bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of age, strain, and the testes on rat prostate hormone sensitivity
Authors: Hildebrand Randall K. , Naslund Michael J. , Oesterling Joseph E. , Coffey Donald S. 
Published: February 2007

AbstractThere are conflicting reports in the literature regarding the response of the rat prostate to various androgen/estrogen combinations. The reason for these conflicting results has been unclear. The purpose of the present study was to assess factors that may determine the effect of sex hormones on rat prostate growth. The results of this study demonstrate that the prostates of Lewis rats respond differently to sex hormone combinations than do those of Sprague Dawley rats. Young rats have a different prostate hormone responsiveness than do old rats. The presence or absence of the testes alters the responsiveness of the prostate gland to androgen‐estrogen combinations. These results suggest that strain, age, and the presence of the testes are important factors which will influence the response of the rat prostate to hormonal manipulation. The importance of these factors should be considered in the design of experiments which deal with the response of the rat prostate to hormone manipulation.
Treatment response with transurethral microwave hyperthermia in different forms of benign prostatic hyperplasia: A preliminary report
Authors: Baert L. , Willemen P. , Ameye F. , Petrovich Z. 
Published: February 2007

AbstractDuring a 7‐month period, 79 patients with benign prostatic hyperplasia (BPH) were treated with 915 MHz transurethral hyperthermia (TUHT). All patients had obstructive and irritative signs and symptoms which warranted surgical treatment considerations. Of the 79 patients treated, 31 had follow‐ups of 12 months or longer and seven additional patients experienced treatment failure requiring surgical management. These 38 patients were studied to evaluate the relationship of treatment response to the pretreatment prostatic morphology assessed during cystoscopy. There was a well‐balanced distribution of patients regarding the important pretreatment characteristics in different morphological types of prostatic hypertrophy. These important characteristics included: prostate volume, postvoiding residual volume, mean peak flow rate, and mean symptom score on the FDA scale.The study patients were scheduled to receive five 60‐min TUHT sessions with temperature controlled on the urethral surface at 45.5°C. The treatments were well tolerated and administered on an outpatient basis without sedation or anesthesia.There was a significant difference in the incidence of major improvement in patients with lateral lobe hyperplasia and those with median lobe enlargement, 73 vs. 30%, P = 0.018. From this study, it appears that BPH patients who are found at cystoscopy to have a predominance of median lobe hypertrophy should, perhaps, be selected for treatment other than TUHT. A Phase I study utilizing a modified transurethral applicator to accommodate the specific problem of patients with median lobe hyperplasia is currently being planned.
The efficacy and safety of terazosin for the treatment of symptomatic BPH
Authors: Lepor Herbert , Henry David , Laddu Atul R. 
Published: February 2007

AbstractAt least 16 clinical investigations have documented the effectiveness of alpha blockade for BPH. In the present review, four clinical studies evaluating the efficacy and safety of terazosin, a selective long‐acting alpha1 blocker, for symptomatic BPH are reviewed. The unique features of these clinical investigations are: the study designs established detailed inclusion and exclusion criteria, the outcome assessments were based upon quantitative outcome parameters, large cohorts of homogeneous patients were enrolled, and appropriate statistical methods were utilized. The dose of terazosin was titrated to maximal doses ranging between 5–20 mg. Only four of the 163 patients developed orthostatic hypotension. Overall, the peak and mean uroflow rates increased 50% and 46%, respectively (P < 0.001). The cumulative improvement in the mean obstructive, irritative, and total symptom scores was 67%, 35%, and 54%, respectively (P < 0.001). The present review of terazosin in males with symptomatic BPH supports the following conclusions: (1) the dose of terazosin can be safely titrated to 10 mg in normotensive and hypertensive patients with symptomatic BPH; (2) the adverse events associated with doses of terazosin up to 10 mg are relatively mild and reversible; and (3) the improvements in the outcome parameters (symptom scores and urinary flow rates) are clinically and statistically significant. Although the ultimate role of terazosin for symptomatic BPH will be determined by multi‐center randomized placebo‐controlled studies, the present review provides further evidence that selective alpha1 blockers are effective and safe for the treatment of symptomatic BPH.
Density‐dependent regulation of epidermal growth factor receptor expression in DU 145 human prostate cancer cells
Authors: Tillotson Joanne K. , Rose David P. 
Published: February 2007

