bluuebunny/crossref_metadata_2025 huggingface dataset:
Early complications of combined pelvic lymphadenectomy and radical prostatectomy versus lymphadenectomy alone
Authors: Livne Pinhas M. , Huben Robert P. , Wolf Richard M. , Pontes J. Edson
Published: February 2007

A comparison of the early morbidity of pelvic lymphadenectomy plus radical prostatectomy versus lymphadenectomy alone is reported. Fifty‐one patients underwent the combined procedure; 26 had lymphadenectomy alone. Incidence of early complications was 35% in patients undergoing prostatectomy and node dissection and 27% in patients undergoing lymph node dissection only, a difference which is not statistically significant. Thrombophlebitis and pulmonary embolus occurred after the combined procedure. There was one postoperative death in the combined surgery group. The results of this study suggest that lymph node dissection may be performed at the time of radical prostatectomy rather than as a staging procedure, and emphasize the importance of pelvic lymph node dissection in the evaluation and treatment of clinically localized prostate cancer.
Lymphographic findings in prostatic carcinoma with distant metastases
Authors: Veronesi A. , Figoli F. , Tirelli U. , Carbone A. , Grigoletto E. , Merlo A. , Francini M.
Published: February 2007

From January 1976 to December 1981, 25 patients with prostatic carcinoma and distant metastases had lymphangiography (LAG) in their initial workup either to obtain a more precise definition of tumor extension or because at the time of LAG asymptomatic metastases had not yet been detected. In 18 patients extensive bone metastases were present while in seven the only indicator of bone metastases was bone scan (limited bone disease). Positivity rate was 48% (20% in T2 cases, 53% in T3–T4; 29% in limited bone disease, 53% in extensive bone metastases). No correlation was found between LAG positivity and degree of differentiation. Patients with N0 survived longer than patients with N2‐N4; however, the difference in survival is not significant and seems to be linked to the extent of bone metastases. Our data substantiate that LAG is of no value in the staging of metastatic prostatic carcinoma.
Biosynthesis of immunoreactive inhibin‐like material (IR‐ILM) by rat prostate
Authors: Sathe V. A. , Sheth A. R. , Sheth N. A.
Published: February 2007

Presence of biologically active inhibin‐like material (ILM) in the rat prostate was demonstrated by suppression of in vitro follicle‐stimulating hormone release from rat pituitaries, and its in vitro biosynthesis was studied by immunoprecipitation of 3H‐leucine incorporated in ILM. In vitro biosynthesis of immunoreactive ILM (IR‐ILM) was greater in prostate from castrated as compared to intact rats and it decreased in prostates from castrated rats treated with testosterone. In prostates from estrogen‐treated castrated animals, an increase in IR‐ILM synthesis was observed. These observations indicated that in addition to the testes prostate could be an additional source of ILM and that IR‐ILM synthesis in prostate is modulated by hormones.
Monoclonal antibody specific to acid phosphatase isoenzyme 4
Authors: Dang Howard , Lam Kwok‐Wai , Li Chin‐Yang , Wold Lester E. , Sun Tsieh , Yam Lung T.
Published: February 2007

Prostatic acid phosphatase isoenzyme 4 was purified by ion exchange column chromatography, followed by high pressure liquid chromatography. The highly purified enzyme was used to produce monoclonal antibody from immunized BALB/c mice. The antibody was specific to isoenzyme 4, with negligible affinity to isoenzyme 2. The specificity of the monoclonal antibody was evaluated by Western blot analysis and by inhibition of radioimmunoassay.

Immunohistochemistry method using the antibody to isoenzyme 2 showed heavy staining on the cell surface in contrast to the even staining throughout the cytoplasm when monoclonal anti‐isoenzyme 4 was used. These results reflect the secretory nature of isoenzyme 2 and the non‐secretory nature of isoenzyme 4.
Acid phosphatase in the rat prostate: Comparison with other organs
Authors: Tseng Charles C. , Tseng Ernest E. , Sensibar Julia A. , Lee Chung
Published: February 2007

Properties of acid phosphatase in the rat ventral prostate were compared with those in seven other organs in adult male rats by the electrophoretic mobility in acrylamide gels, susceptibility to reactions with inhibitors, and by their response to castration and subsequent testosterone replacement. The enzyme in the spleen exhibited the highest values of Km and Vmax. These values in the prostate, the liver, and the kidney showed an intermediate level, while the lowest level was found in the heart, the lung, the adrenals, and the seminal vesicle. Upon electrophoresis, a total of six isoenzyme bands were resolved. Two major zones of activity were noted. They were the slow‐moving anodal bands (isoenzymes 1,2, and 3) and the fast‐moving cathodal bands (isoenzymes 4,5, and 6). The spleen possessed the highest number of isoenzymes (bands 1,2,4,5 and 6) and the prostate had three (bands 1,2, and 3). The heart contained only one (band 2). Two isoenzymes (bands 1 and 2) were found in remaining organs. Results of the effects of inhibitors showed that NaF inhibited all six isoenzymes, while L(+)tartrate inhibited mainly those in the anodal zone. D(−)tartrate and formaldehyde showed no significant inhibition to any of the isoenzymes. PCMB (parachloromercuribenzoic acid) was found to be a specific inhibitor for isoenzyme 3. Upon castration in the hosts, the enzyme activity in the prostate, the liver, and the seminal vesicle was significantly reduced. This reduction in enzyme activity involved all isoenzymes in these three organs, but isoenzyme 3 in the prostate disappeared completely after castration. The activities of these isoenzymes were restored by testosterone replacement. These results indicate that acid phosphatase in rat tissues has multiple forms; each has its own electrophoretic mobility in acrylamide gels, sensitivity to inhibitors, and response to hormonal manipulation. Isoenzyme 3 is specific to the prostate and is uniquely sensitive to PCMB inhibition and to androgen stimulation.
Immunohistochemical localization of keratin in human prostate
Authors: Kitajima Kiyoaki , A. Tökés Zoltán
Published: February 2007

