bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hyperprolactinemia on the accessory sexual organs of the male rat
Authors: Coert A. , Nievelstein H. , Kloosterboer H. J. , Loonen P. , Van Vies J. Der
Published: February 2007

The growth‐promoting effect of prolactin on the ventral prostate lobe, the anterior prostate lobe (or coagulating gland), and seminal vesicles has been studied before, during and after puberty in rats up to 5 months of age. Pituitaries from female rats were grafted under the renal capsule of 23–26‐day‐old male rats. Within 1/2 month substantial (five‐ to ten‐fold) hyperprolactinemia occurred followed by a gradual decline; levels were still high 4 months after grafting. A statistically significant increase in the weight of the seminal vesicles and the ventral and anterior prostate lobes was observed 1 month after implantation. This effect was only maintained for the seminal vesicles during the next 3 months. Hyperprolactinemia did not influence testosterone metabolism. In the ventral prostate lobe, 1 month after grafting, the nuclear androgen receptor content increased, whereas the cytosolic androgen receptor content decreased. These results suggest that the growth‐promoting effect of prolactin, on the ventral prostate lobe of the rat, is brought about by an increased translocation of the androgen receptor.
Qualitative analysis of coomassie‐blue‐stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two‐dimensional protein electrophoresis
Authors: Anderson K. M. , Baranowski J. , Bonomi P. , Economou S. G.
Published: February 2007

Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two‐dimensional (2D)‐protein electrophoresis. Qualitative analysis of Coomassie‐blue‐stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety‐two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered „unique”︁ to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples.

The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs.
Chronic prostatitis: Comments on infectious etiologies and antimicrobial treatment
Authors: Greenberg Richard N. , Reilly Patrick M. , Luppen Kevin L. , Piercy Steven
Published: February 2007

Twenty‐three males with the clinical diagnosis of chronic prostatitis were evaluated for a bacterial etiology by the Stamey and Meares method. In addition, 16 patients, regardless of culture results, were placed on either cefadroxil or oral carbenicillin antimicrobial therapy. Culture results identified only four (17%) of 23 patients with bacterial prostatitis: coagulase‐negative Staphylococcus (2), Enterobocter agglomerons (1), and Haemophilus parainfluenzae, and coagulase‐negative Staphylococcus (1). Four of seven patients who received oral carbenicillin and three of nine patients who received cefadroxil reported symptomatic relief.

This study did not identify a common etiology for chronic prostatitis or a consistently effective antimicrobial treatment. Rather, we observed that the etiologic agent in most cases of chronic prostatitis (83%) could not be identified by routine bacteriologic culture. Future research efforts in chronic prostatitis must address not only treatment regimens but expand the search for etiologic agents.
The relationship of natural killer cells to metastasis of a transplantable prostate adenocarcinoma
Authors: Wade Anedrea C. , Schmidt Marjorie A. , Pollard Morris
Published: February 2007

Natural killer (NK) cells have been proposed to play a significant role in the inhibition of metastasis. The prostate adenocarcinoma (PA‐11) in the Lobund‐Wistar (L‐W) rat provides a unique model of spontaneous metastasis in which to study NK response. Cultured PA‐11 tumor cells were shown to be resistant to NK lysis in vitro, and enhancement or inhibition of NK reactivity in vivo using drugs or antiserum did not change the rate or extent of metastasis evident at autopsy. Exposure to PA‐11 tumor cells, supernatants from cultured tumor cells, or sera from rats with advanced PA‐11 in vitro did not result in inhibition of NK activity. Exposure to PA‐11 tumor cells in vivo also did not cause suppression of NK activity. These data indicate that, in the PA‐11/L‐W system, metastasis is independent of NK activity.
Cytochemistry and biochemistry of acid phosphatases V: Electrophoretic studies on the heterogeneity of acid phosphatases from human prostate, seminal fluid, and leukocytes
Authors: Seitz J. , Aumüller G.
Published: February 2007

Comparison of zymograms of acid phosphatases (orthophosphoric monoester phosphohydrolase, acid optimum, E.C.3.1.3.2) from human prostate, leukocytes, seminal vesicles, and seminal fluid, separated by analytical isoelectric focusing (IEF), resulted in the identification of three individual groups, particularly of the prostate. These groups contain three molecular forms at different molecular weights and activities in varying quantities and combinations. The molecular weights, estimated by SDS gel electrophoresis, were 1) 86,000, 2) 76,000, and 3) 46,000/50,000 (in a doublet) daltons. None of these isoenzymes were restricted to the prostate, but they were present in very high concentrations in the prostate. Compared to the prostate, the seminal vesicles and isolated leukocytes had very closely related zymograms of acid phosphatases. No specific inhibitor has been found that would selectively inhibit one particular isoenzyme without affecting the others. Protein titration and staining activity of IEF gels at different pH values showed that the isoenzymes from all three groups have high hydrolytic activity of orthophosphoric monoesters beyond the acidic pH range of pH 4–5. Incubation of acidic isoforms of acid phosphatases with neuraminidase did not result in the formation of a homogeneous stem molecule. Further analysis of the secretory moiety using the western blotting method showed a binding of peroxidase‐conjugated concanavalin A (Con A), indicating that these isoenzymes are glycoproteins. Moreover, isoenzymes extracted from prostate, seminal fluid, and human leukocytes are immunologically identical.
Cytochemistry and biochemistry of acid phosphatases VI: Immunoelectron microscopic studies on human prostatic and leukocytic acid phosphatases
Authors: Aumüller G. , Seitz J.
Published: February 2007

