bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hormones on growth and ATP content of a human prostatic carcinoma cell line, LNCaP‐r
Authors: Hasenson Michael , Pousette ÅKe , Hartley‐åsp Beryl , Kihlfors Christer , Lundin Arne , Gustafsson Jan‐ÅKe
Published: February 2007

The use of ATP content as a measurement for cell growth was evaluated in the LNCaP prostatic cancer cell line. ATP content was found to correlate well with cell counts and was an easy and reliable method for following the effect of substances on cell growth. During cultivation for 9 days no effect on cell counts or ATP content could be seen when testosterone (10–10 to 10–6 M), estradiol‐17β (10–10 to 10–5 M), 5α‐DHT (10–9 to 10–6 M), prolactin, vitamin A, or antiandrogen was added to the cell medium in different combinations. However, a weak positive effect was seen on the mitotic index when 10 or 100 nM 5α‐DHT was added to the cells, whereas 1 μM 5α‐DHT inhibited cell growth. Thus despite the fact that this LNCaP line contained 16 fmol androgen receptor/mg protein (Kd 0.6 nM), it is unresponsive to hormones and should be designated LNCaP‐r (resistant). Chromosome analysis revealed that a shift in the modal chromosome number had occurred from the original LNCaP line, which could account for the lack of hormonal sensitivity.
Changes in immunohistochemical staining in prostatic adenocarcinoma following diethylstilbestrol therapy
Authors: Grignon David , Troster Michael
Published: February 2007

Twenty‐eight pretreatment and posttreatment biopsies from 11 cases of prostatic adenocarcinoma were stained for prostate‐specific acid phosphatase (PAP), prostate‐specific antigen (PSA), and keratin to determine the effect of hormonal (diethylstilbestrol) therapy on these immunological markers. Treatment intervals ranged from 2 to 63 months. All pretreatment tumors were strongly positive for PAP, and nine were strongly positive for PSA. Two were weakly positive for PSA, and all were negative for keratin. In five of the 11 posttreatment group cases, staining with both PAP and PSA was reduced. In three posttreatment cases, the malignant epithelium showed a squamoid appearance, and in these areas the keratin gave a positive reaction. These findings indicate that immunohistochemical staining with PAP and PSA may change in response to hormonal therapy. These alterations may lead to falsenegative results when using these techniques to identify the primary tumor source of metastatic deposits of prostatic carcinoma.
Measurement of skin blood‐flow and water evaporation as a means of objectively assessing hot flushes after orchidectomy in patients with prostatic cancer
Authors: Frödin Thomas , Ålund Goran , Varenhorst Eberhard
Published: February 2007

Hot flushes can occur after orchidectomy for carcinoma of the prostate and are sometimes greatly distressing for patients. Attacks are difficult to register because of their transient and unpredictable nature and have been the object of very little scientific investigation. In 13 postorchidectomy patients who reported hot flushes we recorded cutaneous blood‐flow and sweating by use of a laser‐Doppler flowmeter and an evaporimeter. A total of 23 attacks were recorded. The rate of evaporation increased by more than 60 g/m2/h in ten attacks, from 10 to 60 g/m2/h in five attacks, and by less than 10 g/m2/h in seven attacks. The cutaneous blood‐flow increased synchronously with the increase in evaporation. The intensity of the attacks as experienced by the patients corresponded closely to recorded measurements.
Benign hyperplasia of ventral prostate in rats induced by a monoterpene (preliminary report)
Authors: Abramovici Armand , Sandbank Uriel , Servadio Ciro
Published: February 2007

This is a preliminary report on the experimental induction of benign prostatic hypertrophy in rats using the nonsteroidal compound, citral, a monoterpene that is widely used in the cosmetics, cleaning, and food industries. The shaved skin of rats 6 weeks of age was smeared daily with citral for 3 months. The ventral prostates of the treated rats were larger and heavier than those of controls, and histology revealed a typical benign process of hyperplasia. Further studies are in progress to assess the nature of the mechanism involved.
Proliferative responses of normal rat ventral prostate in organ culture: Effects of testosterone and its metabolites in chemically defined medium
Authors: Buchanan Lynn J. , Riches Andrew C.
Published: February 2007

Proliferative responses of normal rat ventral prostate to testosterone were compared with that of its major metabolites, 5α‐dihydrotestosterone, androstenedione, androstanedione, and 5α‐androstane‐3β,17β‐diol in serum‐free organ culture medium using the incorporation of 5‐[125I]‐iodo‐2′‐deoxyuridine (125I‐UdR) to monitor DNA synthesis. With the exception of 5α‐androstane‐3β,17β‐diol, these androgens induced comparable increases in DNA synthesis at both 4 × 10−9 and 4 × 10−7 M, and at 4 × 10−5 M they exerted a nonspecific cytotoxic effect, resulting in marked suppression of 125I‐UdR uptake. In contrast, 5α‐androstane‐3β,17β‐diol was not stimulatory at 4 × 10−9 M, whereas at both 4 × 10−7 and 4 × 10−5 M it stimulated marginal increases in DNA synthesis and effectively maintained the histology of the tissue in a state comparable to the intact gland. Unlike 5α‐dihydrotestosterone, its epimer 5β‐dihydrotestosterone was inactive at all concentrations used. These results support the hypothesis that testosterone action in the prostate is mediated by the formation of active 5α‐reduced metabolites.
Hormonal activation of the adenylyl cyclases of the rat and human prostate gland
Authors: Purvis K. , Rui H. , Gordeladze J. O. , Attramadal H.
Published: February 2007

