bluuebunny/crossref_metadata_2025 huggingface dataset:
The prostatic epithelial cell in dysplasia: An ultrastructural perspective
Authors: Devries Catherine R. , McNeal John E. , Bensch Klaus
Published: February 2007

The histologic features of prostatic duct‐acinar dysplasia have been difficult to analyze ultrastructurally, because of the difficulty in properly selecting and processing such small, randomly situated grossly invisible lesions. We have succeeded in identifying dysplastic foci by examination of the cut surfaces of tissue slices under low magnification. Dsyplasia foci were excised from the slices and were compared to adjacent normal tissue by both light and electron microscopy. By electron microscopy (EM), normal secretory cells were filled with myriad tiny clear vacuoles, which were markedly diminished to absent in the cytoplasm of dysplastic cells. Both apocrine and eccrine secretion characterized normal epithelium and were diminished in dysplasia. EM showed striking features of nuclear abnormality more prominently than light microscopy, and qualitative basement membrane abnormalities were revealed. By EM analysis, dysplastic epithelium resembled that of invasive carcinoma more than normal epithelial cells.
Radiation sensitization by estramustine studies on cultured human prostatic cancer cells
Authors: Eklöv Solveig , Nilsson Sten , Essand Magnus , Carlsson JÖRgen
Published: February 2007

In low‐stage prostatic carcinoma, local cure can be obtained with radiation therapy alone, while in locally advanced disease the chances for cure are less. In this study, we have addressed the question of whether estramustine (EM), the main cytostatic metabolite of estramustine phosphate (Estracyt), may act as a radiosensitizing agent. This drug accumulates in prostatic cancer and has also been shown to arrest cancer cells at metaphase both in vitro and in vivo. The human prostatic cancer cell line DU 145 was grown as cultures monolayer and incubated with EM in concentrations varying from 1 to 20 μg/ml. External beam irradiation was performed with doses ranging from 0 to 8 Gy using gamma rays from a 60Co source. Clonogenic cell survival (CS) was used to analyse the radiation sensitizing effect of EM. The radiation dose modifying factor (DMF) at the survival level 0.1 was found to be 0.77 in the presence of EM (5 (μg/ml), i.e., 23% sensitization was obtained. When irradiating cells at the standard fraction dose of 2 Gy in the absence of EM, 22% of the cells lost their clonogenic ability. In presence of EM (5 μ/ml), 2 Gy caused 40% of the cells to lose their clonogenic ability. Thus a radiation sensitizing effect of EM was established in the CS assay. It was also of interest to determine if the radiosensitizing effect of EM could be confirmed in a rapid assay. The rapid fluorescence assay was used to observe early damage of the cells. Results showed that by 2 days after exposure to irradiation a weak tendency towards sensitization was seen, while a clear sensitization was obtained after 4 days. This indicates that the rapid assay might be developed to a predictive assay for detection of the response of primary prostate tumor cells to the radiation sensitizing effect Of EM.
Effects of prolactin on explant cultures of rat ventral prostate: Morphological and immunohistochemical study
Authors: Romero L. , Muñoz C. , Lopez A. , Vilches J.
Published: February 2007

Specimens derived from rat ventral prostate were cultured by an explant culture technique using differents concentrations of ovine prolactin. Sacrified explants embedded on paraffin were sectioned for morphologic and immunocytochemical studies using antibodies against prostatic acid phosphatase, prostatic specific antigen, and wide‐spectrum monoclonal keratin. Prolactin significantly stimulated the growth of these cells in the concentration range of 1 × 10−2 ui/ml, but was inhibitory at a concentration of 1 and 0.1 ui/ml. The 1 × 10−3 and 1 × 10−4 ui/ml prolactin concentrations demonstrated the preservation of a glandular epithelium with a columnar shape, similar to the normal appearance of ventral prostate from rats. © 1993 Wiley‐Liss, Inc.
Castration rapidly results in a major reduction in epithelial cell numbers in the rat prostate, but not in the highly differentiated dunning R3327 prostatic adenocarcinoma
Authors: Westin Patrick , Bergh Anders , Damber Jan‐Erik
Published: February 2007

Rats with implanted highly differentiated Dunning R3327PAP prostatic tumors were castrated, and at 3, 7, and 14 days thereafter, the effects on tumor volume, epithelial cell numbers, and sizes were quantified using morphometrical methods. The castration response on these parameters was also examined in the normal prostate of the same rats. Castration resulted in a rapid decrease in organ volume, epithelial cell number, and size in the normal prostate, and morphological signs of epithelial cell death (apoptosis) were observed. Tumor growth and mitotic index were reduced, but there were no signs of increased apoptosis, and cell numbers remained fairly constant in the Dunning tumors during the study period. It is concluded that the castration‐induced inhibition of tumor growth is caused by factors other than tumor cell death. © 1993 Wiley‐Liss. Inc.
Effects of suramin on the proliferation of primary epithelial cell cultures derived from normal, benign hyperplastic and cancerous human prostates
Authors: Mitchen Jacque , Rago Randall , Wilding George
Published: February 2007

Primary epithelial cultures (PECs) derived from normal, benign hyperplastic (BPH), and cancerous human prostate tissue were treated with increasing doses of suramin, and assayed for cell proliferation over a period of days. The suramin IC50 (inhibitory concentration 50%) value was 0.5 to 1.0 × 10−4 M whereas doses between 2.5 × 10−4 and 5 × 10−4 M resulted in total growth inhibition. This inhibition was reversible by exchange with suramin‐free medium up to day 6. Concentrations ⩾ 5 × 10−4 M resulted in increased cytotoxicity as exposure time increased. No differential response to suramin could be demonstrated among the prostate PECs derived from different tissues. The established cell lines, PC‐3 and DU 145, grown in serum containing medium exhibited IC50s comparable to the PECs grown in serum free medium.