Using different antisera against secretory and lysosomal prostatic acid phosphatases, the localization of the respective antigens was studied in the human prostate at the ultrastructural level. Secretory acid phosphatase was confined exclusively to the secretory vacuoles of the glandular cells. Discharge of the secretory material occurs in a merocrine type of secretion. The identical antigen could be localized in the primary and secondary granules of neutrophil and eosinophil granulocytes separated from human peripheral blood. The antiserum used was also cross‐reactive with the canine prostate, where a very distinct immunoreaction was observed with the secretory granules of the glandular cells.

The antibodies directed against lysosomal acid phosphatases prepared from prostatic homogenates consistently gave a positive immunoreaction with dense bodies, lipofuscin, and secretory granules. The respective antigens were present also in neutrophil and eosinophil granulocytes. These findings do not identify the existence of a prostate‐specific acid phosphatase, which does not exist. The secretory form of the isoenzymes, however, is clearly distinct from the lysosomal form, both of which are present in granulocytes. Therefore the origin of acid phosphatases elevated in peripheral blood in cases of metastatic prostatic cancer could be either the carcinomatous cells or leukocytes destroyed during the process of metastasis.
Regional differences in the inductive activity of the mesenchyme of the embryonic mouse urogenital sinus
Authors: Sugimura Yoshiki , Cunha Gerald R. , Norman Jill T. , Shannon John M.
Published: February 2007

Embryonic urogenital sinuses (UGS) of 16‐day‐old mice were divided into two or three zones (cranial half and caudal half; or cranial third, intermediate, and caudal thirds). Following tryptic digestion, these zones were separated into their mesenchymal (UGM) and epithelial (UGE) components. The cranial and caudal zones of the UGM were recombined separately with the different zones of the UGE or with adult mouse urinary bladder epithelium (BLE). Following four weeks of growth in syngeneic male hosts, tissue recombinants of cranial UGM + caudal UGE contained numerous prostatic ducts and urethral glands. Conversely, recombinants composed of caudal UGM + cranial UGE developed into fibromuscular tissue covered with urethral epithelium and did not contain prostate, but occasionally contained urethral glands. Urethral glands were usually present in grafts of cranial UGM + cranial UGE or in grafts of the intact intermediate third of the UGS. In heterotypic recombinants of the UGM + adult BLE, prostatic glands were induced only when cranial UGM was utilized. Urethral glands were not observed in tissue recombinants prepared with adult BLE. These data suggest that regional differences in mesenchymal inductive ability and epithelial responsiveness play a role in the harmonious morphogenesis of the male lower genitourinary tract.
Relationships between estrogen intake, serum testosterone, and tumor androgen, estrogen, and progesterone receptor levels in diethylstilbestrol‐treated rats bearing the R3327 prostatic adenocarcinoma
Authors: Mobbs B. G. , Johnson I. E.
Published: February 2007

The relationships between intake of diethylstilbestrol (DES), serum testosterone, prostate weight, and the tumor steroid receptor content were investigated in male Copenhagen x Fischer F1 hybrid rats bearing the R3327H tumor after treatment for 20 days with graded doses of diethylstilbestrol diphosphate. It was found that the wet weights of the ventral and dorsolateral prostate glands were positively linearly related to the log of the serum testosterone level (P < 0.001). The cellular distribution of androgen receptor (AR) in the tumors of the treated animals was consistent with the androgen deprivation brought about by the treatment, and nuclear AR concentrations were also linearly related to the log of the serum testosterone levels (P < 0.001). Although nuclear estrogen receptor could not be consistently demonstrated in these tumors, cytosol progesterone levels were linearly related to the amount of DES ingested during the treatment period (P < 0.001).
High‐dose danazol therapy in prostatic cancer patients: Endocrine and clinical effects
Authors: Hedlund P. O. , Freedman D. , Esposti P. , Gershagen S. , Carlström K.
Published: February 2007

