bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration
Authors: English Hugh F. , Kyprianou Natasha , Isaacs John T.
Published: February 2007

Previous studies have demonstrated that the rapid involution of the rat ventral prostate following castration involves the death of the androgen‐dependent epithelial cells present within the gland and that this death is the result of a series of discrete biochemical steps. The degradation of genomic DNA into nucleosomal‐sized fragments is an early event in this process and is catalyzed by calcium magnesium‐dependent endonuclease activity. The morphologic correlation of the involution process involves a serics of structural changes which are collectively referred to as apoptosis. The apoptotic process describes the earliest apparent signs of morphologic change exhibited by the dying cells through their eventual complete destruction and deletion from the tissue. The temporal relationship between these recently described biochemical events and the morphologic changes of the apoptotic process were compared in the present study, in order to test the cause versus effect nature of DNA fragmentation in the programmed death of androgen dependent prostatic cells following castration. These studies demonstrated that the early elevation of the Ca +2 Mg+2 ‐dependent endonuclease activity and the fragmentation of DNA into nucleosomal oligomers occurs within prostatic glandular epithelial cells and probably does not involve the direct participation of extraprostatic cells which may subsequently migrate into the gland. Once the DNA is initially cleaved into the nucleosomal oligomers, the subsequent participation of lysosomal enzymes act in a less restricted fashion to degrade both the nuclcosomal DNA as well as the cytoplasmic elements and the cell becomes morphologically apoptotic. As the elevations in Ca+2 Mg+2‐dependent endonuclease activity and DNA fragmentation are initiated at a time well before the cell is morphologically dead, as defined by apoptosis, these changes in DNA metabolism must not be the consequences of cell death but instead are early causal events in an active process of programmed cell death.
Immunohistochemical localization of laminin in the basement membranes of normal, hyperplastic, and neoplastic human prostate
Authors: Sinha Akhouri A. , Gleason Donald F. , Wilson Michael J. , Staley Nancy A. , Furcht Leo T. , Palm Sally L. , Reddy Pratap K. , Sibley Richard K. , Martinez‐Hernandez A.
Published: February 2007

We examined the effects of fixatives and antibody sources on the immunohistologic localization of laminin in normal and cancer‐containing human prostates and studied the localization patterns in carcinomas of varying degrees of histologic differentiation. Two different polyclonal antibodies were localized in paraffin‐embedded or cryostat sections of fixed (alcohol, formalin, and paraformaldehyde) or unfixed tissue, using the immunofluorescence (IF) or immunoperoxidase (IP) techniques, with positive and negative controls. We found that the IF reactions were more intense in unfixed or alcohol‐fixed sections than in paraformaldehyde‐fixed specimens. IP reactions were very weak or absent in fixed and paraffin‐embedded sections, but pepsin treatment of these sections resulted in more intense and uniform IP reaction products, stronger than in unfixed or ethanol‐fixed cryostat sections. With the IP technique, laminin localization was intense and uniform in the basement membranes (BM) of acini, blood vessels, smooth muscle, and nerve fibers in normal prostate, benign hyperplasia (BPH), and well‐differentiated carcinomas. The BM of poorly differentiated carcinomas showed widespread absence of laminin reactivity. In normal BPH and well‐differentiated tumors, occasional epithelial cells and their surface and acinar lumina had laminin reactivity. However, in higher grade tumors, numerous neoplastic cells had laminin reactivity in cytoplasm, their surface, and secretory material. Some macrophages and neutrophils also contained laminin reactivity, presumably of degraded laminin. In some moderately and poorly differentiated tumors, the BM of small capillaries did not contain laminin. The BM of larger vessels always had laminin reactivity, even in the higher grade tumors.
Prostate epithelial cells utilize glucose and aspartate as the carbon sources for net citrate production
Authors: Costello L. C. , Franklin R. B.
Published: February 2007

The prostate gland (human, rat ventral prostate) has the major function of accumulating and secreting extremely high levels of citrate. This function requires unique and specialized metabolic pathways associated with prostate secretory epithelial cells by which exogenous substrates must be utilized as the six‐carbon sources of citrate. Recent studies demonstrated that aspartate can serve as the four‐carbon source of oxalacetate for citrate synthesis. Identification of the two‐carbon source of acetyl CoA (AcCoA) had not been established. The present study investigated the probability that exogenous glucose, via pyruvate oxidation, is a physiological source of AcCoA for net citrate production by isolated epithelial cells from rat ventral prostate. Under adequate oxygenation, 5 mM glucose in the presence of aspartate plus glutamate markedly stimulated citrate production. Exogenous and endogenous pyruvate also stimulated net citrate production. We propose that glucose via aerobic glycolysis and pyruvate oxidation provides AcCoA, which condenses with oxalacetate obtained from aspartate transamination for citrate synthesis. Prostate epithelial cells do not readily oxidize citrate, which permits accumulation and secretion of the synthesized citrate.
Cultured human prostate‐derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor
Authors: Story Michael T. , Livingston Bonnie , Baeten Laurie , Swartz Susan J. , Jacobs Stephen C. , Begun Frank P. , Lawson Russell K.
Published: February 2007