The localization of keratin was investigated in normal human prostate, benign prostatic hyperplasia (BPH), and prostatic adenocarcinoma using immunohistochemical technique on frozen tissue sections. The purpose of this study was to identify changes in the distribution patterns of keratin due to malignancy. In normal and benign tissue specimens, keratin was detected in the cytoplasm of basal cells and glandular epithelial cells. In the glandular epithelial cells keratin was found as a deposit of fine granules. In the basal cells, the positive staining for keratin had a uniform distribution in the scanty cytoplasm. In specimens of prostatic adenocarcinoma, the basal cells retained a strong positive reaction for keratin. The shapes and the distributions of basal cells were markedly different in malignant specimens. Basal cells formed a discontinuous layer and surrounded the population of neoplastic cells in tissue sections containing the cribriform patterns. The cells expressed characteristic protrusions into extracellular spaces between the cancer cells. Keratin‐positive granules were demonstrated in the adenocarcinoma cells as well. These granules had slightly smaller sizes and were distributed randomly. The study demonstrates that the immunohistochemical localization of keratin provides a refinement for the characterization of cells in tissue sections of prostate.
Characteristics of the β‐adrenergic stimulation of adenylate cyclase activity in rat ventral prostate and its modulation by androgens
Authors: Poyet P. , Gagne B. , Labrie F.
Published: February 2007

Beta‐adrenergic agents cause a 2.5–3‐fold stimulation of adenylate cyclase activity in rat ventral prostate membrane preparations with an order of potency (KD values) typical of a β2‐subtype receptor: (−.)isoproterenol (20 nM) > (‐)epinephrine (70 nM) > (‐)nor‐epinephrine (1 μM) > dopamine (70 μM). The stimulatory effect exerted by high concentrations of dopamine (> 0.1 mM) is completely reversed by propranolol but not by haloperidol or sulpiride, thus indicating an action of dopamine mediated by the β‐adrenergic receptor. One week after castration, basal adenylate cyclase activity in prostatic membranes is 50% reduced. In the same group, the stimulation by isoproterenol is completely abolished in the absence of GTP, while the effect of GTP alone is reduced by 75%. The inhibitory effect of castration on basal as well as isoproterenol‐ and GTP‐stimulated adenylate cyclase activity can be completely reversed by treatment of castrated animals with dihydrotestosterone, thus demonstrating the marked androgen dependency of adenylate cyclase activity in prostatic tissue. Since the response to direct stimulation of adenylate cyclase activity (assessed by NaF and forskolin) is only reduced by 33%‐60% while the response to isoproterenol is 100% abolished, the present data indicates that the complete loss of β‐adrenergic responsiveness of prostatic adenylate cyclase following castration includes many steps, including those preceding adenylate cyclase activity, namely the β‐adrenergic receptor itself and/or its coupling via the GTP‐binding protein. The large amplitude of the effects observed should facilitate study of the mechanisms involved in the marked regulation of the β‐adrenergic receptor‐adenylate cyclase system by androgens in prostatic tissue.
Postradiation biopsy and histological effects in early‐stage prostatic cancer treated with 125iodine implants
Authors: Kandzari Stanley J. , Riley Roger S. , Belis John A. , Jain Pushpa R.
Published: February 2007

One hundred twenty patients with adenocarcinoma of the prostate were treated with 125I irradiation to the prostate and pelvic lymphadenectomy. Clinical stages were A‐2 (13 pts), B‐1 (34 pts), B‐2 (49 pts), and C‐1 (24 pts). The tumors were well differentiated in 44%, moderately differentiated in 39% and poorly differentiated in 17%. Nineteen of 22 patients with positive lymph nodes had either moderately or poorly differentiated tumors. A total radiation dosage between 15,000 and 24,000 rads per year were given to all patients. Seventy‐six patients had been rebiopsied at 1 year, and 26 were positive for malignancy (34%). Thirty‐eight patients had rebiopsy at 2 years, and 16 were positive (42%). Forty‐four percent of the postradiation biopsies were of a different histologic grade from the primary lesion. Radiation injury was identified in 95% of the posttreatment biopsies and were moderate or severe in 71%. One hundred one patients are living from 1 to 9 years. Eight patients have died of metastatic carcinoma, and 11 have died of cardiovascular problems.
Production, clearance, and metabolism of testosterone in men with prostatic cancer
Authors: Meikle A. Wayne , Smith Joseph A. , Stringham John D.
Published: February 2007