EGF, bFGF, α, or β ECGF at the concentrations tested did not reverse suramin inhibition. Increasing concentrations of bovine pituitary extract (BPE) increased cell growth in both the treated and the control cells. However, the percent growth inhibition by suramin at each concentration of BPE remained constant. Flow cytometry examination of cells treated for 7 days with suramin (0–10−3 M) failed to detect any significant cell cycle alterations compared to control.

At high concentrations of suramin (⩾ 10−4 M), large numbers of viable and dead cells were detectable in the medium. The increase in unattached viable cells was most prevalent (80%) in cultures treated with suramin at the time of plating, but also occurred with cells (25–30%) plated hours prior to the addition of suramin. Treatment for several days with low concentrations of suramin (10−7 to 10−5 M) transiently enhanced cell growth compared to Controls. © 1993 Wiley‐Liss. Inc.
Human primary prostate tumor cell line, ALVA‐31: A new model for studying the hormonal regulation of prostate tumor cell growth
Authors: Loop Stephen M. , Rozanski Thomas A. , Ostenson Richard C.
Published: February 2007

A new human prostate tumor cell line (ALVA‐31) has been established from a biopsy specimen of primary tumor obtained during prostatectomy. The cell line has been maintained for more than 48 months in stable growth. The in vitro doubling time was determined to be approximately 26 hr. The chromosome number ranged from 24–112, with a modal number of 59 tested over several time points throughout continuous culture. Karyotypic analysis of late‐passaged cells demonstrated approximately 70 human chromosomes, 8–14 markers, and two × chromosomes without a Y chromosome. Prostatic origin was confirmed by the expression of both prostate specific antigen and prostatic acid phosphatase, using specific antisera and immunoradiolabelling techniques. Prostate tumor xenografts were grown in intact male, castrate male, and female athymic mice; however, the rate of tumor growth was clearly dependent upon serum testosterone levels. © 1993 Wiley‐Liss, Inc.
Induction of metallothionein by CdCl2 administration in rat prostate
Authors: Suzuki Takanori , Yamanaka Hidetoshi , Nakajima Katsuyuki , Kanatani Kazushi , Suzuki Keiji , Kimura Masami , Nakazawa Yasuo , Otaki Noriko
Published: February 2007

Metallothionein (MT) induction in the rat prostate gland was investigated by means of cadmium chloride administration. Ten‐week‐old male Wistar rats housed with cadmium free food were divided into three groups of six rats each and castrated. After seven days, 1 mg of testosterone propionate per rat was injected subcutaneously once a day until the end of the experiment. After three weeks, rats were injected daily for six days with a physiological saline, 0.3 mg/kg CdCl2, and 0.9 mg/kg CdCl2. MT concentration of the ventral and dorsal lobes was significantly increased in the three groups in proportion to the dose of CdCl2. MT content of the lateral lobe in three groups was also increased, but was not significantly different. Immunohistochemically, MT was induced mainly in the ventral lobe in the basal cells, and in the lateral and dorsal lobes in the epithelial cells. The weights of the prostatic lobes were similar in the three groups, and no histological change was identified. These results suggested that MT in the prostate was induced by cadmium administration, and that it may prevent cellular damage from harmful metals. © 1993 Wiley‐Liss, Inc.
Influence of hormone application by subcutaneous injections or steroid‐containing silastic implants on human benign hyperplastic prostate tissue transplanted into male nude mice
Authors: Claus Siegfried , Aumüller Gerd , Tunn Sabine , Senge Theodor , Schulze Harald
Published: February 2007

To study the influence of androgens and estrogens on human benign prostatic hyperplasia (BPH) tissue, BPH fragments were grafted subcutaneously (s.c.) into male nude mice. Testosterone alone (group I) or in combination with 17β‐estradiol (group III) were administered either by s.c. injections as oil suspensions or continuously by s.c. implanted steroidcontaining Silastic implants (groups II and IV). Intact mice without transplants and treatment served as a control (group V). After 4 weeks of treatment, animals were exsanguinated, transplants were removed, and serum was obtained. Ninety‐six percent of the BPH fragments were located; they displayed histologically typical BPH acini and stroma. In transplants of all treatment groups, the majority of secretory, as well as basal, cells displayed a proliferation comparable to the original tissue. In glandular cells of all transplants, prostate‐specific antigen (PSA) and prostatic acid phosphatase (PAP) could be demonstrated immunohistochemically. Specimens removed from animals bearing testosterone implants displayed a very well preserved ultrastructure that was found less frequently in samples from injection‐treated animals. Acini‐bearing metaplastic epithelium were more often present in transplants treated by steroid injections and seemed to be due to lower androgen or higher estrogen serum levels. Endogenous serum testosterone levels (ng/ml ± SD; n) were lower and more variable (i.e., higher standard deviation) in groups treated by injections (group 1: 3.68 ± 2.12; n = 5 and group III: 3.86 ± 1.13; n = 5) and were similar to those seen in intact controls (3.93 ± 1.62; n = 6) compared with groups treated by Silastic implants (group II: 5.11 ± 1.14; n = 10 and group IV: 10.20 ± 0.52; n = 4). These results indicate that by application of steroids via Silastic implants, reproducible hormone effects can be obtained on BPH tissue transplanted into male nude mice, thus providing a reliable new model system for study. © 1993 Wiley‐Liss, Inc.
Neoplastic transformation of a human prostate epithelial cell line by the v‐Ki‐ras oncogene
Authors: Parda David S. , Thraves Peter J. , Kuettel Michael R. , Lee Myeong‐Seon , Arnstein Paul , Kaighn M. Edward , Rhim Johng S. , Dritschilo Anatoly
Published: February 2007

