bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex‐hormone‐induced inflammation and fibromuscular proliferation in the rat lateral prostate
Authors: Lee Robinette C.
Published: February 2007

The subacute administration of estradiol‐17β was shown to be a potent inducer of an inflammatory response specific to the lateral prostate of the castrated Wistar rat. The subsequent administration of dihydrotestosterone restored the wet weight of the gland while maintaining the inflammation established with estrogen treatment. These changes are histologically similar to a spontaneously arising nonbacterial prostatitis previously reported by others in the aging rat lateral prostate.

When the same hormones were administered on a chronic basis, the intensity of the inflammation increased with time and was accompanied by a fibromuscular proliferation that consisted of fibroblasts, smooth muscle cells, and collagen. These chronic changes correlated well with studies by other investigators on human benign prostatic hyperplasia (BPH) where certain forms of BPH were associated with a significant degree of inflammation and fibromuscular growth.

The present studies therefore establish a model system for the hormonal induction of an inflammatory reaction in the rat lateral prostate that precedes and could be causally related to proliferative responses in the fibromuscular stroma. The potentially important similarities that exist between these experimental findings and the human problems of nonbacterial prostatitis and benign prostatic hyperplasia warrant additional study.
Prolactin and luteinizing hormone‐releasing hormone receptors in human benign prostatic hyperplasia and prostate cancer
Authors: Kadar Tibor , Ben‐David Menashe , Edson Pontes J. , Fekete Matyas , Schally Andrew V.
Published: February 2007

Using a sensitive micromethod for the determination of prolactin (PRL) binding sites based on 125I‐human PRL ligand, PRL receptor levels in specimens of benign prostatic hyperplasia (BPH) and human prostate cancer were estimated by the one‐point assay system. Ten of 19 BPH specimens (53%), showed significant PRL binding, four being in the 9–12 fmol/mg range. All ten of these cases had an histological diagnosis of nodular glandular hyperplasia. Of ten adenocarcinomas examined, four samples (40%) exhibited positive PRL binding, the highest receptor levels being 10.2 fmol/mg protein. To characterize the receptors from BPH membranes, samples were then separately pooled according to the results obtained in one‐point assays. In the PRL‐negative pool no displacement could be detected. In the PRL‐positive pool, the Scatchard analysis revealed one class of receptors with an average affinity Kd = 1.1 × 10−9 M and capacity Bmax = 287 fmol/mg protein. In the prostate cancer specimens, luteinizing hormone‐releasing hormone receptors with a high affinity and a low capacity were also found. The results indicate the presence of prolactin receptors in prostate cancer and in BPH. The clinical implications of such findings are not clear, but it is possible that a certain proportion of BPH and prostate cancers might be in part PRL dependent. Further studies are necessary to ascertain this hypothesis in an attempt to improve the treatment of BPH and prostate cancer.
Ornithine decarboxylase and S‐adenosylmethionine decarboxylase activity in the accessory sex organs of intact, castrated, and androgen‐stimulated castrated rats
Authors: Fjösne Hans E. , Strand Harald , Östensen Mari‐Ann , Sunde Arne
Published: February 2007

We have studied the activities of ornithine decarboxylase and adenosylmethionine decar‐boxylase in the 106‐m/s2 supernatants of the different lobes of the prostate and the seminal vesicles of castrates, androgen‐stimulated castrates, and intact controls.

After castration L‐ornithine decarboxylase (ODC) and S‐adenosyl‐L‐methionine decarboxylase (AMDC) activities fell in all tissues examined. The induction of kinetics was followed for 72 h after administration of testosterone propionate to castrated rats. AMDC activities increased more rapidly than ODC activities in every tissue studied. Peak activities were reached more rapidly in the dorsal lobe than in the other tissues. ODC activity of the ventral lobe increased linearly for 48 h after stimulation. In the other tissues studied, ODC activity reached a maximum after 24 h and thereafter leveled off or decreased.

In conclusion we have found distinct differences in ODC and AMDC activity in various tissues and major differences between treatment groups, with near extinction of activity at castration. In castrates stimulated with testosterone, the between‐group differences prevailed but with different patterns of ODC versus AMDC activity. AMDC is seemingly rate‐limiting in polyamine synthesis in stimulated tissues, while ODC controls synthesis in tissues from castrated rats.
Visualization and quantification of transplanted dunning prostate tumors in rats using magnetic resonance imaging
Authors: Rudin M. , Qureshi S. , Tolcsvai L. , Siegel R. A.
Published: February 2007

Quantitative magnetic resonance imaging (MRI) has been used for the in vivo size determination of subcutaneously implanted Dunning R3327–H tumors in male Copenhagen‐Fisher rats (N = 18). Images have been recorded using a multislice spin‐echo sequence SE(1000/36) with a resolution of 0.2 times; 0.2 mm2 in the imaging plane and a slice thickness of 2 mm. The reliability in the MRI size determination was of the order of 10%. The MRI results were compared with caliper measurements. Five months after tumor implantation nine rats were castrated. Orchiectomy led to a marked and statistically significant reduction in tumor growth rate as determined by both methods of quantification. Qualitative MRI information regarding the tumor morphology was compared with that for histological specimens.
Predictive sites of inflammatory manifestation in the prostatic gland: An experimental study on nonbacterial prostatitis in the rat
Authors: Aronsson Anita , Dahlgren Sven , Gatenbeck Lars , Strömberg Lennart
Published: February 2007

