bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical demonstration of nuclear androgen receptor following affinity chromatography with immobilized ligands
Authors: Bruchovsky Nicholas , Rennie Paul S. , To Mary P. , Snoek Robert , Lefebvre Yvonne A. , Golsteyn Elizabeth J.
Published: February 2007

With increasing purification of the androgen receptor from nuclei of rat ventral prostate, a receptor‐like protein could be demonstrated by chemical staining with silver nitrate. After sonication and digestion of nuclei with micrococcal nuclease, the solubilized receptor was applied to a column of Matrex Gel Green A and eluted with a linear gradient of 0‐2 M NaCl. Characterized by specific binding of dihydrotestosterone, this form of the receptor was also androgen dependent and yielded an apparent Mr of 33,000 when analyzed by polyacrylamide gel electrophoresis and silver nitrate staining. To facilitate recovery following chromatography, the receptor was precipitated with 0‐40% ammonium sulfate. Analysis of the 15‐fold enriched fraction by sucrose density‐gradient centrifugation confirmed the presence of a 3S androgen‐binding protein. About 200 ng of the precipitated protein was applied to a column of dihydrotestosterone‐17 β‐succinyl agarose (ligand concentration, 0.25 μmol/ml). The fractions eluted with 50 μM dihydrotestosterone were electrophoresed and stained as before; again, the presence of a 33,000 Mr protein sensitive to castration was demonstrated. Alternatively, when the precipitated protein was fractionated by fast protein liquid chromatography utilizing a SuperoseTM 12 HR 10/30 column, the receptor coeluted with nuclear proteins in the 29,000–36,000 Mr range as determined both by retention time and electrophoresis. In combination, the above methods may be used to obtain a receptor protein purified to near homogeneity with a yield of 5‐10%. The amount of receptor afforded by the purification sequence is small but nevertheless sufficient for chemical detection. We anticipate that with modification, the procedures may prove suitable for the recovery of nuclear androgen receptor on a preparative scale.
Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer
Authors: Tremblay Jacques , Frenette Gilles , Tremblay Roland R. , Dupont André , Thabet Michel , Dubé Jean Y.
Published: February 2007

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate‐specific antigen (PSA) and β‐inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24‐hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and β‐inhibin concentrations were higher in patients with BPH than in young men (p < 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and β‐inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.
Histological findings in the rat prostate cancer model during treatment with a luteinizing hormone‐releasing hormone agonist and novantrone
Authors: Paz‐Bouza Jose I. , Schor Norberto A. , Monje Elvira , Redding Tommie W. , Schally Andrew V.
Published: February 2007

Morphological changes produced by the treatment with the D‐tryptophan‐6 analog of luteinizing hormone‐releasing hormone (D‐Trp‐6‐LH‐RH) and mitoxantrone (novantrone) were studied in the Dunning R3327H rat prostate cancer model. Microcapsules of D‐Trp‐6‐LH‐RH, calculated to release a controlled dose of 25 μg/day, were injected intramuscularly once a month. Novantrone (0.25 mg/kg body weight) was injected intravenously once every 3 weeks. The pathology of tumors was studied in two experiments. In the first experiment, the treatment was started 135 days after tumor transplantation, and the therapy was continued for 105 days. In the second experiment, the treatment was initiated 45 days after tumor transplantation, and was carried on for 70 days. The rats were divided into four groups: 1) untreated control, 2) microcapsule‐injected, 3) novantrone‐injected, and 4) combination of microcapsules and novantrone‐injected. In both experiments, similar results were obtained, which included significant reduction in the tumor volume and weight, a very striking decrease in the number of epithelial tumoral cells with atrophy of the glandular epithelium, and an increase in the stromal connective tissue. All these changes were more prominent in the group treated with the combination of microcapsules and novantrone than in the groups treated with microcapsules or novantrone alone. Pathological results support the view that combined therapy may be more efficacious than the treatment with single agents.
Steroid‐sensitive proteins, growth hormone and somatomedin C in prostatic cancer: Effects of parenteral and oral estrogen therapy
Authors: Stege Reinhard , Fröhlander Nils , Carlström Kjell , Pousette Åke , Von Schoultz Bo
Published: February 2007

The effects of parenteral and parenteral plus oral estrogen therapy on the serum levels of sex hormone binding globulin (SHBG), pregnancy‐associated (α‐PAG), growth hormone (GH), and somatomedin C (SmC) were studied in 26 patients with prostatic cancer. Intramuscular polyestradiol phosphate treatment, yielding a mean serum level of estradiol‐17β of 1,446 pM and a mean testosterone level of 4.5 nM, had no significant effects on α‐PAG, GH, and SmC and increased SHBG levels only marginally. Combined treatment with intramuscular polyestradiol phosphate and oral ethinyl estradiol greatly increased SHBG and α‐PAG levels and caused elevated GH and decreased SmC levels. The route of estrogen administration is probably of major importance for the hormonal effects on hepatic activity as reflected by SHBG and α2‐PAG levels. Bypassing the portal circulation might be advantageous with respect to liver‐related side effects of estrogen therapy. GH and SmC might act as mediators of estrogen effects on the human liver.
Cytochemistry and biochemistry of acid phosphatases VII: Immunohistochemistry of canine prostatic acid phosphatase
Authors: Aumüller Gerhard , Vedder Helmut , Enderle‐Schmitt Ulrike , Seitz Jürgen
Published: February 2007

