bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of isosmotic and hyperosmotic glycine solutions on the fluid balance in conscious sheep
Authors: Hahn Robert , Hjelmqvist Hans , Rundgren Mats
Published: February 2007

Glycine 0.55 g · kg−1 was given as an isosmotic (285 mosmol · kg−1) and a hyperosmotic (approx. 3,000 mosmol · kg−1) solution by intravenous infusion during 30 min to six euhydrated ewes. Urine and blood samples were collected, and the distribution of the administrated water between the intra‐ and extracellular fluids (ICF and ECF) was calculated for up to 150 min after the infusions. Both solutions produced an osmotic diuresis with a marked increase of the urinary excretion of sodium, potassium, and amino acids. A paradoxical increase of the plasma vasopressin concentration occurred from the isosmotic but not from the hyperosmotic glycine solution. At the end of the follow‐up period, the isosmotic glycine solution had resulted in hyperhydration of the ICF and the hyperosmotic solution in dehydration of the ICF, whereas with both fluids, the ECF resumed the same volume as before the experiments.
Amplification, rearrangement, and elevated expression of c‐myc in the human prostatic carcinoma cell line LNCaP
Authors: Nag Abhijit , Smith Roy G.
Published: February 2007

We have investigated the structure and expression of the c‐myc proto‐oncogene in DNA isolated from the immortal cell line LNCaP. This cell line was derived from a lymph node metastasis of human prostate cancer. Msp I digest of LNCaP DNA when hybridized to a human c‐myc probe showed a 1.45 kb band of intensity about two‐fold greater than that observed in normal lymphocytes. In addition, the LNCaP cells contain rearranged and amplified c‐myc structures which are not present in normal lymphocytes. Quantitation of these bands by scanning densitometry is consistant with an approximately 10‐fold amplification of c‐myc. To determine whether this amplification was accompanied by increased expression, RNA was isolated from these cells and compared to RNA isolated from a control cell line in which c‐myc was not amplified. Northern blot analysis showed that the RNA transcripts from LNCaP cells were approximately 50‐fold higher. Although androgens modulate the cell growth of LNCaP, there was no change in the level of c‐myc RNA transcripts in serum‐free medium in the presence or absence of androgens. Further investigation to determine whether altered structure, amplification, and overexpression of c‐myc constitute a common characteristic of metastatic human prostate cancer might prove profitable in understanding this disease.
Incidence and prognostic significance of lymphatic and vascular invasion in radical prostatectomy specimens
Authors: Bahnson Robert R. , Dresner Stephen M. , Gooding William , Becich Michael J.
Published: February 2007

A review of 55 radical prostatectomy specimens from patients with clinically localized carcinoma of the prostate was performed. Blinded review of slides was performed by a single pathologist and urologist. Criteria for invasion were encroachment by tumor of the lymphatic or vascular lumen and evidence of reaction around or in the lymphatic or vascular channel. Notation was made of the degree and location of lymphatic and vascular invasion. All patients had a minimum of 5 years of follow‐up. Twenty‐one of 55 (38%) patients either had lymphatic or vascular invasion, and seven (13%) had both findings. In the majority of these patients the degree of invasion was rare (71%), while multifocal (19%) and diffuse (10%) involvement were seen less frequently. Nine patients experienced either progression of their tumors or death from disease. Those patients with evidence of lymphatic or vascular invasion had a fourfold greater incidence of progression and or death. However, the presence of lymphatic or vascular invasion was clearly related to both tumor grade and stage, and multivariate statistical analysis demonstrated that its prognostic significance was dependent upon tumor grade.
Patterns of metastasis by the human prostate cancer cell line PC‐3 in athymic nude mice
Authors: Shevrin Daniel H. , Gorny Kathleen I. , Kukreja Subhash C.
Published: February 2007

Cells from the PC‐3 human prostate cancer cell line were evaluated in athymic nude mice in order to determine the influence of size of the primary tumor and site of innoculation on the incidence and pattern of metastasis. At autopsy, all organs, including the skeleton, were evaluated for metastasis. Subcutaneous injections resulted in metastases to the draining axillary lymph node and lungs (56% and 13%, respectively), and were correlated with size of the primary tumor. Tail vein injection resulted in a high incidence of lung metastasis, while injection into the peritoneal space, spleen, and seminal vesicles resulted in intraabdominal tumor growth, liver metastasis, and large tumors within the seminal vesicles, respectively. Skeletal metastases were not observed in any of the animals studied. We conclude that injection of PC‐3 cells into various sites results in different patterns of metastasis, but may not constitute an entirely suitable animal model of human prostate cancer due to the lack of metastasis to the skeleton.
Conventional chemotherapeutic agents combined with DMSO or DFMO in treatment of rat prostate carcinoma
Authors: Mickey Don D. , Carvalho Luciano , Foulkes Kathleen
Published: February 2007

Chemotherapy for prostatic carcinoma is usually reserved for those patients who have failed conventional therapy. These patients generally are in poor health and tolerate chemotherapy poorly. If doses of conventional agents could be decreased without altering cytotoxic activity, then conventional chemotherapy could become an attractive treatment modality.

