bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen regulation of polyamine synthesis in seminal vesicle and in different lobes of the rat prostate
Authors: Fjösne Hans E. , Östensen Mari‐Ann , Haarstad Helge , Sunde Arne
Published: February 2007

Endogenous levels of the polyamines putrescine, spermidine, and spermine have been examined in the 106 m/s2 supernatant of different lobes of the rat prostate and in the seminal vesicles of castrates, androgen‐stimulated castrates, and intact controls.

Content of the polyamines varied between the lobes, with spermidine highest in intact animals. After castration, the content of polyamines fell significantly in all lobes but the coagulating gland (CG). Spermidine levels were highest, except in the lateral prostate (LP) and CG, where the content of putrescine was highest. In castrated animals treated with testosterone propionate for 72 h, the amount of the three polyamines examined increased dramatically in the ventral prostate (VP) and moderately in the CG and seminal vesicle (SV). Concerning individual polyamines, spermidine increased significantly in all lobes, while putrescine increased significantly only in the two saccular parts of rat prostate, i.e., CG and SV. Spermidine content decreased significantly in the DP.

Major differences in the content of the three polyamines—putrescine, spermidine, and spermine—in the various tissues studied have been found. Moreover, distinct differences among intact, castrated, and testosterone‐treated castrated animals have been revealed.
Induction of chemical castration in male rats by a new long‐acting LHRH‐antagonist
Authors: Habenicht Ursula‐F. , Schneider Martin R. , Etreby M. Fathy El
Published: February 2007

LHRH‐antagonists might represent a useful new type of androgen deprivation to treat prostatic cancer. In this context adult intact male rats were treated subcutaneously with different concentrations of the new LHRH‐antagonist antide either once (1, 3, 6, 10, 15 mg/kg) or on 5 consecutive days (5 × 3 mg/kg). The effect on serum concentration of LH and testosterone and the effect on the weights of testes, prostate, and seminal vesicles was investigated after different periods of time (24 hours, 1,2,3,5, and 8 weeks). Histological evaluation of the testes was also performed. A clear dose‐dependent inhibitory effect on the above‐mentioned parameters was observed. The most effective treatment schedule was the single application of 15 mg/kg resulting in castration‐like inhibition of prostate weights and marked inhibition of spermatogenesis within 2 weeks, which was maintained 8 weeks after the injection.

Serum LH and serum testosterone concentrations were below the detection limit of the assay within 2 weeks and showed first signs of recovery after 8 weeks. Histologically, no signs indicative of irreversible effects (testes) were observed. To summarize, the LHRH‐antagonist antide was found to have a profound long‐lasting inhibitory but reversible effect on the reproductive system of adult intact male rats. These data emphasize the suitability of this type of compound for the treatment of prostatic cancer.
Treatment of hormone‐refractory stage D carcinoma of prostate with coumarin (1,2‐benzopyrone) and cimetidine: A pilot study
Authors: Marshall M. Ernest , Butler Karen , Hermansen Dane
Published: February 2007

The combination of coumarin (1,2‐benzopyrone) and cimetidine has been reported to render objective tumor regressions among patients with metastatic renal cell carcinoma and malignant melanoma. Subsequently, a pilot trial was conducted to evaluate this regimen for the treatment of stage D hormone‐refractory carcinoma of the prostate. Patients received coumarin 100 mg orally as a single daily dose for 14 days; on day 15 cimetidine 300 mg four times daily was added, and both drugs were continued until progression of disease. Fourteen patients with advanced prostate cancer were treated. Nine patients had evaluable disease only, whereas five patients had both measurable and evaluable disease. All patients had bone metastases. Although there was no objective evidence of tumor regression, three patients (with evaluable disease only) experienced significant improvement in bone pain with decreased analgesic use that persisted until disease progression at 3, 5.5 +, and 9 months. Although coumarin caused no symptomatic or organ dysfunction toxicity, one elderly patient experienced reversible mental confusion from cimetidine. Coumarin and cimetidine, at the dose and schedule described, are not effective for the treatment of advanced prostate cancer. However, the results of laboratory investigations suggest that further clinical trials of coumarin, at higher doses, may be warranted for the treatment of this disease.
Tissue‐specific decline in cytosolic casein kinase II of the ventral prostate in aging rats
Authors: Goueli Said A.
Published: February 2007