In rats that had been subjected to standardized experimental stress stimuli for 3 and 10 days, respectively, prostatic inflammatory changes of type nonbacterial prostatitis were found in a lobe‐differentiated histological examination. The inflammatory manifestations were marked in the ventral lobes, whereas they were sparse in the dorsolateral lobes. The lobe difference in this respect corresponds to a concomitant difference in morphology and tissue chemical content.
Comparative analysis of growth factors in normal and pathologic human prostates
Authors: Nishi Nozomu , Matuo Yuhsi , Kunitomi Kimito , Takenaka Ikumasa , Usami Michiyuki , Kotake Toshihiko , Wada Fumio
Published: February 2007

Growth factors, as detected by DNA synthesis stimulating activity for BALB/c 3T3 cells, in normal, benign hypertrophic and cancerous human prostates were analyzed. The total content (units per gram of tissue) in benign hypertrophic prostate was two to four times higher than those in normal and cancerous prostates. In all the three groups, heparin‐binding growth factor, growth factor adsorbed to heparin‐Sepharose in the presence of 0.5 M NaCI, accounted for about 80‐95% of the total growth factor content. Qualitative analysis using a heparin‐Sepharose column revealed two types of heparin‐binding growth factor in the prostates, one eluted from the column at 1.2‐1.3 M NaCl and the other at 1.5‐1.8 M NaCI. The latter was the predominant type in all groups. In addition to the growth factors detected with BALB/c 3T3, a growth factor with specific action upon MC3T3‐E1 mouse osteoblasts was found in prostatic cancer, but not in normal and benign hypertrophic prostates.
Estramustine inhibits monocyte phagocytosis
Authors: Bjermer Leif , Schoultz Eva Von , Norberg Bo , Henriksson Roger
Published: February 2007

Estramustine‐phosphate (EMP) influence on human monocyte phagocytosis of fluorescein isothiocyanate (FITC)‐labeled yeast cells was measured in vitro. The method used, a modification of Hed's technique (FEMS Microbiol Lett 1:357, 1977), can differentiate between yeast cell engulfment and adherence to the phagocytotic cell surface. EMP is now accepted in the treatment of advanced prostatic carcinoma. In concentrations corresponding to the clinical situation (20‐40 μg/ml), it dramatically inhibited the process of phagocytosis. The engulfment phase was inhibited, whereas cell adherence was less affected. This might be due to direct interaction with the microtubulus system. The effects were totally reversible. In contrast, the metabolites estradiol and normustine did not affect engulfment of yeast cells, either as single agents or combined. The results demonstrate that the EMP complex caused an impaired phagocytosis, which could be of pathophysiological significance in the compromised cancer patients.
Efficacy and advantages in the use of low doses of anandron and estrogen combination in the treatment of prostate cancer
Authors: Rao B. Ramanath , Geldof A. A. , van Der Wilt C. L. , de Voogt H. J.
Published: February 2007

Treatment effects of RU 23908 antiandrogen (Anandron®) and estrogen in low doses on hormone‐dependent rat prostatic adenocarcinoma (R3327‐H) were investigated. Tumorbearing Copenhagen rats were treated for 6 weeks with 8 μg Anandron and 1 μg estradiol‐17β every two days. Reduction and counteraction of androgen synthesis and action was established by an observed decline in serum testosterone level and by changes in both histology and weight of androgen target organs. Prostate tumor growth rate was significantly retarded in rats treated with Anandron/Estradiol combination compared to untreated intact control and was equal to the slow growth rate in castrate tumor‐bearing animals. Tumor histology changes during treatment correlated with the observed growth rate retardation. Areas of necrosis, metaplasia. and acellularity were more frequently observed in tumors of Anandron/Estradiol‐treated compared to castrated rats. These results suggest that low doses of Anandron and estrogen can effectively be combined as a complete androgen counteracting therapy for hormone‐dependent prostatic carcinoma with minimal undesired side effects.
Significance of duct‐acinar dysplasia in prostatic carcinogenesis
Authors: McNeal John E.
Published: February 2007

Duct‐acinar dysplasia of the prostate is defined as a premalignant lesion characterized by cytologic, and especially nuclear, abnormalities that resemble those of carcinoma and affect the lining epithelial cells of preexisting ducts and acini. A progressive continuum of cytologic abnormality is divided into three grades, with grade III identified by the presence of numerous large nucleoli. Foci of carcinoma have been identified at their point of origin from dysplastic ducts, which confirms the malignant potential of this lesion. Foci of dysplasia are found in roughly 80% of prostates with invasive carcinoma and 40% of glands without cancer. It is concluded that the majority of prostate cancers probably arise within dysplasia foci. Foci of grade III dysplasia occasionally evolve by proliferation of cells to fill duct lumens. The intraluminal cell masses display a cribriform pattern, which has previously been interpreted as a variant of invasive Gleason grade 3 carcinoma. Dysplasia is further linked biologically to malignant transformation by the immunohistochemical demonstration of progressive loss of cytoplasmic differentiation markers and inappropriate overexpression of some markers during the evolution of dysplasia.
Application of octadecylsilyl‐silica in purification studies related to the nontransformed rat ventral prostate androgen receptor
Authors: Koutsilieris Michael , Bouthillier François , Grondin Francine , Radwan Farouk , Carmel Michel , Elhilali Mostafa , Lehoux Jean‐Guy
Published: February 2007