Investigations of mechanisms of human prostate carcinogenesis are limited by the unavailability of a suitable in vitro model system. We have demonstrated that an immortal, but nontumorigenic, human epithelial cell line (267B1) established from fetal prostate tissue can be malignantly transformed by a biological carcinogen, and can serve as a useful model for investigations of the progression steps of carcinogenesis. Activated Ki‐ras was introduced into 267B1 cells by infection with the Kirsten murine sarcoma virus. Morphological alterations and anchorage‐independent growth were observed; when cells were injected into nude mice, poorly differentiated adenocarcinomas developed. These findings represent the first evidence of malignant transformation of human prostate epithelial cells in culture, and support a role for Ki‐ras activation in a multistep process for prostate neoplastic transformation. © 1993 Wiley‐Liss, Inc.
LY207320 (6‐methylene‐4‐pregnene‐3,20‐dione) inhibits testosterone biosynthesis, androgen uptake, 5α‐reductase, and produces prostatic regression in male rats
Authors: Neubauer Blake Lee , Best Kevin L. , Blohm Thomas R. , Gates Cynthia , Goode Robin L. , Hirsch Kenneth S. , Laughlin Marie E. , Petrow Vladimir , Smalstig E. Barry , Stamm Nancy B. , Toomey Richard E. , Hoover Dennis M.
Published: February 2007

LY207320 is an in vitro inhibitor (estimated IC50 = 0.06 μM) of steroid 5α‐reductase that catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). In contrast, LY207320 was only moderately active against rat prostatic 5α‐reductase in vivo (32% inhibition at 50.0 mg/kg single dose). LY207320 did, however, inhibit the in vivo uptake of [3H]‐T by the prostate. The antiprostatic and endocrine effects of this agent were evaluated following daily (21 days) administration to castrated, androgen‐supplemented castrate, and intact rats. LY207320, which has modest progestational competitive binding activity, does not bind to rat prostatic androgen or uterine estrogen cytosolic receptors. In the castrated male rat, subcutaneously (s.c.) administered LY207320 had no androgen agonist activity, as evidenced by a lack of accessory sex organ weight gains. Administration of s.c. LY207320 to intact rats for 21 days at doses greater than 5.0 mg/kg‐day produced significant (P <0.05) reductions of seminal vesicle and ventral prostatic weights (maximal regression = −65% and −40% from control values, respectively at 50.0 mg/kg‐day). The compound had no regressive activity on male accessory sex organs when administered orally. LY207320 did not alter circulating prolactin, LH, or corticosterone levels, but at high doses (>m50.0 mg/kg‐day), lowered circulating T[−67% from intact control levels (P <0.05)]. Histological analysis of the rat ventral prostates (RVPs) in LY207320‐treated rats was consistent with an androgen‐deprived state. Decreased circulating androgens and prostatic regression are associated with inhibition of testicular 17α‐hydroxy/C17,20‐lyase enzyme activity (IC50 = 0.06 μM). These findings support the contention that LY207320 is a physiological antagonist of androgen action in male rats, and that its effects are mediated primarily through inhibition of testicular androgen production rather than accessory sex organ 5α‐reductase. © 1993 Wilcy‐Liss, Inc.
Endocrine and antiprostatic effects of raloxifene (LY156758) in the male rat
Authors: Neubauer Blake Lee , Best Kevin L. , Clemens James A. , Gates Cynthia A. , Goode Robin L. , Jones C. David , Laughlin Marie E. , Shaar Carl J. , Toomey Richard E. , Hoover Dennis M.
Published: February 2007

