bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of estradiol‐17β hydroxysteroid oxidoreductase in the urogenital tract of control and neonatally estrogenized male mice: Immunohistochemical, enzymehistochemical, and biochemical study
Authors: Pylkkänen L. , Santti R. , Mäentausta O. , Vihko R. 
Published: February 2007

AbstractThe present study was conducted to investigate the regional distribution of the enzymes catalyzing the interconversion of the hydroxyl and carbonyl groups at C‐17 of the estrogen molecule within the male urogenital tract of adult mouse and to test the hypothesis, whether regional differences in the distribution are critical for estrogen responses.The highest ratios of NADPH‐dependent 3H‐estrogen reduction to oxidation at C‐17 of cell‐free homogenates were obtained from coagulating gland and seminal vesicle as well as from the prostatic and lower intrapelvic urethra, which are considered the most estrogensensitive parts of the male urogenital tract. Both NADP‐ and NAD‐dependent oxidation of 3H‐17β‐estradiol were low or nondetectable at these sites. The epithelium of the lower and prostatic urethra as well as the periurethral collecting ducts were stained with the antibody prepared against human placental 17β‐hydroxysteroid oxidoreductase.The NAD‐dependent 3H‐estradiol‐17β oxidase activity was highest in the bladder epithelium, and the activity declined sharply in the urinary tract from the bladder downward. The lowest detectable activities were found in vas deferens and prostate (combined ventral and dorsolateral lobes). The uneven distribution of estradiol‐17β oxidase activity may provide additional explanation for the regional differences of estrogen responses.The NADPH‐dependent 17β‐reduction of estrone and the immunohistochemical staining of the human placental estradiol‐17β oxidoreductase antigenicity were not significantly altered after neonatal estrogenization. These findings do not lend any support to the idea that the increased estrogen sensitivity observed after neonatal estrogenization is associated with changes in 17β‐oxidoreduction. However, the possibility remains that there are specific sites (e.g., epithelium of prostatic urethra and collecting ducts) in which the changes in 17β‐oxidoreduction of estrogen does play a role in the regulation of estrogen action.
The relative efficacy of terazosin versus terazosin and flutamide for the treatment of symptomatic BPH
Authors: Lepor Herbert , Machi Grace 
Published: February 2007

AbstractPharmacotherapy for the treatment of BPH is currently being targeted to relax prostate smooth muscle (alpha blockade) and decrease prostate volume (androgen suppression). The objective of the present study was to determine the relative efficacy of terazosin vs. terazosin and flutamide (combination therapy) for the treatment of symptomatic BPH. Twenty‐nine males with symptomatic BPH were enrolled into this 6‐month open label study. The entry criteria included peak urinary flow rate between 4–15 ml/sec, a total Boyarsky symptom score greater than 7, and postvoid residual less than 300 ml. The daily dosage of terazosin was titrated to 5 mg over a 2‐week interval. A 750 mg daily dosage of flutamide was added following 1 month of terazosin monotherapy. The dosages were lowered if significant adverse events developed. Efficacy assessments were performed at 1 month (terazosin alone), 6 months (combination therapy), or at the time of early withdrawal from the study. The efficacy of combination therapy was evaluable in 24 patients receiving combination therapy. At one month, the mean peak urinary flow rate and mean total Boyarsky symptom score improved 38% and 56% relative to baseline, respectively. The present study confirmed the previously observed efficacy and safety of terazosin for BPH. The addition of flutamide did not result in statistically significant improvements in the peak urinary flow rate or total Boyarsky symptom score. The adverse events related to flutamide resulted in 16 dose reductions and 14 premature withdrawals. The role of combination therapy will require a randomized placebo controlled study sufficiently powerful to identify clinically and statistically significant improvements in objective outcome parameters relative to the monotherapies.
Temperature mapping in the canine prostate during transurethrally‐applied local microwave hyperthermia
Authors: Roehrborn Claus G. , Krongrad Arnon , McConnell John D. 
Published: February 2007

