bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostatein C3‐mRNA: A sensitive marker of androgen‐responsiveness in prostate explant cultures
Authors: Shao T. C. , Kong A. , Young C. , Chu W. H. , Tindall D. J. , Cunningham Glenn R. 
Published: February 2007

AbstractProstatein is an androgen‐dependent protein which is secreted by the rat ventral prostate. To determine if prostatein or its mRNA were responsive to androgen in vitro, prostate explants were cultured in media containing 0 or 25 nM dihydrotestosterone (DHT), estradiol (E2), or cortisol (F). Prostatein concentrations in medium were measured by radioimmunoassay at 2 and 4 days and in homogenates at 4 days. They were not changed significantly by any of these steroids. The concentration of the mRNA for the C3‐subunit of prostatein was determined by dot hybridization at 0, 2, 4, 6, and 8 days. It was decreased significantly by 2 days when compared with explants cultured in the presence of DHT and significant differences persisted through 8 days.In conclusion, quantitation of the mRNA for the C3‐subunit of prostatein in short‐term cultures of ventral prostate explants appears to be more sensitive to changes in androgen concentration than does measurement of prostatein, per se. Prostatein C3‐mRNA may be a useful marker for in vitro studies of androgen agonists and antagonists.
Effects of androgen and antiandrogen treatment on canine prostatic arginine esterase
Authors: Juniewicz P. E. , Barbolt T. A. , Egy M. A. , Frenette G. , Dube J. Y. , Tremblay R. R. 
Published: February 2007

AbstractA series of experiments were conducted to investigate the regulation of the primary secretory protein of the canine prostate, arginine esterase, by androgens and/or new antiandrogens under development. In the first experiment, castration decreased (P<0.05) prostatic arginine esterase levels relative to intact controls (0.26±0.1 and 17.0±0.1 μmole/min/mg protein, respectively). Treatment of castrate dogs with either 5, 10, or 20 silastic capsules (8 cm length) containing the androgen 5α‐androstane‐3α, 17β‐diol (3α‐diol) plus 1 capsule containing estradiol‐17β (E2) or the i.m. injection of 25 mg 3α‐diol and 0.25 mg E2 for 12 weeks resulted in a dose‐dependent increase (P<0.05) in prostatic arginine esterase activity (6.8±1.7, 19.0±3.6, 21.3±0.9, and 14.2±0.7 μmole/min/mg protein, respectively). In the second experiment, steroid treatment (10 3α‐diol plus 1 E2 silastic capsules) of castrate dogs for 12 weeks resulted in prostatic arginine esterase activity of 17.8±2.3 μmole/min/mg. Co‐administration of the steroidal androgen receptor antagonist Win 49,596 (WIN) at doses of 0.625, 2.5, 10, or 40 mg/kg/day p.o., dose‐dependently inhibited (P<0.05) prostatic arginine esterase activity (14.9±1.1, 14.3±1.3, 3.4±1.9, and 0.21±0.1 μmole/min/mg, respectively) to levels similar to that observed in castrate controls (0.14±0.03 μmole/min/mg). Administration of the nonsteroidal androgen receptor antagonist flutamide at 10 mg/kg/day p.o. to steroid‐induced dogs also inhibited (P<0.05) arginine esterase activity (0.07±0.02 μmole/min/mg). In the last experiment, treatment of intact dogs with WIN at 0.625, 2.5, 10, and 40 mg/kg/day for 16 weeks dose‐dependently reduced (P<0.05) arginine esterase levels (17.0±1.0, 16.3±1.5, 10.2±1.2, and 3.9±2.5 μmole/min/mg, respectively) compared to intact controls (14.4±1.2 μmole/min/mg). Histomorphologic and ultrastructural evaluation of prostates from dogs indicated that antiandrogen treatment resulted in glandular epithelial atrophy as well as a reduction in the number of secretory granules. The results of these experiments support that canine prostatic arginine esterase activity is under androgenic control, can be inhibited by antiandrogen treatment and may serve as a functional marker of the androgenic state of the prostate. Whether the effects of androgen and antiandrogens on prostatic arginine esterase is direct or indirect due to a general inhibitory effect on secretory epithelial cell function requires additional study. Furthermore, subject to further evaluation, the steroidal androgen receptor antagonist, Win 49,596, may be useful in the treatment of androgen‐dependent disorders of the prostate.
Experimental prostatitis in nonhuman primates: II. Ascending acute prostatitis
Authors: Neal Durwood E. , Dilworth J. Patrick , Kaack M. Bernice , Didier Peter , Roberts James A. 
Published: February 2007