The effect of high‐dose—800 mg daily—danazol treatment was studied in ten prostatic cancer patients by repeated hormone analyses, clinical examinations, and cytological evaluations. Danazol caused a prompt decrease in the peripheral serum levels of testosterone, in some cases to castration values, as well as significantly suppressed FSH and LH values. Serum prolactin was not affected by danazol but the level of sex‐hormone‐binding globulin (SHBG) was strongly decreased. Serum danazol values ranged between 552 and 1,411 nM during treatment. Despite markedly decreased testosterone levels, danazol had only limited effect on the course of the prostatic cancer. This is probably explained by the ability of danazol to suppress SHBG levels, thus maintaining a rather high level of non‐protein‐bound, biologically active testosterone, even though total testosterone levels decrease to castration values.
Bifluranol in the treatment of benign prostatic hyperplasia (BPH)
Authors: Beacock C. J. M. , Buck A. C. , Roberts E. E.
Published: February 2007

Bifluranol, a fluorinated bibenzyl drug with antiandrogenic properties has been studied for its efficacy in the treatment of benign prostatic hyperplasia. Thirty five patients with bladder outflow obstruction received either Bifluranol 1.5 mg orally, t.d.s. or placebo in a double‐blind trial. After twelve weeks there was improvement in symptoms of flow, urinary stream (p <0.01) and frequency (p <0.05) in the Bifluranol treated group. A significant reduction in residual urine volume was noted in the active treated group (p <0.05) but mean and peak urine flow rates, voided volume and prostate volume did not reach statistical significance.

It is concluded that Bifluranol has a measurably beneficial effect in urinary outflow obstruction due to BPH and further investigative studies with this drug are in progress.
Free testosterone in carcinoma of the prostate
Authors: Levell M. J. , Rowe E. , Glashan R. W. , Pidcock N. B. , Siddall J. K.
Published: February 2007

Serum concentrations of testosterone (total T), sex hormone‐binding globulin (SHBG), and albumin (A) have been measured, and from these values the free testosterone (free T) has been calculated in the following groups: 50 patients recalled 1‐2 years after prostatectomy for benign prostatic hyperplasia (BPH); 21 patients with BPH at first presentation; and 80 patients with carcinoma of the prostate (CaP) divided into 47 without clinical or radiological evidence of metastases (Mo) and 33 with metastases (M+). The Mo patients were further subdivided by the size of the prostate. Free T showed no change with age in either of the CaP groups. In both of the BPH groups free T fell with age so that in the patients aged 65 or less it was above the mean CaP level and in patients aged 75 or more it was similar to the CaP level. SHBG rose with age so that total testosterone values were a poor guide to free T. Neither presence of metastases nor prostate size in Mo patients was related to marked differences of free T.
Concentrations of 3β‐hydroxy androgens in epithelium and stroma of benign hyperplastic and normal human prostate
Authors: Bartsch Wilfried , Kozák Ivan , Gorenflos Peter , Becker Hermann , Voigt Klaus‐Dieter
Published: February 2007

Androgen metabolites with 3β‐hydroxy configuration—ie, dehydroepiandrosterone (3β‐hydroxy‐5‐androsten‐17‐one, DHEA), 5‐androstene‐3β‐17β‐diol (A‐Diol), and 5α‐androstane‐3β,17β‐diol (3β‐Diol)‐were measured by radioimmunoassay in the homogenate, in the mechanically separated epithelium and stroma, and in the nuclear fractions of epithelium and stroma of benign hyperplastic (BPH) and normal human prostatic tissue, in muscle homogenates and in plasma.

The main results were: 1) Mean prostatic DHEA, A‐Diol and 3β‐Diol were 6–7 times as high as plasma values (1 g = 1 ml). Compared to muscle, prostatic values were more than tenfold higher. 2) The values in homogenates of BPH and normal prostate were not statistically different (pmol/mg DNA, mean ± SEM, BPH: DHEA 46.8 ± 7.2, n = 11; A‐Diol 5.7±1.2, n = 12; 3β‐Diol 3.7 ± 0.6, n = 13; normal prostate: DHEA 56.0 ± 5.5, n = 2; A‐Diol 7.4 ± 2.4, n = 5; 3β‐Diol 5.8 ± 1.7, n = 5). 3) In the nuclear fractions of epithelium and stroma the values were low compared to the homogenates and could not be discriminated from unspecific retention.