Fibrostromal proliferation is believed to be important in the development of benign prostatic hyperplasia (BPH). We found that a mitogen for cultured mesodermal‐derived cells was present in extracts of BPH tissue. The mitogen was identified as basic fibroblast growth factor (bFGF). Previous studies did not determine the cell population(s) responsible for bFGF production in the prostate. This information is important to the understanding of the role of bFGF in the etiology of BPH. Human prostate‐derived fibroblasts (PF) were initiated in culture. Recombinant bFGF and PF lysates stimulated tritiated thymidine uptake by quiescent PF cells. Greater than 90% of the mitogen in PF lysates bound to heparin‐Sepharose and had the same elution profile and apparent molecular weight as bFGF isolated from BPH tissue. The growth factor in PF lysates competed with recombinant iodinated bFGF for binding to antiserum to (1‐24)bFGF. Cultured PF incorporated 35S‐methionine into protein that was precipitated by antiserum to bFGF. The apparent molecular weight of the radiolabeled protein, about 17,000, was similar to authentic bFGF. The observations are consistent with the interpretation that cultured PF synthesize a growth factor that stimulates their growth with properties that are indistinguishable from bFGF.
Phosphoinositide metabolism in human prostate cancer cells in vitro
Authors: Wilding George , Gelmann Edward P. , Freter Carl E.
Published: February 2007

To understand better the mechanism by which 5‐α‐dihydrotestosterone (5‐α‐DHT) influences prostate epithelial cell function, we examined the effects of 5‐α‐DHT on phosphoinositide metabolism in human prostate cancer cell lines. Androgen receptor‐positive LNCaP cells showed dose‐responsive, steady‐state elevations in phosphoinositide metabolism when treated with 5‐α‐DHT. The intracellular pool of 3H‐myoinositol decreased and the incorporation of 3H‐myoinositol into cellular lipids increased with increasing concentrations of 5‐α‐DHT. 5‐α‐DHT increased the release of 3H‐inositol phosphates into the media. The inactive stereoisomer, 5‐β‐DHT, did not increase phosphoinositide metabolism. In androgen receptor‐negative cells, phosphoinositide metabolism was not altered by 5‐α‐DHT. The slow induction of phosphoinositide metabolism by 5‐α‐DHT suggests that the effects may be mediated through other factors that serve as intermediates in 5‐α‐DHT modulation of intracellular signalling. We conclude that this modulation involves increased turnover of phosphatidylinositol, incorporation of myoinositol into cellular lipids, and alterations in the aqueous intracellular myoinositol pool size, possibly as a result of altered transport mechanisms.
Increased expression of genes for basic fibroblast growth factor and transforming growth factor type β2 in human benign prostatic hyperplasia
Authors: Mori Hirotaka , Maki Masatoshi , Oishi Kenji , Jaye Michael , Igarashi Koichi , Yoshida Osamu , Hatanaka Masakazu
Published: February 2007

It is now widely accepted that factors other than androgen are crucial in the normal and abnormal growth of the prostate, including human benign prostatic hyperplasia (BPH). Using a Northern blot analysis, we examined human normal and benign hyperplastic prostates for expressions of basic fibroblast growth factor (FGF), acidic FGF, transforming growth factor type β2 (TGF‐β2), TGF‐β1, and epidermal growth factor (EGF). Basic FGF mRNAs were detectable in all the prostates examined. In addition, levels of basic FGF expression were significantly higher in BPH than in normal prostate. Acidic FGF transcripts were undetectable except in one case of BPH. Although both TGFs were expressed in all the samples, TGF‐β2 showed significantly increased levels of expression in BPH as compared to those in normal prostate, while TGF‐β1 did not. No EGF was expressed in any of the prostates examined. These findings suggest that specific growth factors (basic FGF and TGF‐β2) produced locally in the prostate may be involved in BPH development.
Evidence for two aspartate transport systems in prostate epithelial cells
Authors: Franklin Renty B. , Lao Lixing , Costello L. C.
Published: February 2007

The transport of aspartate was measured in isolated prostate cells. Two kinetically distinct uptake systems of high (Km = 10.0 μM) and low (Km = 0.8 mM) affinity were observed. Transport by both systems was Na+ dependent and saturable. The tissue distribution of aspartate was also determined by measuring the washout kinetics of endogenous and radio‐labeled aspartate from prostate fragments. The distribution of aspartate resulted in 47% of aspartate in the intracellular compartment and 52% in the extracellular (presumably) lu‐menal compartment. The distribution of aspartate resulted in a calculated intracellular to plasma concentration gradient of approximately 43. We concluded that prostate cells maintain a considerable intracellular to plasma gradient for aspartate and that these cells contain a transport mechanism capable of uptake of aspartate against this considerable gradient.
Characterization of the morphonuclear features and DNA ploidy of prostatic disease
Authors: Petein Michel , De Launoit Yvan , Kiss Robert , Deprez Carine , Crols Kaat , Pasteels Jean‐Lambert , Verhest Alain , Van Velthoven Roland
Published: February 2007