AbstractBacterial prostatitis is a common cause of urinary tract infection in males, but little is known of its pathophysiology. To study this, we developed a nonhuman primate model using a wild‐type clinical isolate of Escherichia coli. Primates have a prostatic anatomy that is similar to humans, which makes them ideal as an animal model of this disease. The monkeys had a urethral inoculation of this organism and were then followed with urine, blood, and semen cultures, white blood counts, and renal scans. They were sacrificed at from 10 days to 4 weeks, and their genitourinary tracts histologically examined. The prostatitis paralleled that reported in humans, and we conclude that the infection occurs by the ascending route. The organisms causing the infection in man do so in our primate model, and the histologic change is also the same. Thus, the primate model holds promise for studies to help us understand this disease.
A comparison of Zoladex® and DES in the treatment of advanced prostate cancer: Results of a randomized, multicenter trial
Authors: Citrin Dennis L. , Resnick Martin I. , Guinan Patrick , Al‐Bussam Nazar , Scott Mark , Gau Timothy C. , Kennealey Gerard T. 
Published: February 2007

AbstractThis open, prospective study was conducted to compare ZOLADEX® (goserelin acetate implant) and diethylstilbestrol (DES) in the treatment of stage D2 prostate cancer. Sixtyseven patients were allocated to receive 3.6 mg of ZOLADEX® every 28 days by subcutaneous injection (n=48) or 3 mg of DES daily by oral administration (n=19). Median serum levels of testosterone were reduced to castrate levels (<50 ng/dl) within one month of therapy in each group and remained so for up to 120 weeks. According to modified criteria of the National Prostatic Cancer Project, 88% of patients in the ZOLADEX® group and 84% in the DES group were objective responders. Time to treatment failure and survival were not significantly different between groups, yet the confidence limits for the hazard ratios were wide. ZOLADEX® was better tolerated than DES. We conclude that ZOLADEX® is an alternative to DES in patients with stage D2 prostate cancer.
Steroid receptor profile in human prostate cancer metastases as compared with primary prostatic carcinoma
Authors: Ekman Peter , Brolin Jan 
Published: February 2007

AbstractThe steroid receptor profile in seven prostate cancer metastases was compared with the profile in seven primary prostate cancers. The secondaries were all lymph node metastases, obtained during pelvic lymphadenectomy, preceeding radical prostatectomy or irradiation. Cytosol androgen receptor content was higher in metastases, whereas the nuclear androgen receptor content was only one‐fourth that in primary cancer. Cytosol progesterone as well as estrogen receptor contents were markedly lower in metastases compared with primary cancer. The steroid receptor profile differed very little between primary cancer and normal tissue. Primary prostatic carcinoma is usually obtained at early stages of the disease, whereas metastases represent a dedfferentiated, more aggressive cell population. This may explain the low amounts of progesterone, estrogen, and nuclear androgen receptor levels. The total androgen receptor content was similar in metastatic and primary disease, however, with a shift towards a cytosolic predominance in metastases. Possibly androgen receptors in metastatic disease are “deactivated.”
Estramustine binding protein (EMBP) in rat R3327 dunning tumors: Partial characterization and effect of hormonal withdrawal, hormonal replacement, and cytotoxic treatment on its expression
Authors: Björk Per , Isaacs John T. , Hartley‐Asp Beryl 
Published: February 2007

