bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cyproterone acetate in comparison to flutamide and megestrol acetate on the ventral prostate, seminal vesicle, and adrenal glands of adult male rats
Authors: El Etreby M. Fathy , Habenicht Ursula‐F. , Louton Thomas , Nishino Yukishige , Schröder Helmut G. 
Published: February 2007

AbstractCyproterone acetate (CPA) has a stronger inhibitory effect than megestrol acetate (MGA) and flutamide (FL) on the prostate and seminal vesicle of intact adult rats. Only in the clinically irrelevant regimen of castration and simultaneous androgen substitution is FL as a competitive androgen antagonist more potent than CPA and MGA. The latter inhibit complete involution of the ventral prostate but not of the seminal vesicle of castrated adult rats. This effect is very small in magnitude, cannot be increased by the use of higher doses, and is only reduced but not blocked by simultaneous treatment with high doses of FL. Further, CPA is unable to stimulate proliferation or restore the function of the involuted rat prostate. CPA and MGA inhibit adrenal weight in rats, thus indicating a glucocorticoidlike activity in this species. A critical review of all available data on the antiandrogenic, glucocorticoidlike, and possible paradoxical androgenlike activities of CPA in different animal experiments has no important bearing on the clinical effectiveness of CPA in the treatment of prostatic cancer.
Human PC‐3 prostate cell line DNA synthesis is suppressed by eicosatetraynoic acid, an in vitro inhibitor of arachidonic acid metabolism
Authors: Anderson K. M. , Wygodny J. B. , Ondrey F. , Harris J. 
Published: February 2007

AbstractWhen human PC‐3 cells derived from a metastatic prostatic adenocarcinoma were incubated for 15 min to 4 h with the in vitro inhibitor of eicosanoid biosynthesis, eicosatetraynoic acid (ETYA) at 10–80 μM, DNA synthesis was suppressed. No reduction in cellular viability occurred, as judged by exclusion of trypan blue or unaltered release of 51Cr‐labeled proteins, and the inhibition was partially reversible. Indomethacin (to 12.5 μg/ml) did not inhibit DNA synthesis or alter the suppression of DNA synthesis by ETYA, suggesting a role for a lipoxygenase product in this effect. Addition of leukotriene B4 (LTB4) at 10−8 M did not reverse the inhibition of DNA synthesis produced by ETYA, nor did arachidonic acid (10−5–10−9 M) incubated with control cells mimic the effect of that agent. 3H‐arachidonic acid incubated with PC‐3 cells was rapidly incorporated into phospholipids and this labeling was differentially inhibited by ETYA. Positive modulation of PC‐3 cellular DNA synthesis by lipoxygenase products and inhibition of their synthesis by ETYA is one attractive hypothesis with which to account for these results. Other consequences of producing a selective deficiency of arachidonic acid in cellular membrane phospholipids and even the probable substitution of ETYA for arachidonic acid could also contribute to the inhibition of DNA synthesis by ETYA.
Androgen‐independent epithelial cells of the rat ventral prostate
Authors: Montpetit M. , Abrahams P. , Clark A. F. , Tenniswood M. 
Published: February 2007

AbstractAndrogen‐independent cell lines have been clonally selected from primary cultures of androgen‐dependent epithelial cells from the rat ventral prostate. These rapidly dividing epithelial‐like cells (RDE) have altered morphology and adherence characteristics. Unlike normal prostate epithelial cells, the RDE cell lines do not require androgens for cell division or cell survival. In the presence of physiological concentrations of testosterone, the isoelectric focusing patterns of prostatic acid phosphatases are abnormal in these RDE cells, and the prostate steroid‐binding protein genes are not expressed. The loss of androgen dependence is not due to the inability of RDE cells to metabolize testosterone to 5α‐dihydrotestosterone, the active androgen, since the RDE cell lines metabolize testosterone in a manner similar to normal androgen‐dependent epithelial cells. When RDE cells are grown on collagen matrices, the cells assume ductlike structures, similar to prostatic acini, although PSBP gene expression is not induced. When seeded into soft agar these cell lines form distinct foci, suggesting that they are potentially tumorigenic.
Three predominant proteins secreted by the human prostate gland
Authors: Lilja H. , Abrahamsson P.‐A. 
Published: February 2007

