bluuebunny/crossref_metadata_2025 huggingface dataset:
The alpha‐adrenoceptor subtype mediating the tension of human prostatic smooth muscle
Authors: Lepor Herbert , Tang Rui , Shapiro And Ellen
Published: February 2007

We have characterized the α1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the α1 subtype mediating the tension of prostatic smooth muscle. Fresh human tissue was obtained from 9 males between 50 and 80 years of age undergoing prostatectomy for BPH. The incubation of prostatic tissue with the irreversible antagonist chlorethyclonidine (CEC) resulted in an 80% reduction of the maximal contractile response produced by phenylephrine. However, the α1A‐selective antagonists WB‐4101 and 5‐methylurapidil (5‐MU) competitively inhibited the contractile response induced by phenylephrine, with KB = 2.64 and 4.46 nM, respectively, consistent with their affinity at the αA1 receptor subtype. The pharmacological profile of the α1‐receptor‐mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an α1A or α1B subtype. Alternatively, when compared with the properties of the cloned α1 receptors, our results suggest that the α1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine α1c receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the α1‐receptor subtype expressed by prostate smooth muscle, in order to develop subtype‐selective α1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH). © 1993 Wiiey‐Liss, inc.
Argyrophil crystalloids in adenocarcinoma of the prostate
Authors: Luna‐Moré Sebastian
Published: February 2007

Considering the advantages provided by the study of glandular secretions in proliferative diseases of the prostate, we carried out a study of 100 consecutive cases of benign hyperplasia (68), glandular dysplasia (12), and carcinoma (20). Samples were predominantly obtained by transurethral resection from patients whose mean ages were 64, 67, and 73.5 years, respectively. The paraffin embedded material was sectioned and stained with hematoxylin‐eosin, PAS‐diastase, PAS‐Alcian blue, methenamine silver, and Masson trichrome. Intraglandular secretion in normal, hyperplastic, and even neoplastic samples was predominantly neutral mucin, but in 2 cases of atypical adenomatous hyperplasia, and in all the carcinomas, we found acid mucin secretion. Holmes crystalloids were present in one case of nodular hyperplasia (1.4%), 2 cases of dysplasia (16.6%), and in 5 carcinomas (25%). As another manifestation of altered secretion, we also saw numerous needle‐shaped argyrophilic and isotropic crystalloids, not previously described, in 12 of the 20 carcinomas (60%). These crystalloids were exclusively found in the carcinomas, reached a size of 50 μ, and were completely differentiated from the Holmes crystalloids by their odd needleshape and their staining characteristics. © 1993 Wiiey‐Liss, Inc.
The costs of prostatectomy for benign prostatic hyperplasia
Authors: Weis Kathleen A. , Epstein Robert S. , Huse Daniel M. , Deverka Patricia A. , Oster Gerry
Published: February 2007

Using claims data for a 5% random sample of Medicare beneficiaries, we estimated the costs of surgical treatment for benign prostatic hyperplasia (BPH), including those related to the initial prostatectomy, the treatment of postsurgical complications, and reoperation within one year. We identified 14,480 men who underwent prostatectomy for BPH during 1986–1987, including 13,730 transurethral and 750 open procedures. Mean total inpatient costs (including all hospital charges and professional service fees) for these procedures were estimated to be $6,501 and $10,223, respectively. Among patients who underwent transurethral and open prostatectomy, we identified 938 (6.8%) and 39 (5.2%) individuals who had at least one readmission for postsurgical complications or reoperation. Total expected costs of transurethral and open prostatectomy, inclusive of readmissions for complications and reoperations within one year, were estimated to be $6,823 and $10,477, respectively. Our study indicates the economic burden represented by surgical treatment of BPH. © 1993 Wiley‐Liss, Inc.
Beta‐microseminoprotein immunoreactivity as a new prognostic indicator of prostatic carcinoma
Authors: Hyakutake Hiroyuki , Sakai Hideki , Yogi Yasuo , Tsuda Ryouichi , Minami Yuzo , Yushita Yoshiaki , Kanetake Hiroshi , Nakazono Ichiro , Saito Yutaka
Published: February 2007

Human beta‐microseminoprotein (β‐MSP), isolated from seminal plasma, is one of the proteins secreted by the prostate gland. To determine whether the β‐MSP immunoreactivity can be a prognostic indicator of prostatic carcinoma, the 3‐MSP immunohistochemical distribution has been examined in needle biopsy specimens taken from 96 patients with prostatic carcinoma. Although no significant correlation was found between the β‐MSP immunoreactivity and the histological grade (Gleason score), patients with a positive β‐MSP expression had a significantly better prognosis than those with a negative 3‐MSP expression (P= 0.01). Further, a multivariate analysis of six possible parameters (age, clinical stage, histological grade, serum prostatic acid phosphatase, β‐MSP immunoreactivity, and the type of initial treatment) has shown the difference in the β‐MSP immunoreactivity to be a significant, independent, prognostic indicator of prostatic carcinoma (P= 0.04). © 1993 Wiley‐Liss, Inc.
Effect of p‐Nitrophenyl‐β‐D‐xylopyranoside (β‐D‐xyloside) on the androgen‐induced growth of the lateral prostate of the prepubertally castrated guinea pig
Authors: Wong Y. C. , Chan L.
Published: February 2007