We investigated the application of octadecylsilyl (ODs)‐silica in studies related to characterization and purification of the nontransformed rat ventral prostate androgen receptor. The results indicated that ODS‐silica successfully separates the free [3H]R1881 from the labeled [3H]R1881 transformed (4‐5s) and nontransformed (8‐9s) rat ventral prostate androgen receptors. Partial purification of the 8‐9s receptor form was performed by the fractionation of rat cytosol using cartridges of the ODS‐silica and fast‐flow‐rate phosphocellulose chromatography. Further purification was accomplished by differential chromatography (DEAE‐ cellulose and slow‐flow‐rate phosphocellulose chromatography). This partially purified 8‐9s receptor, when analyzed on a gel permeation high‐performance liquid chromatography column, resulted in a three‐peak pattern of UV absorbance. One of these peaks corresponded to a 59‐kD non[3H]R1881‐binding protein and the remaining two corresponded to 270‐kD and 190‐kD[3H]R1881‐binding proteins. These results demonstrate the usefulness of ODS‐silica in androgen receptor studies. The association of a 59‐kD nonsteroid binding protein with the nontransformed rat ventral prostate androgen receptor is discussed.
Partial purification of a major type of rat prostatic growth factor: Characterization as an epidermal growth factor‐related mitogen
Authors: Nishi Nozomu , Matuo Yuhsi , Wada Fumio
Published: February 2007

The dorsolateral prostate of rats contains a mitogen that shares several properties with epidermal growth factor (EGF), which was designated as prostatic EGF‐related mitogen (PEM). PEM was purified about 2,100‐fold using molecular‐sieve and ion‐exchange chromatography. Final preparation stimulated DNA synthesis in BALB/c 3T3 cells at a concentration as low as 1.5 ng/ml and competed with 125I‐EGF for binding to cell surface receptors. PEM had a molecular weight of about 14,000 and an isoelectric point of about 4.5, being heat‐and acid‐stable but inactivated by dithiothreitol. The primary cultured rat dorsolateral prostate epithelial cells required EGF for maximum growth. Partially purified PEM fully substituted for EGF in the primary culture system at a concentration as low as 90 ng/ml. However, the activity of PEM was hardly suppressed by antimouse EGF antiserum. These findings suggest that PEM is a member of the EGF family but has a higher molecular weight (high molecular weight EGF).
Expression of basic fibroblast growth factor mRNA in benign prostatic hyperplasia and prostatic carcinoma
Authors: Mydlo Jack H. , Michaeli Joseph , Heston W. D. W. , Fair W. R.
Published: February 2007

In our previous work we demonstrated that prostate‐derived growth factor (PrGF) is homologous to basic fibroblast growth factor (bFGF), not acidic fibroblast growth factor (aFGF). Using Northern blot analysis we now show that the messenger RNA for bFGF but not aFGF is expressed in benign prostatic hyperplastic (BPH) tissue as well as in carcinoma of the prostate (CAP). This not only corroborates our previous results, but suggests that prGF is produced locally and not merely stored in the prostate. The demonstration of local production of bFGF by prostate tissue may indicate that this growth factor plays a role, either alone or in conjunction with other factors, in the etiology of benign hyperplasia or prostatic cancer.
Cardiovascular follow‐up of patients with prostatic cancer treated with single‐drug polyestradiol phosphate
Authors: Henriksson Peter , Eriksson Ambjörn , Stege Reinhard , Collste Lars , Pousette Åke , Von Schoultz Bo , Carlström Kjell
Published: February 2007

Thirty‐eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections–160 mg, 240 mg, and 320 mg—in this nonrandomized study. In contrast to studies with oral estrogens, there have been no cardiovascular complications at a mean follow‐up of 12.9 ± 0.7 months (SEM). Twenty‐nine of the 38 patients (76%) have responded to therapy.
Semisynthetic anti‐lhrh vaccine causing atrophy of the prostate
Authors: Jayashankar Radhika , Chaudhuri Manas K. , Singh Om , Alam Anis , Talwar G. P.
Published: February 2007

A modified luteinizing hormone releasing hormone (LHRH) analog (D‐lys)6 was synthesized and linked to ϵ‐amino caproic acid at the 6th position. The free amino group thus generated was used for conjugation to diphtheria toxoid. Immunogenicity and bioefficacy studies of this conjugate vaccine were carried out in rodents. All immunized animals produced antibodies reactive with native LHRH. A gradual decline in testosterone levels accompanied the rise in anti‐LHRH titers. On necropsy, after 10 weeks, a significant reduction in the relative weights of testes and accessory sex organs was noticed. Of particular significance was the marked atrophy of the prostate, indicating a possible therapeutic application of this vaccine in the treatment of androgen‐dependent carcinoma of the prostate.
Determination of canine prostatic size in situ: Comparison of direct caliper measurement with radiologic and transrectal ultrasonographic measurements
Authors: Juniewicz P. E. , Ewing L. L. , Dahnert W. F. , Hamper U. M. , Dembeck C. , Sanders R. C. , Coffey D. S.
Published: February 2007