Dimethylsulfoxide and difluoromethylornithine have been shown to induce differentiation in some tumor systems. Growth alteration effects of these two agents were investigated individually and in association with conventional chemotherapeutic agents cyclophosphamide, cisplatin, and fluorouracil in an experimental prostatic cancer model. Copenhagen rats had subcutaneous tumors induced by injections of cells cultured in vitro from a subline of the Dunning rat prostatic tumor, MAT LyLu. Treatment with chemotherapeutic agents individually and associated with differentiation agents was initiated when tumors were palpable. Tumor growth rates and rat body weights were monitored in all groups.

The differentiation agents used singly were not able to retard significantly tumor growth rates. In higher doses, each conventional agent used singly significantly retarded tumor growth. Used in combination, the differentiation agents induced cytodestructive properties of lower doses of conventional agents, but some combinations also increased host toxicity. These data suggest that differentiation agents may provide additional antineoplastic benefits when administered in combination with selected chemotherapeutic agents in the management of prostatic cancer.
Crystalloids in latent prostatic carcinoma
Authors: Furusato Masakuni , Kato Hiroyuki , Takashashi Hiroyuki , Wakui Shin , Tokuda Tadaaki , Kawashima Yoshio , Aizawa Shigeo , Mostofi F. K.
Published: February 2007

Intraglandular crystalloids have been studied in 108 cases of latent prostatic carcinoma collected at autopsy. The morphological features of these crystalloids are essentially the same as reported by previous authors. The crystalloids were identified in 62.0% of cases over age 50 years. They were present in 76.9% of cases in the seventh decade, the highest prevalence among the decades. The number of crystalloids relative to the number of malignant glands tended to be inveresly proportional to the size of the carcinoma. We conclude that crystalloids are related to the early development of prostatic carcinoma.
Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758)
Authors: Neubauer Blake Lee , Biser Peggy , David Jones C. , Mariotti Angelo , Hoover Dennis M. , Thornton Ted , Thornton Mark O. , Goode Robin L.
Published: February 2007

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY 156758; [6‐hydroxy‐2‐(4‐hydroxyphenyl)benzo(b) thien‐3‐yl] [4‐(2‐1‐piperidinyl) ethoxy] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen‐maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration‐dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen‐induced hyperplastic response of the SVM, whereas no interference with androgen‐induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen‐sensitive SVE as well as the androge/estrogen‐sensitive SVM. Keoxifene‐induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.
Proteolytic cleavage of high‐molecular‐weight microtubule‐associated proteins by the prostatic estramustine‐binding protein
Authors: Rutberg Mikael , Fridén Bo , Björk Per , Wallin Margareta
Published: February 2007

The rat prostatic estramustine‐binding protein was found to inhibit assembly of microtubules in a concentration‐dependent manner. The inhibition was caused by a proteolytic cleavage of the high‐molecular‐weight microtubule associated proteins (MAPS), as judged by sodium dodecyl sulfate‐gel electrophoresis. A proteolytic fragment with a molecular weight of 199 kDa appeared, which remained bound to the assembled microtubules. Fragments of lower molecular weights (170, 149 kDa) were also found, but they did not bind to the assembled microtubules. Fragments with identical molecular weights were also found after incubation of purified MAP2 with the estramustine‐binding protein, indicating that the fragments derive from MAP2. No proteolysis of tubulin, albumin, or casein was found. The estramustine‐binding protein was found to be a Zn2+ ‐dependent protease; it was inhibited by EDTA and reactivated by addition of 1 mM Zn2+. Its proteolytic activity was not affected by binding of the antimitotic drug estramustine.
Separation of mature rat ventral prostate epithelial and fibroblast cells
Authors: Montpetit Michael L. , Tenniswood Martin P.
Published: February 2007