The aim of this study was to examine the effects of β‐D‐xyloside (XYL), a compound which interferes with stromal proteoglycan (PG) synthesis, on androgen induced growth of the lateral prostate (LP). Young male guinea pigs were castrated at 3 weeks of age and divided into three groups 6 weeks after castration. In group one, the animals were injected subcutaneously daily with 80 mg/kg of XYL, followed 3 days later by a daily dose of 10 mg/kg of dihydrotestosterone (DHT) for 2 more weeks. The second group served as control and received DHT only. In the third group, animals were treated first with XYL, like those in group one, and then followed by DHT alone for 2 weeks to check reversibility of the XYL effect. At the end of the experiment, the lateral prostate was removed and processed for morphological and cytochemical examination. The results showed that XYL inhibited the DHT stimulated growth of the lateral prostate. The fibroblasts showed a dilated granular endoplasmic reticulum filled with granular substances. In the interstitial spaces, there was a drastic increase in Cuprolinic Blue (CB) positive filaments and polygonal granules believed to be PGs or glycosaminoglycans (GAGs). Their number was much greater than the control. The distribution and density of the collagen fibers appeared similar to the control. The secretory alveoli were lined by epithelium with few secretory granules of low electron density and a larger number of clear vesicles. There was a slight reduction in glycoconjugate reactivities in the epithelial cells. The lectin binding patterns and the structural features were comparable between the control and recovery groups, indicating the XYL effects were reversible. The results suggest that stromal PG biosynthesis may play a role in epithelial function and an altered stromal matrix would hamper the effects of DHT on the target organ. © 1993 Wiley‐Liss, Inc.
Suppression of plasma testosterone and prostate carcinoma size by a redox‐based, brain‐targeted estrogen delivery system in the rat
Authors: Rahimy Mohamad H. , Bodor Nicolas , Simpkins James W.
Published: February 2007

Studies were undertaken to examine the effects of an estradiol‐chemical delivery system (E2‐CDS) or castration (CAST) on plasma testosterone (T) and growth of the Segaloff 11095 carcinoma. Fischer 344 rats were implanted subcutaneously with the Segaloff 11095 tumor and tumor growth was monitored thereafter. After optimal tumor growth, when the average tumor size was ∼25 × 15 mm (length × width; 4–5 g wet weight), rats were randomized into (1) testis‐intact controls; (2) CAST; (3) intact + E2‐CDS groups (rats received weekly injection of the E2‐CDS at 0.5 mg/kg). Animals were killed 7 or 14 days after the initiation of treatments. Blood and tissue samples were collected for subsequent analysis. Plasma T levels were suppressed by 98% and 97% through 14 days after CAST or E2‐CDS treatment. CAST increased plasma gonadotropin (LH) concentrations, while E2‐CDS reduced LH compared to intact control levels. E2‐CDS treatment increased plasma E2 levels to 24 (one injection) or 75 pg/ml (two injections) at 7 or 14 days, respectively. E2‐CDS, given once a week for 2 consecutive weeks, resulted in a decreased growth of the prostate tumor by 61%, while CAST reduced the weights of these tumors by only 20%. In response to E2‐CDS (one or two injections), weights of the in situ ventral prostate and seminal vesicles were significantly reduced by 70% and 50%, respectively, in tumorbearing rats. Similarly, CAST reduced the weights of these tissues by 80% (prostate) or 52% (seminal vesicle) at 7 or 14 days after treatment. Pituitary weight increased, while testes weight decreased by 20% with two injections of E2‐CDS, compared with intact control rats. Collectively, these data indicate that E2‐CDS is effective in reducing the growth rate of prostatic tumors in the rat. © 1993 Wiley‐Liss, Inc.
p53 oncogene mutations in three human prostate cancer cell lines
Authors: Carroll Alan G. , Voeller H. James , Sugars Lavencia , Gelmann Edward P.
Published: February 2007