The use of transrectal ultrasonography to estimate canine prostatic size in situ was evaluated and compared to that of direct measurement via calipers and an in situ radiologic procedure. The length, width, and depth of prostates were measured by transrectal ultrasound in both the transverse and sagittal planes from which prostatic volume was calculated. Prostatic volumes were subsequently transformed into prostatic weights using the following nomogram: prostatic Weight (g) = 0.602 × prostatic Volume (cm3) + 1.16. Prostatic weights estimated by ultrasound as well as by direct measurement with caliper were similar (P > 0.10) to the true gravimetric weight; however, prostate weights estimated by the radiological X‐ray procedure were significantly (P < 0.01) lower. The relationship between true gravimetric prostate weight and that estimated by ultrasound was described by the following regression equation: estimated weight (g) = 1.127 gravimetric weight (g) — 1.665; r = 0.900; P < 0.001; n = 23. In summary, the results of this study demonstrate that transrectal ultrasonography can be used to accurately predict canine prostatic weight.
Partial characterization of a thyroid‐stimulating hormone‐like peptide in neuroendocrine cells of the human prostate gland
Authors: Abrahamsson P.‐A. , Lilja H.
Published: February 2007

Immunohistochemical identification of the most prevalent type of neuroendocrine (NE) cells in the human prostate gland can be made with polyclonal antisera against human thyroid‐stimulating hormone (TSH). A TSH‐like peptide was characterized by analysis of prostatic tissue homogenates with sodium dodecyl sulfate‐polyacrylamide gel (SDS‐PAGE) electrophoresis followed by immunoblotting. A single protein band, with an apparent mass of about 32 kDa after reduction, was identified both with polyclonal antisera against human TSH and with a polyclonal antiserum raised against a synthetic peptide corresponding to the carboxyterminal part of the β‐subunit of human TSH. The TSH‐like prostatic peptide identified here is, on the basis of its molecular mass and absence of immunoreactivity with an antiserum raised against a synthetic peptide representing the mid‐portion of the β‐subunit of TSH, not identical with the pituitary β‐subunit of TSH. On the other hand, this 32 kDa prostatic peptide may have certain structural elements in common with the pituitary β‐subunit of TSH, since it is recognized both with polyclonal antisera against TSH and with an antiserum against the carboxyterminal part of the β‐subunit of TSH.
PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: Relation to hormone sensitivity and to cytological grading
Authors: Hasenson Michael , Lundh Barbro , Stege Reinhard , Carlström Kjell , Pousette Åke
Published: February 2007

Because a change from hormone‐sensitive to hormone‐resistant carcinoma of the prostate often occurs concomitantiy with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate‐specific antigen (PSA) in LNCaP and LNCaP‐r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.
Cytochemical characterization of cuprolinic blue‐stained proteoglycans in the epithelial—stromal interface of the guinea pig lateral prostate
Authors: Chan L. , Wong Y. C.
Published: February 2007

Three types (T1, T2, T3) of proteoglycan (PG) filaments, as demonstrated by cuprolinic blue (CB) under critical electrolyte concentration method in the epithelial‐stromal interface of the guinea pig lateral prostate, were characterized cytochemically by using a number of glycosaminoglycan(GAG)‐degrading enzymes and nitrous acid. The results showed that T1 filaments located in basement membranes of the epithelium, endothelium, and smooth muscle cells, were removed by nitrous acid, heparitinase, and pronase but resistant to chondroitinase (Ch)‐ABC and Ch‐AC, heparinase, neuraminidase, and Streptomyces (S) hyaluronidase. The T1 filaments, therefore, contain heparan sulfate. The T2 filaments closely linked to collagen fibrils were removed by Ch‐ABC, Ch‐ABC plus S‐hyaluronidase, and pronase but were resistant to nitrous acid, heparitinase, heparinase, neuraminidase, and S‐hyaluronidase. These show that T2 filaments are rich in dermatan sulfate. The T3 filaments in the interstitial spaces and on the surface of fibroblasts were removed by Ch‐ABC, Ch‐AC, and pronase but were resistant to heparitinase, heparinase, hyaluronidase, neuraminidase, and nitrous acid. They are, therefore, rich in chondroitin sulfate.
Ultrastructural localization of proteoglycans by cationic dyes in the epithelial—stromal interface of the guinea pig lateral prostate
Authors: Cha L. , Wong Y. C.
Published: February 2007

Proteoglycans (PGs) in the epithelial‐stromal interface of the guinea pig lateral prostate were localized at ultrastructural level, using cuprolinic Blue (CB), alcian Blue (AB), and ruthenium red (RR). After staining with CB or AB according to the critical electrolyte concentration method (CEC), PGs appeared as short electron‐dense filaments. According to their sizes and location, three type (T1, T2, T3) of CB‐stained filaments were identified. T1 filaments were short (25 nm) and were found on both sides of the lamina densa of the basal laminae of the prostatic epithelium, smooth muscle cells, and capillary endothelial cells. They were regularly spaced with an interval of 60 nm. T1 filaments were more randomly distributed in the lamina densa. T2 CB filaments were ∼30–40 nm long and closely associated with the collagen fibrils. They were usually arranged perpendicular to the long axis of collagen fibrils also at intervals of 60 nm. T3 filaments were found in different regions of the lamina propria, including: 1) reticular layer (pars fibroreticularis) below the basal lamina; 2) interstitial spaces; 3) closely associated with the cell surfaces of fibroblasts; and 4) around the collagen fibrils. Their sizes were variable (60–100 nm) and more densely stained. AB revealed similar patterns of PG distribution, except that the three types of PG filaments were longer but thinner. When the tissues were stained with RR, or RR‐AB combined, PGs appeared as dense granules of various sizes, instead of filaments. Their locations and distributions were similar to those of the CB filaments, except that in the case of combined RR‐AB treatment the PG granules were linked by a fine filamentous network, suggesting the interconnecting nature of the PGs and other extracellular components.
A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy
Authors: Carlström Kjell , Collste Lars , Eriksson Ambjörn , Henriksson Peter , Pousette Åke , Stege Reinhard , von Schoultz Bo
Published: February 2007

