An immunohistochemical technique for localization and semiquantitation of estramustine-binding protein (EMBP) in rat and human prostate

An immunohistochemical technique for determination of "estramustine-binding protein" (EMBP) in rat prostate is described. The localization and staining intensity of this protein were correlated to prostatic morphological structures in intact animals and at different time intervals after androgen deprivation by castration. EMBP was found almost exclusively in epithelial cells, while the fibromuscular stroma seemed to be negative. Intracellularly, immunostaining was confined to the cytoplasm, but was absent in nuclei. In intact rats, acinar lumina demonstrated heavy immunostaining, indicating secretion of EMBP. Orchiectomy caused a diminution of EMBP expression as well as secretion, suggesting that EMBP synthesis is under androgenic regulation. Human benign hyperplastic and cancerous prostatic specimens were also examined. All human specimens examined so far exhibited positive epithelial staining although of varying intensity. Therefore, this immunohistochemical technique may be used for studying the correlation of EMBP with tumor malignancy grade and for clinical investigations of how various treatments affect EMBP expression in prostatic carcinomas.     

Comparison of prostate secretory protein with prostate specific antigen and prostatic acid phosphatase as a serum biomarker for diagnosis and monitoring patients with prostate carcinoma

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP. © 1993 Wilcy-Liss, Inc.     

Biosynthesis and localization of inhibin in human prostate

Inhibin biosynthesis by human prostatic tissue was investigated in vitro. Serum levels of inhibin as well as tissue concentrations in different cells and zones of the normal and benign hyperplastic prostates were determined. Immunocytochemical localization of inhibin identified the involvement of epithelial but not stromal cells in the synthesis and release of prostatic inhibin into the circulation. The endocrine and paracrine functions of prostatic inhibin remain to be elucidated.     

Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer

BACKGROUND: S100A6 and S100A2 are members of the S100 family of calcium binding proteins, which are down regulated in prostate cancer, however the molecular mechanism(s) underlying their loss of expression is unknown. METHODS: The promoter and exon 1 region of the S100A6 and S100A2 genes was sequenced in bisulfite modified DNA from non-malignant, benign prostatic hyperplasia (BPH), malignant and metastatic prostate tissues and in cell lines. Immunohistochemistry was performed to correlate S100A2 expression with methylation status. RESULTS: S100A6 methylation was absent or occurred at isolated sites in 14/14 cases of non-malignant epithelium and 5/5 cases of BPH tissues, whereas methylation was seen in 14/27 (52%) cases of prostatic cancer (P<0.0001), 2/2 cases of metastatic cancer and in the CWR22 prostatic cancer xenograft. Critical CpG sites within the S100A2 promoter were methylated in LNCaP, LNCaP-LN3, and CWR22 cells but not in Du145, PC3 or BPH45 cells. In tissues, S100A2 methylation was seen in 32/34 (94%) cases of adenocarcinoma and 5/5 cases of metastatic cancer. However, S100A2 methylation was also seen in 9/12 (75%) cases of non-malignant tissues and in 5/5 cases of BPH. Immunostaining, showed absent S100A2 expression all 41 cases of prostatic cancer, whereas staining was seen in the basal cells of non-malignant epithelium. CONCLUSIONS: Loss of S100A6 and S100A2 proteins is frequent in human prostatic cancer. A major mechanism underlying the loss of S100A6 expression appears to involve promoter hyper-methylation. However, mechanisms other than methylation of the known promoter are involved in silencing S100A2 in the prostate.     

Pharmacologically induced ultrastructural and immunohistochemical changes in the prostate of the castrated dog

The effects of an aromatase inhibitor and of an antiandrogen on the ultrastructure and the expression of a secretory protein (acid phosphatase) and marker proteins for basal cells (keratin) and fibroblasts (vimentin) were studied in the prostate of castrated, androstenedione-treated dogs. Androstenedione treatment partially restored the normal appearance of the gland and also some secretory activity. In the central portion of the gland, basal cell hyperplasia developed instead of secretory activity after androstenedione treatment. Administration of the aromatase inhibitor reduced the number of secretory cells but did not completely suppress the latter. There was some proliferation of the connective tissue surrounding the atrophic acini. Combined treatment with aromatase inhibitor and antiandrogen resulted in a general atrophy of prostatic acini that was less intense relative to the changes observed after castration. Residual secretory activity, detected in specimens treated exclusively with aromatase inhibitor, were lacking after combined treatment. The influence of all regimens on the ultrastructure of smooth muscle cells was comparably discrete, whereas regional differences in the arrangement pattern of the epithelium and the fibromuscular stroma were impressive. The ultrastructural findings support previous results of a synergic inhibitory effect of aromatase inhibitor and antiandrogens on the canine prostate.     