The benzothiophene anti‐estrogen, raloxifene [LY156758; (6‐hydroxy‐2‐(4‐hydroxyphenyl) benzo(b)thien‐3‐yl)(4‐(2‐1‐piperidinyl)ethoxy)phenyl methanone hydrochloride] has selective estrogen pharmacological antagonist activity in female rats. The present studies were done in the male rat to assess activity of raloxifene related to inhibition of prostatic growth and effects on the hypothalamic‐pituitary‐gonadal axis. Raloxifene did not compete for binding of the androgen, [3H]‐methyltrienolone (R1881) in cytosolic extracts of ventral prostate. Similarly, the compound did not inhibit prostatic 5α‐reductase or testicular 17α‐hydroxy/C17,20‐lyase activities. Raloxifene had no effect on the ventral prostatic uptake of [3H]‐R1881 in vivo. Administration of estradiol to castrated male rats stimulated fourfold increases of in vitro ventral prostatic binding of [3H]‐R1881. Raloxifene was devoid of agonist activity in castrated animals, because the compound had no stimulatory effect on prostatic androgen receptor binding activity. When raloxifene was coadministered with estradiol, the compound markedly antagonized the estrogen‐induced increase of prostatic [3H]‐R1881 binding, confirming its antiestrogenic properties in male rats. Serum prolactin was also elevated significantly (P <0.05) with a single injection of raloxifene (20.0 mg/kg). In these same animals, serum FSH was significantly (P <0.05) decreased by one dose (10.0 mg/kg) of the compound. Luteinizing hormone levels in castrated male rats were unaffected by raloxifene administration. Raloxifene treatment of castrated males significantly (P <0.05) antagonized the stimulatory response of the ventral prostate (VP) to exogenous androgens in a dose‐dependent manner. Raloxifene treatment of intact male rats for 14 and 28 days produced significant (P <0.05) dose‐dependent regression of the VP and seminal vesicles (SV). The VP regressive responses to raloxifene were associated with a decline in serum testosterone levels. Histological analysis of the VPs in raloxifene‐treated rats was consistent with an androgen‐deprived state. These findings support the contention that raloxifene is a pure estrogen antagonist and a physiological antagonist of androgen action in male rats. These pharmacological properties provide support for further structure‐activity and mechanistic investigations with benzothiophenes in the medical management of prostatic neoplasia. © 1993 Wiley‐Liss, Inc.
Use of percutaneous transperineal 198Au seeds to treat recurrent prostate adenocarcinoma after failure of definitive radiotherapy
Authors: Loening Stefan A. , Turner J. Wesley
Published: February 2007

Patients who fail external radiation therapy for prostatic cancer pose a therapeutic challenge. No further external radiation treatment can be delivered safely to the local lesion, although some patients are candidates for salvage surgery. In this study, 31 patients who failed prior external beam radiotherapy received percutaneous transperineal placement of gold seeds (198Au). Initial prostate volume was 17.7 cc and decreased to 10 cc 24 months after 198Au implantation. Of 15 patients biopsied at 12 months after treatment, 4 (27%) were positive, 6 (40%) were negative, and 5 (33%) showed prostate cancer with radiation changes. Two of three patients have died of prostate cancer, with an overall 5‐year estimated survival of 67%. Interstitial brachytherapy was found to be an additional welltolerated treatment modality in this group of 31 patients. © 1993 Wiley‐Liss, Inc.
Expression of NEU/HER‐2 oncoprotein (p185neu) in prostate tumors: An immunohistochemical study
Authors: Giri Dipak K. , Wadhwa Surender N. , Upadhaya Sakti N. , Talwar Gursaran P.
Published: February 2007

The expression of the neu oncogene product was investigated immunohistochemically in 36 cases of benign prostatic hyperplasia (BPH) and seven cases of adenocarcinoma of prostate (CaP). c‐neu oncogene encodes a transmembrane growth factor receptor that has partial structural homology with EGF receptor, and is overexpressed and amplified in a number of human tumors, specially, breast cancers. Using a monoclonal antibody, AB‐3, which recognizes ‐COOH‐terminal of neu oncoprotein, we have analyzed immunohistochemically the expression of this protein in buffered formalin and Zamboni fluid‐fixed surgically removed tissues. Focal patchy and/or diffused cytoplasmic staining of varying intensity was observed in 34 of 36 BPH cases. Four cases showed cell membrane staining as well (4/36 = 11%). All seven cases of adenocarcinomas had moderate to strong c‐neu immunoreactivity, and two gave a distinct cell membrane‐positive reaction (100%). The available data indicate that prostatic tumors as well as a high percentage of prostatic hyperplasia tissues express c‐neu protein; however, its role in cellular proliferation needs further study. © 1993 Wiley‐Liss, Inc.
Regulation of prostate‐specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth, dihydrotestosterone, and extracellular matrix
Authors: Guo Yue , Pili Roberto , Passaniti Antonino
Published: February 2007

We have examined the role of extracellular matrix (ECM), cell growth, and dihydrotestosterone on the expression of prostate‐specific antigen (PSA) by human prostatic carcinoma cells LNCaP. ECM induced a transient decrease in PSA mRNA even in the presence of growth factors. PSA mRNA, but not actin mRNA, was down‐regulated on ECM in a biphasic manner and was not detected up to 48 hr after culture, but was re‐expressed after 3 days. Cycloheximide and actinomycin D pretreatment did not prevent ECM‐induced down‐regulation of PSA mRNA, while actinomycin D‐treated cells on plastic maintained stable PSA mRNA levels. DNA synthesis and PSA glycoprotein secretion were also transiently suppressed on ECM. LNCaP growth inhibition correlated with decreased glyceraldehyde phosphate dehydrogenase mRNA levels. However, the transient growth suppression induced by ECM was not observed with primary endothelial cells on Matrigel. Down‐regulation of PSA mRNA by culture on Matrigel was reversible upon transfer to a different matrix substrate. Re‐expression was highest on heparan sulfate proteoglycan (4‐fold) and fibronectin or collagen I (2‐fold) compared to plastic or laminin. Our results indicate that the morphology and proliferation of LNCaP cells may be regulated by the ability of ECM to control cellular differentiation and proliferation. © 1994 Wiley‐Liss, Inc.
Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep
Authors: Hahn Robert , Stalberg Holger , Carlström Kjell , Hjelmqvist Hans , Ullman Johan , Rundgren Mats
Published: February 2007

We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls.

