bluuebunny/crossref_metadata_2025_split huggingface dataset:
[1, 2‐bis (2, 6‐dichloro‐4‐hydroxyphenyl) ethylenediamine]dichloro‐platinum(II): An endocrine‐active platinum complex with a specific prostatic tumor‐inhibiting activity
Authors: Schneider M. R. , Schiller C.‐D. , Humm A. , Spruß T. , Schönenberger H. , Amselgruber W. , Sinowatz F. 
Published: February 2007

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

AbstractDihydrotestosterone (DHT) concentration, a marker for biochemical differentiation and possible clonal origin of prostate tumors, was measured in cancer present in lymph nodes (LN) from patients with untreated metastatic prostate cancer and compared to levels in untreated primary prostate cancer. The mean DHT of 2. 23 ng/g in LN (S. E. = 0.28, N = 22) was significantly less (P < 0.001) than the mean DHT of 4.8 ng/g in primary cancer (S. E. = 0. 52, N = 20). Since primary prostate cancer may be admixed with stromal tissue, while lymph node represents pure epithelial cell tumor, we chose for this comparison only the 20 prostate cancer tissues that were judged by our pathologist to contain 90% or more epithelial cell tumor. Using this selection criteria, we found that prostate stroma, which has an average DHT concentration 1. 18 times higher than prostate epithelia, would have an insignificant effect on primary prostate tumor DHT concentration.These data suggest that the decreased DHT in prostate tumor cells present in LN metastatses may be a marker for a clone of cells with metastatic potential. These findings are consistent with previous reports from this laboratory indicating that DHT concentration less than 2.4 ng/g in primary prostate cancer is a predictor of a reduced disease‐free interval following androgen blockade in advanced prostate cancer.
Effect of pubertal development on estrogen receptor levels and stromal morphology in the guinea pig prostate
Authors: Tilley Wayne D. , Horsfall David J. , Skinner John M. , Henderson Douglas W. , Marshall Villis R. 
Published: February 2007

AbstractUsing an immunocytochemical assay (ERICA) with a monoclonal antibody (H222Spγ) to the human estrogen receptor, we have demonstrated a stromal localization of the estrogen receptor in the dorsolateral prostate of the guinea pig. Specific staining of estrogen receptor in the guinea pig prostate was confined to the nuclei of periacinar and interacinar stromal cells. In comparison with prepubertal tissues, estrogen receptor staining intensity was markedly reduced in postpubertal prostatic tissues. No immunoreactive estrogen receptor was detected in the acinar epithelial cells irrespective of the developmental stage of the guinea pig prostate. Electron microscopic examination of the guinea pig prostate showed that the stromal component consists predominantly of smooth muscle cells, which, during pubertal development, undergo marked cytological changes and increase in size. These changes in the prostatic stroma were associated with a greater than fivefold reduction in levels of cytosolic and nuclear estrogen receptor determined by either a radioligand binding assay or an enzyme immunoassay (EREIA) and expressed relative to soluble protein. Morphometric analysis of the prostatic stromal cell density (SCD; nuclei/mm2 interacinar stroma), which is inversely proportional to stromal cell size, indicated that the SCD decreased approximately threefold during pubertal development. Furthermore, cytosolic estrogen receptor levels in mechanically separated prostatic stromal fractions were found to vary concordantly with the SCD during pubertal development. To determine whether estrogen influences normal development of the guinea pig prostate, the effect of various hormonal manipulations on stromal development was examined. Castration of prepubertal animals prevented the threefold decrease in SCD that is characteristic of pubertal development. Treatment of prepubertal castrates with estradiol and 5α‐dihydrotestosterone (DHT) in combination over a period equivalent to the transpubertal growth phase resulted in a stromal cell density similar to that seen in prostatic sections from intact postpubertal animals. In contrast, treatment of prepubertal castrates with either estradiol or DHT alone resulted in a prostatic stromal cell density intermediate between that observed in intact prepubertal and postpubertal animals. These findings suggest that both estrogen and androgen are required for the normal development of the guinea pig prostatic stroma.
Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration
Authors: English Hugh F. , Kyprianou Natasha , Isaacs John T. 
Published: February 2007