AbstractAnalyses of the proteins of azoospermic ejaculates from subjects with defective seminal vesicles demonstrated that three prostatic‐secreted proteins were predominant. Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA; or γ‐seminoprotein), and β‐microsemi‐noprotein (β‐MSP; or β‐inhibin), were identified as the three predominant proteins secreted by the normal human prostate gland. Immunohistochemical localization of these proteins, in the epithelium of normal prostatic acini and ducts, with the avidin‐biotin complex procedure demonstrated that each PAP‐immunoreactive cell was invariably immunoreactive both with PSA‐and β‐MSP‐monospecific antisera as well.
Tamoxifen in advanced prostate cancer: An ECOG pilot study
Authors: Horton John , Rosenbaum Charles , Cummings Frank J. 
Published: February 2007

AbstractA group of 19 patients with advanced (Stage D) prostate cancer were treated with one of three dose levels of the anti‐estrogen tamoxifen, 10 mg (3 patients), 20 mg (8 patients), or 30 mg (8 patients) daily. Five patients had received no prior systemic therapy. The treatment was tolerated well, but no objective responses occurred.
A Case‐Control Study of Prostatic Cancer With Reference to Dietary Habits
Authors: Oishi Kenji , Okada Kenichiro , Yoshida Osamu , Yamabe Hirohiko , Ohno Yoshiyuki , Hayes Richard B. , Schroeder Fritz H. 
Published: February 2007

AbstractA case‐control study of prostatic cancer which consisted of 100 patients with prostatic cancer, matched for hospital, age (±3 yr) and hospital admission date (±3 months) to patients with benign prostatic hyperplasia (BPH) and hospital controls, was conducted from 1981 to 1984. Low daily intake of beta‐carotene (RR = 2.13: 95% confidence interval, 1.20–3.77) and of vitamin A (RR = 1.94: 1.10–3.43), as compared to the intake of those substances by BPH controls, were factors significantly correlated with the development of prostatic cancer. Low daily intake of beta‐carotene (RR = 2.13: 1.20–3.77), as compared with hospital controls, were significantly correlated with prostatic cancer development. Infrequent intake of bread (RR = 2.40: 1.31–4.38), intended to represent a westernized diet, and of spinach (RR = 1.96: 1.01–7.73), a typical green and yellow vegetable, as compared to BPH controls and infrequent intake of spinach (RR = 4.55: 1.82–11.11) as compared to by hospital controls, were significant risk factors for prostatic cancer. Intake of carbohydrates, protein, fat, total calories, fibers, vitamin B and vitamin C were not correlated with the development of prostatic cancer.
Prediction of time to progression after orchiectomy by the nuclear androgen receptor content from multiple biopsy specimens in patients with advanced prostate cancer
Authors: van Aubel O. , Bolt‐de Vries J. , Blankenstein M. A. , Schröder F. H. 
Published: February 2007

AbstractThe nuclear androgen receptor (ARn) content of cancerous prostatic tissue has been investigated as a prognosticator for time to progression under endocrine therapy. In 1981 a prospective study was started to investigate whether the ARn content in biopsy specimens of patients with prostatic carcinoma predicts the duration of response following hormonal treatment. ARn was estimated by a microassay which involves extraction of nuclear pellets with a heparin‐containing buffer, exchange labeling of the nuclear extract with 3H‐R1881, and quantitation of the receptor with protamine sulphate precipitation. One hundred and fifteen patients with prostatic cancer entered this study; 47 patients had evidence of metastatic disease as proven by bone scan. Forty‐two patients were treated by orchiectomy; 37 of these patients are evaluable with a minimal follow‐up of 30 months. A relationship between the nuclear androgen receptor content and the time to progression following orchiectomy in these patients with metastatic disease of the prostate was not found. This could possibly be attributed to the heterogeneous nature of the prostatic tumor tissue with respect to the distribution of the ARn. We concluded that androgen receptor assay in needle biopsies, at least in this study, had no value for the prediction of the time to progression after orchiectomy.
Phosphotyrosine phosphatase activity of human and canine acid phosphatases of prostatic origin
Authors: Chevalier Simone , Landry Danielle , Chapdelaine Alcide 
Published: February 2007

