bluuebunny/crossref_metadata_2025 huggingface dataset:
Modalities of chemotherapy and endocrine therapy for growth inhibition of androgen‐stimulated mouse carcinoma (shionogi carcinoma 115)
Authors: Hara Shigeru , Ichikawa Tomohiko , Akimoto Susumu , Wakisaka Masami , Shimazaki Jun
Published: February 2007

Effects of chemotherapy and endocrine therapy applied individually or in combination on growth of an androgen‐stimulated mouse tumor, Shionogi carcinoma 115 (SC 115), were examined. In the present study cyclophosphamide and castration were used as chemo‐ and endocrine therapy, respectively, and simultaneous combination of these two treatments was found to be the most effective in inhibiting tumor growth. When comparing the effect of castration alone with that of injection of cyclophosphamide alone, the former retarded the tumor growth more efficiently, but relapse occurred in both instances. Injection of cyclophosphamide to the relapsed tumor after castration caused a marked effect when compared with the effect of the drug on the untreated or the chemotherapy‐relapsed tumors. Castration caused a retardation of growth in the chemotherapy‐relapsed tumor, but the survival period was shorter than that observed in the mice that received castration followed by injection of cyclophosphamide. From these results, it was concluded that castration followed by chemotherapy was the preferred order among sequential treatments for the SC 115; however, the optimal treatment was produced by simultaneous combination of chemotherapy plus castration.
Cytosolic retinoic acid‐binding protein in human prostatic dysplasia and neoplasia
Authors: Jutley Jaswant K. , Kelleher Jerry , Whelan Peter , Mikel John
Published: February 2007

Prostate samples from 41 patients with acute on chronic prostatitis, benign hyperplasia, chronic prostatitis or adenocarcinoma were assayed for cytosolic retinoic acid binding protein (cRABP). Binding protein was detected in all samples. Scatchard analysis revealed dissociation constant values of 15.0‐31.8 nM and maximum binding capacity of 5.2 ± 2.0 (S.E.) pmo/mg protein. Using sucrose density gradient centrifugation, cRABP was quantitated and values varied from 1.2 to 12.5 pmol/mg protein. High levels (> 3.5 pmol/mg protein) were found in 28/41 samples. There was no correlation between the cRABP binding/mg protein and the volume (%) of glandular tissue (compared with stroma). While there was no significant difference in the quantities of cRABP in the different disease groups, there was a tendency for a progressive increase from acute on chronic prostatitis to chronic prostatitis, the highest levels being present in carcinoma.
Adenocarcinoma of the canine prostate: Immunohistochemical examination for secretory antigens
Authors: McEntee M. , Isaacs W. , Smith C.
Published: February 2007

Thirty‐one canine adenocarcinomas of prostatic origin were examined immunohistochemcally with antibodies generated against three prostate‐specific antigens by using a peroxidase‐antiperoxidase technique. Primary antibodies included two generated with human prostatic antigens (PSA, PSAP) and one generated with a canine prostatic antigen (CPSP). Eight of 31 adenocarcinomas were positive with CPSP, two were positive with PSA, and three were PSAP positive. Normal and hyperplastic canine prostatic epithelium was strongly positive with all three markers. These results contrast with those in human studies in which PSA and PSAP stain normal and neoplastic epithelium with comparable intensity in all but the most anaplastic tumors.
Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls
Authors: Hulka Barbara S. , Checkoway Harvey , Hammond John E. , Ferdinando George Di , Mickey Don D. , Fried Floyd A. , Stumpf Walter E. , Beckman William C. , Clark Terry D.
Published: February 2007

This study sought to identify differences in serum hormone levels between prostatic cancer (Cap) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 Cap, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three‐ to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.
Renewal timing of long‐acting depot luteinizing hormone‐releasing hormone agonist (Zoladex) is critical in the treatment of hormone‐dependent rat prostatic carcinoma (R3327‐H)
Authors: Geldof A. A. , De Voogt H. J. , Rao B. R.
Published: February 2007

The effects of luteinizing hormone‐releasing hormone (LHRH) agonist (Zoladex) treatment on hormone‐dependent rat prostate adenocarcinoma (R3327‐H) were investigated based on changes in tumor volume and histology. Tumor‐bearing rats were treated for 10 weeks with Zoladex in depot preparation by implantation every 2, 4, or 6 weeks. Tumor growth rate was similar in the castrated group and in the rats treated every 2 weeks with Zoladex. This growth rate was significantly slower than in animals treated with Zoladex every 6 weeks and the nontreated group. The growth rate in rats treated every 4 weeks appeared to be faster than that in the castrated animals (not significant). Changes in testosterone levels measured during Zoladex treatment correlated with tumor growth kinetics. Zoladex implantation yields effective and complete androgen deprivation only in the rats with two weekly depot renewal regimen. Tumor histology indicated that the stromal as well as the glandular epithelial cells responded to both castration and to Zoladex treatment. However, in tumors from rats treated with Zoladex every 4 and 6 weeks progressive increasing signs of restoration of normal elements, comparable to non‐treated tumors were observed. These results strongly suggest that careful attention has to be paid to the timing of LHRH depot renewal in prostate cancer treatment.
Induction of estrogen‐related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonization by the aromatase inhibitor 1‐methyl‐androsta‐1,4‐diene‐3,17‐dione
Authors: Habenicht Ursula‐F. , Schwarz Klaus , Neumann Friedmund , El Etreby M. Fathy
Published: February 2007

