bluuebunny/crossref_metadata_2025_split huggingface dataset:
LY207320 (6‐methylene‐4‐pregnene‐3,20‐dione) inhibits testosterone biosynthesis, androgen uptake, 5α‐reductase, and produces prostatic regression in male rats
Authors: Neubauer Blake Lee , Best Kevin L. , Blohm Thomas R. , Gates Cynthia , Goode Robin L. , Hirsch Kenneth S. , Laughlin Marie E. , Petrow Vladimir , Smalstig E. Barry , Stamm Nancy B. , Toomey Richard E. , Hoover Dennis M. 
Published: February 2007

AbstractLY207320 is an in vitro inhibitor (estimated IC50 = 0.06 μM) of steroid 5α‐reductase that catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). In contrast, LY207320 was only moderately active against rat prostatic 5α‐reductase in vivo (32% inhibition at 50.0 mg/kg single dose). LY207320 did, however, inhibit the in vivo uptake of [3H]‐T by the prostate. The antiprostatic and endocrine effects of this agent were evaluated following daily (21 days) administration to castrated, androgen‐supplemented castrate, and intact rats. LY207320, which has modest progestational competitive binding activity, does not bind to rat prostatic androgen or uterine estrogen cytosolic receptors. In the castrated male rat, subcutaneously (s.c.) administered LY207320 had no androgen agonist activity, as evidenced by a lack of accessory sex organ weight gains. Administration of s.c. LY207320 to intact rats for 21 days at doses greater than 5.0 mg/kg‐day produced significant (P <0.05) reductions of seminal vesicle and ventral prostatic weights (maximal regression = −65% and −40% from control values, respectively at 50.0 mg/kg‐day). The compound had no regressive activity on male accessory sex organs when administered orally. LY207320 did not alter circulating prolactin, LH, or corticosterone levels, but at high doses (>m50.0 mg/kg‐day), lowered circulating T[−67% from intact control levels (P <0.05)]. Histological analysis of the rat ventral prostates (RVPs) in LY207320‐treated rats was consistent with an androgen‐deprived state. Decreased circulating androgens and prostatic regression are associated with inhibition of testicular 17α‐hydroxy/C17,20‐lyase enzyme activity (IC50 = 0.06 μM). These findings support the contention that LY207320 is a physiological antagonist of androgen action in male rats, and that its effects are mediated primarily through inhibition of testicular androgen production rather than accessory sex organ 5α‐reductase. © 1993 Wilcy‐Liss, Inc.
Endocrine and antiprostatic effects of raloxifene (LY156758) in the male rat
Authors: Neubauer Blake Lee , Best Kevin L. , Clemens James A. , Gates Cynthia A. , Goode Robin L. , Jones C. David , Laughlin Marie E. , Shaar Carl J. , Toomey Richard E. , Hoover Dennis M. 
Published: February 2007