p53 gene structure and chromosome 17p alleles were studied in the three human prostate cancer cell lines, LNCaP, DU‐145, and PC‐3. Our laboratory has two separate culture lines of the LNCaP human prostate cancer cells. One strain, LNCaP‐GW, had a mutation in one of two alleles at position 273 (arg > his). This mutation could not be detected in a second strain of LNCaP, LNCaP‐ATCC. Immunohistochemical staining for P53 protein in the cell lines indicated that protein overexpression in LNCaP was heterogeneous, even in clonal isolates derived from LNCaP‐GW that contained the codon 273 mutation in every cell. We also performed in vitro and in vivo growth analysis to compare the LNCaP‐GW and LNCaP‐ATCC cells. LNCaP‐GW grew more rapidly than LNCaP‐ATCC in vitro. However, LNCaP‐ATCC formed tumors efficiently when inoculated into nude mice, whereas LNCaP‐GW formed tumors much less efficiently. Consideration must be given to the notion that some of these p53 mutations arose during in vitro passage. We also confirmed published findings with two other human prostate cancer cell lines. In DU‐145, two mutations were found in the p53 gene. A mutation at codon 274 (pro > leu) and a second mutation at codon 223 (val > phe) were present. PC‐3 cells were hemizygous for chromosome 17p. The single copy of the p53 gene had a base pair deletion at codon 138 that generated a frame shift and a new in‐frame stop codon at position 169. © 1993 Wiley‐Liss, Inc.
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
Authors: Huang Chia‐Ling , Brassil Diane , Rozzell Monica , Schellhammer Paul F. , Wright George L.
Published: February 2007

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.
Heat shock protein response in a prostate tumor model to interstitial thermotherapy: Implications for clinical treatment
Authors: Paulus J. A. , Tucker R. D. , Flanagan S. W. , Moseley P. L. , Loening S. A. , Park J. B.
Published: February 2007

Hyperthermia is being utilized individually and in conjunction with other therapies in treating malignant and benign tumors, though few studies have examined cellular effects of elevated temperatures in the prostate model. Highly conserved proteins of the 70 kDa heat shock protein family (HSP 70) are produced in response to environmental stresses, including heat, and are found in all organisms. HSPs are an indicator of cell damage, are associated with thermotolerance, and provide cells with transient resistance to subsequent thermal challenges. Transient thermotolerance is important in the determination of temperature, duration, and sequencing for treatments. This preliminary study analyzes the HSP 70 response of the Dunning R3327 adenocarcinoma model to a single 50°C 1 hr treatment. Elevated HSP levels were found between 10 and 16 hr, returning to baseline by 24 hr. As some fractions of the cells are able to produce HSP 70 following treatment, the data suggest that currently utilized clinical temperatures (42–46°C) administered for 1 hr are inadequate. HSP levels in response to hyperthermia, radiation, and chemotherapy may be useful in finding optimal treatment regimens for prostate cancer. © 1993 wiley‐Liss, Inc.
Effects of cis‐4‐hydroxy‐L‐proline on the androgen‐lnduced growth of the prostate of the prepubertally castrated guinea pig
Authors: Wong Y. C. , Chan Franky L.
Published: February 2007

The present study examined the effects of cis‐4‐hydroxy‐L‐proline (CHP), a proline analog, on the androgen‐induced growth of the lateral prostate of prepubertally castrated guinea pigs. Prepubertal male guinea pigs were castrated at the age of 3 weeks and allowed to recover completely before subjection to an experimental regime to alter the stromal collagen synthesis by CHP. The animals were kept on a special proline‐deficient diet (PDD) for a week before the subcutaneous injection of CHP (200 mg/kg/day) for 3 days, followed by a combined injection of CHP and dihydrotestosterone (DHT) (10 mg/kg/day) for 10 days. Control animals were injected with saline and DHT only. At the end of the experiment, the lateral prostate was removed and examined by 1) conventional transmission electron microscopy (TEM), 2) staining of proteoglycans (PGs) by Cuprolinic Blue (CB) using the critical electrolyte concentration (CEC) method, 3) carbohydrate and lectin histochemistry, and 4) electron microscopy (EM) lectin‐gold labelling. The results showed that the wet weight of prostate from CHP‐treated animals was significantly lower than the control and recovery groups. The epithelium was low columnar with an obvious increase in intercellular spaces and number of basal cells. The glandular cells showed little secretory activity with a decrease in number of granular endoplasmic reticulum (GER) profiles, secretory granules, and a small Golgi apparatus. The stroma was composed of stromal cells separated by large intercellular spaces with very sparse collagen fibrils, and a decrease in stromal PGs especially those PGs normally associated with collagen fibrils. CHP treatment also caused perturbation and disorganization in the epithelial basement membrane. The results suggested that stromal collagen is essential in mediating the response of glandular cells to DHT stimulation. Defective stromal collagens hamper the responsiveness of prostatic gland to androgen. © 1993 Wiley‐Liss, Inc.
Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion
Authors: Decensi A. , Torrisi R. , Pensa F. , Padovani P. , Marroni P. , Boccardo F.
Published: February 2007