AbstractAlthough the therapeutic effects of heat on tumors have been known for more than a century, only recently has hyperthermia been applied in the treatment of various solid tumors in a scientific fashion. In preliminary clinical trials, heat applied by transurethrally or transrectally placed microwave antennas has been used in the treatment of benign prostatic hyperplasia (BPH) with some success. However, basic information about prostatic temperature distribution and the cellular effects of hyperthermia is lacking. In an attempt to establish the safety of local hyperthermia of the prostate and the precise temperature distribution within the gland, we performed temperature mapping studies in canine prostates. Eight mongrel dogs were anesthetized, and a 16 Fr catheter with three helical coil microwave antennas was placed in the bladder through a perineal urethrostomy. Laparotomy was performed and the bladder opened. The antennas were placed under direct control in the prostatic urethra. Linear array and single point thermometers (Clini‐Therm TS1200 thermometry system) were placed (1) within the catheter alongside the antennas, (2) alongside the Foley catheter in the urethra, and (3) longitudinally and radially in the prostate for mapping of tissue temperature. Heating was performed with a 915‐MHz ISM frequency Z‐80 microprocessor controlled microwave power generator (Prostek 3000, Clini‐Therm Corporation, Dallas, TX) using 2–9 watts per channel (6–27 watts total) for 30 min to 1 hr.Baseline body temperatures varied between the individual dogs from 37° to 38°C, but temperature distribution within the prostate was even prior to heating. With relatively low power (6 watts total), temperatures of ˜45°C were reached within the catheter. Therapeutic temperatures of ˜43°C were achieved in the periurethral prostate. Intraurethral temperatures were in general 1–2°C lower than within the catheter. The radial temperature dropoff in the prostate was sharp and about 1°C per 3‐mm distance from the catheter. This would limit the area of effectiveness to a periurethral zone of 1 cm in diameter in this model. No unsafe temperature peaks were noted either intraurethrally or between the prostate and the rectum during steady‐state conditions. Histologic studies demonstrated an intact rectal wall and varying degrees of prostatic inflammation and/or necrosis despite uniform treatment regimens administered. These studies demonstrate the short‐term safety of microwave hyperthermia in the canine prostate. Further studies will be necessary to determine the clinical efficacy and toxicity in men with BPH.
Effects of 6‐methylene progesterone on growth, morphology, and blood flow of the dunning R3327 prostatic adenocarcinoma
Authors: Damber J.‐E. , Bergh A. , Daehlin L. , Petrow V. , Landström M. 
Published: February 2007

AbstractCopenhagen x Fisher F1 rats were implanted with the androgen‐dependent Dunning R3327 prostatic adenocarcinoma. When the tumors had median volumes of ca 470 mm3, the rats were castrated and/or treated with 6‐methylene‐4‐pregnene‐3,20‐dione (6MP) in different doses. Tumor growth inhibition occurred in all castrated and treated groups, with decrease in volume of the epithelial compartment in the intact group. Tumor volumes at the highest dose level of 6MP equalled those observed in the castrate group. Plasma levels of testosterone were within the normal range. The administration of 6MP surprisingly induced an increment of tumor blood flow in the castrate group. Also in castrated and testosterone‐supplemented animals, 6MP induced a reduction of prostatic tumor growth. Through the castration‐like effect on tumor growth, the use of 6MP may represent an attractive alternative to castration for treatment of androgen‐responsive prostate cancer.
Estrogen treatment of dunning tumors in castrated rats: Qualitative and quantitative morphology
Authors: Landström M. , Bergh A. , Thornell L.‐E. , Virtanen I. , Damber J.‐E. 
Published: February 2007

AbstractAdult male rats bearing the Dunning R3327 prostatic carcinoma were randomized to the following treatments: intact controls, castration, and castration + estrogen. After a study period for 6 weeks the rats were killed and the tumors were analyzed morphometrically to determine the amount of epithelium, stroma, and connective tissue fibers in the tumors, and the nuclear size of large stromal cells. Cryostat sections were analyzed with immunohistochemistry using a panel of antibodies against cytokeratins, desmin, vimentin, fibronectin and collagens.Addition of estrogen to castration resulted in an inhibition of tumor growth. The expression of cytokeratin 14 (a marker for basal myoepithelial cells) was reduced, but the expression of cytokeratin 18 (a marker for the luminal epithelial cells) was unaffected by estrogen. The amounts of collagen I, III and fibronectin (plasma and cellular types) were increased in the stroma, and the nuclear size of large stromal cells was also increased by estrogen. It is concluded that castration + estrogen treatment has effects in the epithelium and stroma of Dunning tumors that are qualitatively and quantitatively different from the effects of castration alone.
Prognostic significance of antigenic heterogeneity, gleason grade, and ploidy of lymph node metastases in patients with prostate cancer
Authors: Bazinet Michel , Hamdy Seif M. , R. Bégin Louis , Stephenson Robert A. , Fair William R. 
Published: February 2007