Acid phosphatase (E.C. 3.1.3.2.) has been isolated from canine prostatic gland homogenates by gel permeation chromatography (AcA34 or G150), by affinity chromatography (con A‐Sepharose), or by using fluid phase liquid chromatography (FPLC) using Superose 12 and Mono P columns. Acid phosphatase‐enriched fractions were submitted to analytical SDS‐PAGE or to analytical isolelecuic focusing. A protein with a molecular weight of 30 kD (on SDS gels) was used for immunization of rabbits. The antiserum produced was cross‐reactive with prostatic acid phosphatase (canine and human) as shown by immunoblotting. When applied to paraffin or plastic sections of normal canine prostate, a positive immunoreaction was found exclusively in the secretory cells. In experimentally altered glands (castration and/or hormone treatment), a varying pattern of immunoreactive cells was found. In canine prostatic carcinomas, intensively reacting cell clusters were found along with nonreactive cells. The antiserum was also slightly cross‐reactive with the respective human antigen, but the cross‐reactivity of an antiserum prepared against human prostatic secretory acid phosphatase with canine prostatic acid phosphatase was far more pronounced.
Percutaneous transperineal placement of gold 198 seeds for treatment of carcinoma of the prostate
Authors: Crusinberry Richard A. , Kramolowsky Eugene V. , Loening Stefan A.
Published: February 2007

Thirty‐one patients have been treated for carcinoma of the prostate with 198 Au seeds placed transperineally using transrectal ultrasonic guidance. Twenty patients have been followed postoperatively for periods ranging from 3 to 31 months, with an average follow‐up time of 12 months. Cumulative dose of radiation to the prostate calculated by dosimetry was either 9,000 rads or 15,000 rads. Serial transrectal ultrasound examinations performed on these patients showed a decrease in prostate size in all patients within 6 months of treatment, with a statistically significant decrease observed between the third and sixth months. No significant difference in amount or rate of tumor regression was noted when tumor stage and grade were correlated to volume decrease after treatment. Patients who received the larger doses of radiation (15,000 rads) showed a significantly greater rate of decline in prostatic volume than those who received 9,000 rads. Seven patients underwent prostate biopsy between 12 and 18 months after treatment; six biopsies showed residual tumor. Complications after treatment included urinary retention because of prostatic edema (three), radiation urethritis (three), and rectal ulceration (one). Transperineal placement of 198Au is well tolerated and offers an alternative to external beam radiation for treatment of carcinoma of the prostate.
Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the dunning R3327‐MAT‐LyLu prostatic adenocarcinoma
Authors: Shaw Michael W. , Rubenstein Marvin , Dubin Alvin , McKiel Charles F. , Guinan Patrick D.
Published: February 2007

The Dunning R3327 adenocarcinoma represents a model for studying prostate cancer in rats; early studies have indicated its utility for studying relationships between tumor growth, immunologic markers, and chemotherapy. Normal animals and those bearing the metastatic Dunning R3327 MAT‐LyLu tumor were treated with 10, 30, and 100 mg/kg doses of cyclophosphamide (CTX) and their spleens assayed for leukocytic subset distributions using monoclonal antibodies. Tumor‐bearing animals had significant reductions in helper T cell content as well as reduced helper/suppressor T cell ratios, compared to controls. These effects occurred rapidly following implantation and were not reversed by chemotherapy. When administered to both tumor‐ and non‐tumor‐bearing animals, CTX also depleted T cell populations. Despite reductions produced in all subsets, two administrations of CTX (30 mg/kg) were capable of retaining (in non‐tumor‐bearing animals) or restoring (in tumor‐bearing) normal helper/suppressor T cell ratios. Such studies aid in identifying therapeutically effective dosages of cytotoxic drugs that minimize their deleterious effects on the immune system.
Eight years experience with neutron radiotherapy in the treatment of stages C and D prostate cancer: Updated results of the RTOG 7704 randomized clinical trial
Authors: Russell K. J. , Laramore G. E. , Krall J. M. , Thomas F. J. , Maor M. H. , Hendrickson F. R. , Krieger J. N. , Griffin T. W.
Published: February 2007