The nonsteroidal androgen‐receptor antagonist nilutamide has previously been shown to inhibit adrenal androgen steroidogenesis in patients with prostatic carcinoma treated in combination with an LHRH agonist. In order to understand better the mechanisms subserving this observation, we have studied the effects of nilutamide alone on the serum concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), and DHEA‐sulphate (DHEA‐S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D‐Trp‐6‐LHRH. In addition, the adrenocorticotropic hormone (ACTH)‐stimulated adrenal response and the thyrotropin releasing hormone (TRH)‐stimulated prolactin (PRL) response observed in the patients treated with nilutamide were compared with a control group of healthy age‐matched controls. No significant variation in the basal concentrations of adrenal androgens occurred either within or between both treatment groups. In response to ACTH, a decreased 17‐α hydroxyprogesterone (17‐OHP) accumulation and an augmented A/17‐OHP ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the partial removal of the 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PRL levels were not affected by the antiandrogen, but the response to TRH was increased. We conclude that no significant inhibition of adrenal androgen secretion occurs after nilutamide or LHRH agonist treatment. Rather, administration of the antiandrogen alone may partially remove the physiologic decrease in adrenal androgen secretion observed in the elderly. © 1994 Wiley‐Liss, Inc.
Estramustine potentiates the radiation effect in human prostate tumor transplant in nude mice
Authors: Eklöv Solveig , Westlin Jan‐Erik , Rikner Göran , Nilsson Sten
Published: February 2007

In this study, we have investigated the combined effect of estramustine treatment and external beam radiation on human prostatic cancer tumor cells (DU 145) transplanted in nude mice. The treatment was given according to two different schedules. In the first treatment regimen, estramustine was administered intraperitoneally (i.p.) intermittently for 20 days. The radiation therapy, which was started on day 9, was given with 6 Gy fractions during an 11‐day‐long period to a total dose of 36 Gy. The combination treatment (estramustine + radiation) resulted in a significant tumor growth retardation as compared to the control group. This pronounced effect was seen neither with radiation alone nor with estramustine alone. In order to further extend the radiation treatment time, a second therapy regimen was employed. In this part of the study, estramustine was administrated i.p. intermittently for 26 days. The radiation therapy, which was started on day 6, was given with 4 Gy fractions during a 21‐day‐long period to a total dose of 40 Gy. Under these conditions, a significant tumor growth retardation was disclosed, when comparing the combination treatment (estramustine + radiation) with radiation alone.

The tumors were analyzed for content of necrosis and proliferative activity. The largest proportion of necrosis was seen in the combination (estramustine + radiation) treatment group. Also, the tumors from this group expressed a decreased proliferative activity.

The data indicate that estramustine acts as a radiosensitizing agent in human prostatic cancer cells in vivo. The radiosensitizing properties of the drug encourage further studies with respect to clinical application. © 1994 Wiley‐Liss, Inc.
Responses to the antagonistic analog of LH‐RH (SB‐75, cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer
Authors: Gonzalez‐Barcena David , Vadillo‐Buenfil M. , Gomez‐Orta F. , Garcia M. Fuentes , Cardenas‐Cornejo I. , Graef‐Sanchez A. , Comaru‐Schally Ana Maria , Schally Andrew V.
Published: February 2007

Among new highly potent antagonistic analogs of luteinizing hormone‐releasing hormone (LH‐RH), containing neutral hydrophilic D‐ureidoalkyl amino acids such as D‐Cit and D‐Hci at position 6 and free of edematogenic and anaphylactoid reactions, Ac‐D‐Nal(2)1, D‐Ph(4Cl)2, D‐Pa1(3)3, D‐Cit6, D‐Ala10 (LH‐RH) (SB‐75; Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 μg SB‐75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6 prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of SB‐75 administration. This improvement continued during the course of treatment. Before therapy with SB‐75, the serum levels of prostate‐specific antigen (PSA) (6.73 ± 1.46 ng/ml), acid phosphatases, total (12.67 ± 1.15 U/l), and prostatic (2.27 ± 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 ± 0.59 ng/ml; P < 0.01), (7.68 ± 0.89 U/l; P < 0.01), and (1.39 ± 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 ± 8.86 to 37.92 ± 8.52 cm3; P < 0.01, which represents a reduction of 44%. In patients with prostate cancer, after the first week of therapy with SB‐75, we observed a significant decrease in bone pain, relief in urinary outflow obstruction, and reversal of the signs of prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed analgesics. PSA, acid, and alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum testosterone levels in BPH and prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog SB‐75, fell to castration values. A major fall in free testosterone levels was observed after the first dose; the maximal inhibition was seen after 6‐12 hr, with a simultaneous decrease in levels of both gonadotropins. Our results show that antagonist 58‐75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of prostatism obtained with antagonistic analog SB‐75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a therapeutic alternative in men who are considered poor surgical risks. Antagonist SB‐75 could also be useful for the treatment of prostatic cancer, but further studies are required. © 1994 Wiley‐Liss, Inc.
Effects of chronic oral administration of a selective 5α‐reductase inhibitor, finasteride, on the dog prostate
Authors: Laroque P. A. , Prahalada S. , Gordon L. R. , Noblot S. Molon , Bagdon W. J. , Duprat P. , Peter C. P. , Van Zwieten M. J.
Published: February 2007