The rat ventral prostate and the human hyperplastic prostate contain adenylyl cyclases which can be activated by a variety of neurotransmittors, including vasoactive intestinal peptide (VIP), β2 adrenergic agonists, and dopamine. In both species the response to VIP was predominantly localized to the epithelial fraction. In the human tissue activation of the enzyme could also be achieved with prostaglandin E1 (PGE1) and an α2 adrenergic agonist both associated with the stromal compartment. Castration in the rat caused a marked reduction in the basal activity of the enzyme and the maximal level of the hormone‐stimulated response per cell (per mg DNA), but had only minor effects on the pattern of activation when expressed per mg membrane protein. Androgen treatment (dihydrotestos‐terone propionate, 2.5 mg/day) prevented the castration effects. Estrogen treatment (estradiol benzoate, 125 μg/day) could not prevent the castrational changes but maintained enzyme activity at a level above that of the castrate. There were no major qualitative differences in the pattern of activation of the cyclase between the different lobes of the rat prostate and the seminal vesicle.
Distribution of glycoconjugates in normal rat ventral prostate and their use as markers of androgen‐controlled secretory function in culture
Authors: Martikainen Paula , Malmi Raija , Suominen Jyrki
Published: February 2007

The distribution of glycoconjugates in uncultured and cultured rat ventral prostate was studied by using eight fluorescent lectins. The prostate pieces were cultured in defined medium with or without testosterone for 1–14 days. Each lectin revealed a characteristic binding pattern. Con A, LCA, WGA, and RCA I stained both epithelial and interstitial components. SBA and PNA were specific for the epithelium: SBA stained the region of the Golgi complex; PNA showed the brightest fluorescence in the apical part of the cells representing the region of secretory granules.

In culture without testosterone the epithelial cells gradually lost their fluorescence, whereas the stromal fluorescence increased. The basement membrane was disorganized. With testosterone the integrity of the epithelium and stroma was maintained, and the staining pattern of the lectins was in the main similar as in vivo. However, at 14 days a change in the staining pattern of apical cytoplasm with PNA was noted, indicating that in long‐term cultures, in addition to testosterone, other hormones and growth factors are necessary to complete especially the last stages of the secretory process in the epithelial cells.
Histopathological observations in the canine prostate treated by local microwave hyperthermia
Authors: Leib Z. , Rothem A. , Lev A. , Servadio C.
Published: February 2007

A large series of repeated experiments were performed applying localized microwave hyperthermia to the prostate in dogs using a new water‐cooled skirt‐type antenna [1], operating at 915 MHz, as part of a new hyperthermia apparatus being developed for the treatment of the prostate in humans. The prostate gland of 20 male dogs was heated repeatedly under general anesthesia, at temperatures between 40°C and 47°C, and for different lengths of time up to 10 h. The prostate and other tissues were evaluated histopathologically following treatments. Invariably, all treatments by hyperthermia of the prostate caused a mononuclear inflammatory infiltration in the interstitium and polymorphonuclear inflitration in the glandular elements. Permanent tissue damage was found to be time‐and temperature‐dependent. Heating at 42.5°C (± 0.5°5C) for up to 1.5 h was found to be harmless and could be safely repeated with our equipment. This study was part of a preclinical evaluation of a new antenna and apparatus.
Correlation of pretreatment plasma levels of estradiol and sex‐hormone‐binding globulin‐binding capacity with clinical stage and survival of patients with prostatic cancer
Authors: Haapiainen R. , Rannikko S. , Adlercreutz H. , Alfthan O.
Published: February 2007

Pretreatment plasma concentrations of estradiol‐17β (E2) and the binding capacity of sex‐hormone‐binding globulin (SHBG) were measured in 116 patients with prostatic cancer (PC) categorized into groups according to the UICC classification. By using the SHBG and E2 values, free percentage E2 and free E2 values were calculated. The patients were randomized to orchiectomy or estrogen treatment, and the mean follow‐up time was 42 months. Statistically significant higher (P < .05) pretreatment free E2 and/or E2 values were observed in subjects in which the cancer did not exceed beyond the capsule and was more differentiated and had not metastasized. SHBG values increased significantly (P < .05) with decreasing differentiation. It was observed in addition that survival was statistically significantly longer (P < .05) in subjects with high pretreatment E2 values compared to those with low values when the patients were grouped into three groups according to plasma E2 concentration, ie, 125–175, 75–124, and 20–74 pmol/liter. Survival was particularly poor in the group treated by orchiectomy with the lowest E2 values and statistically significantly different (P < .05) from that of the corresponding group treated by estrogens. However, the overall survival with the two treatments did not differ statistically significantly. Our results support the view that endogenous E2 levels play an inhibitory role in the growth, metastasizing tendency, and differentiation of the tumor and that estrogen treatment may be the treatment of choice for those with low pretreatment E2 levels; for those with medium or high levels orchiectomy seems to be as valuable as estrogen treatment.
Regional variation of cytosol androgen receptors throughout the diseased human prostate gland
Authors: Bowman Susan P. , Barnes Diana M. , Blacklock N. J. , Sullivan P. J.
Published: February 2007