AbstractThe benzothiophene anti‐estrogen, raloxifene [LY156758; (6‐hydroxy‐2‐(4‐hydroxyphenyl) benzo(b)thien‐3‐yl)(4‐(2‐1‐piperidinyl)ethoxy)phenyl methanone hydrochloride] has selective estrogen pharmacological antagonist activity in female rats. The present studies were done in the male rat to assess activity of raloxifene related to inhibition of prostatic growth and effects on the hypothalamic‐pituitary‐gonadal axis. Raloxifene did not compete for binding of the androgen, [3H]‐methyltrienolone (R1881) in cytosolic extracts of ventral prostate. Similarly, the compound did not inhibit prostatic 5α‐reductase or testicular 17α‐hydroxy/C17,20‐lyase activities. Raloxifene had no effect on the ventral prostatic uptake of [3H]‐R1881 in vivo. Administration of estradiol to castrated male rats stimulated fourfold increases of in vitro ventral prostatic binding of [3H]‐R1881. Raloxifene was devoid of agonist activity in castrated animals, because the compound had no stimulatory effect on prostatic androgen receptor binding activity. When raloxifene was coadministered with estradiol, the compound markedly antagonized the estrogen‐induced increase of prostatic [3H]‐R1881 binding, confirming its antiestrogenic properties in male rats. Serum prolactin was also elevated significantly (P <0.05) with a single injection of raloxifene (20.0 mg/kg). In these same animals, serum FSH was significantly (P <0.05) decreased by one dose (10.0 mg/kg) of the compound. Luteinizing hormone levels in castrated male rats were unaffected by raloxifene administration. Raloxifene treatment of castrated males significantly (P <0.05) antagonized the stimulatory response of the ventral prostate (VP) to exogenous androgens in a dose‐dependent manner. Raloxifene treatment of intact male rats for 14 and 28 days produced significant (P <0.05) dose‐dependent regression of the VP and seminal vesicles (SV). The VP regressive responses to raloxifene were associated with a decline in serum testosterone levels. Histological analysis of the VPs in raloxifene‐treated rats was consistent with an androgen‐deprived state. These findings support the contention that raloxifene is a pure estrogen antagonist and a physiological antagonist of androgen action in male rats. These pharmacological properties provide support for further structure‐activity and mechanistic investigations with benzothiophenes in the medical management of prostatic neoplasia. © 1993 Wiley‐Liss, Inc.
Use of percutaneous transperineal 198Au seeds to treat recurrent prostate adenocarcinoma after failure of definitive radiotherapy
Authors: Loening Stefan A. , Turner J. Wesley 
Published: February 2007

AbstractPatients who fail external radiation therapy for prostatic cancer pose a therapeutic challenge. No further external radiation treatment can be delivered safely to the local lesion, although some patients are candidates for salvage surgery. In this study, 31 patients who failed prior external beam radiotherapy received percutaneous transperineal placement of gold seeds (198Au). Initial prostate volume was 17.7 cc and decreased to 10 cc 24 months after 198Au implantation. Of 15 patients biopsied at 12 months after treatment, 4 (27%) were positive, 6 (40%) were negative, and 5 (33%) showed prostate cancer with radiation changes. Two of three patients have died of prostate cancer, with an overall 5‐year estimated survival of 67%. Interstitial brachytherapy was found to be an additional welltolerated treatment modality in this group of 31 patients. © 1993 Wiley‐Liss, Inc.
Expression of NEU/HER‐2 oncoprotein (p185neu) in prostate tumors: An immunohistochemical study
Authors: Giri Dipak K. , Wadhwa Surender N. , Upadhaya Sakti N. , Talwar Gursaran P. 
Published: February 2007

AbstractThe expression of the neu oncogene product was investigated immunohistochemically in 36 cases of benign prostatic hyperplasia (BPH) and seven cases of adenocarcinoma of prostate (CaP). c‐neu oncogene encodes a transmembrane growth factor receptor that has partial structural homology with EGF receptor, and is overexpressed and amplified in a number of human tumors, specially, breast cancers. Using a monoclonal antibody, AB‐3, which recognizes ‐COOH‐terminal of neu oncoprotein, we have analyzed immunohistochemically the expression of this protein in buffered formalin and Zamboni fluid‐fixed surgically removed tissues. Focal patchy and/or diffused cytoplasmic staining of varying intensity was observed in 34 of 36 BPH cases. Four cases showed cell membrane staining as well (4/36 = 11%). All seven cases of adenocarcinomas had moderate to strong c‐neu immunoreactivity, and two gave a distinct cell membrane‐positive reaction (100%). The available data indicate that prostatic tumors as well as a high percentage of prostatic hyperplasia tissues express c‐neu protein; however, its role in cellular proliferation needs further study. © 1993 Wiley‐Liss, Inc.
Regulation of prostate‐specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth, dihydrotestosterone, and extracellular matrix
Authors: Guo Yue , Pili Roberto , Passaniti Antonino 
Published: February 2007

