前列腺癌组织中Ob—R和STAT3的表达变化及意义

目的观察瘦素受体（Ob—R）及信号转导和转录激活因子3（STAT3）在前列腺癌（PCa）组织中的表达,并探讨其临床意义。方法采用免疫组化法检测41例Pea（PCa组）、22例前列腺上皮内瘤（PIN,PIN组）、25例良性前列腺增生（BPH,BPH组）组织中Ob—R和STAT3。结果在BPH、PIN和PCa组中,Pb—R阳性表达率分别为56．00％（14／25）、72．73％（16／22）、90．24％（37／41）,PCa组与BPH组比较,P〈0．01,余组间两两比较,P均〉0．05;STAT3阳性表达率分别为60．00％（15／25）、81．82％（18／22）、87．80％（36／41）,PCa组与BPH组比较,P〈0．01,余组间两两比较,P均〉0．05。Oh-R的表达与PCa病理分级、临床分期无关,STAT3的表达仅与PCa病理分级有关（P〈0．05）。0b—R与STAT3表达呈正相关（r=0．6897,P〈0．01）。结论PCa组织中0b—R和STAT3呈高表达。Ob—R和STAT3可作为判断PCa生物学行为的指标。     

前列腺癌组织中p73的表达变化及意义

目的观察前列腺癌组织中p73的表达变化,并探讨其临床意义。方法采用免疫组化ABC法检测29例前列腺癌和18例前列腺增生（BPH）组织中p73的表达情况。结果前列腺癌组织中p73的表达率为27．4％（8／29）,BPH组织中无表达（P〈0．05）;p73的表达与前列腺癌临床分期有关（P〈0．05）,而与其病理类型、组织学分级无关（P〉0．05）。结论前列腺癌组织中p73呈高表达,p73可能参与了前列腺癌的发生和发展。     

期前列腺癌组织中达变化及意义Caspase-3、survivin的晚表

目的观察晚期前列腺癌（PCa）组织中Caspase-3及survivin的表达变化，探讨其临床意义。方法采用免疫组化法检测46例PCa及24例良性前列腺增生症（BPH）组织中Caspase-3和survivin。结果PCa和BPH组织中Caspase-3阳性表达率分别为58．7％（27／46）和83．3％（20／24），survivin阳性表达率分别为45．7％（21／46）和20．8％（5／24），P均〈0．05。PCa组织中survivin与Caspase-3的阳性表达变化无相关性（r=0．028，P=0．852）。结论晚期PCa组织中Caspase-3和survivin表达均异常，但两者表达无相关性。Caspase-3和survivin均在Pca的发展中起重要作用。     

良性前列腺增生和前列腺癌组织中雄激素受体的表达

目的　探讨雄激素受体 (AR)与良性前列腺增生 (BPH)和前列腺癌 (PCa)的关系。　方法　应用免疫组织化学技术检测 4 0例BPH、4 0例PCa患者及 2 0例正常前列腺组织 (正常对照组 )AR的表达。　结果　BPH组、PCa组、正常对照组AR表达的阳性率分别为 98%、5 3%、75 % ,相互比较差异均有显著性 (P <0 0 5 )。高分化癌、中分化癌、低分化癌的AR表达的阳性率分别为 6 7%、5 6 %、30 % ,高、中分化癌的AR表达的阳性率比低分化癌高 (P <0 0 5 )。早期前列腺癌的AR表达阳性率 (6 9% )比晚期前列腺癌 (4 2 % )高 (P <0 0 5 )。　结论　BPH组织中AR的表达高于正常前列腺组织 ,AR在BPH的发生、发展中起着重要作用 ;PCa组织中AR的表达低于正常前列腺组织。AR的表达与肿瘤分级、分期相关。     

外周血PSA、PSA mRNA联合检测在前列腺癌诊断中的临床应用

目的探讨利用外周血PSA、PSA mRNA联合检测诊断前列腺癌（PCa）的临床应用及意义。方法运用酶联免疫分析和巢式RT-PCR检测22例PCa、10例良性前列腺增生（BPH）患者,5例健康男性和5例健康女性外周血中PSA、PSA mRNA的情况。结果PCa患者血清PSA的水平与临床分期、Gleason评分有关（P〈0.05）,而与年龄无关（P〉0.05）;外周血PSA、PSA mRNA与临床分期、内分泌治疗有关（P〈0.05）,而与年龄、Gleason评分无关（P〈0.05）;22例PCa标本中PSA mRNA阳性表达15例,阳性率68%,10例BPH和10例阴性对照标本无表达。结论利用外周血PSA、PSA mRNA联合检测是一种早期发现PCa微转移,判断其临床变化过程、分期、预计复发和评价疗效的方法。     