Although we could not demonstrate either a specific retention of the 3β‐hydroxysteroids in the nuclei or conclusive differences in steroid accumulation between epithelium and stroma of BPH and normal prostate, which could explain the development of the disease, the high levels in the tissue particularly of A‐Diol would be compatible with estrogenic action at the prostate level.
Growth responses of normal, benign hyperplastic, and malignant human prostatic epithelial cells in vitro to cholera toxin, pituitary extract, and hydrocortisone
Authors: Peehl Donna M. , Stamey Thomas A.
Published: February 2007

Normal, benign hyperplastic (BPH), and malignant prostatic epithelial cells from adult humans can be serially passaged in medium PFMR‐4 supplemented with 20% whole serum, cholera toxin, and epidermal growth factor (EGF). Improved growth of these cells has been achieved by optimizing the concentrations of the components of the basal medium. In the new modified medium, PFMR‐4A, the only supplements required are 5% dialyzed serum, cholera toxin, EGF, pituitary extract, and hydrocortisone. Comparative studies of the growth responses of prostatic cells derived from normal central zone, normal peripheral zone, BPH nodules, and adenocarcinomas did not reveal any qualitative differences; all respond positively to the addition of cholera toxin, pituitary extract, and hydrocortisone to the culture medium. Cells of one cancer strain, however, were much less density‐dependent for growth than were the other strains of normal, BPH, or malignant cells.
Blood loss during and following transurethral resection
Authors: De Campos Freire Geraldo , De Campos Pachelli Laercio , Cordeiro Paulo , Borrelli Milton , De Goes Gilberto Menezes
Published: February 2007

Blood loss measurement in transurethral prostatic surgery (TUR) has been studied with the following objectives: (1) to measure the total lost volume (during surgery and 48 hours postoperatively); (2) to compare surgical bleeding and coagulogram alterations in benign prostatic hypertrophy (BPH) and prostatic carcinoma (CaP); (3) to establish the relationship between blood loss, duration of the procedure, and amount of resected tissue. The method of Jansen was used to measure blood loss, and the “coagulogram” included the following parameters: hematrocrit; prothrombin, recalcification, thrombin, and partial thromboplastin times; fibrinogen; platelets and fibrin split products. The study is based on TUR performed on 75 patients from whom a mean weight of 25.68 grams was resected resulting in a mean total bleeding volume of 305 ml. Blood loss over 400 ml was associated with surgical durations of 60 minutes or with resection of over 40 grams of tissue. There was a slight tendency for fibrinolysis in prostatic cancer, which could explain the relatively higher amount of blood loss observed in these cases.
Bruch's de morbis glandulae prostatae: An early account of prostatic diseases (1835)
Authors: Manci Elizabeth A. , Gardner William A.
Published: February 2007

Editorial Comment: This is a rather unusual paper dealing with a verbatim translation of the thesis by Maximillian J.F. Bruch on the diseases of the prostate gland first published in 1835 and apparently never translated into English. Since in all probability this is the first comprehensive treatise on prostatic disease, it is a welcome and important translation and presents the background as to how our thinking regarding prostatic disease developed for nearly 150 years. Although the manuscript is somewhat lengthy, we decided to publish it in total, since, if it were to be reduced in size, it would be difficult to decide which parts to remove and could run the risk of ruining the work of the authors.

The authors have done an excellent job in translating this thesis from the complex Latin text.

Avery A. Sandberg, MD

James P. Karr, PhD

This Latin dissertation on diseases of the prostate gland was written by the German physician Maximillian J.F. Bruch at the Freiderick Wilhelm University. This English translation permits a rare glimpse into the early medical thinking on prostatic diseases.
The induction of new ductal growth in adult prostatic epithelium in response to an embryonic prostatic inductor
Authors: Norman Jill T. , Cunha Gerald R. , Sugimura Yoshiki
Published: February 2007

Tissue recombinants were prepared with a single epithelial ductal tip from adult prostate and mesenchyme from either the embryonic urogenital sinus or adult urinary bladder. Recombinants were grown in vivo beneath the renal capsule of male hosts. After 4 weeks of in vivo growth, extensive growth of arborizing ducts was apparent in recombinants composed of urogenital sinus mesenchyme and a single adult prostatic ductal tip. One‐dimensional polyacrylamide gel electrophoresis indicated that these recombinants contained many of the proteins of the mature prostate. Heterospecific recombinants (rat urogenital sinus mesenchyme and mouse prostatic epitheiium) showed the ductal tissue to be derived solely from the prostatic epithelium. In recombinants of a prostatic ductal tip with mesenchyme from the urinary bladder, ductal growth was absent, the ductal tip was maintained as a single, discrete, epithelial structure, and the protein composition of these recombinants more closely resembled that of the bladder. The results demonstrate that the epithelial cells of the adult prostate can participate in new ductal growth in response to an embryonic prostatic inductor. These data provide experimental evidence to support the hypothesis that human benign prostatic hyperplasia may result from the anomalous reactivation of embryonic growth potential in the adult prostate.
Acid phosphatase in the lysosomal and microsomal fractions of human prostatic epithelium
Authors: De Vries G. P. , Sanders G. T. B.
Published: February 2007

Polyacrylamide gel electrophoresis of acid phosphatase from prostatic tissue reveals one more band than seminal plasma. It was attempted to ascertain which subcellular fraction was responsible for that intracellularly localized enzyme. Prostatic epithelium from patients with prostatic hyperplasia was homogenized, and a lysosomal and microsomal fraction were prepared by differential centrifugation. These two fractions were further centrifuged on an isopycnic Percoll gradient. The intracellularly localized form of acid phosphatase was associated with the lysosomal as well as with the microsomal fraction. In a fused rocket electrophoresis experiment these acid phosphatases cross‐reacted with antiserum from seminal plasma. After neuraminidase treatment of the acid phosphatase of lysosomal and microsomal origin, only one activity band was found in polyacrylamide gels.