The heterogeneous histology of the normal and diseased human prostate is well established. This study has investigated variations in cytosol andrbgen receptor (AR) content throughout the diseased gland to establish the most suitable sites to obtain tissue for AR assay. Only then can AR be investigated as a potential predictor of response to endocrine treatment.

In a transverse slice of an enucleated prostate showing benign prostatic hyperplasia (BPH) AR levels in 1‐g segments varied from 109 to 1,212 fmol/g tissue (mean 483 ± 273; median 406), with no negative areas. Areas of higher receptor concentrations corresponded to the glandular regions of sections obtained from a slice taken in juxtaposition; areas of low receptor concentrations corresponded to the stromal regions. A significant correlation (P < .02) was observed between AR concentration and the proportion of glandular components of each segment.

Specimens were also obtained from each of three sites from 38 prostates; 45% of all specimens contained AR; however, distribution of receptor throughout the prostate was uneven. AR were significantly more likely to be measured in the peripheral zone (71% positive) than in periurethral tissue (39% positive) whilst only 24% of specimens taken from the limit of the resection possessed AR binding capacity. Similar distribution patterns were observed in both benign and malignant prostates, although 16% more specimens from carcinomatous prostates contained receptor than did those from benign glands; this difference was maintained at each site. In addition receptor levels were consistently lower in benign than in malignant specimens.

It is therefore desirable to know the histological composition of specimens used for AR measurement.
Characterization of steroid receptors in human prostate using mibolerone
Authors: Murthy L. R. , Johnson M. P. , Rowley D. R. , Young C. Y. F. , Scardino P. T. , Tindall D. J.
Published: February 2007

Accurate quantitation of androgen receptors requires a radioactive ligand which has affinity and specificity for the receptor and which is stable to metabolic enzymes. In this report, we have characterized the properties of 7α,17α‐dimethyl‐17β‐hydroxy‐4‐estren‐3‐one (mibolerone) in human benign hyperplastic prostate cytosol and compared them to those of 17β‐hydroxy‐17α‐methyl‐estra‐4,9,11‐trien‐3‐one (R1881). Mibolerone was found to have an affinity (Kd = 1.5 nM) greater than R1881. (Kd = 2.3 nM) for the androgen receptor in human prostate tissue. Surprisingly, mibolerone was found to bind with high affinity to the progesterone receptor in both human prostate (Kd = 5.9 nM) and rabbit uterus (Kd = 1.1 nM). However, binding to this receptor in both species could be blocked with a 500‐fold excess of triamcinolone acetonide. [3H]Mibolerone binding to the androgen receptor was competed effectively with unlabeled dihydrotestosterone, R1881, and mibolerone but not by progesterone, diethylstilbestrol or R5020, in the presence of triamcinolone acetonide. Interestingly, mibolerone was more resistant to metabolism than R1881 in prostate cytosol when exposed to elevated temperatures (30°C) for extended periods of time. However, when exposed to high‐intensity ultraviolet irradiation, both compounds lost 50% of their binding ability in about 30 minutes. Mibolerone was found to have a very low affinity (Ki = 540 nM) for human sex steroid binding protein. These studies demonstrate that mibolerone is a useful ligand for androgen receptor assays. They also emphasize the need for including competitors of progesterone receptor binding in assays utilizing this steroid for androgen receptor measurements.
Association states of androgen receptors in nuclei of human benign hypertrophic prostate
Authors: Kyprianou Natasha , Davies Peter
Published: February 2007

Androgen receptors (AR) were quantified in nuclei purified from unfractionated benign hypertrophic prostate (bph) tissue and from separated epithelium and stroma from bph specimens. Both epithelial and stromal cell nuclei contained AR, although concentrations in epithelial cell nuclei were higher and more variable. Variations in AR levels in epithelial cell nuclei reflected variations in unfractionated‐tissue nuclei. Nuclear AR were further characterized regarding extractability with or resistance to 0.6 mol/lKCl and micrococcal nuclease. Nuclei from unfractionated tissue, epithelium, and stroma contained populations of AR susceptible and refractory to solubilization with KCl and nuclease. Nuclease‐ and salt‐sensitive populations of AR were similar numerically. The observed variability in epithelial cell nuclear AR was attributable to a wide range of solubilizable AR. Nuclease‐digestion profiles and sedimentation analyses revealed that this wide range was not due to AR associated with soluble chromatin oligomers but to AR not detectably associated with other nuclear components. In contrast, AR in stromal cell nuclei was predominantly resistant to KCl and nuclease, and variability in total nuclear AR concentration was due to variation in the nonextractable population.
Biochemical nature of the prostate‐associated antigen identified by the monoclonal antibody, KR‐P8
Authors: Raynor Robert H. , Hazra Tapan A. , Moncure Charles W. , Mohanakumar T.
Published: February 2007