The cynomolgus monkey was selected as an experimental model to investigate the role of estrogens in the pathogenesis of benign prostatic hyperplasia (BPH) because its prostate seems to be more like the human prostate than that of other primate species. The treatment of intact, adult animals with the aromatizable substrate androstenedione for 3 months resulted in no significant changes in prostate weight, but in microscopically clearly detectable estrogen‐related hyperplastic changes, particularly in a marked smooth muscle activation. These effects were antagonized by simultaneous, subcutaneous treatment with the aromatase inhibitor 1‐methyl‐androsta‐1,4‐diene‐3,17‐dione (1‐Methyl‐ADD) and only partially reversed by oral treatment. The serum estradiol (E2) concentration, which was not significantly elevated after treatment with androstenedione in comparison to the control, was drastically decreased after subcutaneous treatment with 1‐Methyl‐ADD and moderately decreased after oral treatment. In conclusion, these results as well as the great anatomical and histological similarities between the prostate of the cynomolgus monkey and that of man indicate that it might be a suitable and interesting model for future BPH studies.
Cell proliferation studies in the rat prostate: II. The effects of castration and androgen‐induced regeneration upon basal and secretory cell proliferation
Authors: Evans G. S. , Chandler J. A.
Published: February 2007

The changes over short and prolonged periods (up to three months) after castration on the proliferative activity of basal and secretory epithelial cells in the rat prostate were studied. Although castration induced widespread apoptosis of the secretory cells, no compensatory hyperplasia of the basal cells in response to this was noted. Instead, observations of the cell kinetics and ultrastructure suggested that both the basal and secretory cells entered a quiescent state as a result of castration. The proliferative potential of secretory cells was not diminished up to three months after castration. During androgen‐induced regeneration of the prostate the pattern of basal and secretory cell proliferation was found to be similar to that observed during normal growth, although it was more rapid and of shorter duration.
Androgen dependence of the dunning R3327G cell line in monolayer culture
Authors: Santen R. J. , Mowszowicz I. , Portois M. C. , Mauvais‐Jarvis P.
Published: February 2007

For optimal application of new treatment strategies for prostate cancer, the basic biologic effects of androgens on cell kinetics and DNA synthesis require detailed examination. An androgen‐responsive prostate cancer cell line in monolayer culture provides a means to study the biochemical mechanisms mediating hormonal stimulation of cell proliferation. We chose to evaluate the proliferative response of the Dunning R3327G tumor cell line (Du‐G cells) to 5α‐dihydrotestosterone (DHT) in monolayer culture. The DU‐G cells grew more rapidly in the presence of increasing concentrations of DHT in the range of 10−8−10−5 M than with vehicle control. At 10−7 M DHT, 3H‐thymidine incorporation increased from 400 ± 34 counts/min/well to 751 ± 77 (p <.01). Effects of DHT were maximal when a plating density of 10,000 cells/well was employed. Androgen effects on cellular growth were reproducible but were limited in magnitude. Rapid metabolism of DHT in culture did not explain this phenomenon. Du‐G cells were not completely dependent on androgen, since cells continued to grow in media containing <10−11 M dihydrotestosterone and hydroxyflutamide.
Tissue type plasminogen activator as a marker for functional zones, within the human prostate gland
Authors: Reese Jeffrey H. , McNeal John E. , Redwine Elise A. , Stamey Thomas A. , Freiha Fuad S.
Published: February 2007

The cellular distribution of tissue plasminogen activator in the prostate central zone, prostate peripheral zone, and seminal vesicle was studied by using immunohistochemistry. Samples of these three regions were taken from 20 radical prostatectomy specimens. Sixteen of 18 central zone samples showed positive staining of 20–90% of the epithelial cells. All 15 peripheral zone samples were negative, and only three of 14 seminal vesicles showed positive staining, which was present in less than 5% of cells.

The distribution of tissue plasminogen activator within the prostate was the same as that previously reported for pepsinogen II. This suggests that the central zone of the prostate may be the selective site of origin for proteolytic enzymes in seminal fluid.
Androgens stimulate both growth rate and epidermal growth factor receptor activity of the human prostate tumor cell LNCaP
Authors: Schuurmans Alex L. G. , Bolt Joan , Mulder Eppo
Published: February 2007

LNCaP cells (derived from a lymph node carcinoma of the human prostate) contain androgen receptors and show androgen‐responsive growth in vitro. Maximal effects on growth were seen at 0.1 nM of the synthetic androgen R1881 or 0.2 nM of epidermal growth factor (EGF); both compounds independently increased the growth rate 2–3 times.

EGF‐receptors were measured after 6 days culture in the presence or absence of 0.1 nM R1881. A 2.3–fold increase in receptor number/cell was found when binding was measured at 0°C (from 12,500 to 28,900 sites/cell in stimulated cells). The kD value (0.45 nM) was not affected by androgen treatment. The increase of EGF‐receptor activity was first observed between 6 and 12 h after exposure to androgen.