AbstractExpression of estramustine‐binding protein (EMBP) was determined in eight variants of the Dunning R3327 rat prostate adenocarcinoma. This secretory protein was previously isolated from the normal rat prostate and binds estramustine and estromustine, the metabolites exerting anti‐mitotic and anti‐proliferative activity of the anticancer agent estramustine phosphate (EstracytR). EMBP was found in relatively high amounts only in the androgenresponsive G and H tumors from intact hosts, whereas low (AT‐1, HI‐F) or nondetectable levels (HI‐S, AT‐3, MAT‐LyLu, MAT‐Lu) were obtained in the androgen‐independent tumors. Castration decreased EMBP expression in both G and H tumors, as did estradiol and estramustine when given separately to intact rats. Supplementation of castrates with exogenous androgen stimulated EMBP expression above the pre‐castration level and was further enhanced when combined with estradiol and in particular estramustine. Partial physicochemical characterization of EMBP in G and H tumors was performed by using ligand‐based and immunoblotting techniques. [3H]Estromustine was bound to cytosols and salt extracts from tumors with the same affinity and displayed similar surface‐charge distribution, sedimentation behavior, and subunit composition as found for ventral and dorsolateral prostatic tissue from tumor‐bearing rats. This study indicates that the synthesis of EMBP is under androgenic control and that its expression may be correlated to androgen responsiveness, metastatic potential, and androgen receptor content but not to growth rate and morphology of the tumors. EMBP may therefore provide a mechanism for concentration of cytotoxic activity at the target site in EMBP‐positive tumors and help in the evaluation of antitumor effects obtained when administering estramustine.
Histological changes in dunning prostate tumors and testes of rats treated with LH‐RH antagonist SB‐75
Authors: Szepeshazi Karoly , Korkut Edib , Szende Bela , Lapis Karoly , Schally Andrew V. 
Published: February 2007

AbstractRats bearing Dunning R‐3327 hormone‐dependent prostate tumors were treated with LH‐RH antagonist SB‐75 in the form of microcapsules for sustained delivery administered every 3 weeks and which released 24, 48, 72 μg/day respectively. The effects were compared with those of microcapsules of the agonist D‐Trp‐6‐LH‐RH releasing 25 μg/day. Both types of LH‐RH analogs significantly inhibited tumor growth over a period of treatment lasting 8 weeks. The effect of SB‐75 was dose‐dependent. The total inhibition of spermatogenesis, as well as atrophic signs in the prostate and seminal vesicles, demonstrated a marked suppression of the pituitary‐gonadal system by these analogs.The histological signs of tumor regression were analyzed. The vascular content of tumors did not change after the treatments, but an increased amount of connective tissue was found in the treated tumors, especially after administration of SB‐75. Both the agonist and the antagonist caused a moderate decrease of the number of mitotic cells and a marked increase of apoptosis in the tumors. The apoptotic index, i.e. the percentage of tumorous glands showing signs of apoptosis, reached 40–50% in treated groups, compared to only 15% in controls. An apoptotic index of 60% was noted in a separate group of rats treated with 200 μg SB‐75/animal/day for 3 days. The signs of enhanced apoptosis disappeared 1 week after the short‐term treatment. The induction of apoptosis by LH‐RH analogs seemed to be of greater importance in tumor growth inhibition than their antimitotic effect. These results extend our previous observations on the efficacy of LH‐RH antagonists in inhibition of various cancers. This histopathologic evaluation clearly supports our contention that modern antagonists of LH‐RH, free of edematogenic effects, inhibit the growth of Dunning prostate tumors. Because of the immediate inhibitory effects, the use of LH‐RH antagonists might lead to an improvement in the clinical response in patients with prostate cancer.
In vivo assay for conversion of testosterone to dihydrotestosterone by rat prostatic steroid 5α‐reductase and comparison of two inhibitors
Authors: Toomey Richard E. , Goode Robin L. , Petrow Vladimir , Neubauer Blake L. 
Published: February 2007