The relationship between several morphonuclear parameters related to nuclear size, densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen‐stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies or fine‐needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine‐needle aspirations from prostate.
Non‐androgenic role of testis in enhancing ventral prostate growth in rats
Authors: Dalton Daniel P. , Lee Chung , Huprikar Shankar , Chmiel Joan S. , Grayhack John T.
Published: February 2007

This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague‐Dawley rats at the time of bilateral epididymo‐orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty‐eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non‐androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non‐androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.
Symptoms and signs of prostatism as risk factors for prostatectomy
Authors: Arrighi H. M. , Guess H. A. , Metter E. J. , Fozard J. L.
Published: February 2007

Symptom questionnaires and physical examinations administered periodically to 1,057 men followed prospectively for up to 30 years in the Baltimore Longitudinal Study of Aging (BLSA) were analyzed to determine which symptoms of prostatism were predictive of subsequent prostatectomy for benign prostatic hyperplasia (BPH). Change in the size and force of the urinary stream (P= 0.0001) and a sensation of incomplete emptying (P= 0.0005) were the only symptoms positively predictive in a multivariate analysis. Prostate enlargement by rectal palpation was an independent risk factor for prostatectomy (P<0.03) and was associated with hesitancy (P<0.02) and a sensation of incomplete emptying (P<0.02). Of the men with all three risk factors, 37% (41/112) eventually had a prostatectomy, in contrast to 8% of the remaining 945 men. This is the first study to document the extent to which urologic symptoms and a digital rectal examination predict subsequent prostatectomy for BPH.
Characterization of castration‐induced cell death in the rat prostate by immunohistochemical localization of cathepsin D
Authors: Sensibar Julia A. , Liu Xianxi , Patai Barbara , Alger Brad , Lee Chung
Published: February 2007

Activities of cathepsin D (EC 3.4.23.5) were determined in three lobes of the prostate during their involution by both biochemical and immunohistochemical procedures. The activity of cathepsin D in noncastrated rats was 0.9 ± 0.2 (mean ± SE) 5.7 ± 0.6, and 13.1 ± 0.8 units/mg protein for the ventral, lateral, dorsal lobes, respectively. Following castration, there was a significant increase in enzymatic activity in all three lobes within 2–3 days. In the ventral lobe, the activity peaked in 5 days to 6.2 ± 0.9 units/mg protein and declined slightly thereafter. In the lateral and dorsal lobes, the activity remained elevated (14–20 units/mg protein) throughout the postcastration period studied.

Immunohistochemical staining of cathepsin D was localized in the cytoplasm of prostatic epithelial cells as fine discrete lysosomal granules. These granules were larger and more abundant in the dorsal and lateral lobes than in the ventral lobe and were not detected in prostatic stromal cells and seldom in the luminal fluid. Castration resulted in an immediate increase in the size and number of these granules in the epithelial cells, followed by a sudden further increase in cathepsin D staining in some but not all epithelial cells. Lysosomal granules gradually coalesced in these cells to form large vacuoles that fit the characteristic description of apoptotic bodies. Finally, after day 7 postcastration, collapse and disintegration of the entire glandular structure was noted. Using this procedure to localize cathepsin D as a tool, we were able to follow the morphological events of prostatic cell death during castration‐induced involution in the rat at the light microscopic level.
Prostatic tumor (R3327) skeletal metastasis
Authors: Geldof A. A. , Rao B. R.
Published: February 2007

Male Copenhagen rats were inoculated with monodispersed R3327‐MatLyLu prostate tumor cells via the tail vein under concomittant temporal occlusion of the inferior vena cava to develop an animal model for skeletal metastasis of prostate cancer. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. Microscopically, tumor growth became visible in the fifth and sixth lumbar vertebrae within 4 days after inoculation. Clinical signs of nerve function disablement (hind leg paresis and paralysis) followed within 14 days of such a procedure. Cell culture technique confirmed the presence of a viable, proliferating tumor cell population within the spinal canal of the fifth and sixth lumbar vertebrae. Histologically, a clear response of osteoclastic and concomittant osteoblastic activities was observed in the lumbar spinal column. In the serum, a transient phase of hypercalcemia could be demonstrated. The development of skeletal metastases in these animals was not reflected by significant alteration in serum levels of acid phosphatase, prostatic‐specific antigen, or osteocalcin. These observations support the concept of the vertebral venous plexus being involved in the dissemination of prostate tumor cells. The surgical procedures described permit experimental investigations of bone metastasis of prostatic cancer.
Morphological and immunohistochemical investigations of the utriculus prostaticus from the fetal period up to adulthood
Authors: Wernert N. , Kern L. , Heitz Ph. , Bonkhoff H. , Goebbels R. , Seitz G. , Inniger R. , Remberger K. , Dhom G.
Published: February 2007