Young mature dogs received finasteride, a selective 5α‐reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size and morphology was evaluated macroscopically and microscopically. Changes in glandular and fibromuscular compartments were quantitated by a point counting method on trichrome‐stained sections. Finasteride administration induced a decrease of mean prostatic weights and epithelial atrophy in all treated groups. No changes in testicular weights and morphology were observed. The greatest prostatic shrinkage was obtained in the group receiving 45 mg/kg/day for 53 weeks; compared to placebo controls, the percent decreases in absolute volumes occupied by epithelium, lumens, fibrovascular stroma, and smooth muscle were 88, 97, 51 and 72, respectively. These results clearly demonstrate that prostatic shrinkage following finasteride administration results from a decrease in both glandular and fibromuscular compartments. © 1994 Wiley‐Liss, Inc.
Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate
Authors: Tawfic Sherif , Goueli Said A. , Ahmed Khalil , Olson Mark O. J.
Published: February 2007

Nucleolin is an abundant nucleolar phosphoprotein which has been implicated as a factor in various stages of ribosome synthesis, including transcription. Since androgens exert a profound effect on the rRNA synthesis in the target organ prostate, we have examined the nature of androgenic regulation of the amount and phosphorylation of nucleolin in this tissue. Phosphorylation of prostatic nucleolin is catalyzed in part by heparin‐sensitive casein kinase 2 (CK‐2) and by another (heparin‐insensitive) protein kinase. Both the amount and phosphorylation of prostatic nucleolin are profoundly sensitive to androgens. Rapid reduction in the level and phosphorylation of nucleolin occurs following androgen deprivation, which corresponds to the ensuing cessation of prostatic growth leading to involution. Further, the loss of nucleolin phosphorylation and its degradation appear to be concordant. Administration of a single injection of 5α‐dihydrotestosterone to castrated animals causes an early increase in the amount and phosphorylation of nucleolin, starting in the prereplicative phase in the prostatic cell nucleus. These data suggest that early androgenic regulation of nucleolin expression and phosphorylation may play a role in nucleolar control mechanisms relevant to prostatic cell growth. © 1994 Wiley‐Liss, Inc.
Immunoglobulin binding factor: A new tumor marker for prostatic tumors
Authors: Maeda Nobuhiko , Kamada Masaharu , Daitoh Toshifumi , Maegawa Masahiko , Hirano Kohki , Aono Toshihiro , Shiotsu Tomoyuki , Kanayama Hiroomi , Kagawa Susumu , Futaki Shiroh , Muraguchi Masahiro , Ohmoto Yasukazu , Liang Zhi Guo , Koide S. S.
Published: February 2007

Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with an estimated molecular weight of 16 kD under reducing condition. IgBF was detected only in the prostate, including benign prostatic hypertrophy (BPH) and neoplasm. The present study was performed to determine whether IgBF is a useful prostatic marker. Serum IgBF levels were measured in patients with prostatic tumors and in control patients without tumor by radioimmunoassay. Serum prostatic‐specific antigen (PSA), the standard prostatic marker, was also determined. Serum IgBF levels in patients with prostate cancer were significantly higher than those in age‐matched controls (P < 0.05). Also, patients with BPH tended to have elevated IgBF levels than the controls, although the values were not statistically significant. In control patients, serum IgBF levels increased with advancing age. There was no correlation between serum levels of IgBF and PSA in patients with prostate cancer. Using cut‐off level at 28.5 ng/ml (2 S.D. above the mean IgBF level of age‐matched control), the sensitivities were 41.2% (7117) for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients. In conclusion, serum IgBF is a useful marker in the diagnosis of patients with prostatic tumor, and in evaluating the course of treatment. © 1994 Wiley‐Liss, Inc.
Isocitric and citric acid in human prostatic and seminal fluid: Implications for prostatic metabolism and secretion
Authors: Kavanagh J. P.
Published: February 2007

Human prostatic secretion is remarkably rich in citric acid but the mechanisms to account for this accumulation are not well understood. One factor may be the extent of citrate oxidation to isocitrate, catalyzed by aconitase. The citrate‐to‐isocitrate ratio will help characterize the relative significance of this reaction in prostatic production and secretion of citrate.

Isocitric acid and citric acid were measured in samples of seminal fluid and expressed prostatic secretion (EPS). A constant ratio between citrate and isocitrate of about 33:1 was found (r = 0.93, P < 0.0001) despite the wide variation in concentrations. Citrate ranged from 1 to 180 mM in EPS and from 13 to 50 mM in seminal fluid while isocitrate varied between 0 to 4.8 mM in EPS and from 0.4 to 1.5 mM in seminal fluid.

