bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical pharmacology of polyestradiol phosphate
Authors: Gunnarsson Per Olov , Norlén Bo Johan 
Published: February 2007

AbstractThe results of the present studies demonstrate that intramuscular injections of polyestradiol phosphate (PEP) produce not only considerably increased estrogen concentration in plasma but also maintain the same estrone/estradiol ratio as in normal men.Monthly injections of PEP produce persistent elevation of the plasma estradiol levels throughout the dose interval, and rising PEP doses produce proportionately increasing steady‐state plasma concentrations of estradiol.The steady‐state plasma concentrations of testosterone are reduced to 45, 25, and 15% of the pretreatment concentrations after treatment every fourth week with 80, 160, and 240 mg PEP, respectively.
Case‐control study of prostate cancer and socioeconomic factors
Authors: Yu He , Harris Randall E. , Wynder Ernst L. 
Published: February 2007

AbstractA total of 1,162 prostate cancer cases and 3,124 age‐matched hospital controls from several U.S. hospitals were studied to identify associations between prostate cancer and life‐style variables. Among white males, college education, professional occupation, and non‐Jewish ethnicity were weakly associated with the risk of prostate cancer (ORs = 1.5, 1.8, and 1.3, respectively, P < 0.01). These relationships retained statistical significance after adjustment for age, marital status, body mass, cigarette smoking, alcohol consumption, and physical activity in multiple logistic regression models. Among black males, similar, though nonsignificant, risk elevations were observed for education and occupation. Weak positive effects of borderline statistical significance were observed for high body mass, low physical exercise, and high serum cholesterol (in elderly males only), and a significant reduction in risk was noted for never married black males. Cigarette smoking and alcohol consumption were not related to the risk of prostate cancer.
Phosphorylation status of nuclear and cytosolic androgen receptors in the rat ventral prostate
Authors: Golsteyn E. J. , Graham J. S. , Goren H. J. , Lefebvre Y. A. 
Published: February 2007

AbstractWe demonstrate that endogenous phosphatases are active in cytosolic and nuclear androgen receptor fractions from the rat ventral prostate. Under our androgen binding assay conditions, the effect of acid phosphatase inhibitors (sodium fluoride, tartaric acid, sodium orthovanadate) on the endogenous phosphatases could be correlated with an increase in dihydrotestosterone (DHT) binding to fractions of partially purified cytosolic androgen receptor. In contrast, tetramisole, an alkaline phosphatase inhibitor, did not alter the binding of DHT to the same receptor fraction. Immunoprecipitation of androgen receptor fractions with polyclonal anti‐phosphotyrosine antibody resulted in the recovery of [3H]‐DHT binding activity from nuclear receptor fractions and partially purified cytosolic receptor fractions prepared from 20‐ to 24‐hr castrated rats. In control fractions depleted of androgen receptor, negligible levels of binding activity were recovered following immunoprecipitation with the antibody. Therefore, acid phosphatases may be acting on phosphotyrosyl residues of the androgen receptor, thus playing a role in the dephosphorylation and inactivation of the androgen receptor.
Receptors for luteinizing hormone‐releasing hormone, somatostatin, prolactin, and epidermal growth factor in rat and human prostate cancers and in benign prostate hyperplasia
Authors: Fekete Matyas , Redding Tommie W. , Comaru‐Schally Ana Maria , Pontes J. Edson , Connelly Robert W. , Srkalovic Gordan , Schally Andrew V. 
Published: February 2007