AbstractHuman and canine prostatic specimens containing high levels of acid phosphatase (AP) activity were tested, at acid pH, for their ability to hydrolyze the major phosphoaminoacids present in phosphorylated proteins, phosphosertne (p‐ser), phosphothreonine (p‐thr), and phosphotyrosine (p‐tyr). The cleavage of a synthetic substrate, para‐nitrophenyl‐phosphate (p‐npp), was also measured as an indicator of AP activity; its inhibition by sodium‐L‐tartrate (T) was used as a criterion to identify prostatic acid phosphatase (PAP). It was found that: 1) the Km of p‐tyr and p‐npp were 2.0 mM and 0.41 mM, respectively, with similar Vmax values (0.078 and 0.087 μmoles of phosphate (Pi) liberated per minute per milligram of protein); 2) the ID50 were 0.25 mM and 0.50 mM with sodium otthovanadate (VO4) and T, respectively, using p‐npp as substrate—with p‐tyr as substrate, the values obtained were 0.016 mM and 0.11 mM, respectively; 3) activity toward p‐ser and p‐thr was minimal; 4) native PAP from dog seminal plasma, with a molecular weight of 90–100 kD, as determined by gel filtration on HPLC, hydrolyzed p‐tyr preferentially, and this phosphatase (Pase) activity was also strongly inhibited by both T and VO4; and 5) the AP present in human and canine prostatic tissue and cells, as well as in their secretions, also preferentially hydrolyzed phosphotyrosine, and it was inhibited by T and VO4. It is proposed that these p‐tyr Pases may be involved in the local regulation of prostatic growth.
Intraprostatic spermatozoa in the squirrel monkey
Authors: Nelson Glenn A. , Scimeca Joseph M. , Abee Christian A. , Gardner William A. 
Published: February 2007

AbstractThe recent observation of spermatozoa within the human prostate prompted this study to determine if spermatozoa were present in prostates of nonhuman primates. Six of 32 squirrel monkey prostates contained intraglandular spermatozoa. No associated pathologic lesions were found. Spermiophages were seen in one case. Although intraprostatic spermatozoa have been postulated to play a role in various prostatic diseases, a normal physiologic phenomenon cannot be excluded.
Heparin‐binding growth factor isolated from human prostatic extracts
Authors: Mydlo Jack H. , Bulbul Muhammad A. , Richon Victoria M. , Heston Warren D. W. , Fair William R. 
Published: February 2007

AbstractProstatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin‐Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated‐thymidine‐incorporation assay. Two peaks of activity were consistently noted—one in the void volume and a second fraction which eluted with 1.3–1.6 M NaCl and contained the majority of the mitogenic activity. Both non‐heparin‐ and heparin‐binding fractions increased tritiated thymidine incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin‐binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC‐3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.
Effect of adrenalectomy, flutamide, and leuprolide on the growth of the dunning rat R‐3327 prostatic carcinoma
Authors: Kung Ted T. , Mingo Garfield G. , Siegel Marvin I. , Watnick Arthur S. 
Published: February 2007