AbstractWe have examined the role of extracellular matrix (ECM), cell growth, and dihydrotestosterone on the expression of prostate‐specific antigen (PSA) by human prostatic carcinoma cells LNCaP. ECM induced a transient decrease in PSA mRNA even in the presence of growth factors. PSA mRNA, but not actin mRNA, was down‐regulated on ECM in a biphasic manner and was not detected up to 48 hr after culture, but was re‐expressed after 3 days. Cycloheximide and actinomycin D pretreatment did not prevent ECM‐induced down‐regulation of PSA mRNA, while actinomycin D‐treated cells on plastic maintained stable PSA mRNA levels. DNA synthesis and PSA glycoprotein secretion were also transiently suppressed on ECM. LNCaP growth inhibition correlated with decreased glyceraldehyde phosphate dehydrogenase mRNA levels. However, the transient growth suppression induced by ECM was not observed with primary endothelial cells on Matrigel. Down‐regulation of PSA mRNA by culture on Matrigel was reversible upon transfer to a different matrix substrate. Re‐expression was highest on heparan sulfate proteoglycan (4‐fold) and fibronectin or collagen I (2‐fold) compared to plastic or laminin. Our results indicate that the morphology and proliferation of LNCaP cells may be regulated by the ability of ECM to control cellular differentiation and proliferation. © 1994 Wiley‐Liss, Inc.
Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep
Authors: Hahn Robert , Stalberg Holger , Carlström Kjell , Hjelmqvist Hans , Ullman Johan , Rundgren Mats 
Published: February 2007

AbstractWe estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls.Glycine infusions resulted in a four‐fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP‐stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the “transurethral resection (TUR) syndrome”.The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow‐up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration.The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance. © 1994 Wiley‐Liss, Inc.
Estramustine potentiates the effects of irradiation on the dunning (R3327) rat prostatic adenocarcinoma
Authors: Widmark Anders , Henriksson Roger , Damber Jan‐Erik , Bergh Anders 
Published: February 2007

AbstractThe present study was designed to determine if estramustine phosphate (EMP) could potentiate the effects of irradiation on the Dunning (R3327) prostatic adenocarcinoma in rats. Two groups of male Copenhagen × Fisher F1 rats carrying bilateral tumors in the flank were used. Irradiation was given with a linear accelerator 6 MV, in a dose of 6 Gy/day for 4 days to the tumor on one side while the tumor on the other side served as control. EMP (360 μg/24 hours) was administered with osmotic pumps to one group of rats for 2 weeks, starting 1 week before irradiation. Tumor growth was calculated by measuring tumor volume, and tumor blood flow was measured 8 weeks after treatment. Irradiation alone effectively delayed tumor growth and EMP enhanced these effects. Tumor blood flow was stimulated by EMP treatment irrespective of radiotherapy. Volume density of tumor epithelium was effectively decreased by irradiation but no significant effects could be seen after EMP. In conclusion, the present study shows that EMP potentiates irradiation on rat prostatic adenocarcinoma, and further evaluation of this therapeutic approach in the clinical treatment of prostatic carcinoma is thus justified. © 1994 Wiley‐Liss, Inc.
Human leukocyte antigen subtype analysis in patients with advanced adenocarcinoma of the prostate
Authors: Akdaş Atif , Türkeri Levent , Alican Yusuf , Şimşek Ferruh , Akoǧlu Tevfik 
Published: February 2007

AbstractHuman leukocyte antigens (HLA) are cell surface glycoproteins that have a significant role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumor cells may escape host immunity. HLA analysis in patients with advanced adenocarcinoma of the prostate revealed the antigens with the highest relative risk factors as DRw52, DRw53, Bw73, DR2, and B5(51). As a result, determination of HLA haplotypes may prove to be useful in determining the men with a higher risk of developing prostate cancer. © 1994 Wiley‐Liss, Inc.
Enhancement of hyperthermic toxicity by lonidarnine in the dunning R3327G rat prostatic adenocarcinoma
Authors: Bloch William E. , Lokeshwar Balakrishna L. , Ferrell Sean M. , Block Norman L. 
Published: February 2007