Several techniques for the separation of rat ventral prostate cells, using density gradient centrifugation or mechanical means have been published, yielding fibroblast and epithelial cell populations of varying purities and viability. These techniques are often tedious, yield relatively limited numbers of cells, demand considerable technical expertise, and result in the isolation of cells of limited viability. Two techniques for the isolation and establishment of epithelial and fibroblast cell cultures from mature rat ventral prostate are described here. Collagenase/trypsin digestion of the tissue yields a single‐cell suspension of both cell types that are separated on Percoll isopycnic centrifugation gradients. A continuous gradient system allows for the separation of a greater number of cells with very high degrees of purity. A second technique based on a step‐gradient system produces reproducible subfractionation of the epithelial cell component of the prostate within a considerable shorter period of time. An improved medium for plating epithelial and fibroblast cells has also been developed. The separated cells are plated on collagen and/or fibronectin‐coated dishes in a serum‐free plating medium that is later replaced with a serum containing growth medium. The plating medium greatly increases the plating efficiency of the isolated cell types, particularly the epithelial cells.
Rectal palpation and transrectal fine needle aspiration of the prostate in the monitoring of prostate cancer: A study of 59 patients during treatment with estramustine phosphate or estrogens
Authors: Hedlund Per Olov , Das Dilip , Löwhagen Torsten , Esposti Pier
Published: February 2007

Fifty‐nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal palpation and fine needle aspiration cytology (FNAC) at 6 month intervals for periods ranging from 6 to 120 months (median follow‐up, 48 months). The cytologic impressions and palpatory findings were divided into four categories, respectively, ranging from benign to clearly malignant. Cytologic material and palpatory descriptions suitable for evaluation were available for 306 follow‐up examinations, with a mean number of follow‐up examinations per patient of five (range, 1‐13). Tumor relapse was noted in 26 patients and was diagnosed at the same time by FNAC and palpation in six patients. In 16 of the patients tumor progression was first noted by cytology, and in four patients relapse was first detected by rectal palpation. Different patterns of cytologic and palpatory findings during the development of remission and progression of the tumors and drawbacks of the methods are discussed.
Binding and functional properties of doxazosin in the human prostate adenoma and canine brain
Authors: Lepor Herbert , Baumann Mary , Shapiro Ellen
Published: February 2007

The binding and functional properties of doxazosin were characterized in the canine brain and human prostate. 3H‐Doxazosin binding sites were characterized in canine brain and human prostate homogenates using saturation experiments. The binding of 3H‐doxazosin in the canine brain was consistently saturable and of high affinity. The mean equilibrium dissociation constant (Kd) and density (Bmax) of 3H‐doxazosin binding sites in the canine brain were 0.19 nM and 2.17 fmol/mg wet wt, respectively. The binding of 3H‐doxazosin in human prostate homogenates was not consistently linear owing to a relatively high proportion of nonspecific doxazosin binding sites. The mean Kd and Bmax of 3H‐doxazosin binding sites in the prostate determined from the saturation experiments yielding linear Scatchard plots were 0.2 nM and 0.51 fmol/mg wet wt. The pharmacology of doxazosin binding sites was further characterized in the canine brain using competitive binding experiments. The rank order of IC50corr values for norepinephrine, clonidine, yohimbine, terazosin, and prazosin indicated that doxazosin binds selectively to alpha1 and alpha2 adrenergic binding sites. The relative affinity of unlabeled doxazosin for alpha1 and alpha2 binding sites in the human prostate was determined by displacing 125I‐Heat or 3H‐rauwolscine with varying concentrations of unlabeled doxazosin. The affinity of doxazosin for alpha1 binding sites in the prostate adenoma was approximately 100‐fold greater than its affinity for alpha2 binding sites. The potency of doxazosin for inhibiting phenylephrineinduced contractions in the prostate indicated that prostate smooth muscle contraction is mediated by alpha1 adrenoceptors.
The prostate: An increasing medical problem
Authors: Ballentine Carter H. , Coffey Donald S.
Published: February 2007

The prostate gland is the major site of medical problems in the U.S. male. Surgery for benign prostatic hyperplasia is the most common surgical procedure performed in males, and the total cost for this surgery exceeds 1 billion dollars per year. The incidence of and mortality from prostate cancer are increasing yearly. Prostate cancer now exceeds lung cancer as the most commonly diagnosed cancer in males and is the second leading cause of male cancer deaths. Of all tumors, the prevalence of prostate cancer increases the most rapidly with age. A shift in age distribution favoring an older population will lead to an increase in the number of patients diagnosed with prostate cancer in the United States. It is estimated that by the year 2000 there will be a 37% increase in prostate cancer deaths per year and a 90% increase in prostate cancer cases per year. Although the factors responsible for the development and progression of prostate cancer to a clinically manifest form are not known, there is evidence that environmental factors may play a role. It will be important for the future to focus on the etiological factors that may lead to a decrease in the prevalence of prostatic tumors.
Effects of intravenous infusion of human prostate tissue substances in dogs
Authors: O'Donnell Pat D.
Published: February 2007