Isocitrate is present in EPS and semen at much higher levels than found in most other animal or plant tissues or fluids and may be actively secreted by the same mechanism as citrate. The high citrate to isocitrate ratio of about 33:1, compared to the expected value of about 10:1, supports suggestions that citrate to isocitrate oxidation by aconitase is a rate limiting step in prostatic citrate metabolism. A low aconitase activity will therefore play a significant role in enabling accumulation of high citrate levels in prostatic epithelia and acini. © 1994 Wiley‐Liss, Inc.
A more objective staging of advanced prostate cancer—routine recognition of malignant endocrine structures: The assessment of serum TPS, PSA, and NSE values
Authors: Tarle Marko , Kovačić Ksenija , Frković‐Grazio Snježana , Kraljić Ivo
Published: February 2007

Bone scans, serum tissue‐specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuronspecific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty‐nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more then 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogenous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear‐cut rise from stage DO subjects to stage D2 patients, with a small number of bone lesions (≥3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (>3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen‐dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ‐specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors. © 1994 Wiley‐Liss, Inc.
Secretion of transforming growth factor‐β by the immature rat prostate
Authors: Atfi Azeddine , Samperez Suzanne , Jouan Pierre
Published: February 2007

Immature rat ventral prostate was used to identify a potent cell growth inhibitory factor in normal prostate. Both conditioned media and peptide extracts derived from ventral prostates inhibit the cellular growth and DNA synthesis in metastatic androgen‐independent human prostate carcinoma cell line (PC3). The prostatic inhibitory factor was partially purified using an hydrophobic HPLC column (C18). Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis (SDS‐PAGE) of partially purified material revealed a major 25‐kDa band. Immunoblot analysis showed similarity of the inhibitory factor to the transforming growth factor‐β (TGF‐β). Furthermore, the proliferation inhibiting activity of the prostatic factor was completely abolished by anti‐TGF‐β antibodies. These data indicate that normal prostate produces a TGF‐β‐like protein under non‐physiological conditions. © 1994 Wiley‐Liss, Inc.
A comparison of transrectal hyperthermia, transurethral thermotherapy, urolume wallstent, and prostatic spiral for benign prostatic hyperplasia patients at poor operative risk
Authors: Montorsi Francesco , Guazzoni Giorgio , Bergamaschi Franco , Consonni Paolo , Rigatti Patrizio , Galli Laura
Published: February 2007

Transrectal hyperthermia, transurethral thermotherapy, prostatic stent, and prostatic spiral were used to treat 120 poor operative risk patients with symptomatic benign prostatic hyperplasia. The preoperative subjective and objective conditions of the four groups (each of 30 patients) were comparable. None of the patients had an indwelling catheter, but according to flow nomograms, all were obstructed. The greatest increase in peak flow rate was observed after stent placement, while the greatest decrease of residual urine volume was seen after the insertion of the stent and transrectal hyperthermia. According to maximum flow nomograms, only the placement of the stent resolved bladder outlet obstruction. The greatest improvement in subjective symptoms was the result of stent insertion, but the heating procedures also caused a significant reduction of symptom scores. The spiral produced satisfactory results only in the short term. © 1994 Wiley‐Liss, Inc.
Regulation of DUI45 human prostate cancer cell proliferation by insulin‐like growth factors and its interaction with the epidermal growth factor autocrine loop
Authors: Connolly Jeanne M. , Rose David P.
Published: February 2007

The DU145 human prostate cancer cell line was shown to possess type I insulin‐like growth factor receptors (IGFR). The addition of either IGF‐I or IGF‐II, but not insulin, to serum‐free culture medium increases the rate of thymidine incorporation by the cells, a response which is suppressed by specific blockade of the previously described epidermal growth factor (EGF) autocrine growth regulatory loop. The DU145 cells secrete into conditional medium a specific IGF‐binding protein (IGFBP) precipitated by an antibody to IGFBP‐1, and whose secretion is also suppressed by interruption of the EGF autocrine loop. This IGFBP may modulate the bioactivity of IGFs arising from endocrine or paracrine sources in vivo. After removal of IGFBPs from the conditioned medium, no secretion of either IGF‐I or IGF‐II by this prostate cancer cell line is detected by radioimmunoassay and radioreceptor assay, respectively. © 1994 Wiley‐Liss, Inc.
Antiandrogens inhibit human androgen receptor‐dependent gene transcription activation in the human prostate cancer cells LNCaP
Authors: Warriar Nalini , Pagé Nathalie , Govindan Manjapra V. , Koutsilieris Michael
Published: February 2007