AbstractAn in vivo assay for steroid 5α‐reductase in rat ventral prostate has been developed and used to compare the inhibitory activity of N,N‐diethyl‐4–methyl‐3–oxo‐4–aza‐5 a‐andro‐stane‐17 β‐carboxamide (4–MA) and 6–methylene‐4–pregnene‐3,20–dione (LY207320). Immature rats (70–80 g) received test compounds 30 min prior to s.c. injection of [3H]‐T. The rats were sacrificed 30 min later and the ventral prostates were analyzed for [3H]‐T metabolites. Intraprostatic [3H]‐T and [3H]‐DHT reached peak levels within 5 min after injection of [3H]‐T and declined to about 25% of peak levels after 2 hr. 4–MA was a very potent inhibitor of [3H]‐DHT formation with an estimated IC50 of 0.2 mg/kg. LY207320, an inhibitor of 5α‐reductase in vitro, was weakly active in vivo and did not achieve greater than 45% inhibition at high doses (> 200 mg/kg, s.c.). Tissue uptake of [3H]‐T was also inhibited by LY207320, which may contribute to its inhibitory activity on accessory sex organ growth in the rat.
Distribution of langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade
Authors: Bigotti Giulio , Coli Antonella , Castagnola Diana 
Published: February 2007

AbstractWe have investigated Langerhans cell (LC) distribution in 38 prostatic carcinomas, of various degrees of differentiation, by immunohistochemistry with a polyclonal anti‐S‐100 serum, furthermore evaluating the expression of HLA class II‐DR by neoplastic cells using a monoclonal antibody (MoAb) that reacts with a monomorphic determinant in formalin‐fixed paraffin‐embedded tissue. Antiserum to S‐100 protein identified LCs mostly in carcinomas ranging from grade 1 to grade 2, while LCs were inconspicuous in grade 4 and virtually absent in grade 5 cancers. Moreover, sections stained with the anti ‐HLA‐DR MoAb displayed an immunoreactivity, both cytoplasmic and apical, especially confined to neoplastic glands of low grade (1–2) carcinomas. Although we did not find a direct correlation between the two parameters under investigation and lymphoid infiltrate, we were able to document an increased number of HLA class II‐positive interstitial cells in low‐grade carcinomas, corresponding mostly to macrophages.Our results indicate that LC number is inversely correlated to the histopathological grade and directly to the expression of HLA class II‐DR molecules by tumor cells; we believe that this might be important in understanding the more favorable biological behavior of low‐grade prostate carcinomas as opposed to the higher grades, since LCs and HLA class II molecules may provide a means of eliciting the immune response, both LCs and epithelial cells expressing HLA class II molecules being capable of direct antigen presentation to immune cells. In this context macrophages might play a primary role in controlling tumor progression. To the best of our knowledge this is the first time that an attempt is made to correlate LCs and HLA class II expression to histopathological grading of prostatic carcinomas. We would also suggest that the presence of LCs and HLA class II molecules, either singly or in combination, in carcinoma of the prostate represents a good prognostic indicator, being constantly associated with the clinically less aggressive low‐grade tumors. The evaluation of these two parameters might prove useful in the assessment of intermediate grades where no valid histologic criteria have been found to predict the clinical course of the disease.
Relation of endocrine‐paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate
Authors: Bonkhoff Helmut , Wernert Nicolas , Dhom Georg , Remberger Klaus 
Published: February 2007

AbstractThe relative distribution pattern of the pan‐endocrine marker Chromogranin A (Chr A) and the proliferation‐associated Ki‐67 antigen was investigated in 20 prospectively sampled prostatectomy specimens. In cryostat sections, the Chr A immunoreactivity showed evidence of endocrine differentiation in all 15 prostatic adenocarcinomas. Nine tumors displayed a weak, 5 a moderate, and 1 adenocarcinoma a strong endocrine differentiation. These findings highlight the importance of endocrine differentiation in prostate malignancy that histologically resembles ordinary adenocarcinomas.The simultaneous demonstration of Ki‐67 and Chr A revealed that in normal, hyperplastic, and neoplastic prostate tissue Chr A‐positive cells were preferentially situated in proximity to Ki‐67‐labeled cells. This relative distribution pattern of both markers may indicate that endocrine cells are involved in controlling cell proliferation through a paracrine hormonal mechanism. However, an obvious correlation was not found between the degree of endocrine differentiation and proliferative activity in prostatic adenocarcinomas. Furthermore, a coexpression of Ki‐67 and Chr A in the same (tumor) cells was not observed suggesting that the endocrine phenotype is only expressed in the G0 phase of the cell cycle as well as in normal, hyperplastic, and neoplastic conditions.
Morphological and functional similarities between cultured prostatic stromal cells and testicular peritubular myoid cells
Authors: Swinnen Kristien , Deboel Ludo , Cailleau Jean , Heyns Walter , Verhoeven Guido 
Published: February 2007