It was previously unknown whether the production and metabolism of testosterone was altered in men with prostatic cancer. We recently observed a familial influence on the plasma concentration of sex steroids in men with the cancer. We have now determined, by isotope dilution techniques, the blood testosterone production and clearance rates and testosterone metabolism to potent androgen metabolites in men with prostatic cancer, their brothers, and unrelated controls. Nineteen men had a diagnosis of prostatic cancer before age 63 (probands), 23 were brothers of these index cases, and nine controls matched for age were selected randomly from the general population. None had received endocrine therapy. The plasma content of testosterone, dihydrotestosterone, sex hormone binding globulin, apparent free testosterone concentration, follicle‐stimulating hormone, and luteinizing hormone were not significantly different between the groups. The metabolic clearance rate of testosterone was significantly (P = .04) higher in probands (458 liters/day/body surface area, median) than in controls (306 liters/day/body surface area). The conversion ratios of both testosterone (1.8%) and dihydrotestosterone (16.9%) to 3α‐androstanediol were significantly greater (P = .04 and P = .004, respectively) in probands than in controls (0.95%, 7.8%). These results indicate that men with prostatic cancer have elevated clearance rates of testosterone and an increased conversion ratio of testosterone to its potent 5α‐reduced metabolites.
Biosynthesis and localization of inhibin in human prostate
Authors: Sathe Vinaya S. , Sheth Nandini A. , Phadke Meena A. , Sheth Anil R. , Zaveri Jayesh P.
Published: February 2007

Inhibin biosynthesis by human prostatic tissue was investigated in vitro. Serum levels of inhibin as well as tissue concentrations in different cells and zones of the normal and benign hyperplastic prostates were determined. Immunocytochemical localization of inhibin identified the involvement of epithelial but not stromal cells in the synthesis and release of prostatic inhibin into the circulation. The endocrine and paracrine functions of prostatic inhibin remain to be elucidated.
Role of prolactin in modulating the effects of tamoxifen on growth of the dunning R3327 rat prostate adenocarcinoma
Authors: Sylvester Paul W. , Ip Margot M.
Published: February 2007

Tamoxifen (TAM) has previously been shown to inhibit growth of the Dunning R3327 rat prostate adenocarcinoma and to elevate serum prolactin levels. The purpose of this study was to determine the role of prolactin in modulating the effects of tamoxifen on growth of the R3327 prostatic adenocarcinoma. Intact and castrated Copenhagen‐Fischer male rats bearing the Dunning R3327 rat prostatic tumor were divided into groups and injected sc five times per week for 16 weeks as follows: vehicle; TAM (0.5 mg/kg); haloperidol (HALO; 0.5 mg/kg); bromocryptine (CB‐154; 5 mg/kg); TAM plus HALO; or TAM plus CB‐154. In both intact and castrated rats, agents that either raised (HALO) or lowered (CB‐154) serum prolactin had little effect on prostatic tumor growth when administered singly. In intact rats, average tumor diameter in vehicle‐treated controls increased 421% 16 weeks after the start of the experiment, and treatment with TAM or TAM plus HALO reduced this tumor growth by approximately one‐half. Interestingly, CB‐154 administered in combination with TAM completely blocked TAM inhibition of tumor growth in intact rats. In contrast to these results in intact rats, average tumor diameter increased 129% in TAM‐ and 118% in TAM plus HALO‐treated castrated rats and was significantly greater than the characteristic retardation of tumor growth (49% increase) that occurred in the vehicle‐treated castrate controls. In addition, combined treatment of TAM plus CB‐154 in castrate rats resulted in an even greater increase (188%) in average tumor diameter. The inhibitory effect of TAM on R3327 prostatic tumor growth in intact rats appears to be an indirect effect resulting from its ability to reduce serum testosterone levels. In contrast, the stimulatory effect of TAM in castrate rats appears to result directly from an estrogen‐like action, which can directly enhance prostatic tumor growth in the presence of low levels of circulating androgens; this stimulatory effect of TAM is more pronounced when prolactin levels are suppressed by CB‐154. Clearly, castration alone is more effective than TAM therapy alone or in combination with castration in the retardation of the growth of the androgen‐dependent R3327 prostatic tumor in rats.
Cell proliferation studies in rat prostate I. the proliferative role of basal and secretory epithelial cells during normal growth
Authors: Evans G. S. , Chandler J. A.
Published: February 2007

In the prostates of rats ranging from 10 days to 8 months of age, the proliferative activity of basal and secretory epithelial cells was studied. No clear evidence was found that basal cells alone represented the proliferative compartment, or that they were responsible for the replacement of secretory cells during normal turnover. Cell kinetic and morphological evidence indicated that basal and secretory cells were self‐replicating cell types with discrete functions.
The effect of 4MA, a potent inhibitor of 5 alpha‐reductase, on the growth of androgen‐responsive human genitourinary tumors grown in athymic nude mice
Authors: Andriole Gerald L. , Rittmaster Roger S. , Loriaux D. Lynn , Kish Marie L. , Linehan W. Marston
Published: February 2007