AbstractHyperthermia alone or with radiation is used therapeutically for localized solid tumors. Clinical experience shows that sustained tumor temperature exceeding 45°C damages normal tissue. Any agent that enhances the effects of hyperthermia at or below this temperature may have clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony‐formation assays, cytotoxic effects of each agent alone and in combination were quantified. Lonidamine to 100 μg/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after fractionated hyperthermia revealed a rapid development and decay of thermotolerance. Measurement of cell‐cycle progression following a single dose of hyperthermia revealed a reduction of S‐phase cells, and subsequent accumulation in G1 over 24 hours. Combination treatment of tumor‐bearing rats significantly reduced tumor growth rate when compared with individual agents. These results suggest a potential use of lonidamine in hyperthermic therapy of prostate tumors. © 1994 Wiley‐Liss, Inc.
Influence of culture media on the morphological differentiation of the PC‐3 and DUI45 prostatic neoplastic cell lines
Authors: Camby Isabelle , Dedecker Robert , Danguy André , Pasteels Jean‐Lambert , Kiss Robert , Petein Michel , Etievant Chantal , Van Velthoven Roland 
Published: February 2007

AbstractThe concept of differentiation of prostate cancer in terms of morphonuclear Characteristics and population dynamics was investigated on the PC‐3 and DU145 cell lines. A software based on the concept of Voronoi paving was set up in order to characterize the structure of these cell lines growing in vitro on histological slides. The morphonuclear characteristics were assessed by means of the digital cell image analyses of Feulgen‐stained nuclei. The in vitro “morphonuclear” and “pseudo‐tissular” differentiations of the PC‐3 and DU145 cells were described in terms of the use of various culture media, i.e., media supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and with (or without) platelet‐derived growth factor and dihydrotestosterone (PA10 and PA1 media). The present data reveal that the PC‐3 cell line would be more hormone‐sensitive than the DU145 one. Indeed, decreasing the FCS concentration in the culture medium while adding DHT and PDGF led to marked modifications to the morphonuclear characteristics of the PC‐3 cells, but not to the DU145 cells. These modifications corresponded to an increase in nuclear size occurring concomitantly with chromatin decondensation. In the same way, spectacular modifications in terms of medium‐induced pseudo‐tissular differentiation were observed in the PC‐3 cell line, but not in the DU145 one. Such modifications corresponded to an increase in clone size related to an increase in the mean distances between neighboring cell nuclei in a given clone. Thus, according to the criteria defined in this study, the PC‐3 cell line would seem to maintain a higher degree of differentiation than the DU145 cell line. © 1994 Wiley‐Liss, Inc.
TRPM‐2 gene expression in normal rat ventral prostate following castration and exposure to diethylstilbestrol, flutamide, MK‐906 (finasteride), and coumarin
Authors: Russo Paul , Warner John A. , Huryk Robert , Perez Gisela , Heston W. D. W. 
Published: February 2007