The records of 91 patients enrolled between June 1977 and April 1983 in the Radiation Therapy Oncology Group (RTOG) randomized study investigating fast neutron radiation therapy in the treatment of locally advanced prostate cancer were reviewed. Patients with stages C and D1 adenocarcinoma were randomized to receive either combined fast neutron and photon irradiation (mixed‐beam) or conventional photon irradiation alone. Survival (actuarial) at eight years for the mixed‐beam cohort was 63% vs 13% for the patients receiving photons alone (P =.01). Corresponding “determinental” survival rates, adjusted by exclusion of intercurrent deaths, were 82% and 54%, respectively (P =.02). Freedom from locally recurrent prostate cancer was 77% for mixed‐beam patients and 31% for patients receiving photons alone (P <.01). Analyses of outcomes accounting for all major prognostic determinants confirm the greater efficacy of mixed beam treatment with P <.05 for survival, determinental survival, and local control.
The major 40‐kDa glycoprotein in human prostatic fluid is identical to Zn‐α2‐glycoprotein
Authors: Frenette Gilles , Dubé Jean Y. , Paradis Gilles , Tremblay Roland R. , Lazure Claude , Chrétien Michel
Published: February 2007

A major 40‐KDA protein secreted by human prostate was isolated from whole seminal plasma by sequential column chromatography on DEAE‐Sepharose CL‐6B, concanavalin A(Con A)‐Sepharose, and Sephadex G‐100. Although the purified preparation still contained minor contaminants, its amino acid composition was found to be identical to the one of a glycoprotein isolated previously from seminal plasma by Lin et al(1983). Antibodies against this protein were produced in rabbits and their use in immunoblotting experiments revealed the presence of the antigen in several tissues including the prostate, the liver, the heart, the kidney, the epididymis, and the testis. A radioimmunoassay confirmed these results and showed that blood serum concentrations of this protein were relatively high in men (81 ± 3 μg/ml), women (68 ± 3 μg/ml), and cord blood of newborns (32 ± 1 μg/ml). The serum concentrations of this protein along with its physicochemical characteristics suggested that it could be identical to Zn‐α2‐glycoprotein, a human serum protein previously isolated by Burgi and Schmid (1961). This hypothesis was confirmed by a double immunodiffusion analysis using a commerical anti‐Zn‐α2‐glycoprotein antiserum. Finally, in vitro translation of prostatic poly(A)+ RNA in rabbit reticulocyte lysate in the presence of canine pancreatic microsomal membranes resulted in the formation of an immunoprecipitable 42‐kDa band. These results show that Zn‐α2‐glycoprotein can be synthesized in the prostate itself. The demonstration of high concentrations of this protein in prostatic tissue and prostatic secretion should facilitate the elucidation of its role in the prostate and in other tissues.
Enhanced expression of the c‐myc protooncogene in high‐grade human prostate cancers
Authors: Buttyan Ralph , Sawczuk Ihor S. , Benson Mitchell C. , Siegal John D. , Olsson Carl A.
Published: February 2007

We examined a series of 29 surgical specimens of benign and malignant human prostate tissue for the expression of both the cHa‐ras and c‐myc protooncogenes. Northern blots were prepared using polyadenylated mRNA extracted from nine prostatic adenocarcinomas, 19 benign hypertrophied prostates (BPH) and one normal prostate. When the Northern blots were hybridized to a probe for cHa‐ras, only one specimen of BPH showed an appreciable amount of the 1.2‐kb transcript homologous to cHa‐ras. Upon reprobing these blots with c‐myc, six cancers showed a considerable amount of a 2.4‐kb transcript homologous to c‐myc. Three other cancers and all the benign tissue showed little or no detectable 2.4‐kb c‐myc transcript. On retrospective analysis, the cancers with elevated c‐myc transcripts were found to have a Gleason score of 5 and above (poorly differentiated tumors), while the cancers with little or no c‐myc transcripts were all of Gleason score 4 and lower. Finally, we compared our ability to detect c‐myc transcripts in mRNA extracted from a surgically derived prostate tumor with mRNA extracted from the same tumor subject to a sham electrocautery procedure, as would occur during transurethral resection. The electrocautery procedure decreased both the intensity and the integrity of the c‐myc signal in mRNA from the tumor. Thus, our exclusive use of surgically derived prostate tumors may be the reason we are able to detect an elevation in the expression of c‐myc mRNA in high‐grade tumors.
Determination of serotonin and 5‐hydroxyindoleacetic acid in guinea pig and human prostate using HPLC
Authors: Davis Nina S.
Published: February 2007

The finding of significant numbers of endocrine‐paracrine (EP) cells in the prostate glands of guinea pigs and man suggests that these cells may be important in the regulation or modulation of prostatic function. Serotonin is a biogenic amine common to most prostatic EP cells. In order to extend current knowledge relating to these cells, an assay was developed using high‐performance liquid chromatography to quantitate serotonin and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in guinea pig and human prostatic tissue extracts. Levels of serotonin and 5‐HIAA in the guinea pig whole‐gland preparation were 105.4 ± 70.6 ng/g and 48.4 ± 95.7 ng/g, respectively. Normal human prostatic tissue contained 1423.9 ± 750.8 ng/g serotonin and 66.7 ± 92.8 ng/g 5‐HIAA. Recoveries ranged between 60 and 100%. The detection limits were 24 pg/injection for serotonin and 12 pg/injection for 5‐HIAA. This assay provides an expeditious, specific and highly sensitive method for the simultaneous determination of monoamines in guinea pig and human prostatic tissue.
Application of the MTT assay to human prostate cancer cell lines in vitro: Establishment of test conditions and assessment of hormone‐stimulated growth and drug‐induced cytostatic and cytotoxic effects
Authors: Romijn J. C. , Verkoelen C. F. , Schroeder F. H.
Published: February 2007