AbstractUsing sensitive multipoint micromethods, we estimated membrane receptors for [D‐Trp6]‐luteinizing hormone‐releasing hormone ([D‐Trp6]‐LH‐RH), somatostatin (SS‐14), human prolactin (hPRL), and epidermal growth factor (EGF) in experimental Dunning rat prostate cancers and in samples of normal human prostate, benign prostatic hyperplasia (BPH), and human prostate cancer (PC) obtained from biopsy, after prostatectomy, or at autopsy. In the Dunning R‐3327 rat prostate adenocarcinoma specimens, the receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist [D‐Trp6]‐LH‐RH and the somatostatin analog RC‐160. Two populations of binding sites were found for [D‐Trp6]‐LH‐RH, one with high affinity and low capacity and another with low affinity and high capacity. Treatment with [D‐Trp6]‐LH‐RH and RC‐160 alone or with the combination of these analogs increased the binding capacity (Bmax) of the low‐affinity binding sites for [D‐Trp6]‐LH‐RH and decreased Bmax for hPRL and EGF. Therapy with [D‐Trp6]‐LH‐RH also reduced Bmax of SS‐14 binding and dissociation binding constant of high‐affinity binding sites for [D‐Trp6]‐LH‐RH, whereas administration of RC‐160 or the combination treatment with both analogs increased Bmax of SS‐14 binding. These findings are compatible with the view that analogs of LH‐RH and SS‐14 might exert some direct inhibitory effects on the Dunning prostate cancer. Among 13 human BPH samples examined, only one had receptors for [D‐Trp6]‐LH‐RH, and seven specimens exhibited binding for prolactin. [D‐Trp6]‐LH‐RH receptors were found in all seven samples of human PC but not in any of the eight specimens of normal human prostate. All samples of normal human prostate, BPH, and human PC exhibited binding sites for EGF but not for SS‐14. Our findings on the membrane receptors in the human and rat prostate cancers raise the intriguing possibility that LH‐RH, acting as a growth factor, along with EGF and prolactin, might be involved in complex interactions that contribute to the promotion of prostate cancer in man.
Development of monoclonal antibody imaging of metastatic prostatic carcinoma
Authors: Meyers Frederick J. , Denardo Sally J. , Macey Daniel , White Ralph Devere , Unger Michael 
Published: February 2007

AbstractIndium‐111‐labeled monoclonal antibody directed against prostate‐specific antigen was injected into ten patients with known prostatic carcinoma, nine with metastatic disease. The monoclonal antibody scan was compared to the standard technetium bone scan, and both were correlated to clinical status and to 2‐year follow‐up. The ratio of target‐to‐nontarget activity and pharmacokinetics of the radiolabeled antibody were determined. Based on these findings we are hopeful that modifications of this radiolabeled antibody approach may be used for staging and may be developed as a therapeutic adjuvant.
Clonal growth of human prostatic epithelial cells is stimulated by fibroblasts
Authors: Kabalin John N. , Peehl Donna M. , Stamey Thomas A. 
Published: February 2007

AbstractThe interaction of fibroblasts with adult human prostatic epithelial cells was studied in vitro. Stimulation of epithelial cell proliferation, measured by clonal growth assay, was demonstrated when prostatic epithelial cells were grown in coculture with fibroblasts. Epithelial growth in cocultures with fibroblasts was greater than could be obtained in isolated culture in an “optimized,” serum‐free medium previously described. Fibroblasts were able to compensate for the deletion of several growth factors from this “optimized” medium, including epidermal growth factor and insulin, but were notably unable to replace bovine pituitary extract. Epithelial growth stimulation identical to that achieved in coculture was produced by medium conditioned by fibroblasts. Similar results were obtained by using fibroblasts of adult human prostate origin, adult human skin, human fetal lung fibroblasts (IMR‐90), and mouse 3T3 cells. No difference in response was demonstrated between prostatic epithelial cells derived from normal or malignant tissues. Fixed fibroblast monolayers and extracellular matrix prepared from fibroblast cultures failed to stimulate prostatic epithelial growth. These results suggest that a soluble growth factor is secreted by prostatic fibroblasts and other human fibroblasts of nonprostatic origin, as well as by embryonic mesenchymal cells from nonhuman species, which is capable of producing a marked proliferative response in vitro from adult human prostatic epithelium. This proliferative response could not be reproduced by the addition of a variety of known growth factors to prostatic epithelial cell cultures.
A form of basic fibroblast growth factor is secreted into the adluminal fluid of the rat coagulating gland
Authors: Smith Eric P. , Russell William E. , French Frank S. , Wilson Elizabeth M. 
Published: February 2007