The five alpha‐reductase inhibitors are a newly developed family of compounds that block the intracellular conversion of testosterone (T) to dihydrotestosterone (DHT). 17‐β‐N, N‐Diethylcarbamoyl‐4‐methyl‐4‐aza‐5‐alpha‐androstan‐3‐one (4MA), the most widely studied of these compounds, has been shown to inhibit the androgen‐dependent growth of both normal animal tissues and of the Noble tumor, an experimental, hormone‐responsive rat neoplasm. 4MA has been found to inhibit androgen‐dependent growth without altering plasma levels of T or DHT. In the present study, we assessed the efficacy of 4MA in inhibiting the growth of PC‐82 and R198, human androgen‐responsive genitourinary malignancies. In the first experiment, 4MA was administered subcutaneously at a dose of 6 mg/kg/day to castrated and hormonally replaced groups of PC‐82‐bearing male athymic nude mice. 4MA therapy when compared to control therapy caused significant PC‐82 growth inhibition in three different groups of hormonally replaced castrated mice: 1) physiologic T‐replaced (P<.001), 2) supraphysiologic T replaced (P<.001), and 3) supraphysiologic T and DHT replaced (P<.001). There was no difference between the post therapy plasma levels of T or DHT in the control‐treated and 4MA‐treated mice. In the second experiment, the effect of 4MA (6 mg/kg/day S.Q.) was compared to that of castration and control therapy on the growth of R198. Both castration and 4MA therapy effectively inhibited R198 growth when compared to control therapy (P = .01 and .02, respectively), but there was no difference in the degree of growth inhibition seen with 4MA or castration (P = .45). Castration and 4MA‐therapy significantly lowered plasma T levels when compared to control therapy; castration also significantly lowered plasma DHT levels, while 4MA and control therapy did not. These studies suggest that 4MA is effective in inhibiting the growth of human androgen‐responsive tumors grown in athymic nude mice and that further studies with other 5 alpha‐reductase inhibitors are indicated.
Ultrastructure and immunohistochemistry of the lateral prostate in aged rats
Authors: Aumüller Gerhard , Enderle‐Schmitt Ulrike , Seitz Jürgen , Müntzing Jonas , Chandler John A.
Published: February 2007

Ultrastructural, histological, and immunohistochemical studies were performed on lateral prostates of 1) aged rats from different strains, 2) rats permitted different levels of sexual activity, and 3) castrated rats. Antibodies against the following proteins were used as immunohistochemical markers: SVS II from seminal vesicle, LP 28 from lateral prostate, acid phosphatase isoenzymes from ventral prostate, transglutaminase from coagulating gland, and a commercial monoclonal antibody against cytokeratin. SVS II is a marker of lateral prostatic secretion, while immunoreactions to LP 28 and acid phosphatase (pI 7.1) were cytoplasmic. In aged animals the amount of intracellular secretion is decreased, and focally metaplastic transformation can be visualized by using immunohistochemical markers. Epithelial ultrastructure varied considerably with experimental conditions. Intensive sexual activity resulted in increased polymorphism and increased number of secretory granules within the glandular cells, while castration was followed by a rapid loss of secretory material. Also, in rats older than 10 months, a reduction in the number of secretion granules was common. The epithelium developed a positive immunoreaction to transglutaminase antibodies that were not observed in juvenile glands. Cells, presumably macrophages, which had an intense immunoreactivity for transglutaminase, were increased in number both within and outside the prostatic acini of aged rats. The possible interaction between secretory SVS II, a substrate of transglutaminase, the release of this enzyme from macrophages or its reflux from coagulating glands, the spontaneous cellular exfoliation that is due to decreased androgen levels, and dietary noxae may be of importance in the development of lateral prostatic nonbacterial inflammation in aged rats.
Immunohistochemical demonstration of metallothionein in the rat prostate
Authors: Umeyama Tomokazu , Saruki Kazuhisa , Imai Kyoichi , Yamanaka Hidetoshi , Suzuki Keiji , Ikei Nobuhiro , Kodaira Tsukasa , Nakajima Katsuyuki , Saitoh Hiroshi , Kimura Masami
Published: February 2007

Metallothionein in the rat prostate was demonstrated by using an indirect immunoperoxidase technique. Strong staining was found mainly in the supranuclear area of the cytoplasm of the glandular epithelium in the dorsal and the lateral glands. Diffuse cytoplasmic staining and nuclear staining were found with less frequency. Secretory granules were found in the lumen with various intensities of staining. Most of the epithelial cells in the ventral lobes and the coagulating glands were negatively stained. Immunoreactive cells were found sporadically. Two types of immunoreactive cells, round cells and spindle‐shaped cells, were scattered in the stroma. Vascular endothelial cells, red blood cells, and smooth muscle cells were negatively stained. These results suggest the synthesis and secretion of metallothionein in the rat prostate.
Isolation of a 41 kilodalton cytosol protein from the dunning rat prostatic adenocarcinoma: Characterization as depolymerized actin isomers
Authors: Nishi Nozomu , Matuo Yuhsi , Matsui Sei‐Ichi , Sandberg Avery A. , Isaacs John T. , Wada Fumio
Published: February 2007

