Immunohistochemical study of metallothionein in normal and benign prostatic hyperplasia of human prostate.

Metallothionein (MT) in the human prostate gland was examined. Prostatic tissues were obtained from patients of urinary bladder cancer who had received radical cystoprostatectomy. MT content was 99.3 micrograms/g wet tissue (w.t.) in the peripheral zone (PZ), 12.0 micrograms/g w.t. in the preprostatic region (PR), 7.3 micrograms/g w.t. in the central zone (CZ), 6.8 micrograms/g w.t. in the anterior fibromuscular stroma, and 29.5 micrograms/g w.t. in benign nodular hyperplasia (adenoma) by radioimmunoassay. Immunohistochemical study demonstrated that MT was localized in the cytoplasm, nuclei of glandular epithelia, and secretory products. In general, a positive immunoreaction was strong in PZ and weak in CZ. It is considered that glandular epithelial cells in PZ, PR, CZ, and adenoma may react differently to heavy metals, e.g., zinc and cadmium.     

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.     

Dysregulation of Dkk-3 expression in benign and malignant prostatic tissue

BACKGROUND: The Dickkopf (Dkk) family comprises four members Dkk-1, -2, -3, and -4. Dkk-3, the most divergent family member, unlike the others does not modulate Wnt signaling. Dkk-3 is proposed to function as a secreted tumor suppressor since it is downregulated in a number of cancer cells and prostate cancer tissue and thus may be a promising candidate molecule for therapeutic interference. METHODS: The in situ tissue localization of Dkk-3 protein in normal prostate (NP), benign prostatic hyperplasia (BPH), and prostate carcinoma (PCa) was investigated by immunohistochemistry (IHC)/immunofluorescence. In addition, biological function of Dkk-3 in terms of proliferation and viability was evaluated in primary prostate basal epithelial cells (PrEC), stromal cells (PrSC), and established human PCa cell lines by treatment with recombinant protein or by overexpression. RESULTS: Stimulation with purified recombinant protein and overexpression of Dkk-3 did not significantly alter in vitro cell proliferation in any primary or tumor cell line evaluated. Dkk-3 was expressed in both the basal and secretory epithelium of NP. In BPH expression was restricted to defined basal cells and was absent in tumor cells of high grade PCa. In contrast to normal prostatic tissue, Dkk-3 was upregulated in subglandular blood vessels of BPH and in the reactive stroma of PCa tissue. CONCLUSIONS: Our results indicate that Dkk-3 expression in the normal epithelium of the prostate is lost during benign and malignant transformation and differentiation processes. The loss of expression seems to be counterbalanced by upregulation of Dkk-3 expression in the blood vessels of the remodeled tissue.     

The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer

OBJECTIVE: To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS: The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS: Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS: TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.     

Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma

7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 n m of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.     

Proliferative responses of cultured rat prostate and human benign prostatic hyperplasia

The proliferative responses of rat prostate and human benign prostatic hyperplasia have been followed in organ culture using [125I] iododeoxyuridine uptake to monitor DNA synthesis. In serum-free cultures, testosterone induced a marked increase in DNA synthesis (three-fold) in 4- to 6-month-old rat prostates at concentrations of 4 x 10(-9) to 4 x 10(-6) M, whereas in greater than 12-month-old rat prostates the response was less marked. Human benign prostatic hyperplasia also showed an increased uptake at similar testosterone concentrations and of a similar magnitude to the response of greater than 12-month-old rat prostates. At 10(-5) M DNA synthesis was markedly suppressed in cultures of both rat and human prostate. The proliferative response of human benign prostatic hyperplasia increases up to days 3 to 4 in culture and then declines in both control and hormone-treated groups and may represent repair processes which appear to be hormone dependent.     