Human androgen receptor (hAR) is a ligand‐dependent transcription factor that mediates androgen‐induced actions on target tissues. Transfection studies in the human prostate cancer cell line LNCaP examine the ability of dihydrotestosterone (DHT), hydroxyflutamide (HO‐FLU), cyproterone acetate (Cypro.A), and RU 23908‐10 to stimulate or to inhibit the transcription activation of mouse mammary tumor virus‐bacterial chloramphenicol acetyltransferase (MMTV‐CAT). DHT stimulated transcription activation of MMTV‐CAT gene in LNCaP cells in a dose‐dependent manner. HO‐FLU, Cypro.A, and RU 23908‐10, though only partially, also stimulated the transcription activation of MMTV‐CAT. Despite this, 100‐ to 1,000‐fold molar excess of all antiandrogens inhibited the agonistic activity of 10 nM DHT in this system. Receptor binding assays confirmed that HO‐FLU, Cypro.A, and RU 23908‐10 competed with DHT for AR binding in LNCaP cells. Western blot analysis using AR antipeptide antibodies raised in rabbits revealed the presence of two AR protein bands in LNCaP cells, following treatment with antiandrogens. Increasing doses of HO‐FLU stimulated the expression of the 114‐kDa AR by 2.5‐fold, but did not affect the 108‐kDa AR. Increasing doses of Cypr0.A and RU 23908‐10 decreased the levels of both the 114‐kDa and the 108‐kDa AR. Although the exact nature of 108‐kDa and 114‐kDa AR in LNCaP cells is still unknown, these data suggest that the regulatory actions of each individual antiandrogen on AR expression in LNCaP cells may be different. © 1994 Wiley‐Liss, Inc.
Effect of 5‐α‐reductase inhibition and dexamethasone administration on the growth characteristics and intratumor androgen levels of the human prostate cancer cell line PC‐3
Authors: Tuttle R. M. , Jones R. E. , Meikle A. W. , Loop S. , Ostenson R. C. , Plymate S. R.
Published: February 2007

The endocrine treatment of metastatic prostate cancer includes castration which reliably lowers the serum testosterone (T); however, the effect on intratumor levels of T and dihydrotestosterone (DHT) is less predictable. In vitro work demonstrated that the human prostate cancer cell line PC‐3 had significant 5‐a‐reductase activity that could be inhibited with 17b‐N, N‐diethylcarbamoyl‐4‐aza‐5a‐androstan‐3‐one (4MA). In this study, we examined the effect of 5‐a‐reductase inhibition with 4MA and androgen suppression with dexamethasone on the growth characteristics and intratumor androgen levels in the PC‐3 cell line in male athymic nude mice (Balb/c). The mice were randomized into six treatment groups: 1) noncastrate vehicle control, 2) 4MA, 0.25 mg/day, 3) 4MA, 1 mg/day, 4) dexamethasone, 25 μg/day, 5) 4MA, 1 mg/day, and dexamethasone, 25 μg/day, and 6) castrate control group. After 21 days of treatment the animals were sacrificed, serum collected, and tumors harvested.

Each treatment produced intratumor DHT levels equivalent to the castrate group. Only the low dose 4MA caused a reduction in intratumor DHT without producing castrate levels of circulating T. The combination of dexamethasone and 4MA was less effective in lowering the intratumor DHT/T ratio than 4MA alone. No significant differences in tumor growth parameters were noted between intact control animals and any of the treatment arms. Serum T levels correlated poorly with intratumor androgen levels.

Five‐a‐reductase inhibition produced castrate levels of intratumor DHT in the nonandrogen‐dependent prostate cancer cell line PC‐3. The combination of dexamethasone and 5‐a‐reductase inhibition with 4MA appears to be less effective in lowering intratumor androgen levels than either therapy alone. © 1994 Wiley‐Liss, Inc.
Kinetic analysis of focal hypoechoic lesion in the prostate treated by castration
Authors: Okihara Koji , Watanabe Makoto , Saitoh Masahito , Ohe Hiroshi , Watanabe Hiroki
Published: February 2007

Dynamic changes in the focal hypoehoic lesion (FHL) in the prostate, visualized by transrectal sonography (TRS), were determined in five patients with prostatic cancer (PC) after treatment by castration. In all cases, the volume of FHL, as well as the volume of the whole prostate, decreased exponentially after castration. In four out of five cases, the volume (not including the FHL, which might suggest the volume of the normal tissues) increased slightly in the early postoperative weeks, and decreased thereafter. In the remaining one case, it decreased consecutively. According to the formula established in our previous study, the reduction time (τ) of the volume of the whole prostate and of the volume of the FHL was calculated, indicating that the τ of the FHL was remarkably shorter than that of the volume not indicating the FHL. This evidence suggested that not only the cancerous tissues but also the normal prostatic tissues might reduce in volume after castration. © 1994 Wiley‐Liss, Inc.
Thermal changes in the canine prostate after transurethral balloon laser prostatectomy
Authors: Suzuki Takanori , Kurokawa Kohei , Suzuki Kazuhiro , Yamanaka Hidetoshi , Suzuki Keiji
Published: February 2007

The histological changes by transurethral balloon laserthermia were examined on 23 canine prostates. Immediately after treatment, three zones were observed; the coagulative zone treated over 60°C for 20 min formed an inner layer, the degenerative zone treated between 60 to 46.1°C surrounded the coagulative zone, and the intact zone treated below 46.1°C formed the outer layer. Coagulative necrosis of the gland, swelling of collagen fibers, and thrombus of the vessels occurred in the coagulative zone, shedding and vacuolation around the nuclei of the epithelial cells and stromal edema were observed in the degenerative zone, while thermal changes were minimal in the intact zone. Both coagulative and degenerative zones developed necrosis and started to slough off within 1 week, forming a cavity in the central portion of the prostate. Reepithelialization of the cavity was complete at 4 weeks and the ducts of the prostate gland opened to the surface of the cavity. This treatment preserved the excretory tract of the prostate gland. © 1994 Wiley‐Liss, Inc.
Characterization of peripheral benzodiazepine receptors in rat prostatic adenocarcinoma
Authors: Batra Satish , Alenfall Jan
Published: February 2007

