bluuebunny/crossref_metadata_2025_split huggingface dataset:
The periurethral zone of the prostate of the cynomolgus monkey is the most sensitive prostate part for an estrogenic stimulus
Authors: Habenicht Ursula‐F. , Etreby M. Fathy El 
Published: February 2007

AbstractIn man, benign prostatic hyperplasia (BPH) develops in the so‐called transition zone of the periurethral region of the prostate. Assuming that estrogens have a specific effect in this context, it would be expected that the periurethral glands are the most sensitive prostate part for an estrogenic stimulus. Morphological and imunocytochemical studies of serial sections of the prostate of castrated male adult cynomolgus monkeys treated with 17β‐estradiol for a period of three months revealed stromal proliferation, hyperplasia, and hypertrophy of the keratin‐positive basal cells and squamous epithelial metaplasia. These estrogen‐induced effects were most marked or found exclusively in the dorsal periurethral glands–a finding that is inconsistent with pertinent animal studies conducted thus far on this subject, and which further bears out the suitability of the cynomolgus monkey as a model for investigating BPH.
Effect of treatment on the expression of estramustine‐binding protein (EMBP) in prostatic cancer patients: An immunohistochemical study
Authors: Flüchter Stephan H. , Nelde Hans J. , Björk Per , Müntzing Jonas , Bichler Karl‐Horst 
Published: February 2007

AbstractEstramustine‐binding protein (EMBP) was determined immunohistochemically in prostatic cancer (PC) specimens taken from patients before and after therapy. The EMBP staining intensity was correlated with the tumor malignancy grade in untreated PCs. The effect of various treatments (i.e., androgen‐withdrawal therapy, treatment with estramustine phosphate or radiation) on the expression of EMBP was also investigated.Although a rabbit polyclonal antiserum raised against rat EMBP was used all through the study, all untreated PCs (n = 53) examined so far displayed a positive immunoreaction. The staining intensity was higher in moderately and poorly differentiated than in well‐differentiated tumors. Furthermore, two types of staining patterns were observed, that is, a diffuse type in about 70% and a focal in the remaining cases, which might reflect the multifocal appearance of PCs. The prognostic significance of these staining patterns is discussed.Irrespective of the treatment used, EMBP staining was reduced to lower or undetectable levels in PCs where cytological as well as clinical regression were indicated after 6–30 months of therapy. In nonresponders or patients with refractory disease, however, EMBP expression reappeared and returned to pretreatment levels. In a short‐term follow‐up, the diminuation of EMBP was evident as early as 10 days after androgen‐withdrawal therapy and persisted as long as the patient responded to therapy. When estramustine phosphate was given as secondary treatment to hormone refractory PCs, EMBP decreased to undetectable levels in 3/4 of the specimens, suggesting response to therapy.In conclusion, a decreased EMBP staining was well correlated with favorable cytological regression as well as with clinical regression, whereas unchanged staining intensity was indicative of clinical progression and a poor cytological regression grade. The high levels of EMBP in moderately and poorly differentiated tumors as well as in relapsing PCs, despite continued androgen withdrawal, strongly support a regulation of EMBP that is not under androgenic control. Based on the present findings, we suggest the use of EMBP as a therapy marker. Provided that immunohistochemical measurements can be performed on fine‐needle aspirates, EMBP analysis may be a direct and early means to distinguish between responding patients and nonresponders.
Hormonal effects of an orally active 4‐azasteroid inhibitor of 5α‐reductase in humans
Authors: Vermeulen A. , Giagulli V. A. , De Schepper P. , Buntinx A. , Stoner E. 
Published: February 2007

