犬前列腺组织中诱导型一氧化氮合酶与前列腺增生关系的实验研究

目的　探讨诱导型一氧化氮合酶 (induciblenitricoxidesynthase ,iNOS)与犬良性前列腺增生 (benignprostatichyperplasia ,BPH)病理变化的关系。 方法　建立犬前列腺增生动物模型 ,用免疫组化法研究模型犬各时期iNOS在前列腺组织中的表达。结果　犬前列腺组织中iNOS阳性染色主要分布于腺泡上皮细胞及上皮下组织中 ,间质和平滑肌组织中均为阴性。iNOS的表达随雄激素注射时间延长而降低 ,各时段差异均有显著性 (P <0 .0 5 )。结论　雄激素对前列腺组织内的iNOS起负性调节作用 ,iNOS的减少参与了前列腺增生的病理生理过程     

前列腺癌组织中前列腺跨膜上皮抗原表达的临床意义

目的 :探讨前列腺跨膜上皮抗原 (STEAP)在前列腺癌 (PCa)组织中的表达及与肿瘤病理分级之间的关系。方法 :采用免疫组化SP法 ,用STEAP单克隆抗体对前列腺不同病变组织及非前列腺肿瘤组织石蜡包埋切片进行免疫组化染色 ,其中PCa组织 131例 ,良性前列腺增生 (BPH)组织 16 4例 ,非前列腺肿瘤组织标本 5 6例。引入阳性面积单位概念判定STEAP染色强度。　结果 :2 95例前列腺病变组织中 ,仅 3例PCa和 5例BPH组织STEAP呈阴性表达 ,STEAP在PCa组织中明显高表达 ,非前列腺肿瘤组织染色均呈阴性。STEAP表达与PCa的Gleason分级之间存在显著负相关性。　结论 :STEAP能够用来判断PCa的预后 ,在PCa的免疫治疗方面具有良好的应用前景。     

Caspase-3在前列腺组织中的表达和意义

目的 研究Caspase-3在良性前列腺增生(BPH)和前列腺癌(Pca)组织中的表达,了解Caspase-3在BPH和Pca发病及细胞凋亡中的作用。方法 30例BPH组织、22例Pca组织及7例正常前列腺石蜡切片组织用多克隆抗体Caspase-3行LSAB免疫组化染色,按表达的阳性率分0(阴性)、1 (<25％)、2 (25％～75％)、4 (>75％)统计染色等级。结果Caspase-3在93％(28/30)BPH组织有不同程度的表达(0～3 ),主要在分泌性上皮和基底细胞表达,而在基质平滑肌罕见表达,且BPH上皮表达明显少于正常组织。Capase-3在22例Pca组织表达阳性率为100％,普遍表达强阳性(4 ),且明显多于非癌性组织,Caspase-3表达与Pca病理分级无相关。结论 Caspase-3表达异常与BPH上皮与基质增生有关;Caspase-3在国人Pca细胞凋亡中有重要作用。     

外周血和组织炎性细胞在鉴别PSA4～10ng/ml的前列腺癌和前列腺增生中的临床意义

目的:评价外周血和前列腺组织炎性细胞在鉴别前列腺特异性抗原(PSA)4～10 ng/ml的前列腺癌(PCa)和良性前列腺增生(BPH)中的临床意义。方法:回顾性分析我院2013年10月～2018年10月PSA水平4～10 ng/ml的PCa和BPH患者共45例,其中PCa组患者20例,BPH组患者25例。PCa组患者行前列腺癌根治术后病理确诊,BPH组患者行耻骨上经膀胱前列腺摘除术或经尿道前列腺电切术(TURP)后病理确诊。所有患者在行前列腺穿刺活检术前检测血常规,记录患者外周血中WBC、中性粒细胞、淋巴细胞和单核细胞计数,分析外周血淋巴细胞与单核细胞比率(LMR)、中性粒细胞与单核细胞比率(NMR)和中性粒细胞与淋巴细胞比率(NLR)等。同时收集患者术后病理石蜡切片,采用免疫组织化学(IHC)染色法检测前列腺组织中炎性细胞表达情况。结果:PCa组和BPH组患者外周血白细胞、中性粒细胞和淋巴细胞计数等指标比较差异无统计学意义。PCa组单核细胞计数明显低于BPH组,差异有统计学意义(P0.05)。两组LMR、NMR和NLR值比较差异无统计学意义。两组淋巴细胞和中性粒细胞表达比较差异无统计学意义,但BPH组单核细胞标志物CD14表达高于PCa组,差异有统计学意义(P0.05)。结论:检测外周血和组织中单核细胞计数有助于诊断PSA浓度4～10 ng/ml的PCa患者。     