Symptoms of postresection syndromes following transurethral prostatectomy have been associated with a transient increase in serum acid phosphatase due to intraoperative absorption of prostate tissue substances. Factors associated with postoperative syndromes include intraoperative absorption of irrigant solution, intraoperative blood loss, and introperative absorption of prostate tissue substance. An animal model was used in this study to determine the isolated physiologic effects of intravenous infusion of a saline prostate tissue extract using an infusion schedule comparable to that of transurethral prostate resection. Twenty‐four animals received either normal saline infusion (control) or saline prostate tissue extract infusion (experimental). The experimental group showed a significant decrease in fibrinogen, platelet count, white blood count, activated clotting time, and plasma volume. These results suggest that the isolated effects of intravascular absorption of prostate tissue substances are due to disseminated intravascular coagulation, most likely resulting from tissue thromboplastin and activation of plasminogen.
Primary explant culture of human prostate tissue: A model for the study of prostate physiology and pathology
Authors: Merchant Donald J.
Published: February 2007

An explant of human prostate tissue containing viable acini will give rise in vitro to an outgrowth of epithelial cells of presumed basal cell origin. These cells can be passaged by trypsinization, undergo numerous population doublings (up to 50–60), and attempt a normal pattern of differentiation, which may succeed, to varying degrees, depending on conditions of culture. The system can serve as a useful model for analysis of the role of hormones, growth factors, cytoskeletal elements, cell‐cell interactions, and of the basement membrane both in normal physiology and in pathology of the prostate. The system also should prove useful in the evaluation of the possible roles of chemical carcinogens, radiation, and viral or cellular oncogenes in carcinogenesis. Moreover, the model system should be useful in the evaluation of chemical, physical, or biological agents for treatment or prevention of prostate cancers.
Changes in tumor characteristics during progression of the R3327 HI experimental prostatic carcinoma
Authors: Mobbs B. G. , Johnson I. E.
Published: February 2007

The R3327 HI experimental prostatic carcinoma was serially transplanted through six generations of castrated host rats to examine changes in the capacity to synthesize progesterone receptor (PgR) in response to diethylstilbestrol (DES) stimulation during progression from a well‐differentiated state containing a significant stromal component to a poorly differentiated state with virtually no stroma. During progression, changes in growth rate and histopathology occurred in stepwise fashion, the most marked changes being observed between the first and second and between the fourth and fifth generations. The capacity for PgR synthesis in response to DES treatment fell progressively, but did not reach statistical significance during the first four generations. By the sixth generation, the stromal component had virtually disappeared, and no estrogen receptor (ER) or PgR was detectable. During the course of the investigation, a monoclonal antibody that reacts with rat PgR became available, and immunohistochemistry with this antibody confirmed that DES‐induced PgR was present in stromal cells. We conclude that this work supports the hypothesis that prostatic stroma is a target tissue for estrogen and that this model may be useful for the investigation of other events associated with progression.
Further studies on the synthesis and secretion of inhibin‐like material by rat ventral prostate explants in vitro
Authors: Kharbanda Kusum , Duraiswami S.
Published: February 2007

To authenticate further the testicular androgen independent status of synthesis and secretion of inhibin‐like material by the rat ventral prostate, explants of this organ were maintained for a period of 6 days in vitro, altering the kind of medium used for culture. The various spent media had significant inhibin‐like activity despite the absence of sera supplement in some cases.
Expression of endogenous receptors for neoglycoproteins in dunning R3327 rat prostatic carcinoma
Authors: Sinowatz F. , Gabius H.‐J. , Hellmann K. P. , Amselgruber W. , Schneider M. R.
Published: February 2007

An important animal model for human prostatic adenocarcinoma is the Dunning R3327 rat carcinoma. In the present study this tumor was further characterized by analyzing the expression of endogenous sugar‐binding proteins using glycohistochemistry and immuno‐cytochemistry as well as affinity chromatography and gel electrophoresis. Our glycohis‐tochemical and glycobiochemical results provide evidence for the presence of specific receptors for various carbohydrate moieties. Remarkably, basal cells of the Dunning tumor contain an endogenous lectin with specificity for β‐galactosides that is not found in basal cells of the normal rat prostate. This finding was corroborated using polyclonal antibodies against an immunologically related β‐galactoside‐specific lectin from bovine heart. Basal cells of prostatic carcinoma may therefore behave different from normal basal cells. This difference could have a significant impact on the development of prostatic cancer.
Epidemiologic evidence regarding predisposing factors to prostate cancer
Authors: Carter Bob S. , Ballantine Carter H. , Isaacs John T.
Published: February 2007

In 1990, prostate cancer will be the most common cancer diagnosed in U.S. men and will be the second‐leading cause of cancer mortality in these men. One in ten U.S. men will develop prostate cancer in his lifetime. Twenty thousand prostate cancer cases occur each year in men under the age of 65. The average number of years of life lost for a man dying of prostate cancer is nine. In addition, both incidence and mortality of prostate cancer are increasing. A review of the literature regarding prostate cancer is timely in light of recent studies examining possible predisposing factors for this disease. In this review, a framework for understanding genetic and environmental factors which may predispose to prostate cancer is presented. The identification of factors which predispose to clinical prostate cancer offers the possibility of lowering the incidence and mortality of prostate cancer in the United States. Epidemiologic evidence regarding possible predisposing factors to prostate cancer is reviewed.
Prostate cancer occurring in identical twins: A case report
Authors: Spaas Philippe G. , Bagshaw Malcolm A.
Published: February 2007