AbstractThe objective of this study was to estimate the minimum in vivo effective oral dose and duration of action of the competitive 5α‐reductase inhibitor MK‐906, a 4‐azasteroid, in humans. Plasma dihydrotestosterone (DHT), 5α‐androstane‐3α, 17β‐diol (AD), and its glucuronide (ADG), as well as urinary androsterone (A) and 5α‐pregnane‐3α, 11β, 17α, 21‐tetrol‐20‐one (aH4F) were determined in 54 healthy young men before and up to 7 days after a single morning dose of the compound. Twenty‐four hours after a single 5‐to 40‐mg dose (n = 24), plasma DHT levels decreased by a mean of ± 65%, with slow recovery of DHT levels. Seven days later, DHT remained decreased by ± 15%. Plasma AD levels decreased to a similar degree, whereas ADG levels decreased by about 75%, indicating inhibition of target tissue 5α‐reductase. Testosterone levels did not show any significant variations. The A as well as aH4F excretion in the 24‐hour urine test following drug administration decreased by 65%, indicating inhibition of the hepatic 5α‐reductase. After a single dose of 1.5 or 0.5 mg, DHT levels decreased by 50% 24 hours after administration, returning to normal within 5–7 days; at this dose, urinary A and aH4F excretion decreased by 50%. A single dose of 0.2 mg appeared to be slightly active as a 5α‐reductase inhibitor, but no statistically significant effect on DHT levels was observed after administration of a single 0.04‐mg dose. It is concluded that MK‐906 is a highly effective 5α‐reductase inhibitor in vivo. The effect on plasma DHT lasts for several days after administration of a single oral dose. The data suggest that both hepatic and extrasplanchnic 5α‐reductases are inhibited.
Regional distribution of opioidergic nerves in human and canine prostates
Authors: Aumüller Gerhard , Jungblut Thomas , Malek Bashar , Konrad Sabine , Weihe Eberhard 
Published: February 2007

AbstractThe regional distribution of opioidergic nerves in the juvenile and adult human prostate and in the adult canine prostate has been studied immunohistochemically using well‐characterized polyclonal antisera against multiple opioid peptides. Nerves displaying immuno‐reactivity (ir) for the proenkephalin (PRO‐ENK) derivatives met‐enkephalin (ME), leuenkephalin (LE), octapeptide, and heptapeptide (ordered in decreasing frequency) were present in the dorsolateral stroma of human prostate. In canine prostate, the situation was similar, but the number of opioid‐ir nerve fibers was lower than in human prostate. In both species, staining for the prodynorphin (PRO‐DYN) derivatives dynorphin A and α‐neoendorphin or staining for the pro‐opiomelanocortin (POMC)‐derived β‐endorphin was not visualized. In addition to their presence in nerve fibers, PRO‐ENK‐ir opioids (octapeptide) occurred in intrinsic ganglionic cells situated in the capsule. Octapeptide but not LE‐ir fibers supplied stromal blood vessels. The periurethral region and tissue adjacent to the ejaculatory ducts appeared to be devoid of opioid‐ir innervation. We conclude that endogenous opioids apparently exclusively derived from PRO‐ENK may fulfill important comessenger functions in the fine regulation of prostatic stromal tonus and of local vascular perfusion.
Prostatic growth effects of rat urogenital sinus and human prostatic tissue in the rat
Authors: Jarow Jonathan P. , Isaacs John T. 
Published: February 2007

AbstractIt is known that fetal urogenital sinus (UGS) implanted into one ventral lobe of an adult mouse prostate produces a significantly increased DNA content in that lobe. In our study, we attempted to determine whether that growth was of host or of graft tissue. UGS from fetal rats and ventral prostate from adult rats were implanted in various sites in syngeneic Fischer rats, alone or as a recombinant tissue complex. Human benign prostatic hyperplasia (BPH) tissue was implanted into the ventral prostate of adult, male, hooded nude rats to determine whether it stimulated prostatic growth. All UGS‐implanted in situ ventral lobes enlarged. Mean DNA content of UGS and ventral prostate implanted together in the flank was not different from the mean DNA content of UGS and ventral prostate implanted separately in the flank (P = 0.69). Mean DNA content of in situ control ventral lobe and of UGS grown singly in the flank was less than that of a UGS‐implanted in situ ventral lobe (P < 0.01). Thus overgrowth in the UGS‐implanted in situ ventral prostate was location‐dependent, but which tissue(s) enlarged remains unclear. Implanted human BPH tissue did not stimulate rat prostatic growth.
Androgen‐supported estrogen‐enhanced epithelial proliferation in the prostates of intact noble rats
Authors: Leav Irwin , Merk Frederick B. , Kwan Paul W.‐L. , Ho Shuk‐Mei 
Published: February 2007