It is concluded that only one acid phosphatase protein exists in prostatic epithelium; differences in electrophoretic mobility are caused mainly by different amounts of sialic acid residues, coupled to the same protein backbone.
Proliferation of dunning R‐3327 rat prostatic adenocarcinoma and of its sublines (CUA and CUB)
Authors: Wakisaka Masami , Miyauchi Taisei , Hara Shigeru , Matsuzaki Osamu , Shimazaki Jun
Published: February 2007

Proliferating cells in tumors of the androgen‐dependent R‐3327 and its partially dependent and autonomous sublines, CUA and CUB, were examined. Two types of cells, myoepithelial cells and large stromal cells, in the R‐3327 have a high proliferating ability, as estimated by thymidine uptake. These cells were also observed in the normal dorsolateral prostate of rats, the lobes from which R‐3327 originated. CUA is a squamous carcinoma, which proliferates at the border of the epithelial layer and large stromal cells. The tumor cells of CUB appear as clusters of large stromal cells which have a strong potential for dividing. Therefore, R‐3327 contains two types of dividing cells, and their uncoordinated proliferation may be responsible for causing the different features seen in the sublines.
Effects of 1.5% glycine infusion on the nonelectrolyte components of serum in dogs
Authors: O'Donnell Patm , McHan Stacie A. , Fody Edward P.
Published: February 2007

Plasma dilution resulting from absorption of a 1.5% glycine solution is difficult to evaluate on the basis of changes in serum sodium alone. In a canine animal model the effects of infusion of a 1.5% glycine solution and a 0.9% saline solution on the nonelectrolyte components of serum were compared with a noninfused control group. The outcome measurements included total serum protein, serum albumin, serum cholesterol, serum globulin, plasma fibrinogen, and serum osmolality. The infusion of each solution resulted in a significantly lower concentration in plasma proteins and cholesterol compared with the control group. The lowest concentration of plasma proteins and cholesterol occurred in the saline infusion group. The dilution produced by saline infusion was consistent with a distribution of the infused fluid in the extracellular compartment. The dilutional effect was less in the glycine solution infused group, which suggested partial distribution of residual free water from the glycine solution in the intracellular space as well as the extracellular compartment. Since plasma proteins are confined primarily to the intravascular compartment, the changes in the concentration of plasma proteins and cholesterol indicate the amount of dilution of the extracellular fluid.
Cytologic regression grading of hormone‐treated prostatic cancer
Authors: Schmeller N. T. , Jocham D. , Staehler G. , Schmiedt E. , Davis J. , Drach G. W.
Published: February 2007

Aspiration cytology during hormone treatment of prostatic cancer has been regularly performed at the University of Munich for 13 years and gives direct information on the primary tumor. To analyse its value in clinical practice, 919 biopsies of 187 patients were reviewed without knowledge of clinical data and the charts were analysed retrospectively. Each biopsy was classified as having good, medium, or poor therapeutic response depending on the regressive changes of the cells. Agreement between two independent observers was 89%

All but 39 of these patients have died and the surviving patients have a minimum observation period of 5.6 years. A poor therapeutic response was seen cytologically in 72 patients (38.5%) at variable times after treatment began. These patients have a statistically significant worse survival in comparison to all other patients. Forty‐seven of these 72 patients had deterioration, but clinical signs developed later in 23 cases (mean 1.1 years); in 21 patients cytology and clinical signs were simultaneous and in only three cases clinical deterioration preceded aspiration cytology (mean 4.8 months). In 25 cases there was a cytologically poor therapeutic response, but no clinical signs of deterioration. These patients had the same survival rate as with good or medium treatment response. Serial aspiration cytology is a very valuable parameter in treatment monitoring and is often the early warning sign of endocrine treatment failure.
Papillary adenoma of the prostatic urethra
Authors: Zeid Mohamed , Gaeta John F. , Asirwatham John E. , Suffrin Gerald
Published: February 2007