Except for albumin, a 41,000‐dalton protein (41K) in the cytosol of the Dunning R‐3327 rat prostatic adenocarcinoma was found to be the most abundant soluble protein. This protein was purified in nearly homogeneous state by conventional chromatographies. After the first chromatography, because of the adhesive nature of the protein, 0.5% SDS and 2 M urea were necessary for subsequent steps of purification. The amino acid composition of the purified 41K was similar to that of actin isolated from rabbit skeletal muscle. Alternatively, 41K could be extracted from the Dunning tumor in the presence of ATP and dithiothreitol, under conditions in which actin molecules are depolymerized, and could be purified by the same method as cytoskeletal actin. The purified protein showed properties similar to rat skeletal muscle actin in amino acid composition and antigenicity. Both 41K proteins were found to be composed of four components having different isoelectric points. These results indicate that most actin exists in a depolymerized form as a cytosol protein of 41,000 daltons in the Dunning tumor and is composed of at least four isomers.
Dihydrotestosterone does not induce prostate adenocarcinoma in L‐W rats
Authors: Pollard Morris , Snyder David L. , Luckert Phyllis H.
Published: February 2007

It has been postulated that dihydrotestosterone (DHT) is the active trophic androgen in initiating pathogenic changes in the prostate gland. Groups of prostate cancer‐susceptible male L‐W rats (age 3 months) were treated with subcutaneous depots of testosterone or of DHT. After 14 months, prostate adenocarcinomas had developed in 24% of the testosteronetreated rats but not in the DHT‐treated rats. In the latter rats, the testes were significantly reduced in weight, there was no evidence of spermatogenesis, and serum testosterone levels were not detectable. It appears that DHT as administered to L‐W rats had an antiandrogenic effect.
Definitive radiotherapy of prostatic cancer: The Norwegian radium hospital's experience (1976‐1982)
Authors: Telhaug Ragnar , Fosså Sophie D. , Ous Sigurd
Published: February 2007

During the years 1976 to 1982 definitive curatively aimed radiotherapy to the primary tumor was given to 53 patients with prostatic cancer confined to the true pelvis (T0, 2; T1‐2, 19; T3, 24; T4, 8; N0, 18; N+, 2; Nx, 33); all patients were of the M0‐category. The pelvic lymph nodes received a total dose of 2 Gy × 25 by means of an anterior and posterior radiation field. The prostatic gland was irradiated by an additional booster dose of 2 Gy × 10 given to a perineal field. Twenty‐four patients have relapsed after their prostatic radiotherapy, only three of them within the irradiated area. For the patients with T0‐T2 tumors, the 5‐year crude survival was 69%, whereas it was only 37% for patients with T3 tumors. Thirty‐five patients developed intestinal (26 patients) and/or urogenital (23 patients) radiation side effects. In three patients a colostomy had to be performed owing to rectal stricture or fistula. The poor survival after radiotherapy in the present series is probably due to a high incidence of unrecognized pelvic lymph node metastases. In the future only prostatic cancer patients without pelvic lymph node spread will be considered candidates for definitive radiotherapy. An optimal radiation technique is mandatory in order to avoid major radio‐therapy‐induced toxicity.
Morphological studies on the effect of taxol on cultured human prostatic cancer cells
Authors: Röyttä Matias , Laine Kirsi‐Marja , Härkönen Pirkko
Published: February 2007

The effect of taxol, an experimental antitumor drug, was studied in vitro on human prostatic cancer cells. Different concentrations of taxol, varying from 5μM to 0.01 nM, were used. The effect of taxol was examined by light and electron microscopy. Taxol had a marked cytotoxic effect on prostatic cancer cells down to a 10 nM concentration of taxol when observed by light microscopy. However, by electron microscopy, the specific effect of taxol was seen even with a 1 nM concentration of taxol. Taxol induced the appearance of numerous round cells after a few days and, subsequently, progressive death of the tumor cells. Among the surviving tumor cells, large tumor cells were noted as well as many multinucleated tumor cells. By electron microscopy, the round tumor cells showed mitotic figures with a high amount of cytoplasmic microtubules. Nonmitotic cells were often multinucleated and contained a high number of cytoplasmic microtubules and microtubule‐related structures. The results show that taxol, even at very low concentrations, has a highly cytotoxic effect on prostatic cancer cells; and when a very low concentration of taxol is used with no obvious cytotoxic effect at the light microscopic level, specific taxol‐induced ultrastructural alterations can be observed.
Immunocytochemical localization of estrogen receptors in spontaneous and experimentally induced canine benign prostatic hyperplasia
Authors: Schulze Harald , Barrack Evelyn R.
Published: February 2007