The KR‐P8 monoclonal antibody identifies an organ‐specific antigen that is associated with normal as well as malignant specimens of human prostate tissue. The antigen is secreted by cells of the prostate and is present in samples of seminal plasma. Data presented here describe the biochemical nature of the antigen that is recognized by KR‐P8 as it occurs in seminal plasma and in extracts prepared from cells of the prostate tumor line, PC3. Antigen contained in seminal plasma migrated as a broad band on SDS‐polyacrylamide gels in the molecular weight range of 48,000–75,000 d. A similar pattern was observed for antigen prepared from detergent extracts of PC3 cells. The antigen was found to be sensitive to treatment with trypsin and chymotrypsin and the contribution of carbohydrate residues to the structure of the molecule was shown by studies that demonstrated binding of the antigen to Concanavalin A and Soybean Agglutinin lectins. Loss of antigenicity subsequent to periodate oxidation suggested that carbohydrate units are involved in the recognition site for KR‐P8 on the antigen.
Water imbibition in the rat prostate during castration‐induced regression
Authors: Lee Chung , Bahnson Robert R. , Blum Michael D. , Anderson Dean P. , Bockrath John J.
Published: February 2007

The present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70°C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%‐84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr‐EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr‐EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration‐induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.
Differential localization and androgen sensitivity of prostatic nuclear protein kinases in euchromatin and heterochromatin fractions
Authors: Norvitch Mary Ellen , Ahmed Khalil
Published: February 2007

We have examined the distribution and androgenic regulation of protein kinases and phosphoproteins in euchromatin and heterochromatin fractions of rat ventral prostate chromatin. Available procedures to prepare euchromatin and heterochromatin fractions were found to result in the loss of various chromatin‐associated protein kinases even though there was no gross change in the gel electrophoretic profile of proteins in these fractions. This loss was prevented by the addition of 0.5 mM phenylmethylsulfonyl fluoride throughout the preparative procedures, which indicates that the protein kinases associated with the chromatin may be particularly susceptible to proteolytic degradation during further subfractionation. By utilizing an improved method for fractionation of chromatin, we have demonstrated a marked enrichment of protein kinase activity (towards phosvitin and endogenous chromosomal proteins) in the euchromatin fraction as compared with heterochromatin. Both of these fractions were also examined for the incorporation of 32P into two main classes of nonhistone proteins (namely, H2SO4‐soluble and ‐insoluble nonhistones). The amount of 32P incorporated into heterochromatin‐associated proteins of both classes was markedly less than that in the euchromatin‐associated proteins. Protein kinase activities (especially those active towards phosvitin and nonhistone proteins) in the euchromatin fraction as compared with the heterochromatin were significantly reduced within 24 h after androgenic deprivation in the animal. The decreased phosphorylation of nonhistone proteins could be attributed to the loss of endogenous protein kinase activity. The results indicate that not only are chromatin‐associated protein phosphokinases preferentially localized in euchromatin fractions but also that these euchromatin‐associated protein kinases display the greatest sensitivity to androgenic status of the animal.
Characterization of androgen receptors in normal and malignant human prostatic tissues
Authors: Radwan Farouk , Léger Francine , Lehoux Jean‐Guy , Carmel Michel , Elhilali Mostafa
Published: February 2007

The aim of this work was to study the physico‐chemical characteristics of androgen receptors of normal and malignant human prostatic tissues. Association (k+1) and dissociation (k−1) rate constants and sedimentation profiles on sucrose density gradients were determined on [3H]androgen receptor complexes. In the presence of 20 mM sodium molybdate, no significant difference in k+1 and k−1 values could be found between cytosolic receptor preparations from normal and malignant specimens. The values obtained for k+1 (mean ± SD) were 5 ± 2 × 106M−1 min−1 (N = 3) and 5 ± 2 × 106M−1 (N = 5); k−1 values of 23 ± 4 × 10−4 min−1 (N = 4) and 25 ± 3 × 10−4 min−1 (N = 5) were obtained for normal and malignant tissues respectively. Similar Nmax values were also obtained for normal [(mean ± SD) 26 ± 10 fmol/mg cytosolic protein (N = 5)] and malignant [20 ± 9 fmol/mg protein (N = 7)] tissues. A statistically significant difference was found however, between k−1 values measured on [3H]androgen receptor complexes of nuclear extracts; values of 15 ± 3 × 10−4 min−1 (N = 4) and 9 ± 1 × 10−4 min−1 (N = 6) were found for normal and malignant tissue preparations respectively. This was also accompanied by a higher level of androgen receptors in nuclear extracts of malignant [Nmax, 308 ± 171 fmol/ g of tissue (N = 8)] compared to normal [Nmax, 68 ± 11 fmol/g of tissue (N = 5)] tissues.