It is concluded that LNCaP cells are sensitive to low concentrations of EGF (or EGF‐like compounds) and that one of the mechanisms involved in androgen action on these cells is an increase of EGF‐receptor expression at the cell surface.
Butyrate effects on growth, morphology, and fibronectin production in PC‐3 prostatic carcinoma cells
Authors: Halgunset Jostein , Lamvik Torarin , Espevik Terje
Published: February 2007

Sodium butyrate (NaBT) induces differentiation in several transformed cell lines. The present paper describes the effects of NaBT on some transformation‐associated parameters in PC‐3, a human prostatic carcinoma cell line. NaBT produces a reversible inhibition of cell proliferation, but anchorage‐independent growth is more sensitive than monolayer growth. Soft agarose colonies are reduced by over 50% at 0.1 mM, a concentration that hardly affects growth on solid substrata. Monolayer cells respond to NaBT by spreading and flattening, as demonstrated by a combined light and electron microscopic, morphometric technique. After 4 days' exposure to 2 mM NaBT, the average cell covers an area of substratum that is approximately double that covered by control cells. The average cell volume, however, remains unchanged. This flattening is paralleled by an increase in the number of stress fibers, as seen by fluorescence microscopy. Only minor changes are observed in the microtubule and intermediate filament patterns. While control cells contain very little antifibronectin reactive material, substantial amounts of such material appear upon NaBT treatment. The amount of fibronectin increases up to 100‐fold in cells exposed to NaBT. The changes observed correspond to a suppression of properties that are generally associated with the malignant phenotype.
Plasma levels of hydroxy‐flutamide in patients with prostatic cancer receiving the combined hormonal therapy: An LHRH agonist and flutamide
Authors: Bélanger Alain , Giasson Marcelle , Couture Jean , Dupont André , Cusan Leonello , Labrie Fernand
Published: February 2007

The present study describes a method for the measurement of the plasma levels of hydroxy‐flutamide (Flu‐OH), the biologically active and main circulating metabolite of flutamide. We have observed that two to four hours after oral administration of 250 mg of flutamide to healthy young men, as well as to patients with prostate cancer, the plasma concentration of Flu‐OH reaches a peak at approximately 1.7 μM. The plasma concentration of Flu‐OH measured at months 6, 12, and 18 of treatment shows a minimal basal level of 3.4 μM with a maximal increase at 6.8 to 8.5 μM at 2 to 4 hours. Since the serum levels of testosterone in these patients are approximately 1 nM, the levels of the active antiandrogen are at a 5000‐ to 10000‐fold excess. However, due to the low affinity of the antiandrogen for the androgen receptor, it is extremely important to maintain this concentration of the antiandrogen in plasma constant.
Histologic changes in the rat prostate cancer model after treatment with somatostatin analogs and D‐Trp‐6‐LH‐RH
Authors: Zalatnai Attila , Paz‐Bouza Jose I. , Redding Tommie W. , Schally Andrew V.
Published: February 2007

Histopathologic changes produced during the treatment of Dunning R3327 prostate cancer with new superactive somatostatin analogs (RC‐121 and RC‐160) and D‐Trp‐6 analog of luteinizing hormone‐releasing hormone agonist (D‐Trp‐6‐LH‐RH) were studied. A significant reduction of the tumor weight could be observed in all treated groups, but the greatest decrease in the tumor volume was seen in the groups receiving the combination of the somatostatin analog and D‐Trp‐6‐LH‐RH. Histologically, the treatments resulted in a loss of the tumorous glandular elements and the proliferation of the stromal cells. In the tumors treated with somatostatin analogs, the amount of connective tissue was greatly increased and was accompanied by the appearance of thick collagenous fibers. In the D‐Trp‐6‐LH‐RH treated groups, regressive changes in the epithelium were seen in addition to the proliferation of connective tissue. The greatest histologic improvement was observed in the group treated with the combination of RC‐160 and D‐Trp‐6‐LH‐RH. This histopathologic evaluation clearly supports our contention that superactive analogs of somatostatin greatly potentiate the inhibitory effect of D‐Trp‐6‐LH‐RH on the growth of Dunning prostate tumors and may improve the clinical response in patients with prostate cancer.
Immunoglobulin‐producing cells in human prostate
Authors: Bene M. C. , Studer A. , Faure G.
Published: February 2007

Immunohistological techniques were used to investigate the presence of immunoglobulin‐producing cells in human prostate. Surgical samples from 14 patients with prostate hyperplasia were analyzed. Lymphoid infiltration was rarely seen and was in no way comparable with the classical structure of mucosae‐associated lymphoid tissue (MALT). Plasma cells were observed in nine cases. They produced predominantly IgA and lambda chains, but noticeable numbers of IgM‐secreting cells were also seen. These cells were most numerous in patients with antecedents of infection or prostatitis. These data suggest that the local immune system of the prostate is in relation with the MALT, and can be colonized by MALT‐derived cells in response to bacterial stimuli.
Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice. III. Effects of estrogens on the growth of the tumor tissue
Authors: van Steenbrugge G. J. , Groen M. , Van Kreuningen A. , De Jong F. H. , Gallee M. P. W. , Schröder F. H.
Published: February 2007