We investigated the utriculus prostaticus from the fetal period up to adulthood in 148 prostates. During the second half of gestation the utriculus had a simple tubular or a cystic form and was lined with metaplastic squamous epithelium which showed immunohisto‐chemical positivity for different keratins, carcinoembryonic antigen, and peanut agglutinin binding sites. After birth, alveolar outgrowths of the utriculus developed. After puberty, the utriculus had become a complicated and variable structure. The epithelium no longer differed from that of the prostate glands either morphologically or immunohistochemically. Within the epithelium numerous endocrine cells were found containing neuron‐specific enolase, chromogranin, and serotonin. The utriculus and ejaculatory ducts were embedded in a fibrous stroma with, after birth, numerous plexus‐like blood vessels. This fibrous zone was peripherally bordered by a layer of smooth muscle. There was no evidence for a function of the utriculus differing from that of the prostate glands. Since the epithelium of both structures is identical immunohistochemically, the epithelium of the sinus urogenitalis most likely participates in the lining of the utriculus during embryogenesis.
Estrogen treatment combined with castration inhibits tumor growth more effectively than castration alone in the dunning R3327 rat prostatic adenocarcinoma
Authors: Landström M. , Bergh A. , Tomic R. , Damber J.‐E.
Published: February 2007

This study was designed to investigate whether the combination of castration with estrogen treatment for 6 weeks (combined treatment) further inhibits growth of the Dunning R3327 rat prostatic adenocarcinoma as compared with castration alone. Combined treatment arrested tumor growth more effectively than castration. Combined treatment also induced morphological changes in both tumor stroma and epithelium that were not found in tumors from castrated animals. The volume density of the tumor epithelium was reduced and the volume density of the tumor stroma was increased by the combined treatment as compared with castration alone. The number of tumor epithelial cells was calculated by morphological methods: combined treatment lowered the number as compared with castration alone. The number of tumor epithelial cells was similar in castrated and intact rats. Both combined treatment and castration alone reduced tumor epithelium cell size as compared with tumors from intact rats. These findings suggest that estrogen may have direct effects on total number and function of prostatic tumor cells.
Differences in growth requirements between epithelial and stromal cells derived from rat ventral prostate in serum‐free primary culture
Authors: Taketa Shigeo , Nishi Nozomu , Takasuga Hirotoshi , Okutani Takuya , Takenaka Ikumasa , Wada Fumio
Published: February 2007

Different procedures of enzymatic digestion of rat prostatic tissue and unique sets of mitogenic factors made it possible to culture practically pure populations of epithelial and stromal cells without previous separation of the two types of cells. Keratin‐positive epithelial cells dissociated by trypsin and collagenase from adult rat ventral prostate proliferated in medium WAJC 404 supplemented with epidermal growth factor, insulin, cholera toxin, and bovine pituitary extract. Proliferation of epithelial cells was completely inhibited by dexamethasone as low as 30 nM. On the other hand, fibroblast‐like stromal cells released by trypsin digestion required a plastic substratum coated with calf serum or fibronectin, and proliferated in Eagle's minimum essential medium supplemented with cholera toxin, bovine pituitary extract, dexamethasone, and bovine serum albumin. Epidermal growth factor and insulin had negligible effect on proliferation of stromal cells. Physiological concentrations of dihydrotestosterone and estradiol showed no effect on proliferation of both types of cells.
Cumulative prevalence of prostatism matches the autopsy prevalence of benign prostatic hyperplasia
Authors: Guess H. A. , Arrighi H. M. , Metter E. J. , Fozard J. L.
Published: February 2007

The age‐specific cumulative prevalence of clinically diagnosed prostatism among 1,057 generally healthy men followed for up to 30 years in the Baltimore Longitudinal Study of Aging was compared with the age‐specific autopsy prevalence of pathologically defined benign prostatic hyperplasia (BPH) from a published compilation of five independent autopsy studies involving 1,075 prostates. Clinical prevalences based on medical histories and digital rectal examinations showed excellent agreement with autopsy prevalences at all ages. Despite the well‐known lack of correspondence between prostatism and objective urologic evidence of BPH in individual patients, these results suggest that the proportion of the male population with clinically recognizable prostatism by a given age is about the same as the proportion with pathological evidence of BPH.
Effects of prolactin and androgens on the prostatic lipids of castrated mature bonnet monkeys
Authors: Arunakaran J. , Aruldhas M. Michael , Govindarajulu P.
Published: February 2007

The effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihy‐drotestosterone (DHT), and the combinations of these androgens with PRL/Br on total lipid, total cholesterol, total glyceride glycerols, and total phospholipid and their fractions in cranial and caudal prostates of castrated mature monkeys were studied. Glyceride glycerols formed the major portion of total lipids (50%) in normal monkeys. Cholesterol and phos‐pholipids were of equal share (25%). Esterified cholesterol formed the major share (75%) of total cholesterol. Diacyl glycerol was the major (60%) glyceride glycerol and phosphatidyl choline and ethanolamine were the major phospholipid classes. Except triacyl glycerol castration markedly descreased all the lipid classes in both the lobes. PRL restored normal free and esterified cholesterol and phosphatidyl inositol but Br invariably decreased all the lipid classes. TP/DHT treatment stimulated the free and esterified cholesterol more than the control; it restored the normal glyceride glycerols in both the lobes. Phosphatidyl inositol, choline, and ethanolamine were stimulated by androgens and other phospholipid classes were brought to normal in both the lobes. Addition of PRL + TP/DHT markedly increased esterified cholesterol, phosphatidyl inositol, choline, ethanolamine, and phosphatidic acid in both the lobes. Br counteracted the effects of androgens and prolactin. In general, the influence of prolactin was more in the caudal lobe than cranial. The results are discussed in detail with available literature.
A case‐control study of prostatic cancer in Kyoto, Japan: Sexual risk factors
Authors: Oishi Kenji , Okada Kenichiro , Yoshida Osamu , Yamabe Hirohiko , Ohno Yoshiyuki , Hayes Richard B. , Schroeder Fritz H. , Boyle Peter
Published: February 2007

