Human Benign Prostatic Hypertrophy Research Articles

Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis.

Telomere shortening has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere shortening is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high-grade androgen receptor-negative adenocarcinomas, which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate glands with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT. IMPLICATIONS: Our results demonstrate that the telomere DNA damage response regulates BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression.

Abstract 1464: Telomere DNA damage links benign prostatic hypertrophy, intraepithelial neoplasia, and prostate cancer

Abstract Telomere DNA damage has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere DNA damage is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. TRF2 expression was deleted in prostate epithelium using conditional null mutant mice. TRF2 expression in prostate glands and tumors was determined by quantitative reverse transcription polymerase chain reaction. Histopathology was analyzed by hematoxylin and eosin staining. Telomere DNA damage response was determined by 53BP1 localization at telomeres, and by ATM/Chk2/p53 western blotting. Androgen receptor, smooth muscle actin, keratin expression, and proliferation index were determined by immunohistochemistry. Cellular senescence was determined by histone H3K9me3 immunofluorescence microscopy. Apoptotic cells were determined by TUNEL analysis. Telomerase activity was determined by telomere repeat amplification protocol. Alternative lengthening of telomeres was determined by PML localization at telomeres and telomere circular DNA analysis. Genomic instability was determined by metaphase telomere fluorescence in situ hybridization. Sca1+/CD49f+ prostate cancer stem cells were sorted by flow cytometry and transplanted subcutaneously with urogenital sinus mesenchyme cells in Matrigel. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high grade androgen receptor negative luminal adenocarcinomas which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate tumors with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT. Our results demonstrate that the telomere DNA damage response links BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression. Citation Format: Jianchun Wu, David L. Crowe. Telomere DNA damage links benign prostatic hypertrophy, intraepithelial neoplasia, and prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1464.

Triptolide inhibits benign prostatic epithelium viability and migration and induces apoptosis via upregulation of microRNA-218.

Benign prostatic hypertrophy (BPH) has become a troublesome disease for elder men. Triptolide (TPL) has been reported to be a potential anticancer agent. However, the potential effects of TPL on BPH have not been shown out. BPH-1 cells were treated with different concentrations of TPL and/or transfected with microRNA-218 (miR-218) inhibitor, pc-survivin, sh-survivin, or their corresponding controls (NC). Thereafter, cell viability was determined by CCK-8 assay. Cell migration was accessed by modified two-chamber migration assay. Cell apoptosis was checked by propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated Annexin V staining. In addition, messenger RNA (mRNA) and protein levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. BPH-1 cell viability and migration were significantly decreased, while cell apoptosis and expression of miR-218 were statistically enhanced by TPL (P < 0.05 or P < 0.01). However, downregulation of miR-218 increased cell viability and migration, while decreased cell apoptosis compared with the negative control group (P < 0.05 or P < 0.01). Furthermore, the expression of cell cycle–related proteins and cell apoptosis–related proteins were also led to the opposite results with NC. In addition, we found that miR-218 negatively regulated the expression of survivin (P < 0.01) and suppression of survivin significantly enhanced cell apoptosis (P < 0.01). Moreover, the results demonstrated that TPL could inactivate mammalian target of rapamycin (mTOR) pathway, while inhibition of miR-218 alleviated the effects. TPL inhibits viability and migration of BPH-1 cells and induces cell apoptosis and also inactivates mTOR signal pathway via upregulation of miR-218. This study provides evidence for the further studies representing triptolide as a potential agent in the treatment of human BPH.

Estramustine binding protein in human benign prostatic hypertrophy

Using a highly sensitive radioimmunoassay (RIA) of estramustine binding protein (EMBP) with the antibody raised against rat-EMBP, the concentration of EMBP in human benign prostatic hypertrophy (BPH) tissue was evaluated. Using mechanical separation procedure, EMBP was found significantly higher in the epithelium (10.7 ng/mg protein) than in the stroma (2.9 ng/mg protein). When human BPH was classified into glandular, fibromuscular and mixed type, the concentration of EMBP was the highest in glandular type (15.7 ng/mg protein) and the lowest in fibromuscular type (10.8 ng/mg protein).