The effects of orchidectomy, combined oral/parenteral estrogen, and single‐drug parenteral estrogen therapy on the serum levels of testosterone (T), 4‐androstene‐3,17‐dione (A‐4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex‐hormone‐binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A‐4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.
Monoclonal antibody that defines the prostate specific antigen
Authors: Donn F. , Bruns T. , von Meyerinck L. , Schulz M. , Becker W.‐M. , Becker H. , Klosterhalfen H.
Published: February 2007

A monoclonal antibody to a protein with a single band in the 30‐kD region was obtained from fusion of Balb/C mouse spleen cells immunized with epithelial fractions of BPH, with the myeloma cell line P3 × 63 Ag8 6.5.3 by standard procedures. This antigen was characterized in immunobinding studies with various cellular and target antigens and in immunoperoxidase staining.
Selective inhibition of androstenedione‐induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1‐methyl‐androsta‐1,4‐diene‐3,17‐dione (1‐methyl‐ADD)
Authors: Habenicht Ursula‐F. , Fathy Etreby M. El
Published: February 2007

Interference with estrogenic and androgenic actions might result in an inhibitory effect of benign prostatic hyperplasia (BPH). In the present study the effects of the treatment of intact, adult beagle dogs with the antiandrogen cyproterone acetate (CPA) and the aromatase inhibitor 1‐methyl‐ADD either alone or in combination on androstenedione‐induced prostate growth and on testes, epididymides, and the pituitary was investigated. 1‐Methyl‐ADD induced a marked counterregulatory increase in the serum testosterone and dihydrotestosterone (DHT) concentrations leading to hyperplasia of the glandular part of the prostate. However, the aromatase inhibitor antagonized the androstenedione‐induced (estrogen‐related) stimulation of the fibromuscular stroma of the prostate. CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA. This indicates a selective inhibition of the prostate of intact beagle dogs treated with CPA and 1‐methyl‐ADD.
Dose‐dependent hormonal induction of benign prostatic hyperplasia (BPH) in castrated dogs
Authors: Juniewiczd P. E. , Lemp B. M. , Barbolt T. A. , Labrie T. K. , Batzold F. H. , Reel J. R.
Published: February 2007

A model for the dose‐dependent hormonal induction of benign prostatic hyperplasia (BPH) in castrated dogs has been established using subcutaneously implanted Silastic capsules containing 5α‐androstane‐3α, 17β‐diol (3α‐diol) and estradiol‐17β. In vivo release rates per capsule approximated 122.0 ± 4.2 μg 3α‐diol and 22.7 ± 0.8 μg estradiol per day based on in vitro studies and resulted in dose‐dependent increases in serum 3α‐diol and dihydrotestosterone concentrations. The implantation of castrated dogs with either 10 or 20 Silastic capsules containing 3α‐diol and one capsule containing estradiol or the intramuscular injection of 3α‐diol (75 mg/week) and estradiol (0.75 mg/week) for 99 days significantly increased (P < .01) prostatic weights and total prostatic DNA over intact controls. These treatments also resulted in a histomorphological pattern similar to that observed in dogs with the glandular form of spontaneous BPH. In addition, normal prostatic secretory function as determined by semen volume was maintained in these dogs. Although subcutaneous implantation of five Silastic capsules containing 3α‐diol and one capsule containing estradiol into castrated dogs resulted in prostatic weights and total prostatic DNA that were similar (P < .10) to intact controls, these prostates were characterized histomorphologically by glandular atrophy and squamous metaplasia. Furthermore, prostatic secretory function was decreased (P < .05) in these animals compared with intact controls at 3 months of treatment. This study has led to the development of a model of steroid‐induced BPH that will facilitate the evaluation of competitive androgen‐receptor antagonists in the dog.
Application of immunohistologic staining to develop a malignant index to aid in distinguishing benign from malignant prostatic tissue
Authors: Rubenstein Marvin , Shaw Michael W. , Ray Veronica , Dubin Alvin , McKiel Charles F. , Guinan Patrick
Published: February 2007

The development of antisera with reactivities against intermediate filaments, differentiation antigens, and secretory products has aided in identification and characterization of tissue specimens. Such evaluations may assist pathologists in distinguishing between benign (BPH) and malignant (CAP) tissue of prostatic origin. However, attempts to employ this technique are thwarted by 1) the use of frequently incompletely characterized antisera, 2) the use of both paraffin‐ and frozen‐sectioned materials, and 3) a lack of quantitation in the degree of antisera immunoreactivity.