The transplantable human prostatic tumor model (PC‐82) in nude mice was used to evaluate the indirect and possibly direct effects of estrogens on the growth of prostatic tumor tissue. High (pharmalogical) doses of plasma estradiol (E2) were achieved in tumor‐bearing mice by using E2‐containing Silastic implants of different lengths. In comparison with the situation in men, in mice much higher concentrations of circulating E2 (exceeding 3 nmol/liter) were necessary to attain (near)‐castrate levels of plasma testosterone (T). Treatment of tumor‐bearing mice with a high dose of E2 resulted in tumor growth arrest and a subsequent decline of the tumor volume, which equals the effects of castration. No evidence was found that either of the two doses of E2 applied had any additive inhibitory effect on tumor growth when compared to castration alone. It was inferred from these findings that in the PC‐82 tumor model, estrogens, rather than having a direct effect on the tumor tissue, mainly act indirectly by their suppressive effect on T secretion in the host animal. A different and unexpected result was obtained in castrated tumor‐bearing mice treated with a combination of E2 and and T. With both doses of E2 this type of treatment led to a smaller increase of the tumor volume compared with mice receiving T only, the result of the high dose being statistically significant. This antagonistic effect of the two steroids on the PC‐82 tissue was paradoxically associated with a sharp increase of nuclear androgen receptor levels and a higher concentration of dihydrotestosterone in the tumor tissue. Plasma and tissue concentrations of T appeared to be unaltered. The present study of the PC‐82 prostate tumor shows that only by careful monitoring of plasma steroid levels in tumor‐bearing mice can conclusions about the effectiveness of hormonal treatment regimens, such as estrogen therapy, be drawn.
Clinical characteristics of prostatic cancer detected by mass screening
Authors: Imai Kyoichi , Zinbo Susumu , Shimizu Kamon , Yamanaka Hidetoshi , Kumasaka Fuminari , Sato Zin
Published: February 2007

Since 1981 we have been studying prostate cancer (Pca) by mass screening in three cities, eight towns and seven villages in Gunma prefecture, Japan. From 1981 to 1985, 5,770 subjects were examined. The clinical character of Pea detected by mass screening is compared with control (i.e., Pca detected in the outpatient clinic in Gunma University). Of the 54 Pca patients detected by mass screening (Stage B: 28, C: 8, D: 18), approximately 50% had early‐stage Pca. The ratio of early‐stage Pca is significantly higher than in the control. An extended survival rate in high‐stage Pca detected by mass screening also was observed through comparison with control. We determined two types of Pca in advanced stage: (1) asymptomatic or less symptomatic and better prognostic Pca found in mass screening and (2) symptomatic and worse prognostic Pca found in control.
Enzymatic and electrolytic profiles of human semen
Authors: Gershbein Leon L. , Thielen David R.
Published: February 2007

Chemical parameters comprising urea and creatinine nitrogen, cations (Na+, K+, and Ca2+), chloride, phosphorus, protein, cholesterol and enzymes, aminotransferases, alkaline and prostatic acid phosphatases, γ‐glutamyltransferase, creatine kinase, and lactate dehydrogenase were ascertained for semen from groups A (vasectomized), B (oligo‐spermic), and C (normospermic) men, 19 to 55 years of age. Of the parameters, the vasectomized group underwent definite depressions in potassium ion, alkaline phosphatase, aspartate aminotransferase, γ‐glutamyltransferase, and lactate dehydrogenase as compared with the normospermic group; the last three enzymes and, possibly, the urea‐creatinine ratio were decreased for the oligospermic group vs. the normospermic men. In the comparison of groups A and B, only the decrements in alaninc aminotransferase and lactate dehydrogenase were statistically significant. In corroboration of past reports, CK‐BB comprised the main isoenzyme of semen creatine kinase.
The long‐term influence of vasectomy on prostatic volume and morphology in man
Authors: Jakobsen Henrik , Torp‐Pedersen Søren , Juul Niels , Hald Tage
Published: February 2007

During the past two decades several papers have described the changes in prostatic secretory capacity following vasectomy. Based upon results indicating a reduction of secretory function, it was suggested that even prostatic size and the incidence of benign prostatic hyperplasia (BPH) might be altered after the operation.

In this study, which included 56 males who had been vasectomized 8 years previously and 56 age‐matched control persons, transrectal ultrasonic scanning of the prostate was used for exact measurements of the prostatic volume and for the investigation of intraprostatic echo pattern.

The total prostatic volume, the volume of the periurethral gland, and the volume of the peripheral zone were not influenced by the vasectomy; nor was the growth rate of these zones affected. In the vasectomy group, the frequency of adenomatous prostates was 19.6%, whereas 30.3% of prostates in the control group had ultrasonic signs of BPH. However, this is not a statistically significant difference. Subdividing the material according to age did not reveal altered BPH frequency in any age group when vasectomized and controls were compared.
Exocrine secretion of epidermal growth factor by the rat prostate: Effect of adrenergic agents, cholinergic agents, and vasoactive intestinal peptide
Authors: Jacobs Stephen C. , Story Michael T.
Published: February 2007