Identification of α-1L and α-1A Adrenoceptors in Human Prostate by Tissue Segment Binding

Silodosin (KMD-3213 or [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]) (Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan) is a selective antagonist for alpha-1A and alpha-1L adrenoceptors. Using this tritiated ligand the 2 alpha-1 adrenoceptors were examined in binding studies with intact tissue segments and membrane preparations of human prostate, and compared with functionally identified alpha-1 adrenoceptor. Binding assays with tissue segments and membrane preparations of human prostate samples were performed using [3H]-silodosin and binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. [3H]-silodosin bound to intact segments and membrane preparations of human prostate with subnanomolar affinity. [3H]-silodosin binding sites in intact segments were divided into 2 distinct components with different affinities for prazosin and RS-17053 (N-[2(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl1H-indole-3-ethanamine hydrochloride) (Research Biochemicals International, Natick, Massachusetts), while binding in membrane preparations showed single high affinity for these drugs. [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations. In functional experiments silodosin and tamsulosin potently inhibited the contractile response to noradrenaline but prazosin, RS-17053 and BMY 7378 showed low antagonistic affinity. The current binding studies in human prostate samples clearly show that alpha-1L and alpha-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations. Also, alpha-1 adrenoceptors involved in the contractile response to noradrenaline are the alpha-1L subtype.

721Alterations in calcium-activated potassium channel expression in human prostate cancer

Duk Yoon Kim, Eun Kyoung Yang, Jung Wook Kim Department of Urology, Catholic University of Daegu School of Medicine, Department of Physiology, Kyungpook National University School of Medicine, Daegu, Korea Purpose: Recent studies have shown that potassium (K) and sodium channels are involved in prostate cell growth. However, a great many of the studies have been done in prostate cancer cell lines and there are only scant studies on prostate cancer and benign prostatic hypertrophy (BPH) tissue. The present study was aimed to evaluate the alterations of the calcium-activated K channel (KCa) expression in prostate cancer, and to compare them with the expression profiles in human BPH tissue to understand their potential role in the progression of prostate cancer. Materials and Methods: The prostate tissues obtained from radical prostatectomy (n=10) and transurethral resection of the prostate (n=18) were quickly frozen in liquid nitrogen for the RNA measurements. The protein and mRNA levels of the KCa subtypes and connexins were measured by performing immunoblot analysis and reverse-transcription polymerase chain reaction, respectively. Results: The mRNA levels of type 2 (SK2) and type 3 (SK3) small-conductance and large-conductance (BK) KCas in the prostate cancer tissues were decreased more than 50% compared with those in the BPH samples. In addition, the BK and SK2 protein levels in prostate cancer were also significantly lower than those in the BPH. As reported previously, the connexin 26 and 43 transcript signals in the prostate cancer were significantly reduced compared with those in the BPH samples. Conclusions: These results suggest that the impaired expression of KCas may have a role in tumor progression via aberrant and uncontrolled prostate cell growth. (Korean J Urol 2006;47:548-552) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

PROSTATIC CANCER/BENIGN PROSTATIC HYPERTROPHY. SUBCELLULAR DISTRIBUTION OF ESTRADIOL/ANDROGEN RECEPTORS

Six microsomal population of estradiol and androgen receptors have been characterized in human benign prostatic hypertrophy (BPH) and prostate cancer (PCa). Estradiol receptor (ER) and androgen receptors (AR) were extracted using 0.6 M KCL and determined by the dextran-coated charcoal method. ER and AR levels were smaller in BPH plasma membranes (PM) than in Pca cases. For functions 3, 4, 6, the ER values in PCa were 25-38% less with regard to BPH ER values. Whereas in PCa, AR values obtained in all fractions were higher when compared to BPH AR values. In benign prostatic hypertrophy and prostatic cancer, ER and AR levels were significantly higher in the nuclear fraction. In the nuclear fraction, ER and AR levels in BPH and PCa were significantly different. The subcellular distribution of AR and ER in BPH and PCa constitutes a reservation mechanism and processing a receptors for their continued growth.

Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture.

There is strong epidemiological evidence that prostate disease is significantly less prevalent in the Orient, where the intake of soy products is very high, than in the United States. We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human-patient benign prostatic hypertrophy (BPH) and prostate cancer tissue in three-dimensional collagen gel-supported histoculture. Surgical specimens of human BPH and cancer were histocultured for 5 days to study the effects of genistein on growth, as measured by inhibition of 3H-thymidine incorporation per microgram protein on day 5. Genistein in doses of 1.25-10 micrograms/ml decreased the growth of BPH tissue in histoculture in a dose-dependent manner, with little additional effect at higher doses. Prostate cancer tissue in histoculture was similarly inhibited by these doses of genistein. Genistein decreases the growth of both BPH and prostate cancer tissue in histoculture. The data suggest that genistein has potential as a therapeutic agent for BPH and prostate cancer.

Alpha-1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy tissue according to the affinities for prazosin.

A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. (1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.

Alpha‐1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy tissue according to the affinities for prazosin

BACKGROUND A novel classification of α-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH)tissue. METHODS Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS (1) Scatchard analysis showed a high-affinity site (Kd:27.18 ± 6.41 pM; Bmax:9.29 ± 0.98 fM/mg protein; mean ± SE) as α1H, and a low-affinity site (Kd:4088.0 ± 744.34 pM; Bmax:140.81 ± 19.98 fM/mg protein; mean ± SE) as α1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), α1 blocker group (n = 5), and antiandrogen group (n = 5), in either α1-high affinity or α1-low affinity subtype. (3) Phenoxbenzamine had different pKi value for the above two adrenoceptor subtypes. Scatchard analysis showed that α1-high affinity binding site disappeared in the presence of 1 μM of phenoxbenzamine, and the Kd and Bmax values in the prescence of 1 μM of phenoxybenzamine were almost identical to the α1-low affinity site of the two subtypes. CONCLUSIONS Human BPH tissue possesses both α1H-and α1L-adrenoceptor subtypes according to the affinities for prazosin, and only the α1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatent by α1 blocker may not change the conditons of α1-adrenoceptors in prostatic tissue.Prostate 31:216–222, 1997. © 1997 Wiley-Liss, Inc.

Role of m1 receptor-G protein coupling in cell proliferation in the prostate

The prostate gland from several animal species contains variable levels of muscarinic subtypes, but only the human prostate expresses significant levels of the m1 subtype. We studied muscarinic receptor activity in human benign prostatic hypertrophy (BPH) as well as several cell lines derived from prostate cancer. The BPH we studied expresses approximately 75% of the m1 receptor and undetectable levels of the other receptor subtypes whereas PC3 cells express only the m3 receptor subtype. DU145 and LnCaP cells express approximately equal levels of m1 and m3 receptor subtypes. Only the PC3 cells responded to carbachol with an increase in turnover of polyphosphoinositides, and none of the cell lines responded with effects on cAMP metabolism. Co-precipitation of receptors with heterotrimeric guanine nucleotide-binding regulatory proteins demonstrated interactions of the m1 receptors with Gi, Gq and G16 in BPH tissue and of the m1 and m3 receptors with Gi, Gq and G12 in PC3 and DU145 cells. Mitogen activated protein kinase (ERK) activity was seen in response to carbachol in PC3 and DU145 but not LnCaP cells. Finally, carbachol promoted cell proliferation in all three cell lines. Thus, there appears to be no consistent relationship between ERK activity, cell proliferation, and the subtype mediating the proliferative response, amongst these prostate cancer cell lines.