Estrogens are believed to play a critical role in the etiology of canine benign prostatic hyperplasia (BPH); however, the mechanism has not been elucidated. To gain insight into this problem, we investigated the immunocytochemical localization of estrogen receptors (ER) in normal prostates, spontaneous BPH, and experimentally induced BPH by using a monoclonal ER antibody (H222). In all canine prostates the majority of ER was localized in nuclei of the same histological components: (1) transitional epithelium and subjacent stroma of the prostatic urethra, (2)periurethral prostatic ductal epithelium, and (3) prostatic stroma. ER content in the stroma was highest in the periurethral region of the prostate. Among the different groups of dogs, differences in ER location were seen only in the glandular epithelium. No ER was found in the glandular epithelium of normal prostates of young untreated dogs. In striking contrast, glandular epithelium of spontaneous BPH contained specific nuclear ER staining, though this staining was heterogeneous and was observed in only a minority (<10%) of the acinar epithelial cells. ER‐positive acini in BPH were located predominantly in the periurethral region. These data demonstrate anatomical and biochemical heterogeneity of prostatic components and indicate that the estrogen sensitivity of prostatic cells is heterogeneous. If estrogen does play a role in BPH, it appears to act selectively rather than uniformly throughout the prostate. We reasoned that if glandular epithelial ER are involved in the development of spontaneous BPH, one might expect to find the same location of ER in BPH that was induced experimentally by specific types of treatment with androgens ± estradiol. However, among hormone‐treated dogs the presence of ER‐positive prostatic glandular epithelium varied with the type of hormonal treatment but did not correlate with the experimental induction of glandular BPH. Some treatment groups with induced BPH had ER‐positive prostatic glandular epithelial nuclei (with the same extent and pattern of ER localization as in spontaneous BPH); however, other treatment groups with induced BPH had ER‐negative glandular epithelium. These data indicate either that glandular epithelial ER may not be involved in the pathogenesis of canine BPH or that there may be different types of BPH that have different etiologies. Possible mechanisms by which estrogen may affect the canine prostate are discussed in light of these new data on ER location.
Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement
Authors: English Hugh F. , Santen Richard J. , Lsaacs John T.
Published: February 2007

Light microscope autoradiography was utilized to investigate the separate proliferative activities of the basal and glandular cell types during androgen‐mediated restoration of the ventral prostatic epithelium in castrated rats. Our objective was to determine whether the proliferative population of the prostatic epithelium is restricted to the basal cell subtype under these experimental conditions. In the intact animal, substantial numbers of basal as well as glandular cells were found to be proliferating. The basal cell labeling index (LI) was 3.75%±0.3% or 1.85±0.4 × 105 labeled cells per prostate. For the glandular cells the comparable figures were 0.38% and 3.32±1.5 × 105. Seven days after surgical castration, both subtypes persisted. However, only the numbers of glandular cells were found to be significantly reduced (66% decrease). When androgens were replaced by daily subcutaneous injection (testosterone propionate, 2 mg/0.2 ml sesame oil), both cell types responded with significantly increased proliferation. The temporal pattern of response displayed by each cell type was very similar. A greater proportion of basal than glandular cells responded, ie, 28% vs 11% LI. However, in terms of approximate numbers of cells labeled during the peak response, the value for the glandular cells was larger, ie, 2.4 vs 1.1 × 106 labeled cells. These data clearly indicate that under normal conditions as well as during testosterone stimulation, basal cells are not the sole population of proliferating cells in the prostatic epithelium. Thus, basal cells, as a distinct morphologic population, are not homogeneously undifferentiated stem cells which give rise to differentiated and nonproliferating glandular epithelial cells. Aspects of these data can nevertheless be interpreted to support the idea that the prostatic epithelium is maintained by a single cell lineage system in which the stem cells comprise a subpopulation of the basal cells. Alternatively, the two populations may be separate and distinct as no data are presented which unequivocally links the two cell types in a precursor‐progeny relationship.
Long‐term results with a long‐acting formulation of D‐TRP‐6 LH‐RH in patients with prostate cancer: An Italian prostatic cancer project (P.O.N.CA.P.) study
Authors: Boccardo F. , Decensi A. , Guarneri D. , Rubagotti A. , Massa T. , Santi L. , Martorana G. , Giberti C. , Giuliani L. , Cerruti G. B. , Tani F. , Zanollo A. , Germinale T. , Borzone C. , Perri F. , Usai E.
Published: February 2007

Ninety‐five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D‐TRP‐6 LH‐RH (“Decapeptyl”) for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn‐RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down‐regulation of testicular LH receptors. Of 88 patients evaluable for response, about one‐half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D‐TRP‐6 LH‐RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.
Xenografted small cell undifferentiated cancer of prostate: Possible common origin with prostatic adenocarcinoma
Authors: van Haaften‐Day Caroline , Raghavan Derek , Russell Peter , Wills Edward J. , Gregory Patricia , Tilley Wayne , Horsfall David J.
Published: February 2007

The first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU‐PR‐2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone‐specific enolasè. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor‐bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.
Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate
Authors: De Voogt H. J. , Rao B. R. , Geldof A. A. , Gooren L. J. G. , Bouman F. G.
Published: February 2007

The effect of androgen blockade on the normal human prostate was studied in 16 healthy volunteers opting for male‐to‐female gender reassignment. Their ages ranged from 19 to 27 years. After 8 weeks of treatment with Anandron, serum hormone levels indicated antiandrogenic action and physical signs of feminization appeared. Prostate volumes (measured by ultrasound) before and following Anandron treatment remained the same. After 18 months of treatment with cyproterone‐acetate and ethinyl estradiol, prostate volumes again were not changed. However, histology revealed glandular atrophy and an increase in stromal tissue. The significance of these findings is discussed.
Immunohistochemical distribution of the three predominant secretory proteins in the parenchyma of hyperplastic and neoplastic prostate glands
Authors: Abrahamsson P.‐A. , Lilja H. , Falkmer S. , Wadströ L. B.
Published: February 2007

Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA), and β‐microseminoprotein (β‐MSP) were regularly localized immunohistochemically to the epithelium of the acini and that of the ducts in the nodules of 24 cases of benign prostatic hyperplasia.