In this study the usefulness of the MTT assay for the quantitation of growth modulating effects on cultured prostate cancer cell lines (PC‐3, PC‐93, and LNCaP) was investigated. The MTT test is based on the enzymatic reduction of the tetrazolium salt MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazoliumbromide] in living, metabolically active cells but not in dead cells. The reaction is carried out in situ in multiwell plates, and the reaction product, a purple‐colored formazan soluble in dimethylsulfoxide, is measured colorimetri‐cally, using a multiwell plate reader. Optimal test conditions were established for each of the cell lines used. With the hormone‐sensitive cell line LNCaP, and stimulatory effect of the synthetic androgen R1881 was demonstrable by the MTT test. A sharp optimum occurred at a concentration of 10−10 M R1881. Treatment of cells of either cell line with antineoplastic agents resulted in a dose‐dependent reduction of MTT converting activity, reflecting the impaired survival of the drug‐treated cells. Good correlations of the results obtained with the MTT‐test, as compared with a thymidine incorporation assay or with direct DNA measurements, were observed. As the MTT test offers a high degree of precision and is easy to do, it is suitable for the purpose of (large‐scale) chemosensitivity testing. Moreover, serial measurements might easily be performed in order to provide additional information on the mode of action of the drugs tested, i.e., to discriminate between cytostatic and cytotoxic drug effects.
Primary endodermal sinus tumor of the prostate: Report of a case
Authors: Palma Paolo Dalla , Dante Stefania , Guazzieri Stefano , Sperandio Paola
Published: February 2007

A 29‐year‐old man was admitted to the Department of Urology of the University of Padova with a diagnosis of prostatic adenocarcinoma. Cystourethrography showed a prostatic urethral obstruction, and CT scan demonstrated a low pelvic solid mass involving the prostate and the seminal vescicle. A radical prostatectomy was performed, and the prostate was found to be widely infiltrated by a neoplasia formed by tubules, papillary structures, and solid cords of cuboidal or flat elements, each having indistint borders and scant cytoplasm, in a myxoid or fibrous stroma. “Schiller‐Duval‐like,” PAS‐diastase‐resistant and alfa‐fetoprotein hyaline bodies were present. An endodermal sinus (yolk‐sac) tumor was diagnosed. There was infiltration of the periurethral prostatic ducts, prostatic urethra, and seminal vesicles and single lymph node metastasis. Testicular echotomography was negative. In spite of aggressive surgery and chemotherapy, the patient died 10 months after diagnosis. This is the third case in the literature after those presented by Benson and Michel.
Antiestrogens do not counteract the inhibitory effect of estradiol‐17β on the growth of the dunning R3327 prostatic adenocarcinoma
Authors: Landström M. , Damber J‐E. , Bergh A. , Tomic R. , Carlsson‐Bostedt L. , Stigbrand T.
Published: February 2007

The purpose of this study was to investigate if the local effects of estradiol on the Dunning R3327 prostatic adenocarcinoma were estrogen‐receptor mediated. All rats with the transplantable Dunning R3327 prostatic adenocarcinoma were castrated on the first day of treatment and were supplemented with daily s.c. injections of testosterone propionate (0.1 mg) during the treatment period, lasting for 6 weeks. The following treatment groups were studied: castration + testosterone supplementation (C + T, control group), C+T and estradiol‐17β (50 μg/daily s.c.), C + T and tamoxifen (1 mg twice a week s.c.), and C + T and estradiol‐17β in combination with tamoxifen. Tumor volumes were measured every week. At the end of the treatment period, pieces of the tumors were taken for morphological studies and estrogen‐receptor analysis. In the groups of rats given tamoxifen treatment no estrogen‐receptor binding was detectable in prostatic tumors, but, despite this, tamoxifen did not prevent either the inhibitory effect of estradiol‐17β on the tumor growth rate or the estrogen‐induced decrease of volume density of prostatic glandular epithelium. In contrast, the estrogen‐induced increase of volume density of the stroma was abolished by tamoxifen, suggesting that this effect may be mediated by the estrogen receptor. A morphometrical method for estimating the growth of different tumor compartments is presented. Treatment with estradiol‐17β, both with or without combined treatment with tamoxifen, reduced the growth of both the tumor epithelium and stroma. The direct effect of estradiol‐17β on the growth and morphology of the Dunning R3327 prostatic adenocarcinoma seemed not to be mediated by the estrogen receptor.
Relationship of prostatic acid phosphatase localization in human prostate by a monoclonal antibody with the gleason grading system
Authors: Sinha Akhouri A. , Gleason Donald F. , Wilson Michael J. , Wick Mark R. , Reddy Pratap K. , Blackard Clyde E.
Published: February 2007