AbstractPrevious studies have demonstrated that the rapid involution of the rat ventral prostate following castration involves the death of the androgen‐dependent epithelial cells present within the gland and that this death is the result of a series of discrete biochemical steps. The degradation of genomic DNA into nucleosomal‐sized fragments is an early event in this process and is catalyzed by calcium magnesium‐dependent endonuclease activity. The morphologic correlation of the involution process involves a serics of structural changes which are collectively referred to as apoptosis. The apoptotic process describes the earliest apparent signs of morphologic change exhibited by the dying cells through their eventual complete destruction and deletion from the tissue. The temporal relationship between these recently described biochemical events and the morphologic changes of the apoptotic process were compared in the present study, in order to test the cause versus effect nature of DNA fragmentation in the programmed death of androgen dependent prostatic cells following castration. These studies demonstrated that the early elevation of the Ca +2 Mg+2 ‐dependent endonuclease activity and the fragmentation of DNA into nucleosomal oligomers occurs within prostatic glandular epithelial cells and probably does not involve the direct participation of extraprostatic cells which may subsequently migrate into the gland. Once the DNA is initially cleaved into the nucleosomal oligomers, the subsequent participation of lysosomal enzymes act in a less restricted fashion to degrade both the nuclcosomal DNA as well as the cytoplasmic elements and the cell becomes morphologically apoptotic. As the elevations in Ca+2 Mg+2‐dependent endonuclease activity and DNA fragmentation are initiated at a time well before the cell is morphologically dead, as defined by apoptosis, these changes in DNA metabolism must not be the consequences of cell death but instead are early causal events in an active process of programmed cell death.
Immunohistochemical localization of laminin in the basement membranes of normal, hyperplastic, and neoplastic human prostate
Authors: Sinha Akhouri A. , Gleason Donald F. , Wilson Michael J. , Staley Nancy A. , Furcht Leo T. , Palm Sally L. , Reddy Pratap K. , Sibley Richard K. , Martinez‐Hernandez A. 
Published: February 2007

AbstractWe examined the effects of fixatives and antibody sources on the immunohistologic localization of laminin in normal and cancer‐containing human prostates and studied the localization patterns in carcinomas of varying degrees of histologic differentiation. Two different polyclonal antibodies were localized in paraffin‐embedded or cryostat sections of fixed (alcohol, formalin, and paraformaldehyde) or unfixed tissue, using the immunofluorescence (IF) or immunoperoxidase (IP) techniques, with positive and negative controls. We found that the IF reactions were more intense in unfixed or alcohol‐fixed sections than in paraformaldehyde‐fixed specimens. IP reactions were very weak or absent in fixed and paraffin‐embedded sections, but pepsin treatment of these sections resulted in more intense and uniform IP reaction products, stronger than in unfixed or ethanol‐fixed cryostat sections. With the IP technique, laminin localization was intense and uniform in the basement membranes (BM) of acini, blood vessels, smooth muscle, and nerve fibers in normal prostate, benign hyperplasia (BPH), and well‐differentiated carcinomas. The BM of poorly differentiated carcinomas showed widespread absence of laminin reactivity. In normal BPH and well‐differentiated tumors, occasional epithelial cells and their surface and acinar lumina had laminin reactivity. However, in higher grade tumors, numerous neoplastic cells had laminin reactivity in cytoplasm, their surface, and secretory material. Some macrophages and neutrophils also contained laminin reactivity, presumably of degraded laminin. In some moderately and poorly differentiated tumors, the BM of small capillaries did not contain laminin. The BM of larger vessels always had laminin reactivity, even in the higher grade tumors.
Prostate epithelial cells utilize glucose and aspartate as the carbon sources for net citrate production
Authors: Costello L. C. , Franklin R. B. 
Published: February 2007

AbstractThe prostate gland (human, rat ventral prostate) has the major function of accumulating and secreting extremely high levels of citrate. This function requires unique and specialized metabolic pathways associated with prostate secretory epithelial cells by which exogenous substrates must be utilized as the six‐carbon sources of citrate. Recent studies demonstrated that aspartate can serve as the four‐carbon source of oxalacetate for citrate synthesis. Identification of the two‐carbon source of acetyl CoA (AcCoA) had not been established. The present study investigated the probability that exogenous glucose, via pyruvate oxidation, is a physiological source of AcCoA for net citrate production by isolated epithelial cells from rat ventral prostate. Under adequate oxygenation, 5 mM glucose in the presence of aspartate plus glutamate markedly stimulated citrate production. Exogenous and endogenous pyruvate also stimulated net citrate production. We propose that glucose via aerobic glycolysis and pyruvate oxidation provides AcCoA, which condenses with oxalacetate obtained from aspartate transamination for citrate synthesis. Prostate epithelial cells do not readily oxidize citrate, which permits accumulation and secretion of the synthesized citrate.
Cultured human prostate‐derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor
Authors: Story Michael T. , Livingston Bonnie , Baeten Laurie , Swartz Susan J. , Jacobs Stephen C. , Begun Frank P. , Lawson Russell K. 
Published: February 2007