AbstractUsing a stathmokinetic in vivo metaphase‐arrest technique, we studied cell proliferation and histological changes in the ventral (VP) and dorsolateral (DLP) prostate lobes of intact Noble (Nb) rats following a 16 week treatment with testosterone (T) or 5α‐dihydrotestosterone (DHT) administered separately or in combination with various estrogens. The combined treatment of rats with T and either estradiol‐17β, estradiol‐17α, or moxestrol induced florid dysplasia and markedly elevated the mitotic index (MI) in affected regions of the DLP. In contrast, joint DHT and estrogen treatment caused only mild proliferative lesions in this lobe. The separate administration of either androgens or estrogens suppressed epithelial proliferation in both the VP and DLP, but they differed in their histological effects on these tissues. Thus DHT or T alone maintained the morphological integrity of VP and DLP, whereas E2‐17β or moxestrol caused massive atrophy of both lobes. Although dysplastic foci were randomly scattered throughout the DLP, the most dramatic lesions occurred in periurethral ducts. With the exception of joint T and E2‐17α treatment, which induced proliferative alterations in the VP, dysplasia was always restricted to the DLP of all animals receiving both androgens and estrogens. Concomitant comparative stathmokinetic studies of the prostates of T‐treated castrates suggest that protracted androgen‐supported estrogen stimulation of the DLP is necessary to overcome factors that normally limit cell proliferation.
Prostatic carcinoma with melanosis
Authors: Furusato Masakuni , Matsumoto Izuru , Kato Hiroyuki , Takahashi Hiroyuki , Kawashima Yoshio , Wada Tetsuro , Suzuki Masafumi , Aizawa Shigeo 
Published: February 2007

AbstractMelanosis in which melanin deposition is found in the epithelia and stroma or blue nevus of the prostate gland is an uncommon lesion, and the histogenesis is still unclear. To our knowledge, there have been only two case reports in which prostatic melanosis and prostatic adenocarcinoma were both present. This article reports a third case having this combination and discusses the existence of melanin pigment in the carcinoma cell with melanosis.
Prevention and treatment of experimental prostate cancer in lobund‐wistar rats. I. Effects of estradiol, dihydrotestosterone, and castration
Authors: Pollard Morris , Luckert Phyllis H. , Snyder David 
Published: February 2007

AbstractThe Lobund‐Wistar (L‐W) rat is unique in its susceptibility to spontaneous and induced metastasizing prostate adenocarcinomas (PAS). A single IV inoculation of methylnitrosourea (MNU) produced PAS in 20% of L‐W rats in 12 months. The combination of MNU plus two to seven slow‐release implants of testosterone propionate (TP) induced PAs in 50‐90% of rats respectively in an average of 11.5 months. The induction of PAs was prevented by early treatments of rats at risk with estradiol and less so with dihydrotestosterone (DHT). However, on a technical basis, the results were not significant. Treatments of MNU‐inoculated rats with estradiol, with DHT, or by castration, at intermediate points in the projected latency time of tumor development, reduced significantly the incidences of PA development. Rats in which overt PAS had already developed in response to 12 months of exposure to implants of TP did not respond to treatment by estradiol, DHT, or castration. Thus there are early stage(s) in induced prostate tumorigenesis in L‐W rats that are sensitive to modulating agents.
Secretion of epidermal growth factor and related polypeptides by the DU 145 human prostate cancer cell line
Authors: Connolly Jeanne M. , Rose David P. 
Published: February 2007

AbstractEpidermal growth factor (EGF)‐like proteins may be important in regulating the growth of human prostate cancer cells and in the development of hormone independence. In the present study, we demonstrated that the DU 145 human prostate cancer cell line secretes EGF‐like polypeptides into serum‐free culture medium. The production of both authentic EGF and transforming growth factor‐α was demonstrated by specific radioimmunoassays. In addition to 6–7k monomers, immunoreactive higher molecular weight species were isolated by gel chromatography. The DU 145 cells also specifically bound human EGF, with both high‐ (Kd 1.8 × 10−10 M) and low‐ (Kd 1.1 × 10−9 M) affinity binding sites. Exogenous EGF stimulated 3H‐thymidine incorporation when cells were plated at low density in serum‐free culture medium, while at higher cell density neither cell division nor 3H‐thymidine incorporation was significantly altered. We postulate that DU 145 cells may be autologously stimulated by endogenously produced EGF and related polypeptides, which, under normal culture conditions, precludes any further effect of exogenous EGF.
Correlation between bone scans and serum levels of osteocalcin, prostate‐specific antigen, and prostatic acid phosphatase in monitoring patients with disseminated cancer of the prostate
Authors: Tarle Marko , Kovaćić Ksenija , Strelkov‐Alfirević Ana 
Published: February 2007