AbstractWe retrospectively evaluated 51 prostate cancer patients found to have pelvic lymph node metastases at the time of pelvic lymphadenectomy and 125I implantation. All of them were followed until death or for a minimum of 70 months. Rabbit polyclonal anti‐PSA, anti‐PAP, anti‐PSP‐94, and mouse TURP‐27 monoclonal antibodies were used in immunohis‐tochemical evaluation of the metastatic lesions. In addition, Gleason grade and ploidy were assessed and correlated.No tumor with a Gleason grade of less than 7 could be found in the metastatic lymph nodes. Time to progression (P = 0.003), disease‐specific survival (P = 0.009), and overall survival (P = 0.003) were significantly shorter in patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10).In the PSA study, patients whose tumors were reactive in more than 75% of cancer cells experienced significantly longer survival than those with less than 75% of cancer cells expressing PSA (P = 0.0006 log rank test). The means of overall survival ± SEM were 71.5 ± 5.0 and 34.9 ± 5.4 months, respectively. Similar correlations were found with disease‐specific survival and time to progression. Patterns of PAP expression and TURP‐27 reactivity were not prognostically useful, whereas PSP‐94 expression may add some additional information.These data suggest that evaluation of tissue PSA heterogeneity in lymph node metastases may offer additional prognostic information on prostate cancer patients. Better prediction of individual prognosis may be possible with the combined use of Gleason grade, flow cytometry, and PSA expression.
Induction of proliferative lesions of ventral prostate, seminal vesicle, and other accessory sex glands in rats by N‐methyl‐N‐nitrosourea: Effect of castration, pretreatment with cyproterone acetate and testosterone propionate, and rat strain
Authors: Bosland Maarten C. , Prinsen Menk K. , Kroes Robert , Rivenson Abraham , Silverman Jerrold , Fiala Emmerich , Williams Gary M. , Weisburger John H. 
Published: February 2007

AbstractWistar (Cpb:WU), F344 or Sprague‐Dawley rats were sequentially treated with cyproterone acetate (CA) for 21 days, testosterone propionate (TP) for 3 days, followed by a single i.v. injection of N‐methyl‐N‐nitrosourea (MNU). One group of Wistar rats was castrated 4 weeks after MNU injection, and another group 58 weeks after MNU, when the first prostatic carcinoma was detected. Control groups received only CA + TP, CA, MNU, or they remained untreated. Early or late castration inhibited the development of atypical hyperplasia of the ventral prostate in Wistar rats. This lesion was induced by the CA + TP + MNU treatment in F344 rats, but not Sprague‐Dawley rats; in Wistar rats, it was induced by CA + TP treatment, irrespective of whether MNU was given. Hypertrophichyperplastic lesions of the seminal vesicle were induced by MNU, irrespective of pretreatment, and their development was prevented by early castration and inhibited by late orchiectomy. Dorsolateral prostate carcinomas and preneoplasia occurred only in low incidence in Wistar and Sprague‐Dawley rats. These lesions were absent in F344 rats that had received treatment with CA + TP + MNU. No dorsolateral prostate (pre)neoplasia was found in Wistar rats subjected to early orchiectomy, but rats castrated at 58 weeks had an incidence similar to that for the intact group treated with CA + TP + MNU. This finding supports the contention that androgens are required for the development of MNU‐induced prostatic cancer in rats but that advanced carcinomas are androgen insensitive. Differences in incidence and localization of prostatic proliferative lesions between F344 and Wistar rats and between dorsolateral and ventral prostate could not be explained by differences in epithelial cell proliferative responses to CA +TP treatment at the time of MNU injection, since they were similar in ventral and dorsolateral prostate and were more prominent in F344 rats than in Wistar rats. DNA damage as estimated by MNU‐induced unscheduled DNA synthesis also did not differ between dorsolateral and ventral prostate.
The development of vascular supply of normal rat prostate during the sexual maturation: An angiographic study
Authors: Scolnik M. , Abramovici A. , Servadio C. , Tykochinsky G. 
Published: February 2007