To overcome these shortcomings, a mathematical approach was evaluated using eight BPH and 23 CAP specimens. These were sectioned and stained using commercially prepared antisera against cytokeratin (Cyto P, Cyto M), epithelial membrane antigen (EMA), NK cells (Leu‐7), prostatic acid phosphatase (PAP), and prostate specific antigen (PSA). Reactivity was quantitated on a scale of 0–5. Mean values for markers elevated in CAP (relative to BPH) were placed in the numerator; those elevated in BPH (relative to CAP) were placed in the denominator: Malignant index

This malignant index was significantly greater (P < .001) in CAP tissues than in BPH regardless of Gleason grade (3.2 ± 0.9 vs. 1.6 ± 0.9). It was also significantly elevated (3.0 ± 0.8; P < .01) in nine specimens representing prostatic atypical hyperplasia.

These data suggest that immunohistologic staining may be applied as an aid in distinguishing between BPH and CAP.
Improved immunohistochemical detection of prostatic acid phosphatase by a monoclonal antibody
Authors: Lam Kwok‐Wai , Li Chin‐Yang , Yam Lung T. , Sun Tsieh , Lee Gregory , Ziesmer Steve
Published: February 2007

A monoclonal antibody with high affinity to acid phosphatase isoenzyme 2 (Ab‐AcP2) was selected to examine its binding to different normal and tumor tissues using the indirect immunohistochemical method. Both mature prostatic epithelial cells in the prostate and the highly dedifferentiated prostatic cancer cells in the bone marrow showed strong binding to the antibody. Among nonprostatic tissues, only bone marrow, breast, and kidney showed trace staining in some specimens. The specificity of Ab‐AcP2 was much better than that of the polyclonal antibody to acid phospatase previously reported. When the antibody to the prostate‐specific antigen (Ab‐PSA) was used, weak background staining was often encountered, and weak to moderate stains were seen in the prostatic stroma, bone marrow, lung, skin, and melanoma.
Intracellular distribution of calcium and zinc in normal, hyperplastic, and neoplastic human prostate: X‐ray microanalysis of freeze‐dried cryosections
Authors: Tvedt K. E. , Halgunset J. , Kopstad G. , Haugen O. A.
Published: February 2007

X‐ray microanalysis has been performed on freeze‐dried cryosections of normal, hyperplastic, and neoplastic human prostates. Needle biopsies from prostates suspected to be malignant were collected from ten patients. Seven of these patients had fully developed nodular hyperplasia, whereas the remaining three specimens were histologically classified as moderately differentiated adenocarcinomas. Prostates with normal light microscopic appearance were obtained from two brain‐dead kidney donors. The concentration of calcium in secretory vesicles was found to be several orders of magnitude higher than the concentration of magnesium and zinc in all of the glands studied, which is consistent with calcium being the major cation secreted by the prostatic acinar cells. Some elderly prostates and neoplastic prostates revealed even lower mean zinc:calcium ratios in secretory vesicles. Even though both elements varied considerably, the wide variation of the zinc:calcium ratios was due mainly to variations in the concentration of zinc. Large, electron‐dense bodies occasionally were found in the cytoplasm of prostatic acinar cells. These bodies contained high concentrations of sulphur which by far was the dominating element.
Differential reaction of secretory and non‐secretory proteins in hormone‐treated dunning tumor
Authors: Aumüller Gerhard , Hartley‐Asp Beryl , Seitz JÜRgen
Published: February 2007

Tumor cells from of the Dunning R‐3327 PAP tumor were grown in vivo in the flank region of male Copenhagen rats for 4 months. Untreated control animals, castrated animals, and untreated or castrated animals supplemented with testosterone and estramustine (alone or in combination) bearing tumors were used for immunocytochemical studies of the tumor cells. Antibodies against the following secretory proteins were applied to paraffin sections of formalin‐fixed tissue: anti‐SVS 11, anti‐PBP, anti‐transglutaminase, anti‐acid phosphatase (isoenzymes, isoelectric points [PI] 5. 6, 7, 1, 8, 0), non‐secretory proteins comprised antiglucocorticoid‐receptor, and antibodies against extracellular matrix proteins and intermediate filaments. A differential expression of marker proteins subsequent to the various treatments was observed immunohistochemically. Castration induced a loss of secretory activity, an increase in keratin‐immunoreactive cells, and regressive activity in the secretory cells. Immunoreactivity of the glucocorticoid receptor in the nuclei of the basal cells was also decreased. Testosterone substitution only partially restored secretory activity of tumor cells in castrated animals. In experiments where estramustine had been administered to normal or castrated animals, metaplastic transformation of the epithelium, focal reduction, or increase of secretory and/or regressive activity and persistence of glucocorticoid receptor‐like imniunoreactivity was observed. The findings indicate that different hormonal situations provide conditions for the development of rather heterogeneous reaction patterns of different tumor cells, allowing partial regression of individual clones of tumor cells along with stimulation of others.
Short‐term primary culture of rat prostate tumor epithelial cells on reconstituted basement membrane as a useful in vitro model to assess drug action on prostatic cancer: Efficacy of the thiazolidinedione derivative CGP 19984
Authors: Shea Wendy K. , Black Jennifer , Ip Margot M.
Published: February 2007