Perfusion of the rat prostatic urethra in vivo provided a means of collecting the rat prostatic secretory product. The secretion of the protein epidermal growth factor (EGF) was investigated by radioimmunoassay (RIA). Baseline secretion of EGF into prostatic fluid was <.03 ± .004 SEM ng/min. The α‐adrenergic agonist phenylephrine caused an increase in EGF to 3.6 ± .4 SEM ng per 30‐min period. The stimulation was blocked completely by prazosin and only partially by yohimbine, indicating primarily α1 control. One mg/kg IV phenylephrine produced a maximal response. The β‐adrenergic agonist isoproterenol caused no increased secretion of EGF. The cholinergic agonist pilocarpine stimulated EGF secretion to 3.2 ± .6 SEM ng per 30‐min period. Atropine blocked the cholinergic stimulation. The combination of phenylephrine and pilocarpine did not result in greater stimulation than either agent alone. Vasoactive intestinal peptide (VIP) did not stimulate EGF secretion, nor did it augment either pilocarpine or phenylephrine‐stimulated secretion. EGF secretion into rat prostatic fluid is under both α1‐adrenergic and cholinergic control.
Treatment with antiandrogens induces an androgen‐repressed gene in the rat ventral prostate
Authors: Léger Jocelyne G. , And Rene Le Guellec , Tenniswood Martin P. R.
Published: February 2007

We have recently described an androgen‐repressed gene in the rat ventral prostate, termed TRPM‐2, that appears to be involved in the processes of cell regression and programmed cell death. We have analyzed the effect of two antiandrogens currently used in the treatment of prostatic carcinoma on the induction of this gene. Cyproterone acetate (10 mg/day) and flutamide (15 mg/day), when administered to castrated rats receiving a maintenance dose of 5α‐dihydrotestosterone proprionate (250 μg/day), induce the expression of TRPM‐2. Northern hybridization and dot blot analysis demonstrate that TRPM‐2 steady‐state levels reach a maximum on day 4 of treatment with cyproterone acetate (520 ppm) and on day 6 of treatment with flutamide (190 ppm). During this time the steady‐state levels of the androgen‐dependent prostate steroid‐binding protein mRNA are reduced dramatically (from approximately 75,000 to 10,000 ppm), but are not eliminated even after extended treatment. Treatment with the two antiandrogens produces a substantial reduction in the organ weight/ body weight ratio and RNA content of the prostate when compared to rats receiving the maintenance dose alone. These results suggest that while neither cyproterone acetate nor flutamide fully repress the androgen‐dependent functions of the prostate, they do induce some of the androgen‐repressed sequences in the prostate that have been implicated in the process of cell death.
Nonrandom involvement of chromosome 4 in the progression of rat prostatic cancer
Authors: Lsaacs John T. , Hukku Bharati
Published: February 2007

Owing to progression of the original spontaneous Dunning R‐3327 rat prostatic cancer, a large series of transplantable prostatic tumors have been isolated that differ widely in their histological degree of differentiation, growth rate, androgen sensitivity, and metastatic ability. Using these parameters as criteria, the full spectrum of disease progression is represented within this Dunning system of rat prostatic cancers, ranging from slow‐growing, well‐differentiated, androgen‐sensitive, nonmetastatic forms to fast‐growing, anaplastic, androgen‐independent, highly metastatic forms.

Cytogenetic analysis of the two least progressionally advanced Dunning cancers (i.e., histologically well‐differentiated, slow‐growing, nonmetastatic variants) demonstrated no structural or numerical chromosomal aberration, suggesting that the initial development of prostatic cancer may not require detectable cytogenetic changes. In contrast, all 16 of the progressionally more advanced Dunning variants analyzed had a series of characteristic structural and/or numerical chromosomal aberrations that minimally involved chromosome 4. This nonrandom involvement of chromosome 4 was consistently observed regardless of whether the karyotype of the cancer was near‐diploid or hyperaneuploid, suggesting that chromosome 4 aberrations are specifically involved in the progression of rat prostatic cancer. In addition, all four variants that were highly metastatic had, besides aberration of chromosome 4, structural aberrations involving chromosomes 1, 2, and 11. Of the 14 variants that did not have a high metastatic ability, only two had a similar aberrations involving chromosomes 1, 2, 4, and 11, suggesting that these specific chromosomal aberrations may be necessary, albeit not sufficient, for a high metastatic ability of rat prostatic cancers.
Immunocytochemical demonstration of insulin or insulin‐like immunoreactivity in the rat prostate gland
Authors: Stahler Michael S. , Pansky Ben , Budd G. Colin
Published: February 2007

The indirect immunocytochemical technique was used in conjunction with anti‐insulin antisera to localize insulin‐like immunoreactivity in tissue sections and primary cell cultures from rat prostate gland. Positive immunostaining for insulin‐like reactivity was demonstrated in the epithelium of the prostate gland. There appeared to be some variation in the intensity and localization of the immunoreactivity within different regions of the gland. Prostatic epithelial cells grown in culture in an insulin‐free medium displayed strong cytoplasmic immunostaining when treated with anti‐insulin antisera, while nuclear staining was absent. These results demonstrate that insulin‐like immunoreactivity is present in the epithelium of the prostate gland and suggest that there may be some local insulin or insulin‐like synthesis in this organ.
Effectiveness of ultrasound in the preoperative evaluation of patients with prostatism
Authors: Hendrikx A. J. M. , Doesburg W. H. , Reintjes A. G. M. , Strijk S. P. , Debruyne F. M. J.
Published: February 2007

To avoid the disadvantages of intravenous urography (IVU) and urethrocystoscopy (UCS), we investigated prospectively their replacement by ultrasound, performed during one visit in the outpatient department, in the evaluation of patients with symptoms of prostatism. One hundred twenty patients (aged 44‐89 years) were included in this study. All patients underwent two main diagnostic procedures: ultrasound of the kidneys and bladder and transrectal ultrasound of the prostate (procedure A1) This was compared with IVU and UCS (procedure A2). Following procedure A1, the main diagnoses made were benign prostatic hypertrophy in 84 patients, prostatitis in 24 patients, and prostatic cancer in 12 patients. By following procedure A2, the diagnosis was changed in 20 cases. Fourteen patients had a bladder neck sclerosis, and six had a urethral stricture. There was no relevant diagnostic difference between IVU and ultrasound of the kidneys and bladder.