Using PK 11195, a high affinity ligand for peripheral benzodiazepine receptors (PBZr), binding sites in isolated mitochondrial (m‐fraction) and microsomal fractions (p‐fraction) from R‐3327 Dunning AT‐1 tumors, ventral and dorsolateral prostate were studied. Binding of PK 11195 in both m‐ and p‐fractions from AT‐1 tumors, but only in m‐fraction from ventral and dorsolateral prostate, was specific, saturable, and of high affinity. The PBZr density in m‐fraction from AT‐1 tumors was 6‐fold and 20‐fold higher than that in ventral and dorsolateral prostate, respectively. The receptor density in p‐fraction from AT‐1 tumors was approximately 25% of that found in the m‐fraction. Clear differences were observed in the competition by both diazepam and flunitrazepam for binding sites in m‐ and p‐fractions from tumors. These data indicate that the receptors were not only localized to the mitochondria, but were also present in considerable amounts in the microsomal fractions. The unusually high amounts of receptors in the fast growing anaplastic prostatic tumor suggest their involvement in the regulation of cell proliferation and possibly in tumorigenesis. © 1994 Wiley‐Liss, Inc.
Immediate vasoactive effect of citral on the adolescent rat ventral prostate
Authors: Scolnik M. , Konichezky M. , Tykochinsky G. , Servadio C. , Abramovici A.
Published: February 2007

The vasoactive effect of a fragrance compound, citral, on rat ventral prostate is presented. A combined method of Indian‐ink perfusion and postfixation transparency was used. One single dose of citral applied on the back skin of the rat induced an immediate triple response‐like effect on the prostatic vascular bed. A slight vasodilatation appeared already after 2 1/2 min, followed by a marked vasoconstriction process after 5‐min postcitral administration. Toward the period of 10 min, a second vasodilatation process was noted which persisted for the following 24 hr of observation.

This study has demonstrated that changes in the microvascularization of the rat prostate can be estimated by counting the number of carbon‐stained blood vessels. The results obtained by this technique are closely related with the findings in the vascular network profile of the macroangiographic observations.

The mechanism of action of citral on the microvascularization of the rat ventral prostate is yet unknown. Based on the present findings, we suggest that the neoplastic capacity of citral upon the prostatic epithelia is activated via a nonspecific inflammatory reaction modulated either by local release of neurotransmitters or throughout a direct effect of citral on the endothelial cells. © 1994 Wiley‐Liss, Inc.
Induction of apoptosis in androgen‐independent human prostate cancer cells undergoing thymineless death
Authors: Kyprianou Natasha , Bains Arvinder K. , Jacobs Stephen C.
Published: February 2007

Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen‐independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen‐independent human prostatic cell lines, PC‐3 and DU‐145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non‐androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5‐fluoro‐2‐deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis‐related genes, such as TRPM‐2/SGP‐2, and TGF‐β1, but not the growth‐related genes, c‐myc, c‐fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine‐induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DMA, indicating that this apoptotic process is due to the induction of “thymineless” state. These results suggest that androgen‐independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a “thymineless” state. © 1994 Wiley‐Liss, Inc.
Smooth muscle contractility in prostatic hyperplasia: Role of cyclic adenosine monophosphate
Authors: Drescher P. , Eckert R. E. , Madsen P. O.
Published: February 2007

The role of cyclic 3′‐5′ adenosine monophosphate (cAMP) on α1‐adreno‐ceptor (α1‐receptor) induced smooth muscle contractions in symptomatic benign prostatic hyperplasia (BPH) was investigated. Application of the selective α1‐receptor agonist phenylephrine (PE) induced fully reversible contractions in a dose‐dependent fashion. Phosphodiesterase (PDE) inhibitors blocking the degradation of cAMP suppressed the PE induced contractions as follows: theophylline (1 mM), 91.1 ± 1.4%; papaverine (0.5 mM), 822.8 ± 3.2%; milrinone (0.5 mM), 68.2 ± 0.6%. Forskolin (50 μM), which elevates cAMP through direct activation of adenylatecyclase (AC), inhibited the PE induced contractions by 82.4 ± 3.6%. To further increase the intracellular cAMP concentration ([cAMP]i), the membrane permeable cAMP analogue N6‐2′‐O‐dibutyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the PE evoked contractions by 69.8 ± 2.3%. We conclude that elevation of [cAMP]i is an important step in inducing smooth muscle relaxation. © 1994 Wiley‐Liss, Inc.