益肾通胶囊治疗后BPH患者前列腺组织中促凋亡蛋白、抑凋亡蛋白的表达变化

摘要：目的观察益肾通胶囊治疗后良性前列腺增生症（BPH）患者前列腺组织中促凋亡蛋白、抑凋亡蛋白的表达变化,并探讨其意义。方法BPH患者60例,其中30例术前口服益肾通胶囊（A组）,另30例术前未口服益肾通胶囊（B组）,手术切除取BPH组织标本;另取非BPH人尸前列腺组织20例份（C组）。采用免疫组化法、Westernblotting法检测各组促凋亡蛋白Caspase-3、bax及抑凋亡蛋白bcl-2、Livind。结果免疫组化法检测结果：A、B、c组bax蛋白阳性率分别为90．0％、86．7％、100．0％,两两比较,P〉0．05;Caspase．3蛋白阳性率分别为86．7％、86．7％、100．0％,两两比较,P〉0．05;bcl-2蛋白阳性率分别为63．3％、90．0％、20．0％,两两比较,P均〈0．01;Livin α蛋白阳性率分别为50．0％、83．3％、5．0％,两两比较,P均〈0．01。Westernblotting法检测结果：A、B、C组bax蛋白阳性率分别为90．0％、83．3％、100．0％,两两比较,P〉0．05;Caspase-3蛋白阳性率分别为86．7％、83．3％、100．0％,两两比较,P〉0．05;bcl-2蛋白阳性率66．7％、90．0％、25．0％,两两比较,P均〈0．01;Livin α蛋白阳性率分别为50．0％、80．0％、0,两两比较,P均〈0．01。结论益肾通胶囊可促进BPH前列腺细胞的凋亡,其可能与降低前列腺细胞bcl-2、Livin α表达有关。     

乳腺癌组织中nm23、PS2蛋白的表达及临床意义

目的探讨乳腺癌组织中的nm23蛋白、PS2蛋白表达及其临床意义。方法采用免疫组化SP法检测63例乳腺癌组织与56例乳腺良性疾病组织中的nm23蛋白、PS2蛋白,分析nm23蛋白与PS2蛋白表达与患者年龄、组织学分级、临床分期、腋窝淋巴结转移、ER表达及预后的关系。结果nm23蛋白在乳腺癌组织中表达阳性率为76．19％（48／63）,与患者年龄无相关性（P〉0．05）,与组织学分级、临床分期、淋巴结转移及ER相关（P均〈0．05）。PS2蛋白在乳腺癌组织中表达阳性率为66．67％（42／63）,与临床分期无相关性（P〉0．05）,与年龄、组织学分级、淋巴结转移及ER表达相关。nm23蛋白和PS2蛋白在乳腺良性疾病中的表达均高于在乳腺癌组织中的表达水平。nm23蛋白与PS2蛋白均阳性的乳腺癌患者预后明显优于均阴性的乳腺癌患者（P〈0．05）。结论nm23蛋白、PS2蛋白可以作为预测乳腺癌预后的指标。     

应用组织微阵列技术研究SATB1在前列腺癌中的表达及意义

目的研究SATB1在人前列腺癌（Pca）组织中的表达及临床意义。方法应用组织微阵列技术结合免疫组化方法检测58例Pca标本和17例良性前列腺增生（BPH）对照组织标本中SATB1的表达状况,并分析其临床病理意义。结果 Pca组织中SATB1表达率为75.9%（44/58）,与BPH组织表达率17.6%（3/17）相比差异有统计学意义（P〈0.01）。SATB1在Pca组织中的表达随病理分级、临床分期增加而增强（P〈0.05）,与病理分化程度呈负相关（P〈0.01）、与临床分期呈正相关（P〈0.01）。结论检测SATB1的表达有助于对Pca病理分级、临床分期和预后进行判断。     

前列腺腺癌组织中p53和P504S的表达及意义

应用免疫组化法检测46例前列腺腺癌组织中p53、P504S的阳性表达水平，结果p53、P504S表达阳性率分别为78．26％、91．30％，且随着病理分级、临床分期递增和淋巴结转移而逐渐增高（P〈0．05）。提示p53、P504S是前列腺癌的特异性标记，二者的高表达与前列腺腺癌的生物学行为密切相关。     

血清tPSA、fPSA/tPSA及PSAD在前列腺良恶性疾病鉴别诊断中的价值

目的探讨血清总前列腺特异抗原（tPSA）、游离PSA（fPSA）与tPSA的比值（F／T）、前列腺特异抗原密度（PSAD）在前列腺增生（BPH）和前列腺癌（PCa）鉴别诊断中的价值。方法检测65例BPH患者及38例PCa患者的血清tPSA、fPSA,经腹部B超测定前列腺的前后径、左右径、上下径,并计算出F／T、前列腺体积（PV）及PSAD,进行比较。结果在灰区外高值区,tPSA、PSAD在两组间差异有显著性（P均〈0．01）,F／T差异无显著性（P〉0．05）;在灰区,两组间tPSA差异无显著性（P〉0．05）,而F／T、PSAD差异有显著性（P均〈0．01）;在灰区外低值区,tPSA、F／T及PSAD在两组间差异无显著性（P〉0．05）。结论以F／T及PSAD作为tPSA的辅助指标,对PSA灰区PCa的诊断具有明显临床意义。     