Ultrasound of the prostate gives better information on prostatic abnormalities than does IVU or UCS. A patient with prostatism can be screened completely during one visit at the outpatient department. Only for detection of bladder neck sclerosis and urethral strictures does UCS remain preferable.
Light microscopic morphometric analysis of castration effects in the different lobes of the rat prostate
Authors: Kiplesund Kjell Magne , Halgunset Jostein , Fjösne Hans E. , Sunde Arne
Published: February 2007

The morphologic effects of androgen deprivation in the different lobes of the rat prostate were examined by light microscopic morphometry. The prostates of Wistar male rats (260‐340 g) were fixed in situ by glutaraldehyde perfusion in castrated animals 1 week after gonadectomy and in intact animals. The ventral (VP), dorsal (DP), and lateral (LP) lobes as well as the coagulating gland (CG) were dissected out, weighed, and processed for light microscopy. Using stereologic methods the following parameters were estimated for each lobe: volume fraction of connective tissue, epithelium and glandular lumina, average epithelial height, average epithelial cell volume, and total number of epithelial cells. Castration leads to a 58‐76% reduction of the wet weight of all prostatic lobes. The decrease of glandular tissue is greater in VP than in LP, DP, and CG. In VP and LP, there is a 39‐45% reduction of the epithelial height, and this effect is less pronounced in DP and CG. For all lobes, the shnnkage of average epithelial cell volume is in the same range (25‐30%). Moreover, in VP and LP, there is a 70% reduction of the total number of cells, whereas the reduction is less in DP and CG. It thus seems that the reduction of prostatic epithelial tissue mass upon castration is due to a reduction of the number of cells as well as a reduction of the volume of individual cells. VP and LP appear to be more androgen‐dependent than DP and CG.
Intraluminal crystalloids in whole‐organ sections of prostate
Authors: Ro Jae Y. , Grignon David J. , Troncoso Patricia , Ayala Alberto G.
Published: February 2007

Demonstration of intraluminal crystalloids and mucin can aid in the diagnosis of prostatic adenocarcinoma. Crystalloids have been reported in 10% to 23% of prostatic adenocarcinomas. This incidence may not be accurate, however, because previous studies were based on specimens obtained by transurethral resection or transrectal biopsy. This study was based on the examination of 54 prostates (9 obtained from radical prostatectomies for prostate cancer and 45 from cystoprostatectomies for bladder carcinoma) processed by a whole‐organ section method. Crystalloids were found in all nine prostatic carcinomas from radical prostatectomy specimens. Thirty‐one of 45 specimens from cystoprostatectomies had single or multiple foci of adenocarcinoma; of these, 20 cases (64.5%) had crystalloids. Numbers of crystalloids vaned not only from case to case but also from area to area within the same case. Crystalloids were occasionally identified in benign and dysplastic glands that were adjacent to areas of carcinoma. Cases without prostatic carcinoma and benign or dysplastic glands distant from areas of carcinoma did not contain crystalloids. Twenty‐four prostatic adenocarcinomas had intraluminal mucin; mucin was not found in benign glands. In conclusion we found the incidence of crystalloids to be higher than that reported in previous studies, a difference we believe is because of sampling. We confirm previous observations that intraluminal crystalloids and mucin are helpful in diagnosing prostate adenocarcinoma.
Oncogene expression in prostate cancer: Dunning R3327 rat dorsal prostatic adenocarcinoma system
Authors: Cooke D. B. , Quarmby V. E. , Mickey D. D. , Isaacs J. T. , French F. S.
Published: February 2007

Steady‐state levels of myc, fos, p53, sis, and neu mRNAs were measured in eight variants derived from the Dunning R3327 rat prostate adenocarcinoma and compared to levels in normal dorsal prostate. Expression of the myb and serbB oncogenes in the Dunning tumors was below the limits of detection. Myc, p53, and sis mRNA levels in all tumors were at or above control levels. Fos mRNA levels were below control levels in four of five anaplastic tumors and were above control levels in the remaining tumors. A comparison of mRNA levels along the two Dunning lineages revealed that increased expression of these oncogenes did not correlate with tumor progression.
Clinical pharmacology of polyestradiol phosphate
Authors: Gunnarsson Per Olov , Norlén Bo Johan
Published: February 2007

The results of the present studies demonstrate that intramuscular injections of polyestradiol phosphate (PEP) produce not only considerably increased estrogen concentration in plasma but also maintain the same estrone/estradiol ratio as in normal men.

Monthly injections of PEP produce persistent elevation of the plasma estradiol levels throughout the dose interval, and rising PEP doses produce proportionately increasing steady‐state plasma concentrations of estradiol.