AbstractFibrostromal proliferation is believed to be important in the development of benign prostatic hyperplasia (BPH). We found that a mitogen for cultured mesodermal‐derived cells was present in extracts of BPH tissue. The mitogen was identified as basic fibroblast growth factor (bFGF). Previous studies did not determine the cell population(s) responsible for bFGF production in the prostate. This information is important to the understanding of the role of bFGF in the etiology of BPH. Human prostate‐derived fibroblasts (PF) were initiated in culture. Recombinant bFGF and PF lysates stimulated tritiated thymidine uptake by quiescent PF cells. Greater than 90% of the mitogen in PF lysates bound to heparin‐Sepharose and had the same elution profile and apparent molecular weight as bFGF isolated from BPH tissue. The growth factor in PF lysates competed with recombinant iodinated bFGF for binding to antiserum to (1‐24)bFGF. Cultured PF incorporated 35S‐methionine into protein that was precipitated by antiserum to bFGF. The apparent molecular weight of the radiolabeled protein, about 17,000, was similar to authentic bFGF. The observations are consistent with the interpretation that cultured PF synthesize a growth factor that stimulates their growth with properties that are indistinguishable from bFGF.
Phosphoinositide metabolism in human prostate cancer cells in vitro
Authors: Wilding George , Gelmann Edward P. , Freter Carl E. 
Published: February 2007

AbstractTo understand better the mechanism by which 5‐α‐dihydrotestosterone (5‐α‐DHT) influences prostate epithelial cell function, we examined the effects of 5‐α‐DHT on phosphoinositide metabolism in human prostate cancer cell lines. Androgen receptor‐positive LNCaP cells showed dose‐responsive, steady‐state elevations in phosphoinositide metabolism when treated with 5‐α‐DHT. The intracellular pool of 3H‐myoinositol decreased and the incorporation of 3H‐myoinositol into cellular lipids increased with increasing concentrations of 5‐α‐DHT. 5‐α‐DHT increased the release of 3H‐inositol phosphates into the media. The inactive stereoisomer, 5‐β‐DHT, did not increase phosphoinositide metabolism. In androgen receptor‐negative cells, phosphoinositide metabolism was not altered by 5‐α‐DHT. The slow induction of phosphoinositide metabolism by 5‐α‐DHT suggests that the effects may be mediated through other factors that serve as intermediates in 5‐α‐DHT modulation of intracellular signalling. We conclude that this modulation involves increased turnover of phosphatidylinositol, incorporation of myoinositol into cellular lipids, and alterations in the aqueous intracellular myoinositol pool size, possibly as a result of altered transport mechanisms.
Increased expression of genes for basic fibroblast growth factor and transforming growth factor type β2 in human benign prostatic hyperplasia
Authors: Mori Hirotaka , Maki Masatoshi , Oishi Kenji , Jaye Michael , Igarashi Koichi , Yoshida Osamu , Hatanaka Masakazu 
Published: February 2007

AbstractIt is now widely accepted that factors other than androgen are crucial in the normal and abnormal growth of the prostate, including human benign prostatic hyperplasia (BPH). Using a Northern blot analysis, we examined human normal and benign hyperplastic prostates for expressions of basic fibroblast growth factor (FGF), acidic FGF, transforming growth factor type β2 (TGF‐β2), TGF‐β1, and epidermal growth factor (EGF). Basic FGF mRNAs were detectable in all the prostates examined. In addition, levels of basic FGF expression were significantly higher in BPH than in normal prostate. Acidic FGF transcripts were undetectable except in one case of BPH. Although both TGFs were expressed in all the samples, TGF‐β2 showed significantly increased levels of expression in BPH as compared to those in normal prostate, while TGF‐β1 did not. No EGF was expressed in any of the prostates examined. These findings suggest that specific growth factors (basic FGF and TGF‐β2) produced locally in the prostate may be involved in BPH development.
Evidence for two aspartate transport systems in prostate epithelial cells
Authors: Franklin Renty B. , Lao Lixing , Costello L. C. 
Published: February 2007