AbstractAndrogen‐independent prostate cancer cells may rely on an autocrine loop for growth stimulation, and have been shown to express both the epidermal growth factor receptor (EGFR) and its stimulatory ligands. We have shown here that DU 145 prostate cancer cells have a decreased amount of EGFR in confluent cultures when compared to levels seen in subconfluent cultures. This down‐regulation of EGFR numbers is not due to cell proliferation or nutrient depletion, but can be correlated only with whether cell‐cell contact exists throughout the culture. This is reminiscent of the situation existing in some tumors whereby EGFR expression is higher in cells at the invading margins of the tumor.
Bladder exstrophy‐epispadias complex: Prostatic evaluation by transrectal ultrasonography
Authors: Hamper Ulrike M. , Gearhart John P. , Dahnert Wolfgang F. , Sheth Sheila , Jeffs Robert D. 
Published: February 2007

AbstractSeven patients with bladder‐exstrophy‐epispadias complex underwent high resolution prostatic ultrasonography in order to establish the presence and appearance of their prostate gland and seminal vesicles. Six patients had been born with classic bladder exstrophy, and one patient with complete epispadias. The size of the prostate gland was in the normal range in three patients. Three patients had small glands, and in one patient no prostatic tissue could be identified. Two patients showed an unusual position or echoappearance of their glands. The seminal vesicles in five patients were relatively large, contained multiple cystic spaces, and/or extended posteriorly and inferiorly to the prostate gland proper.Our study demonstrates that the prostate gland and seminal vesicles are present in patients with bladder exstrophy. The unusual appearance, position, and size in most patients, however, suggests faulty embryologic development or changes secondary to surgery reflecting the complex nature of the condition. Likewise, the enlarged seminal vesicles may indicate impaired drainage of these structures secondary to the initial bladder closure or subsequent bladder neck reconstruction.
Culture of prostatic epithelial cells from ultrasound‐guided needle biopsies
Authors: Peehl Donna M. , Wong Stephen T. , Terris Martha K. , Stamey Thomas A. 
Published: February 2007

AbstractA protocol which was developed for the culture of epithelial cells from radical prostatectomy specimens was slightly modified to permit the culture of cells from ultrasound‐guided prostatic needle biopsies. The collagenase digestion step of the standard protocol was omitted, and biopsies were simply minced and allowed to attach to collagen‐coated dishes in serum‐free medium. Cell outgrowths from biopsies were free of fibroblasts, and expression of keratin, prostate specific antigen, and prostatic acid phosphatase was maintained in vitro. The establishment of a bank of frozen cells from primary cultures permitted repetitive studies with individual cell strains, which could be serially passaged and were capable of clonal growth. The ability to derive cultures from biopsies will facilitate the biological characterization of cells from primary prostate tumors of high malignant grade, which are not commonly available from radical prostatectomy specimens.
Autocrine regulation of DU145 human prostate cancer cell growth by epidermal growth factor‐related polypeptides
Authors: Connolly Jeanne M. , Rose David P. 
Published: February 2007

AbstractThe DU145 human prostate cancer cell line possesses epidermal growth factor (EGF) receptors and synthesizes both EGF and the related polypeptide transforming growth factor α (TGF‐α). A monoclonal antibody to the EGF receptor was used to determine whether these characteristics were indicative of a functional autocrine regulatory system. This antibody competed effectively with [125I]EGF for binding to DU145 cell binding sites over a 1 × 10−11 to 1 × 10−7 M concentration range, and did so with a capability similar to that of the two natural ligands. It inhibited growth of these cells in both 3% fetal bovine serum‐supplemented and serum‐free medium; in experiments with incubation times of 3–5 days there was a 45–50% reduction in cell number. Growth suppression by the EGF receptor blockade of cells plated at a density of 1.5 × 104 cells/ml/well was reversed competitively by the addition of EGF to the medium; 0.3 nM completely eliminated the inhibitory effect of a 1 × 10−9 M antibody concentration. It is concluded that DU145 cell growth is regulated by an EGF‐mediated autocrine loop.
Characterization of Gelatin‐Degrading Metalloproteinase Activities of the Dunning Rat Prostate Tumor Grown in Nude Mice
Authors: Wilson Michael J. , Kapoor Sunil , Vogel Mary M. , Sinha Akhouri A. 
Published: February 2007