The cytosolic [3H]androgen receptor complexes prepared from normal tissues sedimented mainly in the 8–9S area on sucrose density gradient whereas those from malignant tissues sedimented 50% in the 8–9S area and 50% in the 4S area.

In conclusion, in this study, we found a different sedimentation profile of androgen‐receptor complexes from the cytosol of prostatic cancers compared to normal as well as a diminution of their dissociation rate constant in nuclei.
Androgenic induction of DNA synthesis in prostatic glands induced in the urothelium of testicular feminized (Tfm/Y) mice
Authors: Sugimura Yoshiki , Cunha Gerald R. , Bigsby Robert M.
Published: February 2007

It has been shown previously that wild‐type urogenital sinus mesenchyme can induce the formation of prostate‐like glandular structures in urinary bladder epithelium derived from adult Tfm (testicular feminization) mice. Total DNA synthesis within these tissue recombinants has been shown biochemically to be androgen sensitive. To determine which tissue (epithelium or stroma) accounts for this androgen‐dependent DNA synthesis, an autoradio‐graphic study was performed with tissue recombinants composed of rat wild‐type urogenital sinus mesenchyme (UGM) associated with bladder epithelium from either wild‐type (BLE) or Tfm mice (Tfm BLE). Both types of recombinants were grown under the kidney capsule of male athymic nude mice for 4 weeks. The hosts were then castrated, and 2 weeks later were treated with either testosterone propionate (TP), TP plus cyproterone acetate (CA), or oil vehicle for 3 days. DNA synthetic activity was measured through analysis of labelling index (LI) after incorporation of 3[H]‐thymidine in vivo. For both UGM + BLE and UGM + Tfm BLE recombinants thymidine incorporation in epithelial cells greatly exceeded that of the stromal cells. TP stimulated epithelial LI to a similar degree (about 50‐ to 200–fold greater than controls) in both UGM + BLE and UGM + Tfm BLE recombinants; CA antagonized the effect of TP. Nuclear 3H‐DHT binding was observed autoradiographically within the epithelial cells of the induced epithelium of UGM + wild‐type BLE recombinants, but not within epithelium of UGM + Tfm BLE recombinants. Wild‐type mesenchymal cells in both tissue recombinants showed specific nuclear 3H‐DHT uptake. Thus, the proliferative effect of androgens upon prostatic epithelium is not a direct effect mediated by intra‐epithelial androgen receptors, but rather it appears to be elicited indirectly via regulatory influences from androgen‐receptor‐positive stromal cells.
Androgen‐dependent growth regulation of and release of specific protein(s) by the androgen receptor containing human prostate tumor cell line LNCaP
Authors: Berns Els M. J. J. , De Boer Willem , Mulder Eppo
Published: February 2007

Hormone sensitivity, as indicated by the presence of steroid hormone receptors and by the effect of androgens and anti‐androgens on the release of proteins by cultured cells of the human prostate tumor cell line lymph node carcinoma of the prostate‐fast growing colony (LNCaP‐FGC), has been studied.

The growth of the LNCaP‐FGC cells were stimulated by androgens in a dose‐dependent way. Under optimal conditions the synthetic nonmetabolizable androgen 17β‐hydroxy‐17α‐methyl‐(3H)‐estra‐4,9,11‐trien‐3‐one (R1881) (0.1 nM) stimulated cell growth by approximately 2.3 times. Increasing doses of R1881 (1–100 nM) partly decreased the stimulation of the cell growth. The anti‐androgen cyproterone acetate exerted inhibitory effects on cell growth. The nuclear extract of the LNCaP‐FGC cells contained 17,000 ± 2,500 (mean ± SD) KCl‐extractable, nuclear androgen receptor sites/cell. Estrogen and progesterone receptors were not detectable in the nuclear extracts nor in cytosol, indicating that these receptors were absent.

The release of proteins in the culture medium was studied using incorporation of the 35S‐methionine, sodium dodecyl sulfate (SDS)‐gel electrophoresis, and fluorography. Cells grown in media containing charcoal‐stripped fetal calf serum released significantly lower amounts of a protein with an apparent molecular mass of 42,000 daltons. The release of this 42‐kD protein could be restored in cells cultured in the presence of 5α‐dihydrotestosterone (0.1–1 μM) or R1881 (0.1–100 nM), whereas the addition of estrogens or corticosteroids had no effect. In the presence of anti‐androgens, such as cyproterone acetate and 5,5‐dimethyl‐3‐(4‐nitro‐3‐(trifluoro‐methyl)‐phenyl)‐2,4‐imidasolidinedione, inhibitory effects on the release of the 42‐kD protein were observed. The observed parallel between the effects of (anti)‐androgens on the growth of the LNCaP prostate cells and the release of the 42‐kD protein suggests that this protein is involved in the regulation of malignant prostate cell growth.
Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers
Authors: Isaacs John T. , Isaacs William B. , Feitz Wouter F. J. , Scheres Jack
Published: February 2007

In vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines. Some of these in vitro cell lines (i.e., G, AT‐1, AT‐2) retain a low metastatic ability when inoculated back into syngeneic Copenhagen male rats, while others (i.e., AT‐3, MAT‐LyLu, MAT‐Lu) retain a very high metastatic ability. A series of genetic (i.e., DNA content per cell, modal chromosomal number), as well as phenotypic parameters (i.e., morphology, 5α‐reductase, androgen receptor, estrogen receptor) were used to validate that the in vitro cell lines retained the major characteristics of the parental in vivo tumor sublines used for their respective establishment.

A series of additional characteristics (i.e., morphology, growth rate, saturation density in surface culture, anchorage‐dependent and ‐independent clonogenic potential) were compared between the high vs. the low metastatic in vitro cell lines to determine if a discriminatory parameter could be identified which reproducibly predicted the metastatic abilities of the particular prostatic cancer cell line. While the combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, no single parameter yet measured is entirely successful in making this important distinction.
Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia
Authors: Berry Stephen J. , Ewing Larry L. , Coffey Donald S. , Strandberg John D.
Published: February 2007

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5–2.5–yr) and old (6.0–8.5‐yr) groups. Each of these groups was further divided randomly into two additional groups of age‐matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone‐filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two‐dimensional X‐ray procedure [1]. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostrate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.
Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia
Authors: Stone Nelson N. , Fair William R. , Fishman Jack
Published: February 2007

Prostatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,73H] androstenedione in the presence or absence of an aromatase inhibitor, 4‐hydroxyandrostenedione (4‐OHAD) and a 5α‐reductase inhibitor 4‐MA (N,N‐diethyl‐4‐methyl‐3‐oxo‐4‐aza‐5α‐androstane 17β‐carboxamide). Estrogen formation was determined by reverse isotope dilution of [3H] estrone and [3H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/ mg protein/hr (SE ± 57) compared to 102 fmol (SE ± 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE ± 69) and 105 fmol (SE ± 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis‐Menton kinetics with an apparent Km of 90 nM. 4‐OHAD inhibited aromatization in the prostatic tissue by 57‐93%. Aromatization was also strongly inhibited by 4‐MA, indicating that 4‐MA is a potent aromatase as well as a 5α‐reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.
Development of canine benign prostatic hyperplasia with age
Authors: Berry Stephen J. , Strandberg John D. , Coffey Donald S. , Saunders William J.
Published: February 2007

The prevalence and growth of benign prostatic hyperplasia (BPH) in beagles as a function of age were studied. The normal prostate gland was 12 ± 3 gm in beagles 2.1‐3.0 years of age; this weight remained unchanged unless BPH developed. Histologic evidence of BPH developed at an early age with a prevalence of 16% of the dogs by the age 2 years. Fifty percent of the dogs had BPH, determined histopathologically by age 4.1‐5.0 years. The average weight of the prostate gland remained constant until after age 8 years. With age, the pathologic features of BPH changed from glandular to the complex form, with no increase in prostate weight until after 8 years. Reinitiation of growth occurred and prostate weight increased to greater than 36 gm in eight of 185 beagles older than age 8 years.
Role of epithelial‐stromal interactions in the control of gene expression in the prostate: An hypothesis
Authors: Tenniswood Martin
Published: February 2007

An hypothesis that explains the effects of stromal‐epithelial interactions on the mechanism of action of androgens is presented. This hypothesis proposes the existence of three factors, two growth factors referred to as “stromally derived growth factor” (SDGF) and “epithe‐lially derived growth factor” (EDGF), and one inhibiting factor, “epithelially derived inhibiting factor” (EDIF), which together modulate the replicative and transcriptional processes of the prostate. The hypothesis attempts to explain the well documented modulation of epithelial morphology and function by the stromal cells of the prostate that occurs during development. It also describes the role of each of the factors in the mature prostate, and suggests that in the adult the interaction between the stroma and epithelium, while still significant does not greatly influence the action of androgens, which exert their effects via the classical steroid receptor mechanism.
Nuclear protein matrix as a target for estramustine‐induced cell death
Authors: Hartley‐Asp Beryl , Kruse Elisabeth
Published: February 2007

The effect of estramustine [estradiol 3–N‐bis(2–chloroethyl)carbamate] on the human prostatic tumor cell line 1013L was investigated. Cell proliferation experiments revealed that estramustine cytotoxicity varied during the different phases of cell growth. Maximum cell killing was found in early log phase, but cell death also occured in the stationary phase. Mitotic arrest was found at cytotoxic concentrations throughout the log phase. Subcellular distribution studies showed that the cellular uptake of estramustine increased throughout the log phase and remained steady during the stationary phase. Nuclear uptake in contrast was similar in all phases, whereas a preferential binding to the nuclear protein matrix was found to increase throughout the log phase and even during the stationary phase of growth. This implicates the nuclear protein matrix as a target for estramustine cytotoxicity.
Echogenic structure of prostatic cancer imaged on radical prostatectomy specimens
Authors: Salo J. O. , Rannikko S. , Mäkinen J. , Lehtonen T.
Published: February 2007