Caspase 3 expression is altered in a coculture model of neuroblastoma

BACKGROUND: Previously, we demonstrated that neuroblastoma cells cocultured with hepatocytes are protected from apoptosis, while apoptosis is upregulated in the hepatocytes. The mechanisms responsible for these findings are unknown. We hypothesize that caspase 3, a cysteine protease central to the apoptotic pathway, will be altered in this coculture model that simulates metastatic neuroblastoma. METHODS: Control human neuroblastoma cells and liver cells are plated in standard media. For the study group, a noncontact, coculture system is used. Hepatocytes are plated on cell culture inserts, placed above a growing layer of neuroblastoma cells, and incubated. Activated caspase 3 is measured after 1, 2, 3, or 4 days. RESULTS: Activated caspase 3 levels are significantly decreased in the cocultured neuroblastoma cells on days 2, 3, and 4. Conversely, cocultured hepatocytes have a significant increase in caspase 3 activation at all time periods, with the largest difference seen after 1 day in coculture. CONCLUSIONS: The capacity for neuroblastoma to differentially alter caspase 3 activation may provide a significant survival advantage for the neuroblastoma cells in metastatic environments. Understanding the mechanisms for this altered regulation may lead to improved and better targeted therapy for this malignancy.     

Expression of basic fibroblast growth factor mRNA in benign prostatic hyperplasia and prostatic carcinoma

In our previous work we demonstrated that prostate-derived growth factor (PrGF) is homologous to basic fibroblast growth factor (bFGF), not acidic fibroblast growth factor (aFGF). Using Northern blot analysis we now show that the messenger RNA for bFGF but not aFGF is expressed in benign prostatic hyperplastic (BPH) tissue as well as in carcinoma of the prostate (CAP). This not only corroborates our previous results, but suggests that PrGF is produced locally and not merely stored in the prostate. The demonstration of local production of bFGF by prostate tissue may indicate that this growth factor plays a role, either alone or in conjunction with other factors, in the etiology of benign hyperplasia or prostatic cancer.     

良性前列腺增生中的高度前列腺上皮内瘤初步观察

本文观察良性前列腺增生（BPH）中的高度前列腺上皮内瘤（HPIN）现象。回顾性分析54例分析耻骨上前列腺摘除术患者的前列腺标本切片。统计其中HPIN的发生率,并结合患者术前PSA值,分别HPIN与非HPIN之间的血PSA值差别。结果发现54例患者中22例有HPIN表现,占总数的40．7％。HPIN组与非HPIN组之间的血PSA值无显著性差异。在本组BPH患者中,HPIN表现占有一定比例,因此认为HPIN现象并非前列腺癌（Pca）专用。本组中HPIN比例偏高与患者平均年龄较大有关。本研究通过血PSA测定尚无法简单区分HPIN和非HPIN。对于HPIN现象,一方面应提高警惕,密切随访;另一方面也不必盲目悲观,毕竟HPIN只是一种前列腺癌的前驱表现,而并不等于同于前列腺癌。     

经尿道悬浮离子电切治疗BPH

目的:探讨经尿道悬浮离子电切前列腺的临床安全性与有效性。方法:采用悬浮离子切割系统行经尿道前列腺电切术。结果:本组52例BPH患者均成功行经尿道悬浮离子电切术。术中凝固止血效果满意,无前列腺电切综合征;术后膀胱冲洗0.5～2天,留置尿管2～5天,术后1～12个月内随访,国际前列腺症状评分由(28.6±3.0)分降至(8.5±4.5)分。生活质量评分由(5.5±0.5)分降至(1.2±0.5)分,剩余尿量由(72±24)ml减少至(20±8)ml,最大尿流率由(6.8±2.2)ml/s升至(25.3±3.4)ml/s。结论:经尿道悬浮离子电切治疗BPH具有安全性高,并发症少,近期疗效确切等优点。     

AgNOR staining in benign hyperplasia and carcinoma of the prostate.