经直肠超声前列腺癌声像特征及前列腺内腺PSA密度在前列腺癌诊断中的作用

目的通过经直肠超声分析前列腺癌声像特征并测量前列腺内腺、外腺与总体积，参考PSA探讨前列腺内腺PSA密度(IPSAD)在前列腺癌与前列腺增生鉴别诊断中的意义。方法回顾分析经直肠超声前列腺癌声像特征及经超声引导下6点活检病理诊断的49例前列腺癌、96例前列腺增生的临床资料。结果(1)前列腺癌声像特征以低回声为主，晚期可见被膜浸润及不规则。(2)前列腺内腺体积增生与癌有显著性差别。(3)PSA、PSA密度(PSAD)、IPSAD在增生与前列腺癌中的比较，均有显著性差异。(4)IPSAD在前列腺癌诊断的特异度为75．5％，敏感度为93．3％，优于PSAD。结论前列腺癌声像特征及IPSAD是鉴别前列腺癌与增生的重要指标。     

人前列腺特异性膜抗原基因重组腺病毒的构建及其表达

目的 体外构建含有人前列腺特异性膜抗原(PSMA)基因的重组腺病毒载体,并检测其在HEK293细胞中的表达.方法 设计一对含有SfiI酶切位点的PSMA基因上下游引物,以质粒pCMV-SPORT6/PSMA为模板,通过PCR扩增获得PSMA基因全序列.片段回收后经酶切处理,连接到穿梭质粒pShuttle-CMV-EGFP上,获得重组穿梭质粒pShuttle-EGFP-PSMA.经SfiI酶切、PCR及插入片段测序鉴定正确后,将其用I-CeuI和I-SceI双酶切处理,转移到pAdxsi载体上,得到pAdxsi-GFP-PSMA病毒质粒,线性化后经HEK293细胞包装成复制缺陷型腺病毒Ad-PSMA,通过观察绿色荧光蛋白(GFP)的表达,RT-PCR,Western印迹检测目的基因人PSMA的表达.结果 成功构建了含有人PSMA基因的重组腺病毒,病毒滴度为2×1010 pfu/ml.Western印迹检测可见PSMA蛋白的正确表达.结论 该重组腺病毒载体的成功构建及表达,为下一步以人PSMA作为靶抗原构建DC疫苗和基因免疫治疗奠定基础.     

Androgen receptor signalling in prostate: effects of stromal factors on normal and cancer stem cells

The prostate gland is the most common site for cancer in males within the developed world. Androgens play a vital role in prostate development, maintenance of tissue function and pathogenesis of prostate disease. The androgen receptor signalling pathway facilitates that role in both the epithelial compartment and in the underlying stroma. Stroma is a key mediator of androgenic effects upon the epithelium and can regulate both the fate of the epithelial stem cell and potentially the initiation and progression of prostate cancer. Different groups of growth factors are expressed by stroma, which control proliferation, and differentiation of prostate epithelium demonstrating a critical role for stroma in epithelial growth and homeostasis. Paracrine stromal proteins may offer the possibility to control tumour stem cell growth and could permit prostate specific targeting of both therapies and of androgen responsive proteins. The effect of 5alpha-dihydrotestosterone, the more potent metabolite of testosterone, on expression of androgen-regulated genes in stroma from benign prostatic hyperplasia is a key mediator of epithelial cell fate. Global gene expression arrays have recently identified new candidate genes in androgen responsive stroma, some of which have androgen receptor binding sites in their promoter regions. Some of these genes have direct androgen receptor binding ability.     

Effects of perineural invasion in prostate needle biopsy on tumor grade and biochemical recurrence rates after radical prostatectomy