Effects of the Bowman-Birk inhibitor on growth, invasion, and clonogenic survival of human prostate epithelial cells and prostate cancer cells

BACKGROUND: The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with demonstrated anticarcinogenic activity in both in vitro and in vivo systems. METHODS: The effects of BBI and BBI Concentrate (BBIC), a soybean concentrate enriched in BBI, on cell growth, invasion, and/or survival were evaluated by the sulforhodamine B assay, a colony formation assay, the trypan blue dye exclusion assay and an in vitro invasion assay. The cells used in these studies were normal human prostate epithelial cells and prostate epithelial cell lines derived from embryonic prostate tissue (267B1) or benign prostatic hyperplasia (BPH) tissue (BRF-55T) and human prostate cancer cells established by Ki-ras oncogene transfection of 267B1 cells (267B1/Ki-ras) or from metastatic lesions of human prostate cancer (LNCaP and PC-3). RESULTS: BBIC had a statistically significant inhibitory effect on the growth and clonogenic survival of BRF-55T, 267B1/Ki-ras, LNCaP, and PC-3 cells. BBI also inhibited the growth of LNCaP cells and the clonogenic survival of BRF-55T and 267B1/Ki-ras cells and decreased the ability of LNCaP cells to invade across reconstituted basement membrane (Matrigel) when PC-3 cell-conditioned medium was utilized as the chemoattractant. BBI or BBIC did not affect the growth of normal prostate epithelial cells. CONCLUSION: BBI and/or BBIC could be a useful agent for treatment of prostate diseases.     

经尿道激光切除前列腺增生70例报告

目的评价经尿道激光切除前列腺增生的治疗效果.方法自1993年11月至1996年7月经尿道激光治疗前列腺增生70例.术后随访3～32月,平均18.4月.结果手术前后国际症状评分分别为27.1±2.4和5.7±3.5(P＜0.01),最大尿流率为7.8±2.6和15.4±2.1(P＜0.01).治疗效果满意.结论经尿道激光治疗前列腺增生症安全、可靠,尤其适用于高龄体弱或合并其他疾病的前列腺增生患者.     

DNA synthesis in the canine prostate: effects of androgen and estrogen treatment

Canine prostatic DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA of tissue slices in vitro. Among untreated beagles, prostatic DNA synthesis rates in young dogs with normal prostates, young dogs with spontaneous benign prostatic hyperplasia (BPH), and old dogs with BPH were 676 +/- 186, 1,220 +/- 156, and 641 +/- 88 cpm/100 micrograms DNA/hr, respectively. Among 81 young beagles (intact or castrated) that had been treated for 4 months with various steroids, rates of DNA synthesis varied according to the type of hormonal treatment. Prostatic DNA synthesis (cpm/100 micrograms DNA/hr) was significantly different (P less than 0.001) for dogs treated with estradiol alone (1,658 +/- 221 cpm/100 micrograms DNA/hr; n = 10 dogs), androgen alone (testosterone, 5 alpha-dihydrotestosterone, or 5 alpha-androstane-3 alpha,17 beta-diol; 1,000 +/- 61 cpm/100 micrograms DNA/hr; n = 31 dogs). However, there was no correlation between prostate size and rate of DNA synthesis (cpm/100 micrograms DNA/hr). Although treatment with estrogen alone resulted in the highest rate of DNA synthesis, it produced squamous metaplasia and the smallest prostates; these results are indicative of a high rate of cell turnover. Comparing prostates that reached the same size following 4 months of treatment with androgen alone or androgen plus estrogen, the rate of prostatic cell turnover was lower in the androgen plus estrogen group. These results are interpreted to indicate an inhibitory effect of estradiol on the rate of cell death in the presence of androgens.     