Twenty radical prostatectomy specimens were scanned ultrasonically in vitro using a transrectal ultrasonic probe to evaluate the ultrasonic pattern of prostatic cancer. Histological and ultrasonic findings of the same areas were compared. No ultrasonic pattern specific for intracapsular prostatic cancer was found. Most often (in 40% of cases) the areas of prostatic cancer appeared hypoechoic on the ultrasonograms. In 30% of cases the carcinoma had a hyperechoic or mixed ultrasonic pattern, and in 30% the echo structure of the prostate was fairly uniform; intracapsular cancer could not be detected ultrasonically in these latter cases. The lack of a specific ultrasonic pattern for intracapsular prostatic carcinoma reduces the value of transrectal ultrasonography in detecting early intracapsular cancers. The main value of ultrasonography in patients with prostatic cancer is in the preoperative staging of the disease and in the follow‐up of patients.
DNA synthesis in the canine prostate: Effects of androgen and estrogen treatment
Authors: Barrack Evelyn R. , Berry Stephen J.
Published: February 2007

Canine prostatic DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA of tissue slices in vitro. Among untreated beagles, prostatic DNA synthesis rates in young dogs with normal prostates, young dogs with spontaneous benign prostatic hyperplasia (BPH), and old dogs with BPH were 676 ± 186, 1,220 ± 156, and 641 ± 88 cpm/100 μg DNA/hr, respectively. Among 81 young beagles (intact or castrated) that had been treated for 4 months with various steroids, rates of DNA synthesis varied according to the type of hormonal treatment. Prostatic DNA synthesis (cpm/100 μg DNA/hr) was significantly different (P < 0.001) for dogs treated with estradiol alone (1,658 ± 221 cpm/100 μg DNA/hr; n = 10 dogs), androgen alone (testosterone, 5a‐dihydrotestosterone, or 5a‐androstane‐3a, 17β‐diol; 1,000 ± 61 cpm/100 μg DNA/hr; n = 40 dogs), or a combination of androgen plus estradiol (591 ± 49 cpm/100 μg DNA/hr; n = 31 dogs). However, there was no correlation between prostate size and rate of DNA synthesis (cpm/100 μg DNA/hr). Although treatment with estrogen alone resulted in the highest rate of DNA synthesis, it produced squamous metaplasia and the smallest prostates; these results are indicative of a high rate of cell turnover. Comparing prostates that reached the same size following 4 months of treatment with androgen alone or androgen plus estrogen, the rate of prostatic cell turnover was lower in the androgen plus estrogen group. These results are interpreted to indicate an inhibitory effect of estradiol on the rate of cell death in the presence of androgens.
Acid phosphatase activity: A marker of androgen action in prostate explant cultures
Authors: Shao T. C. , Kong A. Y. , Cunningham G. R.
Published: February 2007

Acid phosphatase activity in rat ventral prostate explants has been assayed to determine if this parameter could serve as a specific and quantitative marker of androgen action in this in vitro model. Dihydrotestosterone (10 nM) caused an absolute increase in both total (42.5 ± 2.9 vs control 27.1 ± 4.0 nmoles p‐nitrophenol generated in 30 min/μg DNA, P < .01) and tartrate‐resistant acid phosphatase activity (34.1 ± 1.5 vs control 17.2 ± 2.8 U/μg DNA, P < .05), and this effect was maximal on the 4th day of culture. This was the time when explant weight and DNA content tended to fall or only to be maintained by androgen. Similar changes were observed with the potent synthetic androgen, mibolerone. The addition of either the antiandrogen cyproterone acetate or flutamide in a 100‐fold excess to that of androgen caused significant inhibition in acid phosphatase activity. No significant change was observed at low concentrations of estradiol or progesterone, and only minimal and inconsistent increases in activity were noted at high concentrations. No increase was noted when cortisol, cyproterone acetate, or flutamide was added to the media. We conclude that measurement of acid phosphatase activity in cultured explants of rat ventral prostate provides a biochemical marker of androgenicity that is more specific than measurement of [3H]‐thymidine incorporation.
Medical, life‐style, and occupational risk factors for prostate cancer
Authors: Checkoway Harvey , Diferdinando George , Hulka Barbara S. , Mickey Don D.
Published: February 2007