AbstractTRPM‐2, not normally expressed in the rat ventral prostate, has been identified as an important genetic marker of castration‐induced apoptotic cell death. It is not known whether other agents capable of causing growth inhibition of the rat ventral prostate also induce TRPM‐2 expression. To investigate this further, 270 mature Sprague‐Dawley rats were randomized into one of six groups: control, castration, diethylstilbestrol (DES), flutamide, MK‐906 (finasteride), or coumarin. Five rats per group were sacrificed on days 1, 3, 5, 7, 10, and 21. Serum testosterone, body weights, and prostate weights were determined at each time point. The ventral prostate was removed and cellular RNA extracted. Northern blot analysis using cDNA probes for TRPM‐2 and γ‐actin were performed at each time point.Only DES significantly decreased rat weights. DES and castration reduced serum testosterone to undetectable levels by the next day. Flutamide caused a 3.0‐ to 4.5‐fold increase in serum testosterone above control. Coumarin and MK‐906 did not affect serum testosterone levels. DES and castration reduced prostate weights to 20% and 6% of control, respectively, while inducing TRPM‐2 expression to a maximum on day 5 of the experiment. DES induced TRPM‐2 expression over a longer duration than did castration, suggesting that more than just the decrease of serum testosterone to castrate levels plays a role in the expression of TRPM‐2. MK‐906, coumarin, and flutamide reduced prostatic weights to a lesser extent (50%, 63%, 71% of control, respectively), but these agents did not induce TRPM‐2 expression at any time during the experiment. TRPM‐2 expression in the rat ventral prostate does not correlate simply with catabolic effects on the prostate. © 1994 Wiley‐Liss, Inc.
Natural course of human benign prostatic hyperplasia with relation to urinary disturbance
Authors: Kitagawa Norikazu , Ichikawa Tomohiko , Akimoto Susumu , Shimazaki Jun 
Published: February 2007

AbstractTo examine the natural course of human benign prostatic hyperplasia (BPH), cases in health care examination with or without slight urinary symptoms were examined by echography. In comparison with these cases, the size of the prostate was examined in patients who received prostatectomy. Prostatic sizes of health care cases varied widely along with increasing age, but could be divided into two groups: increasing or no‐change. According to serial determinations of prostatic sizes in the increasing group, the annual growth rate of the prostate was calculated as 1.65 ± 1.13 and 0.85 ± 0.44 g in men <65 years old and in men ≥65 years old, respectively. Distribution of prostatic sizes as a function of age in health care cases was similar to that in operated patients, showing that the size was not correlated with urinary symptoms or surgical indication. Since uroflow rates decreased along with increasing age in the no‐change group of operated patients, aging was a factor in deterioration of uroflow. Between the increasing and the no‐change groups in health care cases, differences were found in total cholesterol and neutral fat in serum, in addition to gamma‐seminoprotein; the latter may be due to differences in the size of the prostate.In conclusion, natural course of the prostatic hyperplasia is separated into two groups, increasing and no‐change. Occurrence of urinary symptoms does not simply relate to an increase in prostatic weight but, at least in part, to the aging process. © 1994 Wiley‐Liss, Inc.
An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer
Authors: Vieweg Johannes , Heston Warren D. W. , Fair William R. , Gilboa Eli 
Published: February 2007

AbstractIn order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327‐MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene‐modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327‐MatLyLu tumors. © 1994 Wiley‐Liss, Inc.
Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy individuals and prostate cancer patients
Authors: Silén Åke , Wiklund Bo , Norlén Bo Johan , Nilsson Sten 
Published: February 2007

AbstractThe serological results from apparently healthy individuals and prostate cancer patients were evaluated with a new assay called TPAcyk ELISA. This assay has a biochemical specificity for fragments of cytokeratins 8 and 18, and exhibits a low within‐ and between‐assay imprecision. The data indicate a significant difference between the results of males and females, but no significant age‐dependent relation was found. The cut‐off value (95% specificity) for healthy individuals was estimated to be 1.27 ng/mL (n = 190) for males and 0.95 ng/mL (n = 81) for females. When using a cut‐off value of 1.27 ng/mL, we found a sensitivity for prostate cancer patients with T2‐3 N0M0 of about 20%. For patients with metastatic disease, a sensitivity of 75% was found. A higher sensitivity was obtained with patient sera analyzed with PSA than with TPAcyk, particularly in patients with early stages of the disease. We conclude that the results from this new TPAcyk assay were significantly elevated in patients initially diagnosed with poorly differentiated tumors, that patients with localized tumors exhibited low concentrations, and that patients with metastatic disease showed, on average, 8 times higher concentrations than patients with localized disease. The combination of the TPAcyk and PSA results increased the sensitivity for prostate cancer, particularly in patients with metastatic disease. © 1994 Wiley‐Liss, Inc.