Glycine infusions resulted in a four‐fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP‐stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the “transurethral resection (TUR) syndrome”.

The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow‐up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration.

The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance. © 1994 Wiley‐Liss, Inc.
Estramustine potentiates the effects of irradiation on the dunning (R3327) rat prostatic adenocarcinoma
Authors: Widmark Anders , Henriksson Roger , Damber Jan‐Erik , Bergh Anders
Published: February 2007

The present study was designed to determine if estramustine phosphate (EMP) could potentiate the effects of irradiation on the Dunning (R3327) prostatic adenocarcinoma in rats. Two groups of male Copenhagen × Fisher F1 rats carrying bilateral tumors in the flank were used. Irradiation was given with a linear accelerator 6 MV, in a dose of 6 Gy/day for 4 days to the tumor on one side while the tumor on the other side served as control. EMP (360 μg/24 hours) was administered with osmotic pumps to one group of rats for 2 weeks, starting 1 week before irradiation. Tumor growth was calculated by measuring tumor volume, and tumor blood flow was measured 8 weeks after treatment. Irradiation alone effectively delayed tumor growth and EMP enhanced these effects. Tumor blood flow was stimulated by EMP treatment irrespective of radiotherapy. Volume density of tumor epithelium was effectively decreased by irradiation but no significant effects could be seen after EMP. In conclusion, the present study shows that EMP potentiates irradiation on rat prostatic adenocarcinoma, and further evaluation of this therapeutic approach in the clinical treatment of prostatic carcinoma is thus justified. © 1994 Wiley‐Liss, Inc.
Human leukocyte antigen subtype analysis in patients with advanced adenocarcinoma of the prostate
Authors: Akdaş Atif , Türkeri Levent , Alican Yusuf , Şimşek Ferruh , Akoǧlu Tevfik
Published: February 2007

Human leukocyte antigens (HLA) are cell surface glycoproteins that have a significant role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumor cells may escape host immunity. HLA analysis in patients with advanced adenocarcinoma of the prostate revealed the antigens with the highest relative risk factors as DRw52, DRw53, Bw73, DR2, and B5(51). As a result, determination of HLA haplotypes may prove to be useful in determining the men with a higher risk of developing prostate cancer. © 1994 Wiley‐Liss, Inc.
Enhancement of hyperthermic toxicity by lonidarnine in the dunning R3327G rat prostatic adenocarcinoma
Authors: Bloch William E. , Lokeshwar Balakrishna L. , Ferrell Sean M. , Block Norman L.
Published: February 2007

Hyperthermia alone or with radiation is used therapeutically for localized solid tumors. Clinical experience shows that sustained tumor temperature exceeding 45°C damages normal tissue. Any agent that enhances the effects of hyperthermia at or below this temperature may have clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony‐formation assays, cytotoxic effects of each agent alone and in combination were quantified. Lonidamine to 100 μg/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after fractionated hyperthermia revealed a rapid development and decay of thermotolerance. Measurement of cell‐cycle progression following a single dose of hyperthermia revealed a reduction of S‐phase cells, and subsequent accumulation in G1 over 24 hours. Combination treatment of tumor‐bearing rats significantly reduced tumor growth rate when compared with individual agents. These results suggest a potential use of lonidamine in hyperthermic therapy of prostate tumors. © 1994 Wiley‐Liss, Inc.
Influence of culture media on the morphological differentiation of the PC‐3 and DUI45 prostatic neoplastic cell lines
Authors: Camby Isabelle , Dedecker Robert , Danguy André , Pasteels Jean‐Lambert , Kiss Robert , Petein Michel , Etievant Chantal , Van Velthoven Roland
Published: February 2007

The concept of differentiation of prostate cancer in terms of morphonuclear Characteristics and population dynamics was investigated on the PC‐3 and DU145 cell lines. A software based on the concept of Voronoi paving was set up in order to characterize the structure of these cell lines growing in vitro on histological slides. The morphonuclear characteristics were assessed by means of the digital cell image analyses of Feulgen‐stained nuclei. The in vitro “morphonuclear” and “pseudo‐tissular” differentiations of the PC‐3 and DU145 cells were described in terms of the use of various culture media, i.e., media supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and with (or without) platelet‐derived growth factor and dihydrotestosterone (PA10 and PA1 media). The present data reveal that the PC‐3 cell line would be more hormone‐sensitive than the DU145 one. Indeed, decreasing the FCS concentration in the culture medium while adding DHT and PDGF led to marked modifications to the morphonuclear characteristics of the PC‐3 cells, but not to the DU145 cells. These modifications corresponded to an increase in nuclear size occurring concomitantly with chromatin decondensation. In the same way, spectacular modifications in terms of medium‐induced pseudo‐tissular differentiation were observed in the PC‐3 cell line, but not in the DU145 one. Such modifications corresponded to an increase in clone size related to an increase in the mean distances between neighboring cell nuclei in a given clone. Thus, according to the criteria defined in this study, the PC‐3 cell line would seem to maintain a higher degree of differentiation than the DU145 cell line. © 1994 Wiley‐Liss, Inc.
TRPM‐2 gene expression in normal rat ventral prostate following castration and exposure to diethylstilbestrol, flutamide, MK‐906 (finasteride), and coumarin
Authors: Russo Paul , Warner John A. , Huryk Robert , Perez Gisela , Heston W. D. W.
Published: February 2007