A case‐control study on prostatic cancer was conducted in Kyoto, Japan, from 1981–1984, including 100 patients with prostatic cancer (PC) and age, hospital, and date‐of‐admission matched controls of benign prostatic hyperplasia (BPH) patients and general hospital patients. Analysis of several sexual factors obtained through a self‐administered questionnaire revealed the following observations: (1) cancer patients had fewer sex partners before marriage (relative risk, RR = 0.35; 95% confidence interval: 0.13–0.93 than the hospital controls; (2) they had more vigorous sexual activities in the third (RR = 2.89: 1.01–8.28 and fourth decades of life (RR = 2.26: 1.03–4.95) than hospital controls, but no significantly different sexual activities from controls in other decades; (3) they had less frequent orgasms (RR = 2.55; 1.11–5.83) than BPH controls or (RR = 4.96: 1.78–13.9) hospital controls, and sexual intercourse appeared to be less satisfactory (RR = 2.08: 1.05–4.13) than that of hospital controls; and (4) they had less frequent episodes of sexually transmitted diseases (RR = 0.36: 0.16–0.83) than BPH controls. Marital status, fertility, ejaculation, masturbation, nocturnal emission, contraceptive use, and wife's episodes of sexually transmitted disease were not linked to prostatic cancer risk.
Reduction of testosterone availability to 5α‐reductase by human sex hormone‐binding globulin in the rat ventral prostate gland in vivo
Authors: Ellison Sean A. , Pardridge William M.
Published: February 2007

The present studies assess the effects of human sex hormone‐binding globulin (SHBG) on the conversion of [3H]testosterone (T) into dihydrotestosterone (DHT) in rat ventral prostate gland in vivo using a constant aortic infusion technique. The DHT/T ratio was determined using two‐dimensional thin‐layer chromatography (TLC), and these results were confirmed with reverse‐phase high‐performance liquid chromatography. The prostatic gland DHT/T ratio was 2.1 ± 0.4, 1.3 ± 0.2, 0.24 ± 0.02, or 1.1 ± 0.2, following a 60 sec aortic perfusion of [3H]testosterone dissolved in either Krebs‐Henselite buffer (KHB), 5 g/dl human serum albumin (HSA), human pregnancy serum (HPS), or heat inactivated HPS, respectively. Heat inactivation (60oC, 60 min) selectively denatured SHBG in HPS. The distribution of [3H]testosterone in rat ventral prostate was examined with thaw‐mount light in microscopic autoradiography. Following an aortic perfusion of [3H]testosterone in buffer alone, the radiolabeled steroid was uniformly distributed among the epithelial and stromal compartments. However, the [3H]steroid hormone was selectively sequestered in the stromal compartment following aortic perfusion of HPS. In conclusion, these studies demonstrate that human SHBG markedly restricts the availability of circulating testosterone to 5α‐reductase in the prostate gland in vivo and that the presence of SHBG in serum causes the selective sequestration of the steroid hormone within the stromal compartment of the gland in vivo.
Immunohistochemical evaluation of the expression of prostate tumor‐association markers in the nude mouse human prostate carcinoma heterotransplant lines PC‐82, PC‐EW, and PC‐EG
Authors: Wright George L. , Haley Cara L. , Csapo Zoltan , van Steenbrugge Gert J.
Published: February 2007

The biotin‐avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma‐associated markers in formalin‐fixed paraffin‐embedded tissue sections of three human prostate nude mouse heterotransplant lines PC‐82, PC‐EW, and PC‐EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP‐27, Leu‐7, 7E11–C5, PSP‐19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC‐82 and PC‐EW lines were the most efficient in terms of expression of multiple prostate carcinoma‐associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP‐27, PSP‐19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti‐prostate carcinoma monoclonal antibodies.
Family history and the risk of prostate cancer
Authors: Steinberg Gary D. , Carter Bob S. , Beaty Terri H. , Childs Barton , Walsh Patrick C.
Published: February 2007

A case‐control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls.

Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P < .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11–fold increased risk of developing prostate cancer.