Prostatic cancer, which is an age‐associated and androgen‐dependent cancer, is the most common malignancy in males in the United States. Although the etiologic factors in prostate cancer are not clear, increased male sexual activity on a hormonal basis [1], a viral‐venereal connection [2], and air pollution [3] have been hypothesized. Genetic factors are suggested by racial variation [4] and by familial incidence of prostate cancer; however, with family studies alone, it is not possible to decide if it is genetically determined or if it is due to a greater than average similarity in environment. For cancer in general, the study of concordance rates among populations of twins has failed to establish a precise role for inheritance, but more detailed study of individual types of tumors in twins may reveal a genetic connection [5]. The following report describes the second recorded monozygotic twin set concordant for prostate cancer.
Antitumoral effects of R 75251 on the growth of transplantable R3327 prostatic adenocarcinoma in rats
Authors: Van Ginckel R. , De Coster R. , Wouters W. , Vanherck W. , Van Veer R. Der , Goeminne N. , Jagers E. , Van Cauteren H. , Wouters L. , Distelmans W. , Janssen P. A. J.
Published: February 2007

The antitumoral activity of a novel imidazole derivative, R 75251, has been studied in the androgen‐dependent R3327G Dunning prostate adenocarcinoma grafted subcutaneously in syngeneic rats. Dietary application resulting approximately in dose levels of 80, 120, and 160 mg/kg reduced tumor weight by 66, 81, and 79%, respectively. This effect was not significantly different from that measured after castration (‐ 82%). In intact animals, however, serum testosterone levels were almost not affected by R 75 251 treatment while LH levels rose two‐ to threefold. In castrated rats a tenfold increase in LH was observed. Moreover, prostate and seminal vesicles weights decreased much less after R 75 251 treatment than after castration. In castrated animals, treatment with R 75 251 induced a slight, non‐significant reduction in tumor weight (‐ 36%) compared with castration alone.

In castrated animals, tumor growth was restored by exogenous administration of testosterone. In such animals R 75 251 also significantly reduced tumor weight by 57%.

Similar results were obtained with Dunning R3327G prostate adenocarcinoma grafted beneath the renal capsule in male syngeneic rats receiving twice daily orally by gavage a dose of 80 mg/kg of R 75 251.

These data suggest that R 75 251 exerts an antitumoral effect independent of its inhibition of androgen biosynthesis.
Prolactin directly stimulates citrate production and mitochondrial aspartate aminotransferase of prostate epithelial cells
Authors: Franklin R. B. , Costello L. C.
Published: February 2007

Prolactin, in vitro, significantly increased citrate production, mAAT (mitochondrial aspartate aminotransferase) and pmAAT (precursor form of mAAT) activity of prostate epithelial cells derived from rat lateral prostate (LP) and pig prostate cultures. In contrast, prolactin had no effect on the cytosolic isozyme, cAAT. This prolactin effect appeared to be independent of testosterone. The phorbol ester TPA (12‐O‐tetradecanoyl‐phorbol‐13‐acetate) induced the same effects as prolactin thereby indicating the involvement of protein kinase C. This report demonstrates that prolactin directly regulates citrate production of prostate epithelial cells and the availability of an in vitro model to elucidate the mechanism of action of prolactin.
Species‐ and organ‐specificity of secretory proteins derived from human prostate and seminal vesicles
Authors: Aumüller G. , Seitz J. , Lilja H. , Abrahamsson P.‐A. , Von Kammer H. Der , Scheit K.‐H.
Published: February 2007

Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Prostate‐Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against β‐MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, β‐MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non‐primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for β‐MSP. The epithelium of the rat dorsal prostate showed a slight cross‐reactivity with the monoclonal antibody against β‐MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species‐dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid.
Fine needle aspiration biopsy of the prostate gland: Our experience concerning 101 cases with histological follow‐up
Authors: Polito M. , Alberti R. , Muzzonigro G. , Baldi A. , Diambrini M. , Vecchi A.
Published: February 2007

Our experience concerning 605 fine needle aspiration (FNA) biopsies performed between 1985 and 1988 is reported.

FNA specimens of the prostate gland were compared to histological material in 101 cases: 37 patients underwent suprapubic prostatectomy, 15 radical prostatectomy, 28 transurethral resection, and 21 core needle biopsies.

Adenocarcinoma was correctly diagnosed by using cytology in 39 out of 40 cases; benign prostatic hypertrophy was confirmed by histology in 54 out of 57 cytologically benign cases.