We have modified existing techniques for silver staining of nucleolar organizer regions of intact interphase cells by hypotonic swelling and by formic acid treatment to reduce background staining. This allowed the microscopic identification and counting of individual AgNORs in the nucleoli. The method was used on nine adenomatous prostatic samples (including one of normal prostate tissue outside a localized tumor) and on seven prostatic adenocarcinomas. In general, the adenomatous samples displayed fewer AgNORs (mean 13 dots/cell) than did the carcinomas (mean 24 dots/cell). Although no cells with very high AgNOR counts were found in specimens from nonmalignant tumors, two of the adenomatous prostates did have AgNOR profiles that to a large extent overlapped with those of carcinomas. A highly differentiated carcinoma (of which only very small amounts were present in the sample) had low AgNOR counts. The three moderately differentiated carcinomas had more silver-positive material than the nonmalignant prostates but less than the three poorly differentiated carcinomas. The latter tumors also had a substantial proportion of cells with greater than 60 AgNOR counts, something that was never seen in carcinomas with higher differentiation. The data indicate that analysis of silver staining-positive material in intact interphase cells may help distinguish between benign and malignant prostatic tumors and between highly malignant and low malignant carcinomas.     

选择性绿激光汽化术治疗良性前列腺增生症

目的探讨选择性绿激光汽化术(PVP)治疗良性前列腺增生(BPH)的方法并评价其疗效。方法采用连续硬膜外麻醉,应用PVP治疗180例BPH患者。使用Laserscope公司生产的绿激光系统,平均功率80W,治疗时间20~140min[(42.5±19.4)min)],能量值10.2~54.2万焦耳[(12.4±5.6)万焦耳],术后留置尿管1~5d。结果术后52例出现一过性的终末血尿,12例暂时性尿失禁,18例短暂性排尿困难,3例迟发性出血。随访3~6个月,术后最大尿流率(Qmax)、IPSS评分、膀胱残余尿量(BRU)均较术前明显改善(P<0.05)。结论PVP治疗BPH操作简单,安全可靠,并发症少,恢复快,是治疗BPH的理想方法。     

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.     

良性前列腺增生组织细胞外基质的研究

利用组织化学和免疫组织化学的方法系统地观察了细胞外基质成分Ⅰ、Ⅲ、Ⅳ型胶原和纤维粘连蛋白在正常前列腺和良性前列腺增生组织中的分布情况。结合计算机辅助图像分析方法对其表达量进行定量分析。结果表明，Ⅰ、Ⅲ型胶原主要分布于前列腺组织的间质部分，纤维粘连蛋白（ＦＮ）和Ⅳ型胶原除呈线状分布于基底膜外，间质中亦可见较多的ＦＮ和Ⅳ型胶原的表达。Ⅳ型胶原和ＦＮ在正常前列腺组织中的相对含量分别为０．１０１±０．０３１和０．０８６±０．０２７，它们在ＢＰＨ组织中的相对含量则分别为０．１６５±０．０３４和０．１１０±０．０２２，两组之间有显著性差异（Ｐ＜０．０１）。     

不同前列腺组织中雄激素受体的表达研究

目的:研究雄激素受体(AR)在正常前列腺、良性前列腺增生(BPH)和前列腺癌(PCa)组织中的表达,探讨AR与BPH和PCa的关系。方法:采用实时定量PCR、免疫荧光和组织蛋白电泳方法,分析15例正常前列腺、20例BPH与40例PCa标本中AR的表达情况。结果:实时定量PCR和组织蛋白电泳检测BPH组织与正常前列腺组织中AR的表达量差异无统计学意义(P>0.05)。但免疫荧光检测发现BPH组织中AR蛋白表达量增高。3种方法检测PCa组织中AR表达量较正常前列腺组织和BPH组织增高(P<0.05)。高分化PCa的AR表达比低分化PCa高(P<0.05)。随着临床分期的增高,AR的表达降低(P<0.05),激素非依赖性前列腺癌(HRPC)组织中AR表达最低。结论:AR在PCa组织中的表达较正常前列腺和BPH组织中增高,AR的表达与PCa的分级、分期相关。