组织激肽释放酶基因7在前列腺癌组织中的表达

目的 探讨组织激肽释放酶基因7(KLK7)在不同前列腺组织中的表达情况.方法运用逆转录聚合酶链反应法检测正常前列腺(5例)、良性前列腺增生(BPH)及BPH细胞株(BPH1,13例)、前列腺癌及前列腺癌细胞株(8例)的上皮细胞中KLK7mRNA表达水平;蛋白质印迹法检测不同前列腺组织上皮细胞中KLK7蛋白表达水平;免疫组化分析正常前列腺(20例)、BPH(50例)、前列腺癌(103例)组织中KLK表达水平.根据染色强度分为4个等级(-,+,++,+++)进行半定量分析,染色强度++及+++者判定为阳性.结果 正常组、BPH组和前列腺癌组KLK7 mRNA表达相对值分别为0.59、0.52、0.02,组间比较差异有统计学意义(F=13.03,P＜0.01),前列腺癌上皮中KLK7 mRNA表达下调(P＜0.01),正常前列腺和BPH上皮中KLK7 mRNA表达差异无统计学意义(P＞0.05).KLK7蛋白在正常前列腺、增生前列腺、DU145、LNCaP、PC3、22RV1、BPH细胞株中表达水平相对值分别为0.22、0.40、0.01、0.05、0、0.03、0.14.免疫组化染色结果 显示正常前列腺组织、BPH组织、前列腺癌中KLK7蛋白表达阳性率分别为65.0%(13/20)、76.0%(38/50)、17.5%(18/103),前列腺癌组与前2组比较差异均有统计学意义(P＜0.01),前2组间比较差异无统计学意义(P＞0.05).结论 KLK7在前列腺癌组织中表达下调,提示KLK7在前列癌的发生和进展中可能起一定作用.     

BPH相关性抗原表达的临床意义

目的:探讨BPH相关性抗原(BPSA)在BPH、前列腺癌(PCa)诊断中的作用。方法:采用免疫组织化学ABC法,用BPSA单克隆抗体对62例BPH患者、37例PCa患者及30例其他肿瘤组织标本中的BPSA表达进行检测。结果:BPSA在100% BPH、88% PCa组织中呈不同程度的阳性表达,且在BPH组织中呈明显高表达。非前列腺肿瘤组织染色均呈阴性。组织BPSA表达与肿瘤病理分级无相关性(P>0. 05)。结论:BPSA具有良好的组织器官特异性,有助于早期PCa和BPH的鉴别诊断。     

前列腺增生症所致膀胱出口梗阻患者逼尿肌中神经生长因子mRNA的变化及意义

目的　探讨前列腺增生症 (BPH)所致膀胱出口梗阻 (BOO)患者膀胱逼尿肌中神经生长因子 (NGF)mRNA的表达变化及意义。方法　对同龄对照组 8例膀胱癌患者、BPH梗阻逼尿肌稳定组 2 4例患者和BPH梗阻逼尿肌不稳定组 16例患者的膀胱壁逼尿肌组织 ,采用逆转录聚合酶链反应(RT PCR)检测膀胱逼尿肌细胞中NGFmRNA的表达。结果　NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组患者的膀胱逼尿肌细胞中均有表达 ,三组患者的平均表达水平两两之间差异均有显著性意义 (P <0 0 1) ,而且NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组的平均表达水平逐渐增加。结论　前列腺增生症引起膀胱出口梗阻后 ,膀胱逼尿肌细胞中NGFmRNA表达水平增高 ,并可能与逼尿肌不稳定 (DI)的发生有关。     

前列腺特异性膜抗原表达的临床意义

目的 探讨前列腺特异性膜抗原(PSMA)在前列腺癌(PCa)组织中的表达及与肿瘤病理分级之间的关系。方法 采用免疫组化ABC法，用PSMA单克隆抗体对前列腺不同病变组织及非前列腺肿瘤组织石蜡包埋切片进行染色。其中PCa 70例，前列腺上皮肉瘤21例，良性前列腺增生20例．其他肿瘤组织标本30例。结果 PSMA在97％前列腺癌、100％前列腺上皮内瘤、80％BPH组织中呈不同程度的阳性表达，且在PCa组织中呈明显高表达，非前列腺肿瘤组织染色均呈阴性。组织 PSMA表达与PCa组织学分级之间存在负相关性。结论 PSMA具有良好的组织器官特异性，能够判断PCa顶后，在PCa的免疫治疗方面具有应用前景。     