AbstractResponse of prostatic cancer bone metastases to therapy (androgen withdrawal and Estracyt) was studied in 43 patients by applying scintiscanning and radioimmunodetective measurement of serum osteocalcin (OC) values. The prostate‐specific antigen (PSA) and prostatic acid phosphatase (PAP) concentrations, as sensitive probes for the overall tumor spread, were used in parallel in a monitoring procedure. A significant rise in OC levels to values elevated from a pretreatment normal level has been found in patients with a partial osseous tumor remission, and this may be easily distinguished from normal and/or subnormal OC level in bony tumor progression (P < 0.01) and during stabilization in metastatic spread (P < 0.01). On these bases, differences between disease progression and the “no change” response category could not be statistically recognized (P > 0.05). A sharp increase in circulating OC level has been recorded 1 months after the beginning of the treatment leading to bone remodeling processes and precedes improvements in scintiscan appearance. Blood OC concentration seems also to be of utility 1) in distinguishing scintigraphic flare phenomenon from a slight bone scan progression and 2) when related to scans with regions of both disease improvement and worsening. Furthermore, serum OC concentration can frequently be measured through a noninvasive procedure, thus serving as a significant addition to bone scintigraphy.
Effects of castration and androgens upon prostatic proteoglycans in rats
Authors: Kofoed J. A. , Tumilasci O. R. , Curbelo H. M. , Fernandez Lemos M. , Arias N. H. , Houssay A. B. 
Published: February 2007

AbstractIn studies performed on male Wistar rats, castration induced atrophy of the prostate with a marked increase in the uronic acid content. The administration of testosterone propionate to castrated rats produced opposite effects. Fractionation of the glycosaminoglycans on cellulose microcolumns showed that the changes in uronic acid content in the dorsolateral lobes were due to variations in hyaluronic acid, chondroitin‐4‐sulfate, and dermatan sulfate, but in the ventral lobes, there were changes in all the chromatographic fractions. There were also changes in the physical properties of proteoglycans. In the ventral lobes, castration induced a wider distribution of molecular weight, increased density, and predominance of lateral chains of greater size. In the dorsolateral lobes, there was a decrease in molecular weight and density of proteoglycans and in the length of lateral chains. Opposite results were obtained when testosterone propionate was given to castrated rats. It is postulated that the effects of androgens upon prostatic growth would depend on an interrelationship between epithelium and stroma mediated by the proteoglycans.
Plasminogen activator activities in the ventral and dorsolateral prostatic lobes of aging fischer 344 rats
Authors: Wilson Michael J. , Ditmanson Janet V. , Sinha Akhouri A. , Estensen Richard D. 
Published: February 2007

AbstractPlasminogen activator (PA) activities were measured in extracts of ventral and dorsolateral prostate lobes in Fischer 344 (F344) rats of different ages. Ventral prostates of 30‐month‐old animals demonstrated widespread epithelial atrophy, some foci of inflammation, in‐traglandular atypical hyperplasia and/or adenocarcinoma, and a marked increase in PA activities compared with younger animals. Both low‐ and high‐molecular‐weight forms of activator were found in zymograms and both forms of activator showed an increase at 30 months. However, the PA activity of the aged rats showed a greater resistance to amiloride inhibition, suggesting a greater relative increase in the tissue‐type activator activity than that of urokinase. These changes were not observed in the dorsolateral prostate. The lobe‐specific changes in activator activity appear related to dysplasia/neoplasia and not aging.
Quantitation of cytosolic and nuclear estrogen and progesterone receptor in benign, untreated, and treated malignant human prostatic tissue by radioligand binding and enzyme‐immunoassays
Authors: Mobbs B. G. , Johnson I. E. , Liu Y. 
Published: February 2007