AbstractVascular distribution of small blood vessels and capillaries using India ink angiography was studied in normal rat prostate from puberty up to full sexual maturation. The study included both macroscopic observation of the lobular vascular irrigation and the histological assessment of the periacinar capillary network. The topographical distribution of the main prostate branches was found to be different among the rat prostate lobes. The ventral lobe seems to be better irrigated than the dorsal one. The former being supplied by two parallel vascular systems, one irrigating the median two‐thirds of the ventral lobe, whereas the remaining external one‐third was found to be conjointly irrigated from the pericapsular branches of the fat pads. The blood vessels of the dorsal and lateral lobes emerged radially from a periurethral circle, with the dorsal branches ending blindly in the connective tissue of the pelvic cavity, whereas the lateral prostate was also conjointly irrigated by a dual vascularization from the pericapsular fat pad and the periurethral circle branch. The histological study revealed quantitative differences between the periacinar capillaries of both ventral and dorsal lobes. The capillary density was found to be age dependent and directly proportional to the acinar size. Small acini were less well irrigated by capillaries than were the larger ones.The number of capillaries per acinar area increased progressively toward the maturation (day 90); thereafter, their number remained constant. Both prostate lobes showed identical patterns. The heterogeneous vascular networks among the rat prostatic lobes might offer an additional clue for their distinctive morphophysiological characteristics, which most probably play a role in various pathogenetic processes.
Cellular differentiation in prostatic explant cultures: Assessed by electron microscopy and X‐ray microanalysis
Authors: Halgunset Jostein , Tvedt KåRe E. , Kopstad Gunnar 
Published: February 2007

AbstractA method developed for X‐ray microanalysis (XRMA) of cell monolayers cultured on Formvar film has been shown to be well suited for the study of explant cultures of human prostate. Adherence and epithelial cell outgrowth occur as readily on the formvar as on ordinary tissue culture plastic, giving rise to cultures with the same morphological characteristics. Conventional transmission electron microscopy revealed intracytoplasmic granules with the appearance of secretory vesicles. XRMA of electron‐dense intracytoplasmic granules in freeze‐dried cryosections showed significant local sequestration of calcium, but not of magnesium or zinc, elements that have previously been shown to colocalize with calcium in secretory granules in vivo. It is concluded that some aspects of the secretory phenotype are supported in this in vitro model. The factors regulating the expression of a differentiated phenotype in prostatic epithelium await further elucidation. XRMA may be useful in assessing the effects on secretory differentiation induced by variations in the Culture conditions.
The prognostic value of histological grading and mean nuclear volume in human prostatic cancer
Authors: Nielsen Karsten , Berild Grete H. , Bruun Eywin , Jøsrgensen Per , Weis Nina 
Published: February 2007

AbstractFifty‐eight consecutive patients diagnosed with prostatic cancer at transurethral resection in the period 1979‐1983 were classified using histological grade according to Shelley, and using an unbiased estimate of mean nuclear volume. We find that both histological grade and mean nuclear volume appear to be significantly associated with survival. In eight of nine patients still alive after 89‐130 months mean nuclear volume at diagnosis was in normal range and the histological grade showed a highly differentiated cancer in eight of the nine cases. These findings suggest highly differentiated cancer and normal range of mean nuclear volume may be important for long‐term survival. In patients with advanced disease requiring endocrine treatment both histological grading and mean nuclear volume estimates failed to show any prognostic properties with regards to time to progression and time of survival. In patients not subjected to endocrine treatment histologic grade, but not mean nuclear volume, was found to be significantly associated with survival. Subtle changes in disease progression may be diagnosed early by repeated biopsies due to the accuracy and high reproducibility of mean nuclear volume measurements; however, a single estimate of mean nuclear volume has not been shown to offer advantage over histological grade with respect to prognostic properties. α 1992 Wiley‐Liss, inc.
Hormonal regulation of prostate‐specific antigen (PSA) glycoprotein in the human prostatic adenocarcinoma cell line, LNCaP
Authors: Montgomery Benjamin T. , Young Charles Y.‐F. , Bilhartz David L. , Andrews Paul E. , Thompson Nels F. , Tindall Donald J. , Prescott James L 
Published: February 2007