TRPM‐2, not normally expressed in the rat ventral prostate, has been identified as an important genetic marker of castration‐induced apoptotic cell death. It is not known whether other agents capable of causing growth inhibition of the rat ventral prostate also induce TRPM‐2 expression. To investigate this further, 270 mature Sprague‐Dawley rats were randomized into one of six groups: control, castration, diethylstilbestrol (DES), flutamide, MK‐906 (finasteride), or coumarin. Five rats per group were sacrificed on days 1, 3, 5, 7, 10, and 21. Serum testosterone, body weights, and prostate weights were determined at each time point. The ventral prostate was removed and cellular RNA extracted. Northern blot analysis using cDNA probes for TRPM‐2 and γ‐actin were performed at each time point.

Only DES significantly decreased rat weights. DES and castration reduced serum testosterone to undetectable levels by the next day. Flutamide caused a 3.0‐ to 4.5‐fold increase in serum testosterone above control. Coumarin and MK‐906 did not affect serum testosterone levels. DES and castration reduced prostate weights to 20% and 6% of control, respectively, while inducing TRPM‐2 expression to a maximum on day 5 of the experiment. DES induced TRPM‐2 expression over a longer duration than did castration, suggesting that more than just the decrease of serum testosterone to castrate levels plays a role in the expression of TRPM‐2. MK‐906, coumarin, and flutamide reduced prostatic weights to a lesser extent (50%, 63%, 71% of control, respectively), but these agents did not induce TRPM‐2 expression at any time during the experiment. TRPM‐2 expression in the rat ventral prostate does not correlate simply with catabolic effects on the prostate. © 1994 Wiley‐Liss, Inc.
Natural course of human benign prostatic hyperplasia with relation to urinary disturbance
Authors: Kitagawa Norikazu , Ichikawa Tomohiko , Akimoto Susumu , Shimazaki Jun
Published: February 2007

To examine the natural course of human benign prostatic hyperplasia (BPH), cases in health care examination with or without slight urinary symptoms were examined by echography. In comparison with these cases, the size of the prostate was examined in patients who received prostatectomy. Prostatic sizes of health care cases varied widely along with increasing age, but could be divided into two groups: increasing or no‐change. According to serial determinations of prostatic sizes in the increasing group, the annual growth rate of the prostate was calculated as 1.65 ± 1.13 and 0.85 ± 0.44 g in men <65 years old and in men ≥65 years old, respectively. Distribution of prostatic sizes as a function of age in health care cases was similar to that in operated patients, showing that the size was not correlated with urinary symptoms or surgical indication. Since uroflow rates decreased along with increasing age in the no‐change group of operated patients, aging was a factor in deterioration of uroflow. Between the increasing and the no‐change groups in health care cases, differences were found in total cholesterol and neutral fat in serum, in addition to gamma‐seminoprotein; the latter may be due to differences in the size of the prostate.

In conclusion, natural course of the prostatic hyperplasia is separated into two groups, increasing and no‐change. Occurrence of urinary symptoms does not simply relate to an increase in prostatic weight but, at least in part, to the aging process. © 1994 Wiley‐Liss, Inc.
An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer
Authors: Vieweg Johannes , Heston Warren D. W. , Fair William R. , Gilboa Eli
Published: February 2007

In order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327‐MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene‐modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327‐MatLyLu tumors. © 1994 Wiley‐Liss, Inc.
Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy individuals and prostate cancer patients
Authors: Silén Åke , Wiklund Bo , Norlén Bo Johan , Nilsson Sten
Published: February 2007

The serological results from apparently healthy individuals and prostate cancer patients were evaluated with a new assay called TPAcyk ELISA. This assay has a biochemical specificity for fragments of cytokeratins 8 and 18, and exhibits a low within‐ and between‐assay imprecision. The data indicate a significant difference between the results of males and females, but no significant age‐dependent relation was found. The cut‐off value (95% specificity) for healthy individuals was estimated to be 1.27 ng/mL (n = 190) for males and 0.95 ng/mL (n = 81) for females. When using a cut‐off value of 1.27 ng/mL, we found a sensitivity for prostate cancer patients with T2‐3 N0M0 of about 20%. For patients with metastatic disease, a sensitivity of 75% was found. A higher sensitivity was obtained with patient sera analyzed with PSA than with TPAcyk, particularly in patients with early stages of the disease. We conclude that the results from this new TPAcyk assay were significantly elevated in patients initially diagnosed with poorly differentiated tumors, that patients with localized tumors exhibited low concentrations, and that patients with metastatic disease showed, on average, 8 times higher concentrations than patients with localized disease. The combination of the TPAcyk and PSA results increased the sensitivity for prostate cancer, particularly in patients with metastatic disease. © 1994 Wiley‐Liss, Inc.
Socioeconomic status, urbanization grade, and prostate cancer
Authors: van der Gulden J. W. J. , Kolk J. J. , Verbeek A. L. M.
Published: February 2007