AbstractThe R‐3327 prostatic tumor implanted in the male Copenhagen x Fischer F1 rat continues to grow because androgen is being supplied from an endogenous source. It follows that regimens which decrease the availability of androgen will retard the growth rate of the tumor. These experiments showed that castration, the antiandrogen flutamide, and the luteinizing hormone‐releasing hormone (LHRH) agonist leuprolide inhibited tumor growth. Adrenalectomy alone had no significant effect on tumor size and did not further retard the growth of the tumor in castrated rats. Further, under the conditions of this study, there was no significant difference in tumor growth rates between the groups of rats treated with either flutamide alone or flutamide combined with leuprolide. Total ablation of androgen may not be needed for maximal inhibition of tumor growth.
Differential expression of keratins in the basal and luminal compartments of rat prostatic epithelium during degeneration and regeneration
Authors: Verhagen Anja P. M. , Aalders Tilly W. , Ramaekers Frans C. S. , Debruyne Frans M. J. , Schalken Jack A. 
Published: February 2007

AbstractThe role of the different epithelial compartments during degeneration and regeneration of the rat prostate is examined on basis of intermediate filament protein (IFP) expression pattern. With the monoclonal antibodies RCK 103 and RGE 53, directed against specific keratins, it was possible to differentiate between the basal (RCK 103 +) and luminal (RGE 53 +) cells of the prostatic epithelium. After testosterone deprivation, by orchiectomy, an extensive and rapid cell loss was observed which appeared to affect mainly the luminal cells. In the process of prostate regeneration, induced by testosterone administration, using silastic implants, the luminal compartment rapidly regained its normal thickness. A heterogeneous population of morphologically luminal cells was observed showing keratin expression patterns intermediate between basal and luminal cells. These findings support the idea of a relationship between basal and luminal cells as being members of the same lineage of differentiation.
Activation of a Ca2+−Mg2+‐dependent endonuclease as an early event in castration‐induced prostatic cell death
Authors: Kyprianou Natasha , English Hugh F. , Isaacs John T. 
Published: February 2007

AbstractPrevious studies have demonstrated that castration‐induced androgen withdrawal results in the fragmentation of prostatic DNA into nucleosomal oligomers, and this process comprises an early event in the activation of programed cell death in the rat ventral prostate. This DNA fragmentation could be due to changes in the chromatin conformation increasing its sensitivity to preexisting nucleases and/or to increases in the activity of the nucleases themselves. However, comparative kinetic analysis of in vitro DNA fragmentation induced by exogenous nucleases did not reveal any differences in the sensitivity of prostatic chromatin between intact and castrated rats. In contrast to these negative findings, using [3H] DNA as an exogenous substrate, it was shown that within the first day following castration there was a twofold increase in a Ca2+‐Mg2+‐dependent nuclease activity without a concomitant increase in other nuclear nucleases. This Ca2+‐M2+‐dependent nuclease activation occurred coincidental with the initial increase in nuclear DNA fragmentation following castration and preceded the enhanced appearance of morphological changes characteristic of dying cells (i.e., apoptosis), as well as the major increase in prostatic DNA loss. These results suggest that castration‐induced androgen deprivation leads to a sequential activation of a Ca2+‐Mg2+‐dependent nuclease leading to the fragmentation of the genome into discrete nucleosomal‐sized fragments of DNA, subsequently followed by the fragmentation of the nucleus itself (i.e., apoptosis) and eventually with the complete digestion of the nucleosomal oligomers into component nucleotides (i.e., DNA loss).Since the castration‐induced nuclease is dependent upon calcium ions for maximal activity, a potential role of intracellular calcium in the early events activating prostatic cell death was investigated. Acute disturbances in intracellular calcium homeostasis within the ventral prostate by means of a potent calcium influx blocker, nifedipine, simultaneous with castration, resulted in a significant delay in the biochemical and morphological changes associated with prostatic cell death (i.e., prostatic weight loss, prostatic DNA loss, and DNA fragmentation). These results point to a potential role of intracellular calcium levels in the mechanism of activation of castration‐induced death of the androgen‐dependent epithelial cells in the ventral prostate.
Calcium channel antagonists delay regression of androgen‐dependent tissues and suppress gene activity associated with cell death
Authors: Connor John , Sawczuk Ihor S. , Benson Mitchell C. , Tomashefsky Philip , O'Toole Kathleen M. , Olsson Carl A. , Buttyan Ralph 
Published: February 2007