Information on suspected risk factors for prostate cancer was obtained from in‐person interviews as part of a case‐control study of tissue sex hormone receptors and serum hormone levels. The risk factors examined were medical history (including venereal disease), sexual history, smoking, alcohol consumption, and occupational exposures. Study subjects were 40 prostate cancer patients and 64 benign prostatic hyperplasia controls who were newly diagnosed during 1984‐1985 at North Carolina Memorial Hospital in Chapel Hill. Subjects were white and black men aged 50 years and older. Comparisons of cases' and controls' past medical histories did not support a venereal disease hypothesis of prostate cancer etiology. The most prominent finding is an association with farming employment: 75% of cases compared to 38% of controls reported farmwork occupations. Exposures to pesticides and herbicides, while more common among the patients, did not account for the association detected for farming. No relationship was observed with cadmium exposure, the most frequently cited occupational risk factor for prostate cancer.
Papillary carcinoma of the prostate, location, morphology, and immunohistochemistry: The histogenesis and entity of so‐called endometrioid carcinoma
Authors: Wernert Nicolas , Lüchtrath Helmut , Seeliger Harro , Schäfer Monika , Goebbels Rolf , Dhom Georg
Published: February 2007

Fifty carcinomas that were partially to completely papillary in nature were examined. According to urethroscopic and rectal palpation findings, six of the carcinomas were located centrally, 40 tumors were in the prostate proper, and four were clinical stage T0. The epithelium of the papillary portions of the tumors was dark in some instances, light in others. Immunohistochemistry revealed that 20 of 22 tumors were positive for prostatic acid phosphatase (PAP) and prostate‐specific antigen (PSA). In no case was a topical relationship to the utriculus prostaticus demonstrable. The epithelium of the utriculus in seven additional patients who were not involved in this series also stained positively for PAP and PSA. Usual carcinomas of the prostate proper can develop endometrioid structures that do not differ immunohistochemically from ordinary portions of the carcinoma. Tumors located in central portions of the prostate are, in our opinion, morphologic variants of usual prostatic carcinomas, and apparently arise in prostatic ducts. We conclude that a distinction between endometrioid carcinomas and tumors of prostatic ducts does not seem justified and that papillary prostatic carcinomas should be treated like common prostatic cancer.
Radioimmunoassay in blood plasma of arginine esterase: The major secretory product of dog prostate
Authors: Frenette Gilles , Dubé Jean Y. , Lacoste Daniel , Tremblay Roland R.
Published: February 2007

We have developped a radioimmunoassay to determine serum levels of arginine esterase, the major secretory product of the canine prostate. Although the antibodies recognized other related proteins in immunoblotting conditions, particularly in the pancreas, the radioimmunoassay appeared specific for arginine esterase of prostatic origin and reacted only slightly or not at all with cytosolic proteins from salivary glands, liver, skeletal muscles, and kidney. In serum samples, the sensitivity limit of the assay was about 2.5 ng per ml. The interassay and intraassay variations for serum samples that contained concentrations of arginine esterase ranging from 6 to 21 ng per ml were, respectively, 14% and 24%. Sera from 30 adult males and 14 adult females contained, respectively, 71 ± 9 and 5.3 ± 0.4 ng per ml. In a group of 12 dogs treated daily for 36‐39 days with 50 μg of D‐Trp6‐luteinizing hormone‐releasing hormone ethylamide, the concentrations of arginine esterase in the serum decreased progressively and became identical with those observed in the females. These results constitute the first evidence for the presence of a serum marker of the normal prostate in an experimental model. It should be particularly useful to test the effects of various agents on the prostate.
Primary culture of epithelial cells derived from the rat ventral prostate: Formation of three‐dimensional acinus‐like structure in collagen gel
Authors: Kawamura H. , Ichihara I.
Published: February 2007

Rat ventral prostate epithelial cells were cultured in collagen gel after collagenase digestion. The primary cultures were mainly composed of single and spherical cells. After 10 days incubation in growth medium containing insulin, transferrin, and cholera toxin, there was a 3.8‐fold increase in cell numbers, aggregates of which formed three‐dimensional acinus‐like structures. These structures consisted of one layer of cells surrounding the lumen. The cells were joined together with a junctional complex and had microvilli on the luminal surface and secretory vacuoles in the cytoplasm facing the lumen. The ultrastructural features of the cells were not altered by growth medium containing steroids. This culture system may prove to be very useful in elucidating proliferation, organization, and differentiation of prostatic epithelial cells in relation to the extracellular matrix and stromal cells.
In vitro growth inhibition of dunning rat prostate tumor by bone marrow factor
Authors: Klose Arthur G. , Bencuya Paul S. , Mickey Don D.
Published: February 2007

Normal Copenhagen rat bone marrow was assayed for growth inhibition of cultured MAT LyLu rat prostate tumor cells. A marrow‐derived factor was identified that had significant growth inhibitory activity in vitro against MAT LyLu as well as against DU‐145 human prostate tumor and MBT‐2 mouse bladder tumor cells but that was noninhibitory to normal rat fibroblasts. The factor was stable to degradation by acid, heat, freezing, trypsin, and carboxypeptidase B. The factor was nonreactive with Coomassie blue, and the molecular weight was estimated as < 620 daltons. A similar factor was identified in normal human and normal rat sera. The presence of this factor in bone marrow may explain the absence of osseous metastases in the Dunning rat prostate tumor model.