An age‐associated decline in the activity of cytosolic casein kinase II in the rat ventral prostate was observed. The decrease in specific and total activity of casein kinase II of prostatic cytosol obtained from 12‐month old rats compared with that from 3‐month old rats was 50% and 70%, respectively. This decrease was tissue specific since no such alteration in enzymic activity was found in liver, lung, or heart. The decline in activity was not due to an increase in the concentration of a casein kinase inhibitor or to altered androgenic status with aging. Rather, the reduction in the activity of the enzyme was commensurate with the decrease in the total concentration of the enzyme protein as determined by an ELISA using anti‐casein kinase II antibodies. The activity of casein kinase II in the nuclear fraction of the rat prostate was not altered in aging animals. It may be concluded that the cytosolic form of casein kinase II in the prostate of older animals is regulated at the transcriptional level (but not via the androgen‐receptor complex mechanism). An alternative explanation for this observation may relate to altered stability of the enzyme in the prostate of older animals.
Analysis of somatic cell hybrids derived from normal human prostatic epithelial cells fused with HeLa cells
Authors: Peehl Donna M. , Wong Stephen T. , McNeal John E. , Stamey Thomas A.
Published: February 2007

Somatic cell hybrids have been instrumental in the recognition of specific chromosomes containing genes capable of suppressing the malignant phenotype. As a first step towards the identification of possible suppressor genes in prostate cells, we created hybrids by fusing normal prostate cells with malignant HeLa cells. Similar to hybrids made with other combinations of normal and malignant cells, the normal phenotype was dominant and the malignant phenotype was suppressed. The phenotype of the nontumorigenic hybrids after injection into nude mice resembled that of normal keratinocyte X HeLa hybrids, and tiny, nonprogressive keratinized nodules were produced. One hybrid clone was tumorigenic, possibly due to the loss of a normal suppressor gene, and displayed glandular as well as squamous elements. Further characterization of these hybrids should permit isolation of specific suppressor genes, as well as promote recognition of elements that regulate the glandular phenotype.
Primary yolk sac (endodermal sinus) tumor of the prostate: Case report and review of the literature
Authors: Schriber Jeff , Flax Stanley , Trudeau Maureen , Cook Gerald T. , Weizel Harold , Katz Alan , Keating Armand
Published: February 2007

A primary yolk sac (endodermal sinus) tumor of the prostate is described in a 40‐year‐old male. This is the second documented case of a yolk sac tumor occurring in the prostate gland. Treatment included surgical removal and subsequent combination chemotherapy. Four months following diagnosis, the patient died of complications. At autopsy, no residual tumor was detected. The role of combination chemotherapy as potentially curative therapy in the treatment of extragonadal yolk sac tumors is discussed.
Role of calcium in the programmed death of rat prostatic glandular cells
Authors: Martikainen Paula , Isaacs John
Published: February 2007

By using a newly developed and validated rat ventral prostatic organ culture system in which prostatic glandular cells can be induced to undergo programmed cell death, the role of an elevation in the intracellular free Ca2+ concentration in this death process was studied. By using this organ culture system, ventral prostatic glandular epithelial cells can be maintained in culture for a period of more than 14 days with a low daily rate of cell death (i.e., ± 5% die per day) if androgen is included in the media. In contrast, if androgen is not included in the media, the daily rate of prostatic glandular cell death increases approximately 3‐fold (i.e., ± 15% die per day). With this organ culture system it has been demonstrated that the daily rate of programmed death of the glandular epithelial cells can be shifted from 5% to 15% of the cells dying per day when testosterone and 10 μM of the Ca2+ ionophore A23187 are both present in the media. Thus, when the intracellular free Ca2+ is elevated within prostatic cells by means of ionophore treatment, the daily rate of glandular cell death in the presence of testosterone is identical to that induced when testosterone is not present in the media. If the organ cultures are maintained in media lacking testosterone but containing 10 μM of the Ca+2 channel blocker nifedipine to inhibit elevations in the intracellular free Ca2+ derived from the extracellular pools, the rise in the daily rate of cell death from 5 to 15% of the cells dying per day induced by androgen ablation can be inhibited by ± 70%. These results suggest that an increase within prostatic glandular cells in their intracellular free Ca+2 derived from extracellular Ca2+ pools is a critical early event involved in triggering the subsequent process of programmed cell death (i.e., specifically DNA fragmentation) in these cells following androgen ablation.
Flutamide has no effect on adrenal androgen response to acute ACTH stimulation in patients with prostatic cancer
Authors: Carlström Kjell , Pousette Åke , Stege Reinhard
Published: February 2007

Basal levels and adrenocorticotropic hormone (ACTH)‐induced increments (Δ‐values) of serum cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), 4‐androstene‐3,17‐dione (A4), and 17‐hydroxyprogesterone (170HP); basal testosterone (T), luteinizing hormone (LH), serum ASAT, gamma‐GT, and albumin were measured in prostatic cancer patients before and after 6 months of treatment with LH‐RH‐agonist, with flutamide, and with LH‐RH‐agonist + flutamide, respectively.