MRS对可疑前列腺癌鉴别诊断价值的研究

目的探讨3.0T三维磁共振波谱成像(MRS)影像学检查对可疑前列腺癌患者鉴别诊断的价值。方法收集2013年1月至2014年4月在本院就诊怀疑前列腺癌并行MRI及MRS检查患者的临床资料,根据病理结果分为前列腺癌(Pca)组、前列腺增生(BHP)组。观察两组患者MRS参数胆碱(Choline,Cho)+肌酸(Creatine,Cre)/枸橼酸盐(Citrate,Cit)值(CC/C),并与病理Gleason评分(G)对照;评估MRS对Pca诊断效能,分析CC/C值与病理分级的关系。结果 32例Pca的CC/C平均值为2.52±1.42,而52例BHP的为0.70±0.77(P0.01),MRS对前列腺癌诊断效率:灵敏度87.5%、特异度86.3%、阳性预测值80%、阴性预测值91.6%;G≤7患者CC/C平均值为1.81±1.09,G7患者为3.38±0.98(P0.01)。结论 MRS的应用有助于对可疑前列腺癌患者进行鉴别诊断,且其参数对前列腺癌病理分级有参考意义。     

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。     

Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume,age, body mass index,and symptoms of prostatism

The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community-based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation. PSA and PSAD did not correlate with the body mass index. Weak correlations were found between PSA and age (r = 0.25; P < 0.001), PSAD and age (r = 0.17; P < 0.001) and between PSA and the total prostate volume (r = 0.58; P < 0.001). PSA did not correlate independently with age after adjustment for volume (P = 0.22). The finding that PSAD correlates with age (r = 0.17; P < 0.001) is partly explained by the incomplete volume adjustment of PSAD which is proved by the positive correlation between PSAD and prostate volume (r = 0.26; P < 0.001). In the main target age-range for prostate cancer screening there is a poor basis for the use of age-specific reference values or volume adjustment for PSA levels in order to increase the clinical usefulness of this serum marker. Comparison of the results of the present study and studies conducted in others regions shows that there may be significant differences in PSA values per age stratum. Further studies are needed to clarify the reasons for these differences. © 1995 Wiley-Liss, Inc.     

Natural history of human prostate gland: Morphometric and histopathological analysis of Japanese men

BACKGROUND: To clarify the pathology of the development of prostatic disorders such as inflammation, cancer, and hyperplasia, we compared histopathological findings of the prostate according to age group. METHODS: Whole-mount sections of prostates were used to assess the relationship between age and prostate weight (n=962), prostate histological composition in the transition zone (TZ) and in the peripheral zone (PZ) (n=68), prostate histopathological findings by zone (n=102), and comparison of latent tumor development by age group (n=1,815). RESULTS: A rapid increase in prostate weight from birth to the 20s was followed by a slow rise thereafter. Volume increases (P<0.01) were observed in all components of glandular epithelium, glandular lumen, and stroma in the TZ from the 40s to 70s inclusive. In the PZ, the epithelial and stromal volumes tended to decrease in an age-dependent manner (P<0.05). Calculi and lymphocyte infiltration were detected at a relatively early age, with a tendency towards an age-dependent increase. Glandular dilation and nodular hyperplasia were noted first in the 30s group, also with a tendency towards age-dependent increase. Latent tumors were first detected in the 30s group (5.6%), and slowly increased thereafter. CONCLUSIONS: There was an age-dependent trend towards prostate glandular dilation and prostate enlargement with inflammation. It was demonstrated that tumor and hyperplasia have a long natural history, usually starting in the fourth decade of life, accompanied by dynamic changes with age in glandular tissue composition as well as cell proliferation activity.     

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.     

Transurethral resection vs microwave thermotherapy of the prostate: a cost-consequences analysis

OBJECTIVE: To compare the costs and outcome of high-energy transurethral microwave thermotherapy of the prostate (HE-TUMT) with transurethral resection of the prostate (TURP), as the former is considered to be the best minimally invasive method for managing lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Between January 1996 and March 1997, 144 patients were randomized to treatment with HE-TUMT (78) using the Prostatron device and Prostasoft 2.5 software (EDAP Technomed, Lyon, France), or TURP (66). At baseline and during the annual follow-up, patients were evaluated by the International Prostate Symptom Score and uroflowmetry (maximum flow rate and postvoid residual volume). Kaplan-Meier survival analyses were used to calculate the cumulative risk of re-treatment. A cost-consequences analysis was performed based on the prospective measurement of healthcare use, with costs expressed as Netherland guilders (NLG). RESULTS: During a 3-year follow-up period, the mean (95% confidence interval) risk of re-treatment was 22.9 (12.5-33.2)% and 13.2 (4.5-21.9)% for HE-TUMT and TURP, respectively (P = 0.215). The mean direct cost of treatment was 3450 (3444-3456) and 6560 (5992-7128) NLG for HE-TUMT and TURP, respectively. The mean total (including re-treatments), discounted (4%) 3-year cost for the HE-TUMT and TURP group was 5300 (4692-5908) and 7800 (7118-8482) NLG, respectively. CONCLUSIONS: In this prospective randomized trial, HE-TUMT and TURP had a comparable 3-year risk of re-treatment. Healthcare expenditure on HE-TUMT, mainly because it is an outpatient treatment, was significantly lower than for TURP.     