In a population‐based case‐referent study, carried out in The Netherlands, the relationship between socioeconomic status (SES) and urbanization grade on the one hand and prostate cancer incidence on the other has been investigated. Two explanations for a potential association have been taken into account. First, there is a relationship with SES class (or with urbanization grade) in the past, referring to an effect on the induction or promotion of prostate cancer caused by variation in exposure to particular risk factors. Second, there is a relationship with current SES (or urbanization grade), resulted in differences in medical screening. Study data were obtained by means of a validated mailed questionnaire, which has been completed and returned by 345 cases (with histologically confirmed prostate cancer) and 1,346 referents (patients with benign prostate hyperplasia). The response was 79%. No clear relationship was observed with SES, based on the major job held between 1960‐1970 (the period of cancer induction), nor was this the case with SES based on the longest‐held job (as a proxy for current SES). A slight, but statistically non‐significant, trend was found of higher risks in subjects living in rural areas, with an urban/ rural ratio of 0.79. Considering the results of this study and those of previous studies reviewed in this paper, it might be doubted that any relationship is to be found between prostate cancer risk and SES or urbanization grade. © 1994 Wiley‐Liss, Inc.
Growth, morphology, and morphometry of human hypertrophic prostate cells treated with suramin in vitro
Authors: De Angeli Sergio , Fandella Andrea , Conconi Maria Teresa , Anselmo Giuseppe , Parnigotto Pier Paolo
Published: February 2007

This work studies the effects of suramin on the growth and morphology of cell strain U285, obtained from human prostate hypertrophic tissue and cultured in vitro. The FRAME cytotoxicity test was performed to evaluate the inhibition of growth induced by suramin. Cells were exposed to suramin at the time of seeding and 24 hours later; neutral red was added with and without suramin. An optical microscope connected to a computer‐aided system and a scanning electron microscope were used to study morphological changes induced by suramin. Growth inhibition depends on drug concentration and exposure period. Moreover, the effect of suramin on neutral red uptake is reversible. Suramin 1,000 μM causes the cells to become spheroid, and they fail to form a monolayer. Our data indicate that the addition of suramin during the lag phase decreases the rate of cell proliferation. © 1994 Wiley‐Liss, Inc.
Comparative analysis of epidermal growth factor receptor gene expression and protein product in benign, premalignant, and malignant prostate tissue
Authors: Turkeri Levent N. , Sakr Wael A. , Wykes Susan M. , Grignon David J. , Pontes J. Edson , Macoska Jill A.
Published: February 2007

In order to more clearly define the status of epidermal growth factor receptor (EGFR) in prostate cancer, expression of EGFR transcript and protein was analyzed in paired samples of benign and malignant tissues from 30 radical prostatectomy specimens. Prostate tumors and high grade prostatic intraepithelial neoplasias (PINs) expressed significantly less EGFR protein than benign tissues or low grade PINs (P < 0.001). Expression of EGFR mRNA was analyzed in a subset of the same samples, and was higher in more prostate tumors than benign specimens (P < 0.05). However, differences in mean mRNA expression between malignant and benign tissues were not significant. EGFR mRNA was expressed at moderate or low levels in equivalent numbers of PIN lesions. These results suggest that, although EGFR mRNA expression is somewhat elevated in prostate tumors, EGFR protein expression may be down‐regulated in the same malignant tissues. Furthermore, our data demonstrate phenotypic similarity between prostate tumors and high grade PIN at the level of EGFR protein expression. © 1994 Wiley‐Liss, Inc.
Western blot assay for prostate‐specific membrane antigen in serum of prostate cancer patients
Authors: Rochon Yvan P. , Horoszewicz Julius S. , Boynton Alton L. , Holmes Eric H. , Barren Robert J. , Erickson Sheila J. , Kenny Gerald M. , Murphy Gerald P.
Published: February 2007

There is a need for the development of new diagnostic tools for the early detection of prostate cancer. A candidate molecule for a new screening test is a prostate‐specific membrane antigen (PSM) recognized by the monoclonal antibody 7E11.C5. We carried out studies aimed at identifying PSM in the serum of normal and benign prostatic hyperplasia (BPH) donors and patients with adenocarcinoma of the prostate, in order to judge whether the development of a serum assay using this marker was feasible. By Western blotting, we found significant levels of PSM in serum samples from prostatic cancer patients, in the seminal fluid of pooled normal donors, in BPH patients, and in normal male sera. Similar to prostate‐specific antigen (PSA), PSM was present in seminal plasma in higher concentrations than in serum, and PSM levels in prostatic cancer patients were significantly higher than in normal controls. These data suggest that the development of an assay utilizing the PSM and new monoclonal antibodies directed against the antigen, could provide a feasible test for prostatic cancers. © 1994 Wiley‐Liss, Inc.
Accumulation of the p53 protein occurs more frequently in metastatic than in localized prostatic adenocarcinomas
Authors: Myers Russell B. , Oelschlager Denise , Srivastava Sudhir , Grizzle William E.
Published: February 2007