AbstractProteinase activities in the Dunning R‐3327 prostatic tumor grown in nude mice and the dorsal lobe of the normal Copenhagen rat prostate were characterized using gelatin‐containing SDS‐polyacrylamide gel electrophoresis. Calcium‐stimulated activities of approximately 33, 42, 64, 71, 76, 85, 98, 115, and 120 Kd as well as a 91 Kd calcium‐independent proteinase were detected in the tumor, whereas the dorsal prostate showed calcium‐dependent activities of approximately 62 and 80 Kd and a calcium‐independent activity >120 Kd. The zymographic calcium‐dependent proteinase patterns in the other rat prostatic lobes (a 62 Kd proteinase in the anterior lobe; 59, 62, and 67 Kd forms in the ventral lobe; and 52, 62, and 72 Kd activities in the lateral lobe) were distinctive from that of the tumor and of the dorsal lobe. The calcium‐dependent and ‐independent proteinases of the tumor were active over a broad range of pH values with optimal activity near pH 8.0–8.4. The calcium‐dependent activities were inhibited by EDTA and EGTA. Barium and strontium could partially substitute for calcium. The calcium‐independent activities were not affected by these chelators nor by the proteinase inhibitors benzamidine, ϵ‐aminocaproic acid, tranexamic acid, hydrocinnamic acid, or iodoacetate. Similarly, the metalloproteinase activities were not affected by the latter inhibitors. There was little change in the predominant molecular forms (64, 71, and 76 Kd) of proteinase following castration of tumor‐bearing nude mice; however, the 98 Kd calcium‐dependent activity decreased and the 91 Kd calcium‐independent activity increased as a result of this treatment.
Distribution of lactoferrin in the normal and inflamed human prostate: An immunohistochemical study
Authors: Reese Jeffrey H. , McNeal John E. , Redwine Elise A. , Sellers Robert G. , Goldenberg S. Larry 
Published: February 2007

AbstractA polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation‐related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate‐specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post‐inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post‐inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin‐positive.Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin‐filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate.
Interactions between epidermal growth factor‐mediated autocrine regulation and linoleic acid‐stimulated growth of a human prostate cancer cell line
Authors: Connolly Jeanne M. , Rose David P. 
Published: February 2007

AbstractHuman prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF‐related polypeptides. We used an EGF receptor‐blocking antibody (anti‐EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega‐6 fatty acid, on PC cell growth. The anti‐EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high‐passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose‐dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration‐related manner over a range of 0.25–2.0 μg/ml. Anti‐EGF.R (10−9 M) caused suppression of LA‐stimulated growth of DU145M cells in serum‐free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R‐mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.
α1‐Adrenoceptor properties of terazosin HCl and its enantiomers in the human prostate and canine brain
Authors: Meretyk Shimon , Tang Rui , Shapiro Ellen , Lepor Herbert , Kyncl John J. 
Published: February 2007

AbstractThe objective of the present study was to characterize the α1‐adrenoceptor binding properties of terazosin and its enantiomers in human prostate and canine brain. Human prostate adenomas were obtained from 7 males undergoing prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from 6 male beagles. Competitive displacement experiments were carried out on these tissue homogenates in the presence of a constant concentration ([80 pM]) of 125I‐Heat and varying concentrations of unlabelled terazosin and its enantiomers. The Ki of terazosin and its enantiomers were determined from these binding studies. The mean Ki of rac‐terazosin, R(+)‐terazosin, and S(−)‐terazosin in human prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between these mean Ki values were not statistically significant. The mean Ki of rac‐terazosin, R(+)‐terazosin, and S(−)‐terazosin in canine brain were 6.7 nM, 8.4 nM, and 5.6 nM, respectively. The differences between these mean Ki values were not significantly different. The mean Ki of terazosin and its enantiomers were consistently lower in the human prostate compared to canine brain (P>0.05). The present study does not provide any evidence suggesting differential effects of terazosin enantiomers on the human prostate. The twofold difference between the Ki values in the prostate and brain suggests that different subtypes of the α1‐receptor might be present in these tissues.
Effects of clonidine‐induced hypotension and dopamine‐induced hypertension on blood flows in prostatic adenocarcinoma (dunning R3327) and normal tissues
Authors: Jonsson Östen , Widmark Anders , Grankvist Kjell , Damber Jan‐Erik , Henriksson Roger 
Published: February 2007

AbstractIn the present study it was investigated whether hypertension induced by dopamine or hypotension induced by clonidine could influence the relative blood distribution in a s.c. transplanted prostatic adenocarcinoma in relation to blood flow in normal tissues in rats. The blood flow was measured by using a radioactive microspheres technique. A bolus injection of 5 μg clonidine caused a decrease in the systemic blood pressure with 15–45 mm Hg, and blood flow to the central parts of the tumor, decreased with more than 50%. In the prostate, testes and ileo‐psoas muscle a similar reaction was seen. During an infusion of 95–120 μg/kg/min dopamine, the blood pressure increased with 15–30 mm Hg, but the blood flow to the tumor was unchanged. However, in the testes and kidneys a decreased blood flow was observed. Moreover, mean blood flow to the central parts of the tumor decreased with increase in tumor size. The results further indicated that hyper‐ or hypotension or concomitantly given vasoactive drugs with the specific cancer treatment can have unwarranted effects on the distribution of cytotoxic drugs and oxygenation of the tumor.
Effect of pentosan, a novel cancer chemotherapeutic agent, on prostate cancer cell growth and motility
Authors: Pienta Kenneth J. , Murphy Brian C. , Isaacs William B. , Isaacs John T. , Coffey Donald S. 
Published: February 2007