The absolute sensitivity of the FNA biopsy was 98.2%; specificity was 98.1%; efficiency was 96%; and false negative rate was 6.6%.

Our data support the value of transrectal aspiration biopsy as a precise and easy method for diagnosing prostatic cancer; the low false negative rate and the high number of correct diagnoses underline the great accuracy of the method.
Anti‐androgenic effects of Win 49,596 on development of the neonatal mouse bulbourethral gland in culture
Authors: Cooke Paul S. , Reicherts Michael R.
Published: February 2007

The effects of the anti‐androgen Win 49,596, a steroidal androgen receptor antagonist, on the testosterone (T) dependent development of neonatal mouse bulbourethral glands (BUGs) were examined in vitro. Day of birth (day 0) BUGs were grown in organ culture for 6 days in Dulbecco's modified Eagle's medium:Ham's F‐12 media (1:1, volume/volume) with 10% fetal calf serum. Cultures were grown with or without T (10 nM) and various concentrations of Win 49,596 (0–57.6 μm). The DNA content of BUGs grown with T alone increased 4‐fold over the culture period and the epithelium grew and branched extensively; without T only minimal growth and epithelial morphogenesis occurred. In the presence of T, Win 49,596 inhibited development in a dose‐dependent manner, with an ED50 of 0.8 μM; concentrations at or above 3.6 μM produced maximal inhibition of development. Win 49,596 alone at 14.4 μM did not stimulate BUG growth, demonstrating a lack of agonist activity. BUGs grown for 3 days with Win 49,596 and T, then an additional 6 days with only T, did not resume development. In summary, Win 49,596 produced a dose‐dependent suppression of BUG development in vitro, and was not androgenic. Additionally, the inhibitory effects of Win 49,596 persist for at least 6 days following cessation of treatment.
Epidemiology of prostatic cancer: A case‐control study
Authors: Fincham Shirley M. , Hill Gerry B. , Hanson John , Wijayasinghe Chandrani
Published: February 2007

A population‐based case‐control study of prostatic cancer in Alberta was undertaken to determine the risk factors associated with the disease. Cases were 382 newly diagnosed prostatic cancer patients and 625 controls, group‐matched to the anticipated age distribution of the cases, chosen at random from the health insurance roster. Subjects were interviewed in their homes by using a pre‐tested questionnaire including questions related to ethnic group, education, puberty, marital history, family history, residence, water supply, smoking, and diet.

Factors significantly related to the risk of developing prostatic cancer included ethnic group (British high, Ukrainian low), education (elementary high, university low), age at first marriage (early high, late low), family history (high risk for those with relatives with prostatic cancer), and increased masculinity among the children of cases.

The results with respect to smoking, occupation, medical history, birthplace, residence, water supply, and diet were generally negative.
Experimental prostatitis in nonhuman primates: I. Bacterial adherence in the urethra
Authors: Dilworth J. Patrick , Neal Durwood E. , Fussell Everett N. , Roberts James A.
Published: February 2007

Both man and monkey possess urothelial (transitional cell) receptors for P‐fimbriae of Escherichia coli; however, the male urethra has pseudostratified columnar cells. We studied adherence using scanning electron microscopy and found that P‐fimbriae were the principal mediators of adherence to these cells as well. The monkey, therefore, should be a good model for the study of the ascending route of infection in prostatitis, the route thought to occur in man.
Dunning rat prostate tumors and cultured cell lines fail to express human prostate carcinoma‐associated antigens
Authors: Newhall Kathleen R. , Isaacs John T. , Wright George L.
Published: February 2007

The objective of this study was to determine if human prostate carcinoma‐associated tumor markers were expressed by Dunning rat prostate carcinomas. Frozen and formalin‐fixed paraffin‐embedded tissues from 12 different sublines of Dunning tumors were evaluated for marker expression by immunoperoxidase staining by using a panel of 9 monoclonal antibodies, including antibodies against human PAP and PSA. None of the Dunning tumors were found to express any of the human prostate tumor markers. Both fixed and live immunofluorescent assays were performed on 5 cultured Dunning tumor cell lines, evaluated either as single cells or as monolayers. As with the Dunning tumor tissues, none of the cell cultures expressed any of the 9 human prostate tumor markers. The lack of antigen expression by the Dunning tumor tissues and cell lines suggests that these human prostate tumor markers are quite species specific. These results limit the use of the Dunning prostate tumors as models to explore the preclinical application of these human prostate carcinoma‐associated monoclonal antibodies and their target antigens.
Differential effects of growth factor antagonists on neoplastic and normal prostatic cells
Authors: Morton Ronald A. , Isaacs John T. , Isaacs William B.
Published: February 2007