AbstractA number of androgen effects on epithelial cells may be mediated by androgen‐regulated paracrine factors produced by underlying mesenchymal cells. In previous studies we demonstrated that prostatic stromal cells and testicular peritubular cells, derived from immature rats, produce mediators of androgen action with identical effects on Sertoli cells. In the present paper we further compared the morphological and functional characteristics of both mesenchymal cell types. Cultured prostatic stromal cells and testicular peritubular cells look identical under phase‐contrast microscopy, share the ability to form tubular structures and „balls”︁ when cocultured with Sertoli cells, and contain proteins immunoreactive with an antiserum against α‐smooth muscle isoactin. Two‐dimensional gel electrophoresis shows that the pattern of proteins produced by both cell types is nearly identical. Conditioned media from stromal and peritubular cells contain a factor that stimulates transferrin and cGMP production in Sertoli cells. The behavior of the active principle in the media from both cell types is comparable. On reverse‐phase HPLC the elution profile of this factor is comparable for media from both cell types. In conclusion, these data point to a striking similarity in the morphological and functional characteristics of mesenchymal cells cultured from the prostate and testis.
Prostate plasma membrane receptor: A hypothesis
Authors: Farnsworth Wells E. 
Published: February 2007

AbstractBased on 50 years of emerging knowledge about and changing views of prostate biochemistry and physiology and especially on the belief that there is an underlying mechanism of androgen control, the hypothesis is developed and tested that the rates of proliferation, biosynthesis, metabolism, and secretion are modulated through the hormone‐sensitive Na,K‐ATPase of the plasma membrane. These preliminary experiments, constituting a novel synthesis of technologies from endocrinology, intermediary metabolism, and membrane transport, attempt to explain the extraordinary production and secretion of citrate and how this may be coupled to sustaining prostate cell number and function. Attention is focused on learning where androgen is bound and how it interacts with the Na,K‐ATPase. Both the dissimilar properties of epithelial and stromal cells in the separate regions of the acinus and the changing environment of growth factors in which these cells are bathed help account for their unlike reactivities during development and ongoing mature function. Little wonder that one hormone can have so many effects!
Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells
Authors: Murphy Brian C. , Pienta Kenneth J. , Coffey Donald S. 
Published: February 2007

AbstractThe extracellular matrix (ECM) has been shown to play a major role in cell structure and function. Several studies have demonstrated that the ECM can alter cell morphology and effect DNA synthesis and gene expression. The ECM also interacts with growth hormones which have been shown to be located in or near the ECM where they are believed to effect cell structure and function. In the nontransformed cell, these ECM and hormone‐mediated effects appear to be tightly regulated and this is believed to be accomplished through cell receptor‐tissue matrix interactions. We, therefore, undertook a study to determine the effects of a variety of ECM components and the androgenic hormone dihydrotestosterone (DHT) on the structure and function of the human prostate cancer cell line, LNCaP. The effects of individual matrix components in the presence and absence of 1 nM DHT on the static and dynamic morphology, growth rate, and PSA production of the LNCaP cell line were studied. We determined that the ECM and DHT interact in complex ways to effect cell structure and function. DHT produced alterations in cytoplasmic structure that increased cell size and decreased the nuclear area/cytoplasmic area ratio. Dynamic cell structure as measured by cell motility was very sensitive to the ECM components and the presence of DHT. PSA and growth could be regulated by substratum and DHT and there was an inverse relationship between PSA production and growth rate. These data exemplify the complex interactions which occur between prostate cancer cells, ECM components, and exogenous DHT that are reflected in cell structure and function.