Prostatic acid phosphatase (PAP) was localized in human prostate with a monoclonal antibody prepared against PAP isoenzyme II to determine patterns of its expression in normal, hyperplastic (BPH), and cancerous glands. The monoclonal antibody reacted with both isoenzymes II and IV in immunoblot studies. Formalin‐fixed, paraffin‐embedded tissue was used from patients who had not been treated with hormones or chemotherapy. In normal glands and BPH, there was marked variation in the intensity of PAP staining in morphologically otherwise similar epithelial cells. There was similar heterogeneity of staining in the adenocarcinomas. Rough quantification of the intensity patterns in the clinical groups indicated a slight shift to more intense staining in BPH and well‐differentiated carcinomas but a progressive decline in the PAP staining in the moderately and poorly differentiated tumors. This decrease in intracellular staining with decreasing differentiation is not inconsistent with the clinical observation that serum levels of acid phosphatase generally increase with higher grade and disseminated tumors, since the enzyme is simply more accessible to the circulatory system in those cases. The same decrease may explain the few disseminated tumors that are not associated with elevated serum levels.
Influences of dihydrotestosterone, testosterone, estradiol, progesterone, or prolactin on the cell kinetics of human hyperplastic prostatic tissue in organ culture
Authors: De Launoit Yvan , Kiss Robert , Jossa Veronique , Coibion Michel , Paridaens Robert J. , de Backer Emile , Danguy Andre J. , Pasteels Jean‐Lambert
Published: February 2007

In an effort to characterize the hormone sensitivity of human benign prostatic hyperplasia (BPH) maintained in organ cultures for 12‐72 h, the influence of 5‐alpha‐dihydrotestosterone (DHT), testosterone (T), 17‐beta‐estradiol (E2), progesterone (Pg), or prolactin (PRL) was assessed on the cell proliferation rate of 25 BPH specimens by the use of tritiated thymidine incorporation followed by autoradiography. Significant increases in the thymidine‐labeling index (TLI: percentage of labeled nuclei) were observed in glandular tissue after a 36‐h incubation period in presence of DHT, E2, Pg, or PRL in 52%, 44%, 28%, and 60% of BPH cases, respectively. Nonparametric statistics (Spearman and Kendall rank correlation tests) have shown that 1 the steroid‐induced TLI increases are dependent on the basal rate of cell proliferation, while the PRL‐induced effect is independent of it, and 2 all the steroid‐mediated effects on BPH TLI are correlated together, whereas they seem to be independent of the PRL‐induced TLI increase. When T was compared with DHT on nine BPH specimens, three were found to be sensitive to both hormones, and two responded to DHT only. We propose that our study methods are suitable as a means to assess the hormone sensitivity of individual cases of BPH and possibly prostatic tumors.
Expression of ras proto‐oncogenes in the dunning R3327 rat prostatic adenocarcinoma system
Authors: Cooke D. B. , Quarmby V. E. , Petrust P. , Mickey D. D. , Der C. J. , Isaacs J. T. , French F. S.
Published: February 2007

Steady‐state levels of c‐Ha‐ras mRNA were measured in eight sublines of the Dunning R3327 rat prostatic adenocarcinoma. As a control, normal dorsal prostate tissue was studied. Increased expression of c‐Ha‐ras is associated with tumor progression in one lineage of the Dunning R3327 system (H to AT1 to MAT‐Lu and MAT‐Ly‐Lu). Here ras mRNA increases as the tumor advances from androgen dependence and a high degree of differentiation to an anaplastic aneuploid phenotype with high metastatic potential. However, in the other Dunning lineage (H to HI to HI‐F to AT3), expression of c‐Ha‐ras is variable and does not correlate with tumor progression. Immunocytochemistry showed that levels of the c‐Ha‐ras p21 protein paralleled steady‐state mRNA levels in all variants. Transfection assays, using NIH/3T3 cells, suggested that the ras loci were not activated in the R3327 tumors. Levels of c‐Ki‐ras mRNA were also measured in the Dunning tumors; these did not correlate with tumor progression in either lineage. Expression of N‐ras mRNA was not detected in the Dunning tumors.
Striated muscle in the biopsy specimen of the prostate
Authors: Hasui Yoshihiro , Shinkawa Tohru , Osada Yukio , Sumiyoshi Akinobu
Published: February 2007

We had a chance to see striated muscle fibers in the biopsy specimen of the prostate. We examined the prostate specimens of autopsied cases and biopsy specimens. The distribution of striated muscle fibers was studied with an immunohistochemical method for myoglobin to obtain their anatomical distribution in detail. We showed that the striated external sphincter muscle fibers were present in the peripheral zone of the prostatic gland (9.1%). Therefore, if striated muscle fibers are found in biopsy specimens of prostatic cancer, pathologists and urologists should not diagnose simply that the cancer invades beyond the prostatic capsule.
Aberrant response in vitro of hormone‐responsive prostate cancer cells to antiandrogens
Authors: Wilding George , Chen Michael , Gelmann Edward P.
Published: February 2007

Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen‐responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone‐responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose‐dependent fashion. These cells contained approximately 31,000 high‐affinity (Kd = 9 × 10−10 M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]‐thymidine. Competitive uptake studies using [3H]‐R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 × 10−7 M for hydroxyflutamide, 2 × 10−7 M for RU23908, and 1 × 10−7 M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells.
Case‐control study of prostatic cancer in Kyoto, Japan: Demographic and some lifestyle risk factors
Authors: Oishi Kenji , Okada Kenichiro , Yoshida Osamu , Yamabe Hirohiko , Ohno Yoshiyuki , Hayes Richard B. , Schroeder Fritz H.
Published: February 2007

Demographic risk factors for prostatic cancer were examined in a case‐control study of 100 triplets of prostatic cancer patients and age‐, hospital‐, and admission date‐matched control series of benign prostatic hyperplasia (BPH) patients and general hospital patients. A higher risk of prostatic cancer was associated with the following factors: 1) long‐term occupation in transport or communication (relative risk [RR] = 4.92, 95% confidence interval [CI]: 1.18–20.5) as compared with hospital controls; 2) the wife having a lower educational level (RR = 1.88, 95%CI: 1.02–3.45) as compared with hospital controls; 3) no past episode of hypertension as compared with BPH controls (RR = 2.30, 95%CI: 1.27–4.15); 4) having several sisters (more than four) as compared with both BPH and hospital controls (RR = 3.82, 95%CI: 1.35–10.8 and RR = 2.94, 95%CI: 1.08–8.03 respectively); 5) dense body hair as compared with hospital controls (RR = 4.28, 95%CI: 1.19–15.4). No significant links were found with blood type, daily drug use, head hair, skin color, body type, smoking habits, religion, body weight, and mental characteristics.
Binding of epidermal growth factor by human normal, hypertrophic, and carcinomatous prostate
Authors: Davies Peter , Eaton Colby L.
Published: February 2007

Saturable binding sites for radioiodinated epidermal growth factor (EGF) have been quantified in surgical specimens of benign prostate hypertrophy (BPH), histologically normal (HN) prostate, and prostate cancer. Values for EGF binding did not differ significantly between HN prostate and prostate cancer, although dedifferentiated samples tended to higher levels. These were coincident with lower comparative levels of androgen receptors. Unfractionated BPH tissue contained lower levels of EGF binding than either HN or carcinomatous prostate, but in separated epithelial cells EGF binding fell into the same range. Saturation analyses showed two affinity classes of binding in all except dedifferentiated tissues.
Site‐specific growth of the prostate xenograft line UCRU‐PR‐2
Authors: Jelbart M. E. , Russell P. J. , Russell P. , Wass J. , Fullerton M. , Wills E. J. , Raghavan D.
Published: February 2007

J. Wass<3>

A xenografted small‐cell, undifferentiated prostate (SCUCP) cancer line, UCRU‐Pr‐2, was implanted at different sites within nude mice to examine the effect of local environmental factors on tumor growth and behavior. All tumors that grew were small‐cell carcinomas. Fragments implanted within muscle and under the kidney capsule were locally invasive; however, tumors that grew subcutaneously or intraperitoneally showed no invasion. UCRU‐Pr‐2 did not grow in the spleen or the liver. No induced metastases were observed in the lung after intravenous injection. The sites of implantation did not allow the outgrowth of subpopulations as detected by the parameters used: light and electron microscopy, expression of tumor markers, levels of hormone production, and DNA flow cytometry. Electron microscopy, which showed both glandular and neuroendocrine differentiation within the same cell, does not support a dual‐cell origin of SCUCP.
Estradiol—progesterone‐induced growth of the rat dorsolateral prostate: Effects on protein phosphorylation
Authors: Belis John A. , Durham John P.
Published: February 2007

The combination of estradiol and progesterone can affect growth of the rat dorsolateral prostate by a mechanism that appears to be independent from androgen‐mediated activity. The effects of estradiol and progesterone on protein kinase activity and endogenous protein phosphorylation in the castrate rat dorsolateral prostate were compared with androgenic effects on these intracellular events. Differences in protein kinase activity and protein phosphorylation were found with each type of hormonal therapy. Changes in protein kinase activity and protein phosphorylation produced by estradiol and progesterone in the rat dorsolateral prostate were not found in the rat ventral prostate, which was not affected by these hormones in the 28 day length of this study.
Transrectal ultrasonography as a method to monitor canine prostatic size in situ: Measurements following endocrine manipulation and ejaculation
Authors: Juniewicz P. E. , Lemp B. M. , Batzold F. H. , Reel J. R.
Published: February 2007