AbstractThe transport of aspartate was measured in isolated prostate cells. Two kinetically distinct uptake systems of high (Km = 10.0 μM) and low (Km = 0.8 mM) affinity were observed. Transport by both systems was Na+ dependent and saturable. The tissue distribution of aspartate was also determined by measuring the washout kinetics of endogenous and radio‐labeled aspartate from prostate fragments. The distribution of aspartate resulted in 47% of aspartate in the intracellular compartment and 52% in the extracellular (presumably) lu‐menal compartment. The distribution of aspartate resulted in a calculated intracellular to plasma concentration gradient of approximately 43. We concluded that prostate cells maintain a considerable intracellular to plasma gradient for aspartate and that these cells contain a transport mechanism capable of uptake of aspartate against this considerable gradient.
Characterization of the morphonuclear features and DNA ploidy of prostatic disease
Authors: Petein Michel , De Launoit Yvan , Kiss Robert , Deprez Carine , Crols Kaat , Pasteels Jean‐Lambert , Verhest Alain , Van Velthoven Roland 
Published: February 2007

AbstractThe relationship between several morphonuclear parameters related to nuclear size, densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen‐stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies or fine‐needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine‐needle aspirations from prostate.
Non‐androgenic role of testis in enhancing ventral prostate growth in rats
Authors: Dalton Daniel P. , Lee Chung , Huprikar Shankar , Chmiel Joan S. , Grayhack John T. 
Published: February 2007

AbstractThis study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague‐Dawley rats at the time of bilateral epididymo‐orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty‐eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non‐androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non‐androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.
Symptoms and signs of prostatism as risk factors for prostatectomy
Authors: Arrighi H. M. , Guess H. A. , Metter E. J. , Fozard J. L. 
Published: February 2007

AbstractSymptom questionnaires and physical examinations administered periodically to 1,057 men followed prospectively for up to 30 years in the Baltimore Longitudinal Study of Aging (BLSA) were analyzed to determine which symptoms of prostatism were predictive of subsequent prostatectomy for benign prostatic hyperplasia (BPH). Change in the size and force of the urinary stream (P= 0.0001) and a sensation of incomplete emptying (P= 0.0005) were the only symptoms positively predictive in a multivariate analysis. Prostate enlargement by rectal palpation was an independent risk factor for prostatectomy (P<0.03) and was associated with hesitancy (P<0.02) and a sensation of incomplete emptying (P<0.02). Of the men with all three risk factors, 37% (41/112) eventually had a prostatectomy, in contrast to 8% of the remaining 945 men. This is the first study to document the extent to which urologic symptoms and a digital rectal examination predict subsequent prostatectomy for BPH.
Characterization of castration‐induced cell death in the rat prostate by immunohistochemical localization of cathepsin D
Authors: Sensibar Julia A. , Liu Xianxi , Patai Barbara , Alger Brad , Lee Chung 
Published: February 2007

AbstractActivities of cathepsin D (EC 3.4.23.5) were determined in three lobes of the prostate during their involution by both biochemical and immunohistochemical procedures. The activity of cathepsin D in noncastrated rats was 0.9 ± 0.2 (mean ± SE) 5.7 ± 0.6, and 13.1 ± 0.8 units/mg protein for the ventral, lateral, dorsal lobes, respectively. Following castration, there was a significant increase in enzymatic activity in all three lobes within 2–3 days. In the ventral lobe, the activity peaked in 5 days to 6.2 ± 0.9 units/mg protein and declined slightly thereafter. In the lateral and dorsal lobes, the activity remained elevated (14–20 units/mg protein) throughout the postcastration period studied.Immunohistochemical staining of cathepsin D was localized in the cytoplasm of prostatic epithelial cells as fine discrete lysosomal granules. These granules were larger and more abundant in the dorsal and lateral lobes than in the ventral lobe and were not detected in prostatic stromal cells and seldom in the luminal fluid. Castration resulted in an immediate increase in the size and number of these granules in the epithelial cells, followed by a sudden further increase in cathepsin D staining in some but not all epithelial cells. Lysosomal granules gradually coalesced in these cells to form large vacuoles that fit the characteristic description of apoptotic bodies. Finally, after day 7 postcastration, collapse and disintegration of the entire glandular structure was noted. Using this procedure to localize cathepsin D as a tool, we were able to follow the morphological events of prostatic cell death during castration‐induced involution in the rat at the light microscopic level.