EFFECT OFSERENOA REPENSEXTRACT (PERMIXONR) ON ESTRADIOL/TESTOSTERONE-INDUCED EXPERIMENTAL PROSTATE ENLARGEMENT IN THE RAT

The effect of the lipidosterolic extract ofSerenoa repens(LSESR) on experimental prostate enlargement was investigated in three groups of rats: shams treated with LSESR (sham rats), castrated animals treated with estradiol and testosterone (castrated rats), castrated animals treated with estradiol/testosterone and treated with LSESR (castrated and treated rats). Following three months of continuous hormonal treatment, the weight of prostates in estradiol/testosterone-treated castrated rats was significantly increased in comparison with sham-operated rats. Such an increase started rapidly, reached a maximum by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate total weight induced by the hormone treatment was inhibited by administration of LSESR. Indeed, the weight was significantly lower at day 60 and day 90 for the dorsal and lateral regions of the prostate. The weight of the ventral region of the prostate was significantly lower after 30 and 60 days treatment with LSESR. These results demonstrate that administering LSESR to hormone-treated castrated rats inhibits the increase in prostate wet weight. This effect of LSESR may explain the beneficial effect of this extract in human benign prostatic hypertrophy.

Estradiol causes the rapid accumulation of cAMP in human prostate.

Androgens are widely acknowledged to be central to the pathogenesis of benign prostatic hypertrophy (BPH). However, BPH increases in prevalence as men age, at precisely the stage of life when plasma androgens are decreasing. The decrease in total plasma androgens is amplified by an age-related increase in plasma sex hormone-binding globulin (SHBG) that results in a relatively greater decrease in free androgens than in total androgens. In addition, estrogens have long been suspected to be important in BPH, but a direct effect on the human prostate has never been demonstrated. We present data that are consistent with a role for estradiol, and for a decrease in androgens and an increase in SHBG, in the pathogenesis of BPH. We show that estradiol, but not dihydrotestosterone, acts in concert with SHBG to produce an 8-fold increase in intracellular cAMP in human BPH tissue. This increase is not blocked by an antiestrogen and is not provoked by an estrogen (diethylstilbestrol) that does not bind to SHBG, thus excluding the classic estrogen receptor as being operative in these events. Conversely, dihydrotestosterone, which blocks the binding of estradiol to SHBG, completely negates the effect of estradiol. Finally, we demonstrate that the SHBG-steroid-responsive second-messenger system is primarily localized to the prostatic stromal cells and not to the prostatic epithelial cells. Thus, we have shown a cell-specific, powerful, nontranscriptional effect of estradiol on the human prostate.

High-intensity focused ultrasound in the treatment of prostatic tissue

Objective. Beginning in 1987, high-intensity focused ultrasound was investigated in the canine model to determine the feasibility of destroying prostate tissue. After demonstrating the ability to ablate prostate tissue reliably in a canine model, a 15-patient pilot clinical study was undertaken at Indiana University in the fall of 1992. This pilot study was undertaken to assess the safety in the human clinical situation, as well as to give some early efficacy results. Methods. The early canine feasibility studies were conducted via a suprapubic extracorporeal approach using two separate transducers, one for imaging and the other for therapy. Subsequent to this, a transrectal probe, which had the dual capability of both imaging and therapy, was developed and used to treat canine prostates in a formal, “good laboratory practice” study to determine the safety of this technology prior to beginning treatment of human benign prostatic hypertrophy. Results. The formal canine studies demonstrated that prostatic tissue could be reliably ablated in the therapy zone. The dosimetry and duty cycle required to ablate canine prostatic tissue effectively was also determined in this study. The study also demonstrated that the prostatic tissue could be ablated without injury to the intervening rectal tissue or periprostatic tissue. The human pilot study has also demonstrated safety of high-intensity focused ultrasound, as well as early efficacy. conclusions. These early clinical results are encouraging, but assessment of efficacy will require a randomized study comparing high-intensity focused ultrasound to sham and to transurethral prostatectomy. This multicenter trial is currently planned.

Immunohistochemical evaluation of estrogen receptor status in benign prostatic hypertrophy and in prostate carcinoma and the relationship to efficacy of endocrine therapy.