AbstractRat coagulating gland and its secreted fluid contain a mitogenic substance that, by numerous criteria, appears to be similar to basic fibroblast growth factor (basic FGF). It is a potent competence factor in the BALB/c3T3 mouse embryo fibroblast assay, elutes from heparin‐agarose at concentrations of NaCl greater than 1.0 M, and has an isoelectric point (pI) between 8 and 9. In coagulating gland fluid, its molecular weight was 20,000 ± 5,000, as indicated by gel filtration on Sephadex G‐200. Western blot analysis of purified factor from coagulating gland cytosol and fluid, respectively, revealed immunoreactive bands of 16,000 and 17,000 relative molecular weight similar to that of purified bovine basic FGF.
Immunohistochemical localization of metallothionein in the rat prostate gland during postnatal development
Authors: Timms B. G. , Hagen J. A. 
Published: February 2007

AbstractImmunocytochemical and electrophoretic techniques were used to investigate the presence of metallothionein, a metal‐binding protein, in the dorsolateral and ventral lobes of the developing rat prostate. Male rats aged 7 and 14 days were injected subcutaneously with 6 and 20 mg/kg body weight of cadmium and zinc, respectively, or with saline for controls, 24 h prior to tissue sampling. Immunohistochemical localization of metallothionein was observed in the epithelial tissues of the dorsolateral prostate from 7 and 14 day‐old animals and in 1 day‐old untreated rats. This staining pattern did not appear to be significantly affected by cadmium or zinc treatment. In contrast, metallothionein localization in the ventral prostate decreased with age but demonstrated a slight response to metal‐ion treatment in the 7 day‐old animals. Electrophoretic and immunoblot analysis confirmed the presence of metallothionein in the control and metal‐induced prostate samples from neonatal rats. Lobe‐specific differences in localization suggest a functional significance for metallothionein, independent of inducible protein.
Estrogen therapy and liver function—metabolic effects of oral and parenteral administration
Authors: von Schoultz Bo , Carlström Kjell , Collste Lars , Eriksson Ambjörn , Henriksson Peter , Pousette Åke , Stege Reinhard 
Published: February 2007

AbstractOral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver‐derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.
Role of transforming growth factor ‐α in human prostate cancer cell growth
Authors: Wilding George , Valverius Eva , Knabbe Cornelius , Gelmann Edward P. 
Published: February 2007

AbstractBecause of the influence of transforming growth factor‐α (TGFα) on the cell growth in other cancer cell systems, we investigated the growth‐regulatory role of TGFα in human prostate cancer cells. TGFα (5 ng/ml) stimulated LNCaP cell growth in monolayer to 60% of the level seen with dihydrotestosterone (DHT). Both DHT and TGFα increased cloning in soft agar twofold above that in controls. Metabolism of thymidine and uridine was also increased as evidenced by increased uptake of these macromolecule precursors. In addition, intracellular signalling as indicated by phosphatidyl inositol turnover was also increased by TGFα and DHT. Conditioned media contained TGFα by radioimmunoassay (RIA), transforming activity by rat kidney fibroblast (NRK) colony formation, and epidermal growth factor (EGF) receptor competable activity by radioreceptor assay. EGF receptors were present by binding assay and immunoprecipitation. These data demonstrate the presence of an autostimulatory growth loop in hormone‐responsive human prostate cancer cells.
Effects of isosmotic and hyperosmotic glycine solutions on the fluid balance in conscious sheep
Authors: Hahn Robert , Hjelmqvist Hans , Rundgren Mats 
Published: February 2007

AbstractGlycine 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

AbstractWe 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

AbstractA 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

AbstractCells 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

AbstractChemotherapy 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

AbstractIntraglandular 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

AbstractUsing 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

AbstractThe 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.