Six patients with papillary adenoma of the prostatic urethra are described. Their ages ranged from 39 to 70 years old. Two of them showed evidence of clincal recurrence 1 year after treatment. The pathological features as well as the immunohistochemical demonstration of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) are illustrated. A brief review of the literature is discussed with special emphasis on the histogenesis and nature of this lesion.
Danazol treatment of advanced prostate cancer: Clinical and hormonal effects
Authors: Cole R. M. , Raghavan D. , Caterson I. , Pearson Bruce , Boulas John , Teriana Nory , Rosen M.
Published: February 2007

Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15–18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.
Two‐dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid
Authors: Lee Chung , Tsai Yvonne , Sensibar Julia , Oliver Lyda , Grayhack John T.
Published: February 2007

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two‐diemnsional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two‐dimensional gels, those that are related to prostate‐associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase‐antiperoxidase as the staining reagent. Each protein spot in the two‐dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2–8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6–6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum‐related proteins by an extensive absorption with anti‐human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non‐serum proteins. These non‐serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two‐dimensional gels should be considered as the characteristic property of the prostatic secretions.
Design of cytotoxic steroids for prostate cancer
Authors: Petrow Vladimir , Padilla George M.
Published: February 2007

Our object was to determine 1) if the aromatic nucleus of estramustine (I) is optimal for binding affinity to prostate cytosolic proteins, and 2) if C3 is the preferred position for the N‐mustard carbamate moiety. To this end we have submitted 34 steroids for in vitro assay of binding affinity to total prostate cytosolic proteins. Our structures included aromatic and hydroaromatic steroids containing N‐mustard carbamate and other substituents at C3, C6, C11, C16, C17, C20, and C21. Our results show that binding affinity to prostate proteins is optimally present in C3‐nitrogen mustard carbamates attached directly to a totally planar aromatic ring as in (IV). Partial deviation from total planarity as in enol‐carbamates (V) leads to some loss of binding affinity, which largely disappears in hydroaromatic structures (VI). Thus, our data lead to the Ring A aromatic structure (X) as a basis for the design of steroidal N‐mustard carbamates with prostate selectivity.

Preliminary in vivo studies using the Dunning R3327AT prostatic adenocarcinoma implanted in the Copenhagen rat generally support our in vitro data.
Role of adrenal androgens in prostate regression in rats treated with an antiandrogen and an lhrh agonist
Authors: Foldesy Robin G. , Vanderhoof Mary M. , Canton Lucila E. , Hahn Do Won
Published: February 2007

Histrelin, a potent luteinizing hormone releasing hormone (LHRH) agonist, and flutamide, an antiandrogen, were administered to intact and adrenalectomized rats to determine the role of adrenal androgens in the additive effects of the two drugs on prostate regression. Each compound, given separately, was effective in decreasing prostate weights in intact rats. When given together, additive effects were demonstrated by even greater atrophy of the prostates. It has previously been proposed that this additive effect may be primarily attributed to the ability of the antiandrogen to block the action of adrenal androgens. However, in adrenalectomized rats, the combination of histrelin and flutamide still produced a greater reduction in prostate weights than did either drug alone, indicating that the role of adrenal androgens in this effect is negligible. This experiment also was repeated with castrate, androgen‐supplemented rats, and the additive effects previously described were not observed. In a final experiment, prostatic atrophy in castrate rats was not enhanced by either adrenalectomy or flutamide treatment. Thus, the additive effects of histrelin and flutamide appear to focus on testicular rather than adrenal androgens.
Androgen and estrogen effect on guinea pig seminal vesicle muscle: A combined stereological and biochemical study
Authors: Bruengger A. , Mariotti A. , Rohr H. P. , Stahel W. , Wiederkehr P. , Bartsch G. , Carmichael S. W. , Mawhinney M. G.
Published: February 2007

A combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone‐ or estradiol‐treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels. The estrogen‐induced increase in muscle weight and DNA content appeared to be due only to hyperplasia of muscle cells and not to a proliferation of fibroblasts or to infiltration by inflammatory cells. In all treatment groups, including the estrogen‐treated castrates, more than 95% of the cells in the tissue were smooth muscle cells, and there was no evidence that polyploidy contributed to changes in DNA levels. In addition, in the estrogen‐treated muscles, DNA concentration remained high, and the stereologically determined cell size remained low. Therefore, both morphological and biochemical evidence indicate that androgen induces hypertrophy, whereas estrogen induces hyperplasia of muscle cells.