Recognizing that 9–10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.
Similarities in the modulation of pituitary and prostatic FSH by inhibin and related peptides
Authors: Shah Madhavi G. , Sheth Anil R.
Published: February 2007

Prostatic inhibin peptide (PIP) suppresses the synthesis as well as release of FSH from the rat pituitary whereas the carboxy terminal nonapeptide (86–94) of PIP elevated the release of pituitary FSH. Addition of a tyrosine residue at the NH2‐terminal end of nonapeptide and blocking the sulfydryl group of the cysteine residue at position 87 resulted in a decapeptide having the property of suppressing FSH release from rat pituitary.

Human prostate has been shown to synthesize FSH in vitro. PIP, nonapeptide, and decapeptide modulate the prostatic FSH biosynthesis, the pattern of which was similar to that observed for pituitary.
Concepts of citrate production and secretion by prostate 1. Metabolic relationships
Authors: Costello Leslie C. , Franklin Renty B.
Published: February 2007

Accumulation and secretion of extraordinarily high levels of citrate are principal functions of the prostate gland of humans and other animals. To achieve this, prostate secretory cells must possess unique metabolic relationships which distinguish them from virtually all other cells. Furthermore, citrate metabolism is markedly altered in benign prostatic hyperplasia (BPH) and in prostatic carcinoma (CA). This review assimilates existing information and presents current concepts related to 1) the pathway of metabolism associated with net citrate production, 2) the involvement of transporting mechanisms associated with citrate secretion, 3) energy implications of citrate production, 4) altered metabolic relationships in BPH and CA, and 5) the importance of citrate relationships as biochemical markers for characterizing prostate secretory epithelial cells. It is hoped that this review will bring attention to the importance and urgency of elucidating and understanding the metabolic relationships associated with citrate production by normal and neoplastic prostate epithelial cells. Research in these areas has been severely neglected despite the fact that the combined incidence of BPH and CA constitutes the most prevalent neoplastic disease among men.
Role of cyclic AMP and polypeptide growth regulators in growth inhibition by interferon in PC‐3 cells
Authors: Okutani Takuya , Nishi Nozomu , Kagawa Yorikazu , Takasuga Hirotoshi , Takenaka Ikumasa , Usui Tsuguru , Wada Fumio
Published: February 2007

Participation of growth factors and intracellular cAMP in direct antiproliferative action of interferon α (IFN‐α) was investigated in PC‐3 human prostate carcinoma cell line. IFN‐α inhibited proliferation of PC‐3 cells in a dose‐dependent manner in vitro, and the effect was reversible. Fibroblast growth factor, epidermal growth factor and platelet‐derived growth factor, when added to the culture medium, showed no effect on growth of PC‐3 cells in presence or absence of IFN‐α. Transforming growth factor β (TGF‐β) significantly inhibited PC‐3 cell growth, and the effect was additived to that of IFN‐α. TGF‐β content in conditioned medium of PC‐3 cells was not affected by treatment with IFN‐α. On the other hand, IFN‐α increased intracellular cAMP concentration about 20‐fold. Dibutyryl cAMP and reagents which elevated intracellular cAMP level also inhibited PC‐3 cell growth. These indicated that direct antiproliferative effect of IFN‐α on PC‐3 cells was at least partly mediated by cAMP, and that neither growth factors nor a growth inhibitor participated in the action of IFN‐α.
Localization of type IV collagen in the basement membranes of human prostate and lymph nodes by immunoperoxidase and immunoalkaline phosphatase
Authors: Sinha Akhouri A. , Gleason Donald F. , Deleon Onofrea F. , Wilson Michael J. , Limas Catherine , Reddy Pratap K. , Furcht Leo T.
Published: February 2007

The object of these studies was to examine the localization of type IV collagen (Coll‐IV) in the basement membranes (BM) of epithelial and stromal elements (smooth muscle, nerves, vessels) in normal, hyperplastic, and neoplastic (primary and metastatic) prostate. We also examined the relationship of Coll‐IV distribution to the degree of tumor differentiation (Gleason grading system). We compared immunoperoxidase (IP) and immunoalkaline phosphatase (AP) techniques in these studies and in selected samples we also evaluated immunofluorescence (IF) localization of Coll‐IV and the effects of tissue fixation and pepsin digestion. We found that IF localization of Coll‐IV was intense in unfixed sections. IP and AP reactions were absent in fixed, paraffin‐embedded sections but pepsin treatment yielded intense and uniform reaction products in these same preparations. Both the IP and AP techniques showed similar localization of Coll‐IV in the BM of normal, hyperplastic, and well‐differentiated tumor. In most of the higher‐grade tumors Coll‐IV localization was reduced and a similar pattern of distribution was observed after IP and AP techniques. However, in some high‐grade tumors the IP technique showed good localization but AP did not, and vice versa. Such discrepancies were noted in the BM of the tumor cells, as well as in the BM of the stromal elements and in lymph nodes with metastatic tumor. Thus, our study shows decreased Coll‐IV localization in higher‐grade tumors and suggests that the use of a single technique (IP or AP) may exaggerate this apparent loss of Coll‐IV BM components. The exact cause of these discrepancies is unknown but they must reflect variable losses in the ability of the tumor cells to form BM, degradation or decreased synthesis of BM components by high‐grade tumors, or a combination of the above.
Cardiovascular and all‐cause mortality in prostatic cancer patients treated with estrogens or orchiectomy as compared to the standard population
Authors: Aro J.
Published: February 2007