A model system has been developed that permits short‐term culture of rat R3327 prostate adenocarcinoma epithelial cells on a reconstituted basement membrane. Growth of prostate tumor cells under these conditions resulted in an enriched epithelial cell population that exhibited an eightfold increase in cell number in 10 days. This model system was used to test the efficacy of the thiazolidinedione derivative CGP 19984, a drug that inhibits luteinizing hormone secretion in vivo. At concentrations ranging between 1 and 25 μg/ml, CGP 19984 inhibited growth of the prostate tumor epithelial cells in a dose‐dependent manner. The results thus demonstrate a direct effect of CGP 19984, which complements its indirect antitumor action in vivo, and suggest that this drug might be an effective agent for treatment of prostatic cancer. Moreover, growth of prostate tumor epithelial cells on a reconstituted basement membrane provides a useful system for in vitro testing of drugs for prostate cancer.
Synthesis of α1‐acid glycoprotein by the human prostate
Authors: Dubé Jean Y. , Paradis Gilles , Tětu Bernard , Tremblay Roland R.
Published: February 2007

In order better to define the extent of protein synthesis capacity of the human prostate, we have studied the translation of selected serum proteins using isolated poly(A)+ RNA preparations and the rabbit reticulocyte lysate system. The translation of α1‐acid glycoprotein could be conclusively demonstrated but there was no apparent translation of albumin and plasmatic transferrin. Labeled α1‐acid glycoprotein was identified by specific immunoprecipitation with a commercial anti α1‐acid glycoprotein antiserum and correct processing by canine pancreatic microsomal membranes. Furthermore, we have shown by the immunoperoxidase technique that α1‐acid glycoprotein was indeed localized mainly in prostatic epithelial cells in 2 out of 2 patients with benign prostatic hypertrophy and in 3 out of 11 patients with prostatic adenocarcinoma. The significance of the synthesis and secretion of α1‐acid glycoprotein by prostatic cell themselves is presently unknown. However, we think that it could represent an interesting subject to explore further in relation with prostatic inflammation.
Evaluation of average life span of epithelial and stromal cells of human prostate by superoxide dismutase activity
Authors: Tunn Sabine , Nass Ralf , Ekernkamp Axel , Schulze Harald , Krieg Michael
Published: February 2007

Little is known about the cell kinetics on which development of benign prostatic hyperplasia is based. This prompted us to study the superoxide dismutase (SOD) activity, which is known 1) to correlate with the life span of cells and 2) to decrease with advancing age of cells. Therefore, SOD was measured in epithelium and stroma of the human prostate from patients of various ages (20–86 years) and compared with the activity in the postmitotic skeletal muscle. It was found that the highest mean specific SOD activity is present in skeletal muscle (4.0 mU. mg protein−1), followed by the stroma (2.1 mU. mg protein−1) and epithelium (1.4 mU. mg protein−1). Similar results were obtained when SOD activity was expressed per DNA (5.03, 1.73, and 0.16 mU. μg DNA−1, respectively). Comparing the slope of the age‐dependent regression lines, it was demonstrated that the slope of the stroma is much closer to the slope of the postmitotic skeletal muscle than the slope of the epithelium. From the data, it was calculated that the average life span of stromal cells is probably longer than 30 years and of epithelial cells longer than 2 years. Hence in human prostatic tissue the average cell death rate might he rather low.
Looking for human glandular kallikrein‐1 in the prostate
Authors: Paradis Gilles , Tremblay Roland R. , Dubé Jean Y.
Published: February 2007

Based on recent studies indicating that human glandular kallikrein‐1 (hGK‐l) mRNA was present in the prostate, we have undertaken to determine whether the prostate contained trypsin‐like proteases with properties compatible with those deduced from hGK‐1 gene nucleotide sequence. The first series of experiments showed that only minimal levels of trypsin‐like enzymatic activity, determined with synthetic substrates, were present in chromatographic fractions of prostatic glycoproteins having a molecular weight in the range expected for hGK‐l, i. e., 25,000‐35,000. Because of this, we used [3H]diisopropylfluorophosphate (DFP) labeling alone or in the presence of various serine‐protease inhibitors to identify trypsin‐like proteases in the prostate. Two‐dimensional gel electrophoresis of prostatic glycoproteins showed the presence of minor spots of 18‐32 kDa. These spots were slightly more acidic than were those of prostate specific antigen (PSA) and were completely inhibited by preincubation with tosyl lysine chloromethyl ketone and p‐nitrophenyl‐p‐guanidobenzoate in contrast to PSA spots that were not affected by these treatments. When a similar procedure was applied to total cytosolic proteins instead of glycoproteins, an additional 30 kDa DFP binding protein was observed. This relatively abundant protein was much more acidic than was PSA and was not inhibited by any of the protease inhibitors tested. In conclusion, this study has permitted us to demonstrate the presence of two sets of proteins that have physicochemical properties compatible with those that can be deduced from the information contained in the hGK‐1 gene.
Effect of the steroidal androgen receptor antagonist win 49,596 on steroid‐induced benign prostatic hyperplasia in the castrate beagle dog
Authors: Juniewicz P. E. , Lemp B. M. , Barbolt T. A. , Labrie T. K. , McCarthy M. , Reel J. R. , Batzold F. H.
Published: February 2007