AbstractEstrogen receptor (ER) and progesterone receptor (PgR) were quantitated in benign and malignant human prostatic tissue by using radioligand binding assays (RBA) and enzyme‐immunoassays (EIA). Using a hydroxylapatite exchange method for ER, little or no nuclear ER (ERN) could be detected, but with the EIA both cytosolic (ERC) and ERN were detected in almost all specimens, although in meager concentrations. Tissue from patients with carcinoma had significantly higher ERC concentrations than tissue from patients with benign disease. Specimens from estrogen‐treated patients had significantly lower ERC:ERN ratios than those from untreated patients.Progesterone receptor was detected in virtually all specimens by both methods, at concentrations higher than those of ER. Carcinoma tissue with a high malignant involvement contained significantly less PgR than benign tissue. Using either method, the highest concentrations of PgR were observed in tissue from carcinoma patients treated with estrogen. Overall, the data suggest that although human prostatic tissue contains only modest amounts of ER, this is active in that treatment with estrogen promotes association of this receptor with the nuclear fraction and increases PgR content.
Interactions of retinoic acid and androgens in human prostatic tissue
Authors: Jutley Jaswant K. , Reaney Sue , Kelleher Jerry , Whelan Peter 
Published: February 2007

AbstractThe effect of retinoic acid (RA) on testosterone metabolic pathway was investigated in hyperplastic and neoplastic human prostatic tissues, and also the effects of steroids on RA binding to its receptor. Steroids only had a minimal effect on the binding of RA by its receptor. The conversion of testosterone to DHT by 5α‐reductase was reduced in the presence of retinoic acid. The inhibition was probably due to competition with NADPH for enzyme binding sites. The degree of inhibition found with retinoic acid at a concentration of 10−4M was greater for hyperplastic (41%) than that for neoplastic tissue (24%). The inhibition of 5α‐reductase by retinoic acid was dose‐dependent. The activity of 5α‐reductase is significantly less in neoplastic compared with hyperplastic tissue.
Relationship of age to histologic grade in prostate cancer
Authors: Borek Deborah , Butcher David , Hassanein Khatab , Holmes Frederick 
Published: February 2007

AbstractWe studied 4,968 cases of prostatic carcinoma to determine if there is a relationship between tumor grade and patient age at diagnosis. Cases were stratified into arbitrary age groups and classified as either better differentiated (Grades I and II) or worse differentiated (Grades III and IV). The 4,596 graded cases were distributed by stage as follows: Local 3,451 (75%), Regional 509 (11%), and Distant 636 (14%). When patients in all stages were considered together, the percentage of men with better differentiated tumors dropped from 77.8% of patients under 60 to 67.5% of patients 80 or older (P<0.00001). This trend for older patients to have more poorly differentiated tumors was also seen in patients with localized disease (P>0.0005). The fact that occult, biologically inactive prostate cancer is common in older men has led some to extrapolate that clinically apparent disease follows a more benign course in the elderly. Our findings suggest that, on the contrary, elderly men with clinically apparent disease have worse differentiated tumors than their younger counterparts.
R 75251, a new inhibitor of steroid biosynthesis
Authors: Bruynseels J. , De Coster R. , Van Rooy P. , Wouters W. , Coene M.‐C. , Snoeck E. , Raeymaekers A. , Freyne E. , Sanz G. , Vanden Bussche G. , Vanden Bossche H. , Willemsens G. , Janssen P. A. J. 
Published: February 2007

AbstractR 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11‐deoxycorticosterone to corti‐costerone in human placenta microsomes, subcellular fraction of rat testis, bovine adreno‐cortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side‐chain cleavage was found at concentrations up to 10 μM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed.In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17α‐hydroxy‐progesterone and progesterone.As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco‐ and mineralocorticoids such as 11‐deoxycortisol and 11‐deoxycorticosterone accumulated more than after ketoconazole administration.The data show that the cytochrome P450‐dependent aromatase, 17‐hydroxylase/17,20‐lyase, and 11‐hydroxylase are the target enzymes for R 75251.