The immunohistochemical distribution of these three prostatic‐secreted proteins was also examined, with monoclonal antisera against PAP and PSA and with polyclonal antisera against PAP, PSA, and β‐MSP, in a series of 40 cases of prostatic adenocarcinomas graded according to the WHO classification. Highly differentiated (grade I) carcinomas showed a high incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. As in the normal and hyperplastic prostate parenchyma, highly differentiated (grade I) carcinomas were found to contain an almost equal number of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. When semiquantitatively assessed, the incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells was found to be lower in the moderately and poorly differentiated (grades II and III) tumors than in the highly differentiated ones; they also showed greater staining variability. Tumor cells immunoreactive with a monoclonal antiserum raised against PAP in carcinomas of grades II and III were less frequent than tumor cells immunoreactive with antisera against PSA, β‐MSP, and a polyclonal antiserum against PAP. The almost identical distribution of PSA and β‐MSP in carcinomas of grades II and III suggests that PSA and β‐MSP are not less sensitive tumor markers than PAP for the monitoring of the course and the treatment of prostatic carcinomas.
Treatment of metastatic prostate carcinoma with the depot LRH analog zoladex
Authors: Holdaway I. M. , Ibbertson H. K. , Croxson M. S. , Harvey V. , Boulton J. , List A. , Rutland M. , Knox B. S.
Published: February 2007

A long‐acting LRH agonist (ICI 118630, Zoladex) was given by monthly subcutaneous injection to 25 patients with previously untreated symptomatic advanced prostatic carcinoma. The medication was well tolerated with the only side effect being hot flushes in 15 patients. Subjective improvement occurred in 22 patients, and disease remission or stabilization judged by objective criteria was seen in 21 and 18 patients from the total group at 3 and 6 months of treatment, respectively. Twelve of 18 patients followed for 1 year were still in objective remission/stabilization. Prostate volume measured by ultrasound decreased by a mean value of 75% and urine flow increased significantly. There were significant falls in serum testosterone and gonadotrophin levels and significant although lesser reductions in serum androstenedione and dehydroepiandrosterone. These changes were accompanied by significant reductions in serum acid and alkaline phosphatase and a rise in serum osteocalcin. Four patients (16%) experienced an initial tumor flare. Although only a small number of patients were studied, Zoladex appeared to be a well‐tolerated agent for treatment of prostatic carcinoma, with an initial clinical response similar to that seen with standard endocrine therapy.
Growth of a spontaneous canine prostatic adenocarcinoma in vivo and in vitro: Isolation and characterization of a neoplastic prostatic epithelial cell line, CPA 1
Authors: Eaton C. L. , Pierrepoint C. G.
Published: February 2007

Neoplastic epithelium derived from a spontaneous canine prostatic adenocarcinoma has been maintained and grown in cell culture and as xenografts in athymic mice. An epithelial cell line (CPA 1) has been isolated from primary cultures and has been partially characterized in vitro. The growth of this cell line was not modified by either androgens or estrogens, and high‐affinity receptors for these steroids could not be demonstrated in these cells'. Xenografts were serially transplantable, with growth being similar in both sexes. Receptors for androgens and estrogens could not be detected in homogenates of xenografts or primary tumor. The histological appearances of serially transplanted tumors, and of xenografts generated by inoculation of the cell line (CPA 1) and several cloned substrains, were very similar to that of the primary tumor and were judged to be well differentiated. The characteristics of this neoplastic cell type have been compared with those of normal prostatic epithelium.
Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice. II. Tumor growth and androgen receptors
Authors: Van Steenbrugge G. J. , Bolt‐De Vries J. , Blankenstein M. A. , Brinkmann A. O. , Schröder F. H.
Published: February 2007

Androgen receptor (AR) levels were measured in PC‐82 tumor tissue grown in hormonally manipulated nude mice. In the nuclei of tumor tissue from intact male mice a relatively low concentration (mean 25 fmol/mg protein) of androgen receptors (ARn) was found, while no receptors for estrogens or progestins were detected. The total number of androgen receptors in the PC‐82 tumor tissue (measured in the nuclei 1 h after injection of a single high dose of testosterone (T)) was found to be 100 fmol/mg protein. The antiandrogen cyproterone acetate, administered in combination with the high dose of T, significantly lowered the amount of ARn in the tumor tissue. In the nuclei of tumor tissue from intact tumor‐bearing male mice with T‐containing Silastic implants, a 4‐times higher amount of tightly associated AR was found. In addition, an increased growth rate of the tumor was observed following T implantation. This finding suggests that the increased growth rate of the PC‐82 tumor is associated with a continuous occupancy of AR in the nuclei of the tumor tissue. Castration of tumor‐bearing male mice, which arrests the growth of this tumor, did not affect the concentration of ARn in the tissue compared to that of tissue in the intact control situation. In addition, the total amount of AR measured after T injection was not affected by castration. Therefore, the availability of a sufficient and steady level of T in the plasma and consequently the duration of the presence of AR in the nucleus of the PC‐82 tumor tissue, rather than the total concentration of AR, appear to be the limiting factors in the modulation of hormonal responses in this androgen target tissue.
Prolactin effect on the permeability of human benign hyperplastic prostate to testosterone
Authors: Farnsworth Wells E.
Published: February 2007