AbstractPentosan is a new chemotherapeutic drug which is currently in Phase I clinical trials. In our experimental systems, in vivo, pentosan inhibits the growth of the highly metastatic MAT‐LyLu (MLL) Dunning R3327 prostate cancer cell line only at toxic doses and has no apparent effect on growth in vitro. The mechanism of tumor inhibition of this drug is unknown; however, in vitro, pentosan exhibits a potent inhibition of cell motility. Cell motility is essential for tumor cell metastasis and angiogenesis. By blocking cell motility, pentosan has the potential to inhibit both tumor growth and metastasis. We have characterized the mechanism of motility inhibition by pentosan and believe it alters cell‐extracellular matrix interactions. The mechanism of motility inhibition by pentosan appears to be independent of cytoskeletal structural alterations, including changes in microfilament and microtubule networks. Pentosan acts through a different mechanism than suramin, a drug which inhibits motility through inhibition of growth factor effects. In vitro, pentosan alters cellular contacts with the extravascular matrix and inhibits cell motility. In vivo, pentosan prolongs survival of rats injected with MLL cells by 25%, but did not appear to decrease the rate of primary tumor growth or the number of metastatic lesions in the treated animals. These data suggest that, in vivo, pentosan acts through an as yet undefined mechanism.
Infrequent RAS oncogene mutations in human prostate cancer
Authors: Moul Judd W. , Friedrichs Paul A. , Lance Raymond S. , Theune Sheila M. , Chang Esther H. 
Published: February 2007

AbstractThe RAS gene family includes three functional genes, H‐RAS, K‐RAS, and N‐RAS, which have been most widely studied in human tumors. Point mutations most commonly occurring at codons 12, 13, or 61 of these genes allow the RAS protooncogene to be converted to a RAS oncogene. A variety of human tumors have been studied for RAS mutations to date, however, conflicting data has been reported regarding prostate cancer. Cell line studies and two American studies of clinical material have found a low incidence of RAS mutation in prostate cancer. The few mutations found were predominantly in the H‐RAS gene. Conversely, a recent study of Japanese occult autopsy specimens found an approximate 25% incidence of K‐RAS mutations.In this current study, DNA was extracted from 24 archival paraffin‐embedded, formalin‐fixed radical prostatectomy specimens. Twenty‐one of the 24 cases had pathologic stage C disease, and paraffin blocks were selected having the most concentrated area of neoplasm. Twelve, seven, and five cases demonstrated moderate, well and poorly differentiated histologic grade respectively. Polymerase chain reaction (PCR) was used to amplify the K‐RAS, N‐RAS, and H‐RAS 12, 13, 61 codons of these specimens and mutations were detected with mutation‐specific oligonucleotide probe hybridization of southern and slot blots. No definite point mutations were detected. PCR's and hybridizations were performed three separate times by three investigators to confirm these results. PCR‐generated mutation‐specific positive controls and known negative controls were used and found to be important to interpret oligonucleotide hybridization assays. RAS gene mutations appear to be infrequent in clinical prostate carcinomas in American males.
Regulation of prostatic carcinoma cell proliferation and secretory activity by extracellular matrix and stromal secretions
Authors: Fong Chau‐Jye , Sherwood Edward R. , Braun Eva J. , Berg Lori A. , Lee Chung , Kozlowski James M. 
Published: February 2007

AbstractPrevious studies from our laboratory have shown that reconstituted basement membrane and stromal secretory products are important regulators of benign prostatic epithelial cell growth and differentiation. In the present study we evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory products on the proliferation and secretory activity of the androgen‐responsive prostatic carcinoma cell line LNCaP. In these studies, dihydrotes‐tosterone (DHT) was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen. The growth response to DHT was greatly attenuated when LNCaP cells were grown on prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered morphology compared to the monolayer growth observed on plastic and secreted elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will promote the expression of differentiated functions. In additional studies, stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT‐induced PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies indicate that prostatic stromal ECM and soluble secretory products will promote differentiated function in cultured LNCaP cells. In addition, we show that DHT can act as either a growth or differentiation‐promoting stimulus depending on the presence of stromal factors.