AbstractAndrogen deprivation subsequent to castration of an adult male rat results in the regression of sexual accessory tissues. Regression of these tissues involves the massive death of androgen‐dependent cells. Using the rat ventral prostate gland as a model to study androgen‐programed cell death, we have characterized a series of molecular events that accompany its regression. This analysis has shown that there was a sequential induction of specific gene transcripts in the ventral prostate gland following castration. The first event in this cascade was an abrupt induction of transcripts encoding c‐fos. Since c‐fos expression has been linked to perturbations in intracellular Ca2+ levels, we investigated whether membrane‐mediated Ca2+ flux might be an early physiological step involved in the death of prostatic cells. To test this, rats were treated simultaneously upon castration with either verapamil or nifedipine, two different calcium channel antagonist drugs. Compared to the ventral prostate glands of untreated castrated rats, the glands of the calcium channel antagonist‐treated rats showed a significant delay in all parameters associated with regression (loss of wet weight and DNA content and delay in histological changes associated with prostatic regression). The seminal vesicle glands of treated rats also showed signs of delayed regression. Furthermore, calcium channel antagonists suppressed the induction of transcripts encoding both c‐fos and testosterone‐repressed prostate message‐2 (TRPM‐2), a gene expressed exclusively by dying cells, during the first 62 hr following castration. These findings further support a role for calcium ion influx in the pathway leading to hormonally programed prostate cell death, and suggest the intriguing possibility that modulation of this activity can alter the process by which cells die.
Prognostic value of serum hormone concentrations in prostatic cancer
Authors: Eriksson Ambjörn , Carlström Kjell 
Published: February 2007

AbstractSeventy‐eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17α‐ hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tEl;sum of unconjugated and conjugated estrone, ≥85% estrone sulfate), cortisol, luteinizing hormone, follicle‐stimulating hormone, prolactin, growth hormone, sex hormone‐binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment.Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tEl, and albumin and a significantly lower T/SHBG‐ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome.The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal “rest androgen” in prostatic cancer tumor growth.
Effect of a 4‐methyl‐4‐aza steroid on androgen metabolism by rat ventral prostate epithelial and stromal cell cultures: Selective inhibition of 5α‐reductase activity
Authors: Orlowski John , Clark Albert F. 
Published: February 2007

AbstractThe effect of a potent steroid metabolic inhibitor, 17β‐N,N‐diethylcarbamoyl‐4‐methyl‐4‐ aza‐5α‐androstan‐3‐one (DMAA), on androgen metabolism was investigated in primary monolayer cultures of rat ventral prostate epithelial and stromal cells. Using testosterone (T) as substrate, 5α‐reductase (5α‐R) activity in both cell types was inhibited by greater than 98% at an inhibitor concentration of 1000 nM. The concentrations required to produce a 50% inhibition (IC50) were 7.4 and 9.0 nM for epithelial and stromal cells, respectively. To examine the specificity of this compound, its effect on other steroid‐metabolic enzymes was examined. DMAA at a concentration of 1,000 nM had no effect on 3α‐hydroxysteroid oxidase (3α‐HSORox), 3‐ketosteroid reductase (3α‐HSORred), and 6/7‐hydroxylase (6/7‐HSH) activities in both cell types; 17β‐hydroxysteroid oxidase (17β‐HSORox) activity, located primarily in epithelial cells, also was not influenced by DMAA. In contrast, epithelial 3β‐hydroxysteroid oxidase (3β‐HSORox) and 3‐ketosteroid reductase (3β‐ HSORred) activities were inhibited by 65% (P < .001) and 58% (P > .05), respectively, albeit the latter result was not statistically significant. Stromal 3β‐HSORox and 3β‐ HSORred activities were negligible; hence the effect of the inhibitor on these enzymes could not be assessed. In conclusion, DMAA is a relatively selective and potent inhibitor of 5α‐R activity in primary cultures of rat ventral prostate epithelial and stromal cells and should be a useful compound for antagonizing androgen‐mediated actions in the prostate and other androgen target tissues.