The levels of estrogen receptors in human benign prostatic hypertrophy and in various pathological classifications of prostate carcinoma were assessed using immunohistochemical methods. All cases of benign hypertrophy showed elevated levels of estrogen receptor, while receptor-positive cells were detected in only 48% of carcinomas, indicating a negative correlation between receptor status and malignancy. Furthermore, the prognosis for effective endocrine therapy was poor in cases where tissues demonstrated low or negative receptor levels. In addition, the estrogen receptor status was compared to cell kinetic index such as proliferating cell nuclear antigen and argyrophilic staining of the nuclear organizer region.

High-Intensity Focused Ultrasound in the Treatment of Prostatic Disease

Beginning in 1987, high-intensity focused ultrasound was investigated experimentally in a canine model to determine whether or not prostate tissue could be destroyed with good aiming and control. Subsequently a transrectal probe was developed and used to treat canine prostates in a formal study to determine whether or not this technology could be used to treat human benign prostatic hypertrophy. Next, after FDA approval, 15 patients were treated at Indiana University in the fall of 1992. Both canine and human studies have shown that high-intensity focused ultrasound administered via a transrectal probe is capable of creating prostate lesions without injury to intervening and surrounding tissue.

Purification and Properties of Gamma-Glutamyl Transpeptidase from the Tissue of Human Benign Prostatic Hypertrophy

The enzyme of gamma-glutamyl transpeptidase was purified to homogeneity from the tissue of human benign prostatic hypertrophy and its enzyme properties were studied. The enzyme activity was detected mainly in the luminal border of the epithelium lining ducts by histochemical staining. The enzyme was purified 759-fold that of the crude extract. The specific activity of the purified enzyme was 79,900mU/mg protein. The following enzyme properties were obtained: Michaelis constant of the enzyme was 0.83mmol/1. The molecular weight was 72kDa, consisting of two subunits, 45kDa and 27kDa. The isoelectric point of the enzyme was 8.5. The optimum pH ranged from 8.2 to 8.5. By Concanavalin A-sepharose affinity chromatography, more than 60% of the enzyme activity was eluted in the weakly bound fraction, suggesting biantennary complex sugar chain was the major type among the asparagine-linked sugar-chains of the enzyme.

Analysis of the Androgen Binding in Human Benign Prostatic Hypertrophy

In order to delineate optimal conditions for the determination of androgen specific binding in human benign prostatic hypertrophy tissues (BPH), extracts of these tissues were prepared using buffers of different compositions. The binding of 5 alpha-dihydrotestosterone (DHT) and of methyltrienolone (R 1881) was analyzed using agar gel electrophoresis. This method allowed the detection of 3 different high affinity tissular binding peaks with similar specificity. Moreover, the inhibition by each of the competitors was also the same for both ligands. It could be demonstrated that none of the observed peaks resulted from the binding of 1 of the ligands to sex hormone binding globulin (SHBG) or to a progesterone receptor. Hypotheses about the possible origin of these peaks are discussed.

Establishment of Monoclonal Antibody to Human Androgen Receptor and Its Clinical Application for Prostatic Cancers

Hybrid cell lines were prepared by the fusion of BALB/c myeloma NS-1 cells with the lymphocytes of BALB/c mice that were immunized with partially purified androgen receptor (AR) from human prostates. One of the clones, 5F4, was chosen for detailed specificity analysis. The avidin-biotin-peroxidase complex (ABC) procedure was used for immunohistochemical staining of the 5F4 monoclonal antibody. In human benign prostatic hypertrophy (BPH) tissues, cytoplasm and nuclei were stained. Of 16 prostatic cancer tissues, 2 were composed of AR-positive cells exclusively, 7 were composed of AR-negative cells, and 7 contained both AR-positive cells and AR-negative cells (mixed). Of nine cases that were AR-positive or mixed, seven cases responded to the hormone therapy, and two were not determined for responsiveness because the patients died early of other diseases. Of seven AR-negative cases, all but one inestimable case had no response to the hormone therapy. Immunohistochemical analysis of AR by using the monoclonal antibody 5F4, was a useful tool for determining androgen dependency of prostatic cancers.

491 - Serenoa Refens in the Treatment of Human Benign Prostatic Hypertrophy (BPH)

491 - Serenoa Refens in the Treatment of Human Benign Prostatic Hypertrophy (BPH)