Four hundred and seventy‐seven prospectively randomized patients with prostatic carcinoma were treated with a combination of intramuscular polyestradiol phosphate (PEP) and oral ethinyl estradiol, with intramuscular PEP alone, or with orchiectomy. The cardiovascular and all‐cause mortality of the two estrogen therapy modalities and orchiectomy were compared with those of the Finnish male population in general. The age‐standardized rate ratios (∼ relative risk) for cardiovascular mortality and for all‐cause mortality were 1.51 and 2.31 in the combination estrogen therapy group, 0.17 and 1.50 in the PEP monotherapy group, and 0.78 and 1.78 in the orchiectomy group, respectively. Further mortality rates by cause for all three treatment groups were standardized for age using the age‐specific personyears at risk as standard. Age‐standardized mortality from cardiovascular diseases was very low in the PEP group, as compared to other treatment modalities, and the mortality rates for prostatic cancer were about equal in all three treatment groups. It is concluded that intramuscular PEP monotherapy is associated with low cardiovascular mortality and with an all‐cause and prostatic cancer mortality equal to orchiectomy.
DNA flow cytometric study of the hyperplastic and neoplastic canine prostate
Authors: Madewell B. R. , Deitch A. D. , Higgins R. J. , Marks S. L. , White R. W. Devere
Published: February 2007

Flow cytometric DNA measurements were carried out on 45 formalin‐fixed, paraffin‐embedded canine prostate tissues. The tissues were categorized as normal, hyperplastic, or neoplastic on the basis of light microscopic examination, and DNA ploidy was compared with histologic classification. Ten normal prostate samples showed diploid DNA histograms, but with proliferation greater than that found in the normal human prostate. Thirteen specimens of benign prostate hyperplasia showed diploid or near‐diploid DNA histograms. Of 22 prostatatic carcinomas, 12 were diploid and 10 were aneuploid, with the majority of the aneuploidy being near‐triploid. The frequency of DNA aneuploidy recognized in canine prostatic carcinoma is similar to findings in human prostatic carcinoma if all their grades of malignancy are included.
Immunoscintigraphy of prostatic cancer: Preliminary results with 111in‐labeled monoclonal antibody 7E11‐C5.3 (CYT‐356)
Authors: Wynant Gordon E. , Murphy Gerald P. , Horoszewicz Julius S. , Neal Charles E. , Collier B. David , Mitchell Edith , Purnell Gary , Tyson Ian , Heal Albert , Abdel‐Nabi Hani , Winzelberg Gary
Published: February 2007

A phase 1 study was conducted with the investigational immunoscintigraphic agent, 111In‐CYT‐356, a radiolabeled, site‐specific immunoconjugate of monoclonal antibody 7E11‐C5.3, in 40 patients with prostatic carcioma and known distant metastases. Each patient received a single intravenous infusion of CYT‐356 (dose range, 0.1–5 mg) radiolabeled with approximately 5 mCi of 111In. None of the patients experienced adverse reactions. One patient who received a 5‐mg dose developed antibodies to the CYT‐356 immunoconjugate. 111In‐CYT‐356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow‐up imaging tests, in one patient. Higher CYT‐356 doses may clear the blood pool more slowly. These results suggest that 111In‐CYT‐356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.
Determination of prostatic secretion in rats: Effect of neurotransmitters and testosterone
Authors: Wang Jin‐Min , McKenna Kevin E. , Lee Chung
Published: February 2007

To study the neuronal and hormonal control of prostatic secretion, the prostatic urethra was cannulated in urethane anesthetized rats. The volume of prostatic secretion was measured following infusion of cholinergic and adrenergic agonists in intact animals. Prostatic secretion was elicited by norepinephrine, phenylephrine, and carbachol; but not by clonidine, isoproterenol, pilocarpine, or acetylcholine. Phenylephrine and norepinephrine infusions caused a high initial rate of secretion, which then declined rapidly. Carbachol infusion, in contrast, produced a low but constant rate of secretion that was maintained for up to 1 hour. Histological examination of the prostate revealed contraction of smooth muscle surrounding prostatic ducts after infusion of phenylephrine and norepinephrine, but not carbachol. Prostatic secretion was also measured in castrated rats supplemented with various doses of testosterone. Testosterone exerted a dose dependent control of prostatic weight and secretory volume. These results indicate 1) α 1 receptor agonists can cause contraction of smooth muscle to expel fluid from the rat prostate, 2) carbachol induces prostatic secretion through a mechanism other than contraction of gland, and 3) testosterone has a primary role in controlling prostatic size.
Morphometric and stereological study of the glandular epithelium of the lateral prostate of the intact and castrated guinea pig
Authors: Tam C. C. , Wong Y. C. , White F. H. , Fowler J. P.
Published: February 2007