To predict local invasive disease before retropubic radical prostatectomy (RRP), the correlation of perineural invasion (PNI) on prostate needle biopsy (PNB) and RRP pathology data and the effect of PNI on biochemical recurrence (BR) were researched. For patients with RRP performed between 2005 and 2014, predictive and pathologic prognostic factors were assessed. Initially all and D'Amico intermediate-risk group patients were comparatively assessed in terms of being T2 or T3 stage on RRP pathology, positive or negative for PNI presence on PNB and positive or negative BR situation. Additionally the effect of PNI presence on recurrence-free survival (RFS) rate was investigated. When all patients are investigated, multivariate analysis observed that in T3 patients PSA, PNB Gleason score (GS) and tumor percentage were significantly higher; in PNI positive patients PNB GS, core number and tumor percentage were significantly higher and in BR positive patients PNB PNI positivity and core number were significantly higher compared to T2, PNI negative and BR negative patients, separately (p < 0.05). When D'Amico intermediate-risk patients are evaluated, for T3 patients PSA and PNB tumor percentage; for PNI positive patients PNB core number and tumor percentage; and for BR positive patients PNB PNI positivity were significantly higher compared to T2, PNI negative and BR negative patients, separately (p < 0.05). Mean RFS in the whole patient group was 56.4 ± 4.2 months for PNI positive and 96.1 ± 5.7 months for negative groups. In the intermediate-risk group, mean RFS was 53.7 ± 5.1 months for PNI positive and 100.3 ± 7.7 months for negative groups (p < 0.001). PNI positivity on PNB was shown to be an important predictive factor for increased T3 disease and BR rates and reduced RFS.     

Regulation of growth hormone receptors in human prostate cancer cell lines

We previously demonstrated the gene expression of two growth hormone (GH) receptor (GHR) isoforms in prostate cancer (PCa) patient tissues and human PCa cell lines. In that initial study, we characterized LNCaP cell GH binding characteristics to GHR and its activation of relevant signal transduction pathways. We now show that GH binding to GHR and GHR mRNA expression in the cell lines studied are hormonally regulated. In the androgen-dependent LNCaP cells, the potent, specific and stable androgen analogue, mibolerone, caused a time- and biphasic dose-dependent, stimulation of ¹²⁵I-hGH specific binding to cells cultured in serum-free medium (SFM); however, when LNCaP cells were grown in chemically defined Gc full medium, long-term mibolerone-induced inhibition was observed. This effect of Gc on the androgen response was mimicked by the triiodothyronine (T₃) contained in GC. In contrast, oestradiol (E₂), cortisol, and insulin-like growth factor (IGF)-I and -II all caused stimulation of GH binding. Furthermore, we also observed homologous and heterologous, isoform- and cell-type-specific regulation of GHR mRNA expression in all three cell lines. In LNCaP cells, GH caused stimulation of both GHR mRNA and of its exon 9-truncated isoform, GHR_tr; however, mibolerone, E₂ and T₃ all stimulated GHR_tr mRNA more potently than they did GHR. In androgen-independent PC3 cells, GH stimulated GHR_tr expression, but almost not GHR, while in contrast, in androgen-independent DU145 cells, GH caused a clear reduction in GHR and less so in GHR_tr. The differential regulation of GHR isoform gene expression in human PCa cell lines and of GHR functional capacity (GH binding), by hormones and growth factors relevant to disease progression, suggests that GHR may prove to be an additional therapeutic target to slow down/prevent progression of human prostate cancer.     

Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia

Purpose We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage.Methods Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6–15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators.Results Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively.Conclusion Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.     

Impact of transrectal prostate needle biopsy on erectile function: Results of power Doppler ultrasonography of the prostate

We evaluated the impact of transrectal prostate needle biopsy (TPNB) on erectile function and on the prostate and bilateral neurovascular bundles using power Doppler ultrasonography imaging of the prostate. The study consisted of 42 patients who had undergone TPNB. Erectile function was evaluated prior to the biopsy, and in the 3rd month after the biopsy using the first five-item version of the International Index of Erectile Function (IIEF-5). Prior to and 3 months after the biopsy, the resistivity index of the prostate parenchyma and both neurovascular bundles was measured. The mean age of the men was 64.2 (47–78) years. Prior to TPNB, 10 (23.8%) patients did not have erectile dysfunction (ED) and 32 (76.2%) patients had ED. The mean IIEF-5 score was 20.8 (range: 2–25) prior to the biopsies, and the mean IIEF-5 score was 17.4 (range: 5–25; p < 0.001) after 3 months. For patients who were previously potent in the pre-biopsy period, the ED rate was 40% (n = 4/10) at the 3rd month evaluation. In these patients, all the resistivity index values were significantly decreased. Our results showed that TPNB may lead to an increased risk of ED. The presence of ED in men after TPNB might have an organic basis.     

Nested RT—PCR方法测定PSM诊断前列腺癌的临床意义

采用巢式转录聚合酶链（Nested RT-PCR）方法,对31例前列腺癌患者和35例对照组的外周血及前列腺癌组织中的前列腺特异膜抗原（PSM）mRNA 的表达进行测定。结果显示,前列腺癌组外周血PSMmRNA术前总检出率为61．29％,术后为58．06％;3例骨转移者为阳性。前列腺癌组织均为阳性。对照组PSM mRNA均为阴性。认为PSM检测有助于前列腺癌的早期诊断和治疗,对预测其转移和血行播散具有特异性和敏感性。