The steady‐state plasma concentrations of testosterone are reduced to 45, 25, and 15% of the pretreatment concentrations after treatment every fourth week with 80, 160, and 240 mg PEP, respectively.
Case‐control study of prostate cancer and socioeconomic factors
Authors: Yu He , Harris Randall E. , Wynder Ernst L.
Published: February 2007

A total of 1,162 prostate cancer cases and 3,124 age‐matched hospital controls from several U.S. hospitals were studied to identify associations between prostate cancer and life‐style variables. Among white males, college education, professional occupation, and non‐Jewish ethnicity were weakly associated with the risk of prostate cancer (ORs = 1.5, 1.8, and 1.3, respectively, P < 0.01). These relationships retained statistical significance after adjustment for age, marital status, body mass, cigarette smoking, alcohol consumption, and physical activity in multiple logistic regression models. Among black males, similar, though nonsignificant, risk elevations were observed for education and occupation. Weak positive effects of borderline statistical significance were observed for high body mass, low physical exercise, and high serum cholesterol (in elderly males only), and a significant reduction in risk was noted for never married black males. Cigarette smoking and alcohol consumption were not related to the risk of prostate cancer.
Phosphorylation status of nuclear and cytosolic androgen receptors in the rat ventral prostate
Authors: Golsteyn E. J. , Graham J. S. , Goren H. J. , Lefebvre Y. A.
Published: February 2007

We demonstrate that endogenous phosphatases are active in cytosolic and nuclear androgen receptor fractions from the rat ventral prostate. Under our androgen binding assay conditions, the effect of acid phosphatase inhibitors (sodium fluoride, tartaric acid, sodium orthovanadate) on the endogenous phosphatases could be correlated with an increase in dihydrotestosterone (DHT) binding to fractions of partially purified cytosolic androgen receptor. In contrast, tetramisole, an alkaline phosphatase inhibitor, did not alter the binding of DHT to the same receptor fraction. Immunoprecipitation of androgen receptor fractions with polyclonal anti‐phosphotyrosine antibody resulted in the recovery of [3H]‐DHT binding activity from nuclear receptor fractions and partially purified cytosolic receptor fractions prepared from 20‐ to 24‐hr castrated rats. In control fractions depleted of androgen receptor, negligible levels of binding activity were recovered following immunoprecipitation with the antibody. Therefore, acid phosphatases may be acting on phosphotyrosyl residues of the androgen receptor, thus playing a role in the dephosphorylation and inactivation of the androgen receptor.
Receptors for luteinizing hormone‐releasing hormone, somatostatin, prolactin, and epidermal growth factor in rat and human prostate cancers and in benign prostate hyperplasia
Authors: Fekete Matyas , Redding Tommie W. , Comaru‐Schally Ana Maria , Pontes J. Edson , Connelly Robert W. , Srkalovic Gordan , Schally Andrew V.
Published: February 2007

Using sensitive multipoint micromethods, we estimated membrane receptors for [D‐Trp6]‐luteinizing hormone‐releasing hormone ([D‐Trp6]‐LH‐RH), somatostatin (SS‐14), human prolactin (hPRL), and epidermal growth factor (EGF) in experimental Dunning rat prostate cancers and in samples of normal human prostate, benign prostatic hyperplasia (BPH), and human prostate cancer (PC) obtained from biopsy, after prostatectomy, or at autopsy. In the Dunning R‐3327 rat prostate adenocarcinoma specimens, the receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist [D‐Trp6]‐LH‐RH and the somatostatin analog RC‐160. Two populations of binding sites were found for [D‐Trp6]‐LH‐RH, one with high affinity and low capacity and another with low affinity and high capacity. Treatment with [D‐Trp6]‐LH‐RH and RC‐160 alone or with the combination of these analogs increased the binding capacity (Bmax) of the low‐affinity binding sites for [D‐Trp6]‐LH‐RH and decreased Bmax for hPRL and EGF. Therapy with [D‐Trp6]‐LH‐RH also reduced Bmax of SS‐14 binding and dissociation binding constant of high‐affinity binding sites for [D‐Trp6]‐LH‐RH, whereas administration of RC‐160 or the combination treatment with both analogs increased Bmax of SS‐14 binding. These findings are compatible with the view that analogs of LH‐RH and SS‐14 might exert some direct inhibitory effects on the Dunning prostate cancer. Among 13 human BPH samples examined, only one had receptors for [D‐Trp6]‐LH‐RH, and seven specimens exhibited binding for prolactin. [D‐Trp6]‐LH‐RH receptors were found in all seven samples of human PC but not in any of the eight specimens of normal human prostate. All samples of normal human prostate, BPH, and human PC exhibited binding sites for EGF but not for SS‐14. Our findings on the membrane receptors in the human and rat prostate cancers raise the intriguing possibility that LH‐RH, acting as a growth factor, along with EGF and prolactin, might be involved in complex interactions that contribute to the promotion of prostate cancer in man.
Development of monoclonal antibody imaging of metastatic prostatic carcinoma
Authors: Meyers Frederick J. , Denardo Sally J. , Macey Daniel , White Ralph Devere , Unger Michael
Published: February 2007