The correction of stereological and biochemical data validates the application of stereological cell size determination for smooth muscle cells in organs that hardly can be separated into stromal and epithelial components; eg, the prostate.
Complete response of lung metastases caused by prostatic cancer after chronic administration of a gonadotropin‐releasing hormone analog, buserelin (HOE 766)
Authors: Koutsilieris Michael , Ackmanr C. F. Douglas
Published: February 2007

A stage D2 prostate cancer patient with biopsy‐proven lung metastases and negative work‐up for metastases is discussed. Treatment consisted of hormonai therapy in the form of chronic administration of an analog of gonadotropin‐releasing hormone (GnRH‐A), Buserelin, with follow‐up for 24 months. The complete response of the patient to GnRH‐A therapy provides an interesting and unusual case in the understanding of the biological behavior of prostate cancer.
Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue
Authors: Hulka Barbara S. , Beckman William C. , Checkoway Harvey , Diferdinando George , Hammond John E. , Fried Floyd A. , Mickey Don D. , Stumpf Walter E. , Clark Terry D.
Published: February 2007

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.
Evolution of fetal and adult thymidine kinase isoenzymes in rat ventral prostates during development
Authors: Derré P. , Samperez S. , Jouan P.
Published: February 2007

Thymidine kinase activity exhibited important changes during prostate growth. It increased considerably during the prepubertal period and reached a maximum level on day 55 of age. Then, it decreased gradually to the low values observed on and after day 90. Changes in enzyme activity were due mainly to variations in the activity of the fetal isoenzyme, which was maximum from day 45 to day 55 and decreased to undetectable levels on and after day 90 of life. The low thymidine kinase activity observed at the same time was due to the adult isoenzyme alone. Administration of 5α‐dihydrotestosterone to animals resulted in the considerable increase in fetal thymidine kinase activity. The stimulation of the fetal isoenzyme by androgens was maximum during the prepubertal period and decreased thereafter.
Interaction of sex steroids and prolactin on phosphatases, transaminases, and citric acid in the ventral prostate of male albino rats
Authors: Srinivasan N. , Aruldhas M. Michael , Govindarajulu P.
Published: February 2007

The interaction of androgens, testosterone propionate (TP), and dihydrotestosterone (DHT) with prolactin (PRL) and estradiol‐17β (E2) on phosphatases, transaminases, and citric acid were studied in the ventral prostate of prepubertal and adult intact and castrated rats. None of the secretory products studied were affected by androgens or their combinations with E2/PRL in prepubertal rats except for the increase observed in organ weight and DNA content. However, in adults the hormonal combinations produced some significant changes. Among the secretory products, phosphatases, glutamate oxaloacetic transaminase (GOT), and citric acid increased significantly in adult rats after the administration of TP/DHT. Glutamate pyruvic transaminase (GPT) required PRL along with TP/DHT to show an appreciable increment in intact adult rats. The synergistic effect of PRL with androgens was observed in the adult ventral prostatic secretory acid phosphatase and citric acid. Unlike PRL, E2 in combination with androgens produced an antagonistic effect in intact adult rats, which was well pronounced in the case of prostatic weight, DNA content secretory acid phosphatase, and citric acid. None of the androgens or their combination with PRL produced any significant change in DNA content compared to intact controls.
Quantal relationship between prostatic dihydrotestosterone and prostatic cell content: Critical threshold concept
Authors: Kyprianou Natasha , Isaacs John T.
Published: February 2007

The shape of the prostatic dihydrotestosterone (DHT) dose vs prostatic cell number response curve can be used to determine if the androgen‐induced increase in prostatic cell number occurs as a continuous graded process increasing with all levels of prostatic DHT, or whether the process is quantal, beginning to occur only when a critical threshold of prostatic DHT is reached. To make this determination, castrated‐adrenalectomized rats, castrated rats given no treatment, and castrated rats given testosterone‐filled silastic implants of varying lengths were used to construct such a prostatic DHT dose/prostatic cell number response curve ranging from undetectable to pharmacologically high levels of prostatic DHT. The shape of this dose‐response curve was found not to be continuously hyperbolic, but instead, to be discontinuously sigmoidal. This demonstrates that, in the rat, androgen‐induced increase in prostatic cell number occurs as a quantal process which can only begin when the concentration of prostatic DHT is above a critical threshold value (ie, 0.4 ng/108 cells for the rat ventral prostate). Thus, in order to completely prevent this androgenic stimulation of prostatic cell number, the prostatic DHT level has to be lowered to below this critical threshold but does not have to be completely eliminated.
Immunoscintigraphic evaluation of lymph node involvement in prostatic carcinoma
Authors: Vihko Pirkko , Kontturi Matti , Lukkarinen Olavi , Martikainen Paula , Pelliniemi Lauri , Heikkilä Juhani , Vihko Reijo
Published: February 2007