Transrectal ultrasonography was utilized to estimate canine prostatic size in situ following various experimental manipulations. By the use of dogs (n = 24) of various endocrine states, whose true prostatic weight varied from 2.28 to 73.25 g, a highly significant correlation (r = 0.99; P < 0.0001) was obtained between actual prostate weight determined gravimetrically and that estimated by ultrasound. The relationship between these two parameters was described by the regression equation: estimated prostatic weight (g) = 1.11 × gravimetric weight (g) ‐ 0.12. In addition, prostatic weight as estimated by ultrasound was comparable (P < 0.10) to that estimated by direct caliper measurement. The coefficent of variation associated with repeated ultrasound measurements averaged 8.88 ± 2.31% (mean ± SD; n = 5). Ejaculation induced by either digital massage or pilocarpine administration (0.7 mg/kg, i.v.) had no effect on prostatic weight as estimated by ultrasound. These results demonstrate that transrectal ultrasonography can accurately estimate and detect differences in prostate size owing to various experimental manipulations without the need for surgical intervention.
Inhibition of the pituitary‐gonadal axis by a single intramuscular administration of D‐trp‐6‐LH‐RH (decapeptyl) in a sustained‐release formulation in patients with prostatic carcinoma
Authors: Gonzalez‐Barcena David , Perez‐Sanchez Patricia L. , Graef Alicia , Gomez Ana Maria , Berea Hector , Comaru‐Schally Ana Maria , Schally Andrew V.
Published: February 2007

For the past 6 years we used daily injection of luteinizing hormone‐releasing hormone (LH‐RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary‐testicular axis over a 2‐month period and evaluated the safety and tolerance of the single intramuscular administration of sustainedrelease formulations of D‐Trp‐6‐LH‐RH microcapsules designed to release 50, 100, or 200 μg/day for over 1 month. Serum levels of LH, testosterone, and D‐Trp‐6‐LH‐RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D‐Trp‐6‐LH‐RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6 LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D‐Trp‐6‐LH‐RH microcapsules suppresses of the pituitary‐testicular axis for at least 50 days. D‐Trp‐6‐LH‐RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.
Comparative contractile responses among ventral, dorsal, and lateral lobes of the rat prostate
Authors: Steidle Christopher P. , Cohen Marlene L. , Hoover Dennis M. , Neubauer Blake Lee
Published: February 2007

Prostatic zonal heterogeneity as a factor influencing urogenital smooth muscle contractile mechanisms was evaluated in the dorsal, lateral, and ventral lobes of the sexually mature rat. Additionally, using the ventral lobe, we assessed the role of the prostatic capsule to determine its contribution to tissue contractility. Smooth muscle contractile responses were determined for the alpha‐adrenergic agonists norepinephrine and methoxamine; the cholinergic agonist carbamylcholine; the alpha2‐adrenergic agonist UK‐14,304; serotonin; and potassium chloride. The dorsal, lateral, and ventral lobes contracted in response to all agonists. In the three lobes, norepinephrine was the most potent contractile agent; alpha2 receptor activation with UK‐14,304 resulted in the lowest maximum response. Carbamylcholine and serotonin were only weak contractile agonists in all three lobes. Maximum contractile responses to alpha agonists were greatest in the ventral prostate relative to the other two lobes, based on contractile responses to norepinephrine and methoxamine relative to KCl. The contractions of the ventral lobe in the presence and absence of the capsule were similar; thus the observed responses were not enhanced by the capsule but were attributable primarily to the presence of prostatic smooth muscle. Insofar as these studies with anatomically distinct lobes in the rat may reflect zonal homology in other species, these results support the contention that all zones may contribute to prostatic contractility.
Contractile properties of human prostate adenomas and the development of infravesical obstruction
Authors: Gup Daniel I. , Shapiro Ellen , Baumann Mary , Lepor Herbert
Published: February 2007

The contractile response of human prostate adenomas to KCI, phenylephrine (alpha1 adrenergic agonist), UK 14304 (alpha2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine‐induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine‐induced contractions by prazosin was 3.2 nM, confirming that phenylephrineinduced contraction in the human prostate is mediated by the alpha1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.
[1, 2‐bis (2, 6‐dichloro‐4‐hydroxyphenyl) ethylenediamine]dichloro‐platinum(II): An endocrine‐active platinum complex with a specific prostatic tumor‐inhibiting activity
Authors: Schneider M. R. , Schiller C.‐D. , Humm A. , Spruß T. , Schönenberger H. , Amselgruber W. , Sinowatz F.
Published: February 2007