前列腺间质组织成分变化在BPH病程中的意义

目的:探讨良性前列腺增生(BPH)患者前列腺组织是否存在间质成分改变,以及这种改变在BPH病程中的意义。方法:BPH患者手术或穿刺标本43例,尸检正常前列腺标本5例。所有标本行M asson染色显示前列腺间质组织肌纤维和胶原成分。以肌纤维成分与胶原成分比值量化前列腺间质组织成分变化程度。评估前列腺间质成分变化程度与膀胱出口梗阻程度、IPSS评分及药物治疗效果之间的关系。结果:正常前列腺间质组织中肌纤维和胶原成分比例平均为(3.2±0.2)∶1,而BPH患者前列腺间质组织中肌纤维与胶原成分比例平均为1(∶4.7±3.1),两组前列腺间质组织中成分比较差异有统计学意义(P<0.01)。有膀胱出口梗阻的BPH患者前列腺间质组织中肌纤维和胶原成分比例平均为1∶(5.4±3.7),明显低于无膀胱出口梗阻的BPH患者[1∶(2.5±1.1)](P=0.02)。重度前列腺症状的BPH患者前列腺间质组织中肌纤维和胶原成分比例平均为1∶(9.1±2.9),明显低于中度前列腺症状的BPH患者[1∶(5.3±3.4)]和轻度前列腺症状的BPH患者[1∶(2.8±1.7)](P均<0.01)。药物治疗效果差的BPH患者前列腺组织中肌纤维和胶原成分比例平均为1(∶7.6±4.3),明显低于药物治疗效果好的BPH患者[1∶(2.3±1.9)](P<0.01)。结论:BPH患者存在不同程度的间质成分改变。BPH临床症状越明显,药物治疗效果越差,前列腺间质组织中肌纤维成分越低,胶原纤维成分越多。前列腺间质成分的改变可能在BPH发生发展中起重要作用。     

维汉族BPH患者前列腺形态与尿流动力学的相关性

目的 探讨维汉民族前列腺增生患前列腺的体积、症状积分和膀胱排尿症状的相关性。方法 对71例住院手术的维汉不同民族前列腺增生症(BPH)患进行国际前列腺症状评分(BPSS)，生活质量评分(L)，前列腺体积(V)，重量(M)，患年龄(age)，尿流动力学指标的直线相关分析。结果 40例汉族及31例维族BPH患的前列腺体积与膀胱颈压，膀胱颈压与膀胱顺应性，最大尿流率与膀胱顺应性均呈正相关。结论 最大尿流率、前列腺体积、膀胱顺应性、膀胱颈压四个参数不但能了解膀胱排尿功能和形态改变，也可做为临床上手术切除增生前列腺组织，解除梗阻，缓解症状，评价治疗效果的指标。     

Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma.

OBJECTIVE: To elucidate the incidence of inducible nitric oxide synthase (iNOS) expression in benign prostatic hyperplasia (BPH), low- and high-grade prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma lesions, and to explore the role of iNOS in prostate tumorigenesis. MATERIALS AND METHODS: Immunoreactivity for iNOS was examined in 20 samples each of BPH, high-grade PIN, low-grade PIN and prostatic carcinoma. RESULTS: Positive iNOS immunostaining was detected in all samples from all patients; iNOS was detected in both basal epithelial cells and secretory cells of the glandular epithelium. High-grade PIN and prostatic carcinoma samples had more intense iNOS immunostaining than low-grade PIN and BPH samples. In all samples, smooth muscle cells showed weak or moderate iNOS immunoreactivity and endothelial cells showed moderate immunostaining. CONCLUSIONS: Nitric oxide generated by iNOS may be involved in prostate tumorigenesis and further studies with immunohistochemical and molecular biology are needed to determine the exact role of iNOS in the pathogenesis of prostatic carcinoma.     

Apoptosis and hormonal milieu in ductal system of normal prostate and benign prostatic hyperplasia

Aim: To study the apoptotic rate (AR) and the androgen and estrogen milieu in the proximal and distal ductal sys-tems of prostate, in order to help exploring the effects of these factors on prostatic growth and the pathogenesis of be-nign prostatic hypertrophy (BPH). Methods: The proximal and distal ends of the ductal system were incised from20 normal prostate as well as the hypertrophic prostate tissue from 20 patients with BPH. The AR was determined bythe DNA end-labeling method and dihydrotestosterone (DHT) and estrodiol (E_2), by radioimmunoassay. Results:There was no significant difference in DHT and E_2 density between the proximal and distal ends of the ductal systems innormal prostate. E_2 appeared to be higher in BPH than in normal prostatic tissues, but the difference was statistically in-significant. In normal prostatic tissue, the AR was significantly higher in the distal than in the proximal ends of theductal system (P<0.05), while the AR of the proximal ends was significantly higher (P <0.     

