enhances castration-induced prostate involution and reduces testosterone-stimulated prostate growth in adult rats

BACKGROUND: The epidermal growth factor receptor (EGFR) mediates regulatory signals in the normal prostate, but the functional importance of this is unclear. METHODS: Adult male rats were castrated, or castrated + treated with gefitinib (Iressa, ZD1839), an EGFR tyrosine kinase inhibitor, for 3 days. Seven-day castrated rats were treated with testosterone, or testosterone + gefitinib, for 3 days. RESULTS: Both castration alone and testosterone treatment in castrated animals increased the mRNA and protein levels of EGFR and phospho-EGFR in the ventral prostate. Inhibition of EGFR during castration and during testosterone-stimulated prostate growth resulted in a decrease in total epithelial weight, epithelial cell proliferation, endothelial cell proliferation, and increased epithelial cell apoptosis. CONCLUSIONS: This study suggests that increased EGFR signaling during castration mediates stimulatory effects balancing castration-induced prostate regression, and that EGFR signaling is a necessary component in testosterone-stimulated prostate growth.     

Treatment of castration-induced menopausal symptoms with low dose diethylstilbestrol in men with advanced prostate cancer.

Menopausal symptoms manifesting as hot flashes and sweats occur in up to 75 percent of patients following either orchiectomy or treatment with a luteinizing hormone-releasing hormone agonist for prostate cancer. As many as one third of these patients will experience symptoms severe enough to seek palliation. We treated 12 such patients with low dose diethylstilbestrol (1/3 mg daily). Nine patients demonstrated both objective and subjective improvement in their menopausal symptoms. Five patients experienced toxicity including new onset of gynecomastia or breast soreness although no patient discontinued treatment on this basis. No cardiovascular complications were noted. We conclude that low dose diethylstilbestrol is an inexpensive, effective means of controlling troublesome postorchiectomy menopausal symptoms in carefully selected patients.     

The role of lymphadenectomy in prostate cancer

It has been shown that an adequate lymphadenectomy for exact staging of prostate cancer consists of removal of all the tissue along the external iliac vein, in the obturator fossa and along the internal iliac artery. Morbidity associated with this procedure is low, if certain technical details are respected. This review discusses in detail the indications for lymphadenectomy and the extent of dissection, based on the localization of the positive nodes. The potential therapeutic impact of extended lymph node dissection in men with prostate cancer is also addressed.