The glandular epithelium of the lateral prostate of the guinea pig was described within the framework of a morphometric model in terms of relative densities and absolute dimensions. A combination of direct measurement and point and intersection counting techniques was used. The quantitative data generated in the intact animals were compared with those of castrated controls. Castration was accompanied by a significant decrease in height of the glandular epithelium and in sizes of secretory and basal cells and their corresponding nuclei. On a per cell basis, significant decreases in total volume and surface area of granular endoplasmic reticulum were detected after castration. This was accompanied by a significant reduction in the total volume of Golgi cisternae. The total volume, surface area, and number of highly electron‐dense and clear granules decreased significantly compared with the intact control animals. However, no significant changes in these parameters of low electron‐dense granules were found. Significant reductions in the total volume and surface area of condensing granules, lysosomes, and mitochondria, but not their number, were detected. The average sizes of condensing granules, secretory granules, lysosomes, and mitochondria were decreased significantly after castration. The present study showed that the alterations in the secretory function of the secretory cells of the lateral prostate was reflected by the quantitative changes in granular endoplasmic reticulum, Golgi complexes, and secretory granules on a per cell basis. The data generated in the present study will serve as a baseline for further studies of the lateral prostate of the guinea pig.
Family aggregation of cancer of the prostate in quebec: The tip of the iceberg
Authors: Ghadirian Parviz , Cadotte Marcel , Lacroix André , Perret Chantal
Published: February 2007

Cancer of the prostate is one of the most common cancers among males in North America. Although some causative factors have been suggested by several surveys, the etiology of this common cancer is poorly understood. In a case‐control study of prostatic cancer in Greater Montreal, 21 of 140 patients with prostatic cancer (15.0%) gave a positive family history of the same cancer, as compared with two cases among 101 (2.0%) population‐based controls. This indicates about an eightfold difference in occurrence of cancer of the prostate among first‐degree family members of the case group with an odds ratio (OR) of 8.7 and 95% CI, 2.00–38.17. In this report we present the pedigrees of three families (two cases and one control) with four pathologically confirmed cases of cancer of the prostate in each family. This data suggest that a familial predisposition to prostatic cancer may become apparent in later decades of life. In these family aggregations, in addition to the genetic factors, environmental factors may also play an important role in the etiology of the same cancer among family members.
Beta adrenergic receptor alterations in diabetic rat prostate: Effects of insulin and dietary myoinositol
Authors: Gousse Angelo , Yoshida Masaki , Weiss Robert M. , Latifpour Jamshid
Published: February 2007

As sexual dysfunction is a well‐recognized manifestation of diabetes mellitus and as the function of the prostate, a major accessory organ in the male reproductive system, is regulated by the autonomic nervous system, we studied beta adrenergic receptors in the prostate of streptozotocin‐induced diabetic rats, using radioligand receptor binding techniques. Four groups of rats were maintained for 8 weeks: controls, diabetics, insulin‐treated diabetics, and myoinisitol‐treated diabetics. The diabetic and myoinisitol‐treated diabetic animals were smaller, had higher blood glucose levels, higher water intake and urine output, smaller prostates, and lower serum insulin levels than the other groups. Saturation experiments with [3H]dihydroalprenolol showed that the induction of diabetes decreased the density of beta adrenergic receptors in prostatic membrane particulates. Inhibition studies with selective beta adrenergic antagonists demonstrated that these receptors were of the beta2 subtype. Furthermore, insulin but not myoinositol treatment normalized blood glucose and insulin levels, maintained normal prostate and body weight‐gain, and prevented the decrease in the density, i.e., down‐regulation, of the prostatic beta adrenergic receptors.
Glycoconjugates of the lateral prostate of the guinea pig: A lectin histochemical study
Authors: Chan L. , Wong Y. C.
Published: February 2007

The present study examined the glycoconjugates of the lateral prostate using a battery of lectins. The results indicated that the secretory epithelium was rich in mannose (Man), N‐acetylglucosamine (GlcNAc), galactose (Gal), N‐acetylgalactosamine (GalNAc), and complex oligosaccharides. Con A (concanavalin A), LCA (Lens culinaris agglutinin), PSA (Pisum sativum agglutinin), WGA (wheat germ agglutinin), PWM (pokeweed mitogen), RCA‐I (Racinus communis isolectin I), and PHA‐P (Phaseolus vulgaris agglutinin‐P) reacted intensely with both epithelia and stroma, while SBA (soybean agglutinin) and PNA (peanut agglutinin), which bind to terminal Gal, GalNAc, and Gal β1,3 GalNAc appeared to be specific to the secretory epithelium. SBA and PNA were useful as markers in the study of the secretory function of the prostate gland. The present study has shown that the Golgi apparatus of prostatic epithelial cells was rich in fucose (Fuc), oligomers of GlcNAc, Gal β1,3 GalNAc, Gal, and Man containing glycoconjugates, indicating that the gland was actively involved in glycosylation. The present study has also shown that LTA (Lotus tetragonolobus agglutinin) is a good marker for the epithelial Golgi. PNA also bound to the epithelial basement membrane and the connective tissue in the lamina propria. The present study has thus established, for the first time, the glycoconjugate patterns in the lateral prostate of the guinea pig.