Mutations of the p53 gene result in increased stability and accumulation of the p53 protein, permitting p53 protein detection by immunohistochemical techniques. We have utilized immunohistochemistry to examine accumulation of the p53 protein at various stages of progression in prostatic adenocarcinomas. p53 protein accumulation was detected using the monoclonal antibody BP53‐12‐1 in 3 of 28 (11%) localized prostatic adenocarcinomas, and in prostatic intraepithelial neoplasia (PIN) in 1 of 16 (6%) specimens. In contrast, p53 protein was detected in 9 of 16 (56%) primary prostatic adenocarcinomas that were metastatic (stage D), and in 10 of 18 (56%) matching metastases to lymph nodes from these same patients. Thus, we observed a higher incidence of p53 protein accumulation in matching primary and metastatic lesions of patients with stage D adenocarcinoma than in localized (nonmetastatic) adenocarcinomas. We also found that an antigen retrieval solution (ARS) aided in the detection of p53 protein accumulation in prostatic adenocarcinomas. The results indicate that accumulation of p53 protein occurs prior to metastasis, and identifies a subclass of prostatic adenocarcinomas that express a high potential for metastasis. © 1994 Wiley‐Liss, Inc.
Proliferation‐dependent vs. independent programmed cell death of prostatic cancer cells involves distinct gene regulation
Authors: Furuya Yuzo , Isaacs John T.
Published: February 2007

Androgen‐independent Dunning R‐3327 AT‐3 rat prostatic cancer cells can be induced to undergo programmed cell death in either a proliferation‐dependent or independent manner depending upon the therapeutic agent used. In the present study, 5‐fluorodeoxyuridine (5‐FrdU) was used to induce proliferation‐dependent death of the AT‐3 cells via its ability to inhibit thymidylate synthetase. Ionomycin and thapsigargin were used to induce proliferation‐independent death of these cells via their ability to sustain an elevation in intracellular free Ca2+. Based upon the temporal sequence of DNA fragmentation, morphologic changes, and loss of cell viability, each of the three test agents, at the doses used, induces the programmed death of AT‐3 cells with essentially identical kinetics. Based upon these similarities, comparisons of the pattern of gene expression during the proliferation‐dependent (i.e., 5‐FrdU‐induced) vs. proliferation‐independent (i.e., ionomycin and thapsigargin‐induced) programmed death of AT‐3 cells allow identification of genes whose enhanced expression is involved in the initiation vs. completion of programmed cell death. Based upon this approach, enhanced H‐ras and TRPM‐2 expression is associated with initiation of proliferation‐dependent programmed death of AT‐3 cells while enhanced c‐myc, calmdulin, and α‐prothymosin expression is associated with initiation of proliferation‐independent programmed death of these cells. In contrast, enhanced expression of glucose‐regulated 78 kilodalton and tissue transglutaminase genes are associated with the completion of programmed cell death, since their expression is enhanced in both proliferation‐dependent and independent programmed cell death of AT‐3 cells. © 1994 Wiley‐Liss, Inc.
Mitotic activity and prognosis in prostatic adenocarcinoma
Authors: Vesalainen S. , Talja M. , Lipponen Pertti , Syrjänen K.
Published: February 2007

Mitotic figures were quantitated by two different methods (number of mitotic figures in 10 high power fields, MI; number of mitotic figures/mm2of neoplastic epithelium, M/V) in a series of 303 prostatic adenocarcinomas, and the results were related to clinical and histological features as well as to prognosis. Gleason score and mitotic indices were significantly interrelated. Invasive T3–4 tumors showed higher mitosis counts than did the local ones, and metastasis at the time of diagnosis was related to mitotic indices as well. Progression and progression‐free survival were related significantly to Gleason score and mitoric indices. In univariate survival analysis, T‐category, M‐category, Gleason score, MI, and M/V were significant prognostic factors. In multivariate analysis, independent predictors of survival were M‐category, T‐category, Gleason score, patient age, and the M/V index. If the Gleason score was not included, M/V included all the available prognostic information in T1–2M0 carcinomas. The results show that, in addition to the conventional Gleason grading system, mitotic indices are useful prognostic parameters while evaluating the long‐term prognosis in prostatic adenocarcinoma.
Evaluation of three different AgNOR counting methods in advanced carcinoma of the prostate
Authors: Ahiskah Rengin , Ekicioǧlu Gülsün , Küllü Sevgi , Alican Yusuf , Çevik Ibrahim , Akdaş Atif
Published: February 2007

We applied the silver staining of nucleolar organizer regions (AgNOR) technique to the pretreatment biopsies of 50 cases of advanced prostate cancer. Three different counting methods were utilized in the enumeration of AgNORs. All methods yielded statistically significant differences of mean AgNOR counts of groups defined by high and low WHO, and by Gleason grades. However, there was overlap among groups, and further analysis of counts by grouping of patients according to their stage, response to treatment, and prognosis was not conclusive. Replicate counts were performed in 10 cases. While intraobserver reproducibility was high by all methods, only the second counting method yielded nonsignificant interobserver variability. There was a significant intratumoral heterogeneity of AgNOR scores. Lack of technical standardization, low reproducibility, and lack of correlation with prognosis limit the use of AgNOR counts in advanced carcinoma of the prostate. &1995 Wiley‐Liss, Inc.