Growth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen‐dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen‐independent AT‐2 subline of the Dunning R‐3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT‐2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells.
Evaluation of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer
Authors: Juniewicz P. E. , Fetrow N. , Marinelli J. , Wolf M. , Young E. , Lamb J. , Isaacs J. T.
Published: February 2007

A series of experiments were conducted to evaluate the effects of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer. In the first experiment, oral administration of Win 49,596 at doses of 30, 100, or 300 mg/kg/day for 28 days inhibited (P <0.05) the growth of the androgen‐sensitive PAP variant of the Dunning R‐3327 prostatic carcinoma in intact male rats relative to intact controls. The degree of inhibition at 100 and 300 mg/kg/day Win 49,596 was similar (P >0.10) to that observed in castrate controls as well as in intact rats administered the nonsteroidal androgen receptor antagonist flutamide orally at 15 mg/kg/day. Castration as well as treatment with either Win 49,596 or flutamide also decreased (P <0.05) the weight of the prostate in tumor‐bearing animals.

Additional studies were conducted to determine the effect of Win 49,596 on the growth of the androgen‐dependent PC‐82 human prostatic carcinoma xenografted into athymic nude male mice. Oral administration of Win 49,596 at 30, 100, or 300 mg/kg/day for 35 days inhibited (P <0.05) tumor growth relative to intact controls. The degree of tumor inhibition was similar to that observed in intact male mice administered the nonsteroidal androgen receptor antagonist flutamide orally at 30 mg/kg/day but was less than that observed following castration. Ventral prostate weights were also reduced (P <0.05) in castrate mice as well as in intact mice administered either Win 49,596 or flutamide. In the last experiment, at equivalent total daily dosages of either 150 or 300 mg/kg/day Win 49,596, twice a day (BID) dosing was more effective than once a day (SID) dosing in inhibiting tumor growth. The inhibitory effects of Win 49,596 at 150 mg/kg BID on tumor growth were similar to those observed following castration. Although Win 49,596 treatment reduced (P <0.05) ventral prostate weights relative to intact controls, there was no difference (P >0.10) between SID vs. BID dosing.

Based on the results of these studies and subject to further testing, Win 49,596 may have utility in the treatment of hormonally dependent metastatic prostate cancer in humans.
Regional differences in the prostate of the neonatally estrogenized mouse
Authors: Pylkkänen L. , Santti R. , Newbold R. , McLachlan J. A.
Published: February 2007

Neonatal estrogenization of the mouse with diethylstilbestrol resulted in time‐of‐exposure and dose‐dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1–6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5α‐dihydrotestosterone in terms of nuclear 3H‐thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma.

Secondary estrogen treatment of neoDES mice with 17β‐estradiol did not increase 3H‐thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation.

When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship.
H‐ras expression, genetic instability, and acquisition of metastatic ability by rat prostatic cancer cells following v‐H‐ras oncogene transfection
Authors: Ichikawa Tomohiko , Schalken Jack A. , Ichikawa Yayoi , Steinberg Gary D. , Isaacs John T.
Published: February 2007

To study the relationship between metastatic ability, mutated H‐ras expression, and genetic instability, a cloned, nonmetastatic rat prostatic cancer cell line (AT2.1) was transfected with the v‐H‐ras oncogene. The parental AT2.1 clone, 4 control transfectants (Neo/Only), and 9 v‐H‐ras transfectants (Neo/Ras) were characterized with regard to their H‐ras content by using Southern, Northern, and Western blot analysis and their biological behavior in vivo. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors. All 4 (Neo/Only) transfectants like the parental untransfected cell were non‐metastatic. Six of 9 Neo/Ras transfectants were metastatic to the lungs and lymph nodes, while the other 3 Neo/Ras transfectants were not metastatic. There was no simple dose‐response relationship between the level of v‐H‐ras integration, mRNA or p21 protein expression, and the development of metastatic ability by the Neo/Ras transfectants. Cytogenetic analysis demonstrated that the frequency of additional structural and/or additional numerical chromosomal changes among the Neo/Ras transfectants was significantly higher than that in the Neo/Only transfectants (P <0.05). Loss of chromosome 10 was observed in all of the Neo/Ras transfectants, whereas that was observed in only one of the 4 Neo/Only transfectants (P <0.05). There were no specific chromosomal changes, however, which were statistically correlated with the development of metastases in the Neo/Ras transfectants. These results demonstrate that development of the metastatic ability in AT2.1 cells is not a single‐step reaction regulated by the level of H‐ras expression alone, but rather a complex process requiring additional events. One of the additional events appears to be an increase in genetic instability and cytogenetic changes following v‐H‐ras transfection.
Heterogeneity in plasminogen activator (PA) levels in human prostate cancer cell lines: Increased PA activity correlates with biologically aggressive behavior
Authors: Keer Harold N. , Gaylis Franklin D. , Kozlowski James M. , Kwaan Hau C. , Bauer Kenneth D. , Sinha Akhouri A. , Wilson Michael J.
Published: February 2007