AbstractProstate‐specific antigen (PSA) has emerged as the most useful marker for management of patients with prostate cancer. The regulation of this glycoprotein in vivo has important clinical implications. Indirect evidence indicates that the PSA glycoprotein might be regulated by androgens, and previous studies in this laboratory have demonstrated that PSA mRNA is upregulated by androgens. The current work reports a detailed study of PSA glycoprotein expression as influenced by steroid hormones in a human prostatic adenocarcinoma cell line, LNCaP. First, we have examined the steroid binding specificity of the androgen receptor in this cell line. In comparison with wild‐type rat androgen receptor in prostate, the receptor in LNCaP cells has altered affinity for a number of steroids or analogs such as progesterone (R5020), antiprogesterone (RU486), two antiandrogens (cyperoterone acetate and hydroxyflutamide), and an androgen metabolite (epitestosterone). However, its affinity for androgens (mibolerone, dihydrotestosterone, and testosterone) is not changed. The receptor does not bind to the synthetic glucocorticoids (triaminolone acetonide and dexamethasone) nor to a synthetic estrogen DES (diethylstilbestrol). The change of the steroid binding specificity of the receptor is correlated with a single mutation (A → G at nucleotide #876 relative to the initiation codon) of the steroid binding domain of the receptor. The mutation and alteration of steroid‐binding specificity of the androgen receptor is also correlated with PSA glycoprotein expression affected by different ligands tested. We have demonstrated that the PSA glycoprotein is upregulated by androgens and is affected by neither epidermal growth factor nor basic fibroblast growth factor. Moreover, PSA glycoprotein could be induced by R5020, estradiol, and epitestosterone; but neither glucocorticoids nor DES had any effect on PSA induction. Interestingly, although the antiandrogen, cyperotone acetate, had the ability to induce PSA, both RU486 and hydroxyflutamide could block androgen and progesterone induction of PSA glycoprotein. Therefore, we conclude that the PSA glycoprotein expression is influenced predominantly by androgens via its receptor, and the mutation of the receptor can affect the expression of this cellular gene by the steroids other than androgens.
Presence of calcitonin‐like immunoreactivity (iCT) in human prostate gland: Evidence for iCT secretion by cultured prostate cells
Authors: Shah Girish V. , Noble Mark J. , Austenfeld Mark , Weigel John , Deftos L. J. , Mebust Winston K. 
Published: February 2007

AbstractImmunoreactive calcitonin (iCT) has been detected in human prostate tissue extracts as well as seminal plasma. The present studies were undertaken to examine whether iSCT (immunoreactive salmon CT‐like human peptide) co‐exists with iHCT (thyroid CT‐like substance) in human prostate tissue extracts, and whether these substances are secreted by primary prostate cells in culture. Since the local secretion of these substances seems to increase in some neoplasms, a second objective of the study was to examine whether basal secretion of iCTs from primary prostate cells is increased in carcinoma. The present results have shown that both iHCT and iSCT were present in prostate tissue extracts. The mean iHCT levels in extracts of benign hyperplastic prostates (BPH) were 0.59 ng/g prostate, and these were significantly lower than iHCT concentrations in prostatic carcinoma (PC) (2.53 ng/g). No significant differences in their iSCT contents were observed. However, the results from culture of over 90 individual prostate tissue specimens from BPH or PC indicate that primary prostate cells secreted detectable quantities of iSCT and the basal release of this material from PC prostate cultures was almost four‐fold higher than that from BPH prostate cultures.These results suggest that a CT‐like immunoreactive material is secreted by primary prostate cells in culture, and the basal secretion of this material is significantly higher in PC cells as compared to BPH cells. Endogenous secretion of prostatic CT, and the elevation of its expression in PC suggest that it may serve as a regulatory factor in the pathophysiology of the prostate gland.