[1, 2‐Bis (2, 6‐dichloro‐4‐hydroxyphenyl) ethylenediamine] dichloro‐platinum(II), (C), a platinum complex with endocrine activity and a specific effect on hormone‐dependent mammary tumors, was tested for its tumor‐inhibitory activity in the hormone‐sensitive R 3327 and Nb prostate carcinoma models of the rat and for its endocrine activities in comparison to the ligand L and diethylstilbestrol (DES). Established tumors of the R 3327 prostate tumor were strongly inhibited by C. Its effect equaled that of DES and was significantly better than that of L. Accessory sex organ weights and testosterone levels were strongly reduced by C as well as L. This antigonadotrophic effect, which is almost comparable to DES, was confirmed in 10 day experiments with intact, mature mice and rats, whereas a direct antiandrogenic activity was not given. A part of the antitumor action of C is therefore due to this antigonadotrophic activity. Affinities to estrogen, progesterone, and androgen receptors, however, were very low. The hormone‐sensitive Noble Nb‐R prostatic carcinoma was almost completely inhibited by C, whereas L had only a weak effect. As C has no significant effect on the hormone‐independent R 3327 HI prostate tumor and as its effect on hormone‐dependent tumors is significantly better than that of the ligand L in spite of their similar endocrine properties, an apparently specific antiproliferative effect of C only on hormone‐dependent prostate tumors is obvious. This was further shown in a long‐term experiment with the R 3327 prostate carcinoma. Whereas tumors in the castration group relapsed from androgen ablation and exerted a progressive tumor growth, therapy with C almost completely prevented this relapse phenomenon. After 25 weeks of treatment, C inhibited tumor growth by 90% compared to castration. Owing to these results, this new endocrine active platinum complex with an apparently specific effect on hormone‐dependent prostate tumors can be of value for the therapy of the prostatic carcinoma.
Comparison of dihydrotestosterone levels in prostatic cancer metastases and primary prostate cancer
Authors: Geller Jack , Candari Cesar D.
Published: February 2007

Dihydrotestosterone (DHT) concentration, a marker for biochemical differentiation and possible clonal origin of prostate tumors, was measured in cancer present in lymph nodes (LN) from patients with untreated metastatic prostate cancer and compared to levels in untreated primary prostate cancer. The mean DHT of 2. 23 ng/g in LN (S. E. = 0.28, N = 22) was significantly less (P < 0.001) than the mean DHT of 4.8 ng/g in primary cancer (S. E. = 0. 52, N = 20). Since primary prostate cancer may be admixed with stromal tissue, while lymph node represents pure epithelial cell tumor, we chose for this comparison only the 20 prostate cancer tissues that were judged by our pathologist to contain 90% or more epithelial cell tumor. Using this selection criteria, we found that prostate stroma, which has an average DHT concentration 1. 18 times higher than prostate epithelia, would have an insignificant effect on primary prostate tumor DHT concentration.

These data suggest that the decreased DHT in prostate tumor cells present in LN metastatses may be a marker for a clone of cells with metastatic potential. These findings are consistent with previous reports from this laboratory indicating that DHT concentration less than 2.4 ng/g in primary prostate cancer is a predictor of a reduced disease‐free interval following androgen blockade in advanced prostate cancer.
Effect of pubertal development on estrogen receptor levels and stromal morphology in the guinea pig prostate
Authors: Tilley Wayne D. , Horsfall David J. , Skinner John M. , Henderson Douglas W. , Marshall Villis R.
Published: February 2007

Using an immunocytochemical assay (ERICA) with a monoclonal antibody (H222Spγ) to the human estrogen receptor, we have demonstrated a stromal localization of the estrogen receptor in the dorsolateral prostate of the guinea pig. Specific staining of estrogen receptor in the guinea pig prostate was confined to the nuclei of periacinar and interacinar stromal cells. In comparison with prepubertal tissues, estrogen receptor staining intensity was markedly reduced in postpubertal prostatic tissues. No immunoreactive estrogen receptor was detected in the acinar epithelial cells irrespective of the developmental stage of the guinea pig prostate. Electron microscopic examination of the guinea pig prostate showed that the stromal component consists predominantly of smooth muscle cells, which, during pubertal development, undergo marked cytological changes and increase in size. These changes in the prostatic stroma were associated with a greater than fivefold reduction in levels of cytosolic and nuclear estrogen receptor determined by either a radioligand binding assay or an enzyme immunoassay (EREIA) and expressed relative to soluble protein. Morphometric analysis of the prostatic stromal cell density (SCD; nuclei/mm2 interacinar stroma), which is inversely proportional to stromal cell size, indicated that the SCD decreased approximately threefold during pubertal development. Furthermore, cytosolic estrogen receptor levels in mechanically separated prostatic stromal fractions were found to vary concordantly with the SCD during pubertal development. To determine whether estrogen influences normal development of the guinea pig prostate, the effect of various hormonal manipulations on stromal development was examined. Castration of prepubertal animals prevented the threefold decrease in SCD that is characteristic of pubertal development. Treatment of prepubertal castrates with estradiol and 5α‐dihydrotestosterone (DHT) in combination over a period equivalent to the transpubertal growth phase resulted in a stromal cell density similar to that seen in prostatic sections from intact postpubertal animals. In contrast, treatment of prepubertal castrates with either estradiol or DHT alone resulted in a prostatic stromal cell density intermediate between that observed in intact prepubertal and postpubertal animals. These findings suggest that both estrogen and androgen are required for the normal development of the guinea pig prostatic stroma.