Five patients who were candidates for radical prostatectomy were investigated. One milligram of diethylene triamine pentaacetic acid derivatives of purified F(AB′)2 fragments of monoclonal antibodies against prostatic acid phosphatase, labeled with 99mTc, were bilaterally injected into the periprostatic space. The amount of radioactivity injected varied between 3 and 7 mCi. Imaging took place dynamically for the first hour following injection, then at 6 and 24 hr. In one patient, lymph node metastases were detected in the left paraaortic, iliac, and obturator lymph nodes by this technique. The lesions incorporating radioactivity were confirmed to be metastases of prostatic cancer following staging pelvic lymphadenectomy. Immunolabeling electron microscopy studies revealed internalized antibody in prostatic cancer cells. In the four other patients, radioimaging did not show any lymph node metastases, and this negative finding was confirmed at surgery. These early data indicate the possibility of preoperative staging of prostatic cancer using radiolabeled derivatives of monoclonal antibodies raised against prostatic acid phosphatase and injected into the periprostatic area.
Synergic inhibitory effects of the aromatase inhibitor 1‐methyl‐androsta‐1, 4‐diene‐3, 17‐dione and the antiandrogen cyproterone acetate on androstenedione‐ induced hyperplastic effects in the prostates of castrated dogs
Authors: Habenicht Ursula‐F. , El Etreby M. Fathy
Published: February 2007

We examined whether the induction of estrogen‐related hyperplastic changes in the prostate (ie, activation and stimulation of the stroma, especially of the smooth muscle) of castrated beagle dogs was reproducible. The effectiveness of the aromatase inhibitor 1‐methyl‐androsta‐1, 4‐diene‐3, 17‐dione (1‐Methyl‐ADD) in antagonizing such estrogen‐related alterations was investigated in comparison with a combined treatment of 1‐Methyl‐ADD and the antiandrogen CPA. These studies have demonstrated the suitability of the androstenedione model for testing the efficacy of aromatase inhibitors. In addition, it has been demonstrated that an aromatase inhibitor in combination with an antiandrogen can synergically inhibit the glandular and stromal components of the prostate.
Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue
Authors: Van Steenbrugge G. J. , Van Dongen J. J. W. , Reuvers P. J. , De Jong F. H. , Schroeder F. H.
Published: February 2007

This paper is the first part of a series of three describing a number of observations made on the PC‐82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen‐dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1‐90 nmol/liter) has been levelled out by the use of T‐containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC‐82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC‐82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC‐82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC‐82 tumor tissue. Androgen withdrawal from T‐implanted, tumor‐bearing female mice caused a rapid reduction (90% within one day) of the tissue‐T and a slower decline (up to 90% within seven to ten days) of tissue‐DHT concentrations.
Pharmacologically induced ultrastructural and lmmunohistochemical changes in the prostate of the castrated dog
Authors: Aumüller G. , Habenicht U. F. , El Etreby M. F.
Published: February 2007

The effects of an aromatase inhibitor and of an antiandrogen on the ultrastructure and the expression of a secretory protein (acid phosphatase) and marker proteins for basal cells (keratin) and fibroblasts (vimentin) were studied in the prostate of castrated, androstenedi‐one‐treated dogs. Androstenedione treatment partially restored the normal appearance of the gland and also some secretory activity. In the central portion of the gland, basal cell hyperplasia developed instead of secretory activity after androstenedione treatment. Administration of the aromatase inhibitor reduced the number of secretory cells but did not completely suppress the latter. There was some proliferation of the connective tissue surrounding the atrophic acini. Combined treatment with aromatase inhibitor and antiandrogen resulted in a general atrophy of prostatic acini that was less intense relative to the changes observed after castration. Resi dual secretory activity, detected in specimens treated exclusively with aromatase inhibitor, were lacking after combined treatment. The influence of all regimens on the ultrastructure of smooth muscle cells was comparably discrete, whereas regional differences in the arrangement pattern of the epithelium and the fibromuscular stroma were impressive. The ultrastructural findings support previous results of a synergic inhibitory effect of aromatase inhibitor and antiandrogens on the canine prostate.
Autochthonous prostate adenocarcinomas in Lobund‐Wistar rats: A model system
Authors: Pollard Morris , Luckert Phyllis H.
Published: February 2007

An experimental model system for autochthonous prostate adenocarcinoma (PA) has been developed in Lobund‐Wistar (L‐W) rats. Large primary PAS were induced in 31 of 40 (77.5%) L‐W rats within an average of 10.7 months after a single dose of methylnitrosourea (MNU) and subcutaneous implants of testosterone. Metastatic tumors had developed in over 60% of the tumor‐bearing rats. In addition, localized in situ PAs had developed in 5 of the 40 test rats. At 14 months 50 untreated L‐W rats were free of demonstrable PAs. Two of 20 (10%)L‐W rats developed PA at 14 months after inoculation of MNU alone. Six of 42 (14%) L‐W rats developed PAs within 14 months after s.c. administration of testosterone implants. Thus, testosterone acted as a tumor promoter of PA for cells that had been initiated by MNU. The manifestations of the PAs in the L‐W rats resembled many aspects of the counterpart disease in man.