前列腺增生症再手术原因分析

目的：探讨前列腺增生症（ＢＰＨ）再手术的原因。方法：回顾分析２６例ＢＰＨ术后再入院手术患者的临床资料,再手术原因为膀胱颈挛缩１３例、腺体残留复发１０例、前列腺癌３例。结果：对膀胱颈挛缩及腺体残留复发者均施行开放手术或经尿道电切治疗,术后尿路梗阻症状解除。３例前列腺癌就诊已属晚期,施行去势术加氟他胺治疗,术后分别于１０～２８个月因全身广泛转移导致衰竭而死亡。结论：ＢＰＨ开放手术后膀胱颈挛缩,ＴＵＲＰ     

Bladder compliance in patients with benign prostatic hyperplasia

Factors influencing bladder compliance were examined in 116 patients with benign prostatic hyperplasia (BPH), by evaluating patients' histories, response of isolated bladder strips to acetylcholine, and the effect of prostatic urethral anesthesia. Patients' age, frequency of micturition, and duration of voiding difficulty were not correlated with bladder compliance. Bladder compliance was significantly low in patients within 30 days after urinary retention, as compared with bladder compliance in patients without an episode of retention. More than 30 days after retention, however, there was a tendency toward increased bladder compliance. Restricted to patients without an episode of retention, bladder compliance in the overactive detrusor group was found to be significantly lower than in the normal group. The responses to acetylcholine of bladder strips were compared between patients with low and normal-compliance bladders. The dose-response curve of patients with low-compliance bladders did not differ from that of those with normal compliance bladders, even when patients with an episode of retention were excluded. After prostatic urethral anesthesia, a significant increase of bladder compliance was observed in patients with an overactive detrusor, while the increase was not significant in patients with a normal detrusor. Our results strongly suggest that easy irritability of the anatomically altered prostatic urethra, as well as bladder overdistension caused by urinary retention, are important factors affecting bladder compliance in BPH patients.     

膀胱癌合并前列腺增生经尿道同期电切术30例分析

目的　探讨同期行经尿道膀胱肿瘤加前列腺电切术治疗膀胱癌合并前列腺增生症患者的可行性及疗效。方法　回顾分析30例膀胱癌并前列腺增生患者的手术方法。 18例同期行经尿道膀胱肿瘤加前列腺电切术 (A组 ) ;12例单纯行经尿道膀胱肿瘤电切术 (B组 )。结果　随访 4～ 6 0个月 ,A组有 10例术后复发 ,异位复发 6例 (占 6 0 % ) ,无尿道、前列腺窝及膀胱造瘘口的转移或种植。B组 7例复发 ,异位复发 5例 (70 .1% ) ,3例随访期内因前列腺增生症再行经尿道前列腺电切术。结论　膀胱肿瘤合并前列腺增生患者同期行经尿道电切术 ,在切除肿瘤后应用Ellick吸除器吸尽切下膀胱内组织后再切除增生的前列腺组织 ,可以减少膀胱内肿瘤细胞种植机会 ,缩短住院时间 ,提高疗效     

Influence of prostatic disease and prostatic manipulations on the concentration of prostate-specific antigen.

We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value.     

Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.     

Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia

BACKGROUND: Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. Previously we showed that senescent epithelial cells accumulate in the prostate of aging men and secrete interleukin-1 alpha (IL-1 alpha). IL-8 is also present at increased levels in BPH tissues and induces expression of FGF2, a potent stromal growth factor. Therefore, we sought to determine if IL-8 is also expressed at increased levels by senescent epithelial cells and if this secreted IL-8 plays a role in the pathogenesis of BPH. METHODS: Expression of IL-8 in human BPH tissue and primary cultures of prostatic epithelial cells was analyzed using an enzyme-linked immunoabsorption assay (ELISA). Tissue senescence was assessed by a quantitative assay for senescence-associated beta galactosidase (SA-beta gal). Proliferation of primary and immortalized prostatic epithelial cells in response to IL-8 was determined by counting of cells at intervals after addition of IL-8. RESULTS: Expression of IL-8 is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. Quantitative assay of BPH tissue extracts revealed that tissue IL-8 levels are correlated with both SA-beta gal activity and prostate weight. IL-8 promotes proliferation of primary and immortalized prostatic epithelial cells in culture. CONCLUSIONS: Senescence of prostatic epithelial cells results in increased expression of IL-8, which can promote proliferation of non-senescent epithelial and stromal cells by direct and indirect mechanisms, and in this manner contributes to the increased tissue growth seen in BPH.     

Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.