Indium‐111‐labeled monoclonal antibody directed against prostate‐specific antigen was injected into ten patients with known prostatic carcinoma, nine with metastatic disease. The monoclonal antibody scan was compared to the standard technetium bone scan, and both were correlated to clinical status and to 2‐year follow‐up. The ratio of target‐to‐nontarget activity and pharmacokinetics of the radiolabeled antibody were determined. Based on these findings we are hopeful that modifications of this radiolabeled antibody approach may be used for staging and may be developed as a therapeutic adjuvant.
Clonal growth of human prostatic epithelial cells is stimulated by fibroblasts
Authors: Kabalin John N. , Peehl Donna M. , Stamey Thomas A.
Published: February 2007

The interaction of fibroblasts with adult human prostatic epithelial cells was studied in vitro. Stimulation of epithelial cell proliferation, measured by clonal growth assay, was demonstrated when prostatic epithelial cells were grown in coculture with fibroblasts. Epithelial growth in cocultures with fibroblasts was greater than could be obtained in isolated culture in an “optimized,” serum‐free medium previously described. Fibroblasts were able to compensate for the deletion of several growth factors from this “optimized” medium, including epidermal growth factor and insulin, but were notably unable to replace bovine pituitary extract. Epithelial growth stimulation identical to that achieved in coculture was produced by medium conditioned by fibroblasts. Similar results were obtained by using fibroblasts of adult human prostate origin, adult human skin, human fetal lung fibroblasts (IMR‐90), and mouse 3T3 cells. No difference in response was demonstrated between prostatic epithelial cells derived from normal or malignant tissues. Fixed fibroblast monolayers and extracellular matrix prepared from fibroblast cultures failed to stimulate prostatic epithelial growth. These results suggest that a soluble growth factor is secreted by prostatic fibroblasts and other human fibroblasts of nonprostatic origin, as well as by embryonic mesenchymal cells from nonhuman species, which is capable of producing a marked proliferative response in vitro from adult human prostatic epithelium. This proliferative response could not be reproduced by the addition of a variety of known growth factors to prostatic epithelial cell cultures.
A form of basic fibroblast growth factor is secreted into the adluminal fluid of the rat coagulating gland
Authors: Smith Eric P. , Russell William E. , French Frank S. , Wilson Elizabeth M.
Published: February 2007

Rat coagulating gland and its secreted fluid contain a mitogenic substance that, by numerous criteria, appears to be similar to basic fibroblast growth factor (basic FGF). It is a potent competence factor in the BALB/c3T3 mouse embryo fibroblast assay, elutes from heparin‐agarose at concentrations of NaCl greater than 1.0 M, and has an isoelectric point (pI) between 8 and 9. In coagulating gland fluid, its molecular weight was 20,000 ± 5,000, as indicated by gel filtration on Sephadex G‐200. Western blot analysis of purified factor from coagulating gland cytosol and fluid, respectively, revealed immunoreactive bands of 16,000 and 17,000 relative molecular weight similar to that of purified bovine basic FGF.
Immunohistochemical localization of metallothionein in the rat prostate gland during postnatal development
Authors: Timms B. G. , Hagen J. A.
Published: February 2007

Immunocytochemical and electrophoretic techniques were used to investigate the presence of metallothionein, a metal‐binding protein, in the dorsolateral and ventral lobes of the developing rat prostate. Male rats aged 7 and 14 days were injected subcutaneously with 6 and 20 mg/kg body weight of cadmium and zinc, respectively, or with saline for controls, 24 h prior to tissue sampling. Immunohistochemical localization of metallothionein was observed in the epithelial tissues of the dorsolateral prostate from 7 and 14 day‐old animals and in 1 day‐old untreated rats. This staining pattern did not appear to be significantly affected by cadmium or zinc treatment. In contrast, metallothionein localization in the ventral prostate decreased with age but demonstrated a slight response to metal‐ion treatment in the 7 day‐old animals. Electrophoretic and immunoblot analysis confirmed the presence of metallothionein in the control and metal‐induced prostate samples from neonatal rats. Lobe‐specific differences in localization suggest a functional significance for metallothionein, independent of inducible protein.
Estrogen therapy and liver function—metabolic effects of oral and parenteral administration
Authors: von Schoultz Bo , Carlström Kjell , Collste Lars , Eriksson Ambjörn , Henriksson Peter , Pousette Åke , Stege Reinhard
Published: February 2007

Oral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver‐derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.
Role of transforming growth factor ‐α in human prostate cancer cell growth
Authors: Wilding George , Valverius Eva , Knabbe Cornelius , Gelmann Edward P.
Published: February 2007

Because of the influence of transforming growth factor‐α (TGFα) on the cell growth in other cancer cell systems, we investigated the growth‐regulatory role of TGFα in human prostate cancer cells. TGFα (5 ng/ml) stimulated LNCaP cell growth in monolayer to 60% of the level seen with dihydrotestosterone (DHT). Both DHT and TGFα increased cloning in soft agar twofold above that in controls. Metabolism of thymidine and uridine was also increased as evidenced by increased uptake of these macromolecule precursors. In addition, intracellular signalling as indicated by phosphatidyl inositol turnover was also increased by TGFα and DHT. Conditioned media contained TGFα by radioimmunoassay (RIA), transforming activity by rat kidney fibroblast (NRK) colony formation, and epidermal growth factor (EGF) receptor competable activity by radioreceptor assay. EGF receptors were present by binding assay and immunoprecipitation. These data demonstrate the presence of an autostimulatory growth loop in hormone‐responsive human prostate cancer cells.