Rotoresect for bloodless transurethral resection of the prostate: a 4-year follow-up

OBJECTIVE: To report the results and long-term follow-up of transurethral resection of the prostate (TURP) with a new resection device, the Rotoresect (Karl Storz, Tuttlingen, Germany). PATIENTS AND METHODS: Most endoscopic resection techniques for benign prostatic tissue aim for high ablation rates and minimal bleeding. Available resection electrodes are effective, but cause high blood loss (loop electrode), or less bleeding but poorer ablation rates (electrovaporization). To resolve these conflicts the Rotoresect was developed in 1995; it consists of a specially designed rotating resection electrode, driven by a micromotor, and a high-frequency current to enable simultaneous coagulation, vaporization and mechanical tissue removal during resection. To date, 84 patients with benign prostatic hyperplasia have had their prostate resected with this device (mean prostate size 46.0, sd 18.4 mL) and have been assessed for up to 4 years. RESULTS: During resection there was very little bleeding, with no significant changes in haemoglobin or sodium levels. The mean (sd) duration of catheterization was 1.4 (1.1) days; the urinary peak flow rate was improved from 9.7 (3.2) to 24.2 (8.23) mL/s and the residual urine volume reduced from 187.3 (109.6) to 22.7 (19.5) mL. The International Prostate Symptom Score and quality-of-life index were both improved, from 24.0 (7.5) to 4.1 (2.7), and 4.2 (3.2) to 0.8 (0.9), respectively. Overall the results were stable during the 4 years of follow-up. CONCLUSION: The Rotoresect combines the advantages of standard resection (high ablation rate) by actively rotating the resection electrode, and the haemostatic effect of electrovaporization (minimal blood loss) by simultaneous tissue coagulation and vaporization.     

TRPC6在人良性与恶性前列腺组织中的表达

观察瞬时受体电位通道C6（TRPC6）在人良性与恶性前列腺组织及前列腺癌细胞系中的表达,进一步探讨TRPC6的表达与前列腺癌分期、分级及激素依赖性的关系。利用免疫组织化学技术,检测发现45．0％的前列腺增生和86．6％的前列腺癌病例表达TRPC6,两者比较有显著性差异沪〈0．01）。TRPC6的表达与前列腺癌分级和前列腺外转移有关（P〈0．01）。前列腺癌分期增高,TRPC6表达增多,但在T2、T3和DT4期肿瘤病例中,TRPC6表达无显著差异。此外TRPC6在激素依赖性前列腺癌与激素非依赖性前列腺癌中的表达也无显著差异。应用RT-PCR及Westernblot,检测到TRPC6在前列腺癌细胞系中的表达。本研究发现,TRPC6在良性与恶性前列腺组织及前列腺癌细胞系中表达。TRPC6的表达与前列腺癌的组织分级、Gleason评分及前列腺外转移有关。     

前列腺癌与良性前列腺增生患者血清细胞因子差异的蛋白质组学研究

目的:探讨前列腺癌与BPH患者血清细胞因子的差异,为前列腺癌的早期诊断提供血清蛋白质组学依据。方法:应用细胞因子抗体芯片技术,对12例PSA在灰度范围内、经穿刺活检证实的前列腺癌和BPH患者的血清进行细胞因子芯片检测。结果:筛选出19种有明显差异表达的蛋白质(差异>1.5倍),其中前列腺癌组表达明显上调的有IL-3、IL-6、IL-16等16个细胞因子,表达明显下调的有Fas/TNFRSF6、TRALR-3、IGFBP-6等3个细胞因子。其中多个蛋白与细胞的转录、增殖、信号转导和细胞凋亡等生物过程有关。结论:细胞因子抗体芯片技术能够对较小血清样本同时检测多个指标,能够筛选出与癌细胞生物学行为密切相关的"关键细胞因子",有助于寻找用于前列腺癌早期诊断、判断疗效和预后的分子标志物。