Plasminogen activators (PA), particularly the lower Mr urokinase (u‐PA) type, have been associated with tumor cell invasion and metastasis. We have examined the expression of PA by two human prostate cancer cell lines (PC‐3 and DU‐145) using functional and immunologic techniques. The culture media and cell extracts of the more aggressive PC‐3 cell line contained more than two‐fold greater PA activity than the relatively indolent DU‐145 cell line. Zymographic studies identified the PA expressed as u‐PA. PC‐3 cells expressed an additional lower molecular weight form of u‐PA not noted in DU‐145 cells. Heterogeneity in u‐PA expression was shown by the fibrin lysis assay, immunohistochemistry, and dual parameter flow cytometry indicating the presence of phenotypically divergent cell populations. Increased u‐PA expression may identify those tumor cells that possess aggressive biological potential.
Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines
Authors: Rose David P. , Connolly Jeanne M.
Published: February 2007

Dietary Fatty acids (FAs) may be involved in the carcinogenic process within the prostate gland and progression to clinically manifest disease. We have shown that growth of the androgen‐unresponsive PC‐3 human prostate cancer cell line is stimulated in vitro by the presence of linoleic acid (LA), an omega‐6 polyunsaturated FA. The response was positively related to the FA concentration over the entire range examined (5–750 ng/ml). Conversely, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega‐3 FAs present in fish oils, inhibited PC‐3 cell growth in a dose‐dependent manner; both were equally effective, with an approximately 65% reduction in growth occurring at a concentration of 2.0 μg/ml (P < 0.001). The DU 145 human prostate cancer cell line, which is also androgen‐unresponsive, showed no growth response to LA and was less susceptible to growth inhibition when cultured in the presence of omega‐3 FAs. Growth experiments with indomethacin, esculetin, and piroxicam, pharmacological inhibitors of eicosanoid biosynthesis with differing sites of action, indicated that human prostate cancer cell growth requires intact metabolic pathways for both leukotriene and prostaglandin production.
Prostate—an extrapituitary source of follicle‐stimulating hormone (FSH): Occurrence, localization, and de novo biosynthesis and its hormonal modulation in primates and rodents
Authors: Garde Seema V. , Sheth Anil R. , Shah Madhavi G. , Kulkarni Sujata A.
Published: February 2007

A comparative study on the immunocytochemical localization, de novo biosynthesis, and hormonal modulation of follicle‐stimulating hormone (FSH) was carried out in the prostates of man, monkey, dog, guinea pig, hamster, rat, and mouse. FSH was localized in the cytoplasm of the prostatic epithelial cells. In some specimens, staining was also observed in the nucleus. Both pituitary as well as prostatic FSH were coeluted on a Sephadex G‐100 column and high‐performance liquid chromatography (HPLC) indicating physicochemical similarities of FSH in both the tissues. Surprisingly, the modulation of pituitary and prostatic FSH by inhibin and its related peptides were comparable. The intensity and grandularity of FSH staining was stronger in the case of benign prostatic hyperplasia as compared with normal prostatic specimens. In view of the well‐known effects of FSH on the cellular growth, differentiation, and function of gonadal tissues, a similar role for FSH in pathophysiology of prostate is postulated.
Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate
Authors: Sherwood Edward R. , Theyer Gerhard , Steiner Georg , Berg Lori A. , Kozlowski James M. , Lee Chung
Published: February 2007

The purpose of the present study was to identify cytokeratin polypeptides that are specifically associated with the basal and luminal epithelia of the human prostate. This aim was accomplished by immunohistochemical and immunoblot analysis of human prostate using cytokeratin‐specific monoclonal antibodies. In immunohistochemical studies, monoclonal anticytokeratin 8.12 exhibited immunoreactivity with the basal, but not luminal, epithelial cells of fetal, juvenile, normal adult, and hyperplastic prostate. The 8.12 antibody did not stain prostate cancer tissues. Epithelia of 30 and 36 week fetal prostate contained only basal cells whereas both luminal and basal cells were noted in 7 month and 1 year old juvenile prostate. This finding suggests a stem cell function for the prostatic basal cells. Immunoblot analysis of proteins separated by two‐dimensional electrophoresis showed that cytokeratins 5 and 15 were basal‐cell‐specific cytokeratins that were absent from prostatic carcinoma while cytokeratins 8 and 18 appear to be luminal‐cell‐specific. These results indicate that antibodies to specific cytokeratin polypeptides can be used not only to differentiate between prostatic basal and luminal cells but also to study the biological processes of prostatic organogenesis and carcinogenesis.