While it has been known for over 30 years that prolactin (Prl) synergizes with androgen in the support and stimulation of prostatic growth and metabolism, the evidence that this is accomplished through increasing access of the steroid to the cellular machinery of the gland has arisen only since about 1970. There is widespread uncertainty as to how the Prl effect takes place: by 1) increasing the free steroid concentration in the blood; 2) facilitating the uptake of protein‐bound androgen; 3) increasing, by metabolism or receptor‐binding, the concentration gradient that can support passive diffusion of the steroid across the plasma membrane; or 4) modification of the fluidity of the membrane itself to increase the solubility of the steroid in the lipoprotein and, thus, the ease of penetration of the cell. The present study attempted to learn if Prl is an effective stimulus of androgen uptake when the first three options are not operative. Using an equilibrium exchange procedure to track the uptake of [17α‐3H]‐testosterone ([17α‐3H]‐T) into minced benign hyperplastic human prostate tissue and the irreversible metabolism of the entering steroid to [17α‐3H]‐dihydrotestosterone [17α‐3H]‐DHT, it was found that the rate of production of the 5α‐reduced metabolite, during a 1‐hr incubation in vitro, was directly proportional to the concentration of ovine Prl over the dose range of 0–160 ng/ml. The clinical significance of Prl mediation of steroid uptake is discussed, and suggestions are made as to how the Prl might alter the permeability of the plasma membrane.
Requirements for attachment and subsequent growth of canine prostatic epithelial cells in culture
Authors: Chevalie Simone , Chapdelaine Alcide
Published: February 2007

The attachment and spreading of canine prostatic epithelial cells in primary monolayers and their subsequent proliferation were studied in Primaria and in polystyrene dishes either uncoated or coated with collagen type I, fibronectin, laminin, poly‐D‐lysine, or natural extracellular matrices (nECM) produced by canine prostatic epithelial or fibroblastic cells. Cells were inoculated in serum‐free medium or in medium supplemented with either dialyzed fetal bovine serum (dFBS) or charcoal‐treated dog serum at 10%. Dihydrotestos‐terone (DHT) and 5α‐androstane 3α, 17β‐diol (3α, 17β‐diol) at 10−6 M or a mixture of steroids (androstenedione, testosterone, DHT, 3α, 17β‐diol, 5α‐androstane 3β, 17β‐diol, estrone, and estradiol) were also added. Of all components and dishes tested, only dFBS and the nECM produced by prostatic epithelial cells increased cell attachment (850% and 450%, respectively). When the latter preparations were used in combination, an additive effect (1,500%) was observed, and the subsequent addition of dog serum after the attachment period yielded the highest number of growing prostatic epithelial cells. When prostatic epithelial cells were inoculated either in dishes coated with a nECM derived from prostatic fibroblasts or in presence of dog serum, a 50% inhibition in their plating efficiency was observed. The presence of collagen type I, fibronectin, laminin, or an nECM in the cultures, together with various steroids, had no effect on the cell unresponsiveness to steroids nor did it alter the mitogenic effect of dog serum. Thus, the attachment and spreading of canine prostatic epithelial cells in monolayers are mediated by nonsteroidal factors present in dFBS and in their nECM. Their presence, together with steroids, does not elicit a proliferative response to steroids nor did it increase the effect of growth‐promoting factors in dog serum.
5α‐reductase activity in epithelium and stroma of prostates from intact and castrated dogs treated with androstenedione, the aromatase inhibitor 1‐methyl‐1,4‐androstadiene‐3, 17‐dione, and cyproterone acetate
Authors: Tunn Sabine , Hochstrate Holger , Habenicht Ursula‐F. , Krieg Michael
Published: February 2007

In addition to the histology of epithelial and stromal elements of prostates from intact dogs (group 0) and castrated dogs (group I), the latter of which were treated with androstenedione (group II), androstenedione plus the aromatase inhibitor 1‐methyl‐1,4‐androstadiene‐3,17‐dione (group III), or androstenedione plus aromatase inhibitor and cyproterone acetate (group IV) (Habenicht and El Etreby: The Prostate 11:133–143, 1987) it was of interest to study the influence of such in vivo treatment on the prostatic 5α‐reductase, which is responsible for the cellular conversion of testosterone to 5α‐dihydrotestosterone. Michaelis constants (KM) and maximal activities (Vmax) of 5α‐reductase were determined under optimized incubation conditions in mechanically separated epithelium and stroma. The metabolites were separated by high‐performance liquid chromatography and determined radiometrically. The main results were: 1) The mean KM (nM ± SEM) was significantly (P < .001) higher in epithelium (892 ± 132) than stroma (70 ± 11). The same was true concerning the Vmax (pmol · mg protein−1 · h−1 · SEM) in epithelium (54.6 ± 5.8) as compared to stroma (13.0 ± 2.0). 2) No specific in vivo or in vitro effect of the aromatase inhibitor on the KM and Vmax data was found. 3) In prostates of intact dogs and dogs of group II the proportion of epithelial 5α‐reductase exceeded distinctly that of stromal 5α‐reductase. 4) In groups I, III, and IV the proportion of epithelial 5α‐reductase was rather low. These data were discussed in the light of the histological findings.