The effects of the steroidal androgen receptor antagonist Win 49,596 on steroid‐induced prostatic growth, histomorphology, and secretory function were studied in the castrate male beagle dog. At oral doses ranging from 0.625 to 40 mg/kg/day for 12 weeks, Win 49,596 inhibited prostatic growth in terms of both weight and total DNA in a dose‐dependent manner. In addition, both the incidence and severity of diffuse glandular hyperplasia/hypertrophy were dose‐dependently inhibited by Win 49,596, resulting in diffuse glandular atrophy. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at a dosage of 40 mg/kg/day were similar to that observed for the nonsteroidal androgen receptor antagonist flutamide at 10 mg/kg/day. Oral administration of Win 49,596 to castrate dogs at a dosage of 40 mg/kg/day for 12 weeks failed to produce any evidence of agonist activity. These results demonstrate that Win 49,596 prevented the experimental induction of benign prostatic hyperplasia in dogs and suggest that on further evaluation this compound may be efficacious in the treatment of the numan disease.
Evidence of mucin M1 antigens in seminal plasma and normal cells of human prostatic urethra in relation to embryonic development and tumors
Authors: Daher N. , Gonzales J. , Gautier R. , Bara J.
Published: February 2007

By employing immunoperoxidase methodology, using monoclonal antibodies against the peptide core of gastric mucins (M1 antigens), we demonstrate the presence of M1 mucinproducing cells that are associated with the prostatic urethral epithelium and located mainly in the veru montanum area near the prostatic ductal and utriculus junctions. The significance of these M1 cells is not yet clear. Using an immunoradiometric assay, these M1 mucins were found predominantly in the prostatic fraction obtained from seminal plasma. By chromatography on Sepharose 6B and 2B and cesium chloride gradient centrifugation, we demonstrate that high‐molecular‐weight components (> 107 Da) show a density of 1.45 g/ml, similar to mucins, and are immunochemically related to peptidic gastric M1 mucins. The particular location of these M1 antigens in prostatic adult urethra and their fetal expression in cloacal structures suggest that, in males, the prostatic urethral epithelium includes some remnant cells from the enteric cloaca. Finally, the presence of mucincontaining cells in the prostatic urethra could possibly explain the histogenesis of the rare benign villous tumors and primary mucinous adenocarcinomas arising from the prostatic urethral epithelium.
Radiolocalization of human prostate tumor in a mouse subrenal capsule model by monoclonal antibody turp‐27
Authors: Wright George L. , Wilson Eileen , Klinger Mark , Roland Wendy , Beckett Mary Lou , Daddona Peter E.
Published: February 2007

The subrenal capsule assay was used to determine if 125I‐labeled anti‐prostate monoclonal antibody TURP‐27 could target human prostate tumor fragments implanted under the renal capsule of normal immunocompetent C57 BL/6 mice. Maximal binding and optimal tumor to non‐tumor tissue ratios occurred within 24–48 hours postadministration of 125I‐TURP‐27. No significant localization was observed in mice bearing TURP‐27 antigen‐negative human colon tumor tissue implants or with an isotype‐matched control monoclonal antibody. These preclinical data suggest that TURP‐27 may have clinical application for imaging metastatic prostate tumors and further application in immunoconjugate and/or radiotherapy of prostate cancer.
Production of epidermal growth factor and transforming growth factor‐α by the androgen‐responsive LNCaP human prostate cancer cell line
Authors: Connolly Jeanne M. , Rose David P.
Published: February 2007

Epidermal growth factor (EGF)‐related polypeptides may be involved in the growth of human prostate cancer cells, and in the androgen stimulation of hormone‐responsive prostatic carcinomas. We have shown that androgen‐responsive LNCaP cells, like the autonomous DU 145 human prostate cancer cell line, synthesize and secrete EGF and related polypeptides, including immunoreactive transforming growth factor‐α (TGF‐α). As determined by radioimmunoassay, intracellular EGF levels were approximately 100 times those of TGF‐α, but together these accounted for less than half of the total EGF‐like polypeptides detected in a radioreceptor assay. Although LNCaP cell growth was stimulated by dihydrotestosterone (DHT), there was no evident effect on immunoreactive EGF levels in the medium after correction for cell number. Moreover, metabolic labeling experiments showed no effect of the androgen on EGF synthesis by LNCaP cells. Gel filtration chromatography of conditioned medium showed both high molecular weight species and the mature 6,000 dalton form of immunoreactive EGF. We conclude that although LNCaP prostate cancer cell growth is stimulated by DHT, it is unlikely that this is mediated directly via increased EGF synthesis by the tumor cells.
Effects of epidermal growth factor and androgen influences on accessory sex glands in prepubertal swiss‐webster mice
Authors: Lehman Brenda L. , Smith Roger , Leichty Kerry D. , Kauffman Clint L. , Miller Roman J.
Published: February 2007

The effects of epidermal growth factor (EGF) on androgen stimulation of accessory sex gland growth and biochemistry were determined for prepubertal male Swiss‐Webster mice. For the seminal vesicle and anterior prostate, 5αdihydrotestosterone (5αDHT) treatment significantly increased the quantitative levels of organ wet weight, DNA content, polyamine content, and stereologically determined epithelium and lumen volumes above the control group. EGF treatment alone slightly enhanced the levels of most measured parameters from control values. However, when a combined EGF5αDHT treatment was compared with 5αDHT treatment alone, the 5αDHT treatment effects on epithelial and lumen volumes and polyamine content were antagonized by the action of EGF.