Basal DHA and DHAS were decreased during flutamide and LH‐RH‐agonist + flutamide treatment and basal A4 during treatment with LH‐RH‐agonist and with LH‐RH‐agonist + flutamide. Basal 170HP, T, and LH decreased during LH‐RH‐agonist and LH‐RH‐agonist + flutamide treatment and increased during single drug flutamide treatment.

Slightly decreased Δ cortisol values were observed during LH‐RH‐agonist and during flutamide treatment and slightly increased Δ 170HP values during LH‐RH‐agonist and LH‐RH‐agonist + flutamide treatment. Values for Δ DHA and Δ A4 were completely unaffected by any of the treatment regimens. Elevated ASAT values were observed during treatment with flutamide and with LH‐RH‐agonist + flutamide.

It is concluded that flutamide has no effect on the adrenal androgen response to acute ACTH stimulation.
Characterization of muscarinic cholinergic receptors in membrane preparations from rat prostatic adenocarcinoma
Authors: Batra Satish , Christensson Per‐Inge , Hartley‐Asp Beryl
Published: February 2007

The binding characteristics of 3H‐quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions from R‐3327 Dunning tumors (H and AT‐1 sublines); ventral, dorsolateral prostate; and urinary bladder of the rat were studied. QNB binding to all preparations, except from AT‐1 tumors, was specific, saturable, and of high affinity. The AT‐1 tumors completely lacked specific QNB binding. The muscarinic receptor density in H tumors was twofold and twentyfold higher than that in the ventral prostate and dorsolateral prostate respectively. The receptor density in the urinary bladder was approximately twofold higher than that in H tumors. The Kd values in H tumors and ventral prostate were very similar and significantly higher than that in dorsolateral prostate or the urinary bladder. QNB binding in H tumors was strongly inhibited by classical muscarinic receptor antagonists atropine and scopolamine, but poorly by the agonists carbacholine and pilocarpine. In contrast to scopolamine or atropine, inhibition by pirenzepine and AF‐DX116 was relatively low. These data indicate that the muscarinic receptor in Dunning H tumors is of M3 type.
Immunohistochemical study of androgen receptor in benign hyperplastic and cancerous human prostates
Authors: Masai Motoyuki , Sumiya Hidenori , Akimoto Susumu , Yatani Ryuichi , Chang Chawnshang , Liao Shutsung , Shimazaki Jun
Published: February 2007

Androgen receptor was detected immunohistochemically in benign as well as malignant prostatic tissues by using a monoclonal rat anti‐human androgen receptor antibody (AN 1–15). In both benign and malignant cells, the androgen receptor was exclusively localized in nuclei. In hyperplastic prostate, the androgen receptor was stained in the glandular and the stromal cells. In the gland, cells facing the lumen were stained more intensively than those adjacent to the basal membrane. In cancer tissue, receptor‐positive and ‐negative cancer cells were intermingled. The percent of strongly positive cancer cells was correlated inversely with grade. Relapsed cells showed a low population of strongly positive cells irrespective of grade.
Effect of dimethylsulfoxide on the proliferation and glycosaminoglycan synthesis of rat prostate adenocarcinoma cells (PAIII) in vitro: Isolation and characterization of DMSO‐resistant cells
Authors: Kaneski Christine R. , Constantopoulos George , Brady Roscoe O.
Published: February 2007

Dimethylsulfoxide (DMSO) modulates the tumorigenicity and other characteristics of some malignant cell lines in vitro. We have investigated DMSO effects on cell proliferation and glycosaminoglycan (GAG) synthesis in rat prostate adenocarcinoma (PAIII) cells in culture. DMSO inhibited cell proliferation and GAG synthesis and shedding. Cells that survived the initial exposure to 2.5% DMSO could be propagated in this concentration of the agent and were designated PAIII‐DMSO resistant (PAIII‐DMSOr). PAIII‐DMSOr cells showed reversible indications of increased differentiation such as decreased growth rate and saturation density. Although the PAIII‐DMSOr cells were grown in 2.5% DMSO, they had normal or elevated GAG content. The major GAG of both PAIII and PAIII‐DMSOr cells was undersulfated heparan sulfate. Verapamil, a calcium channel blocker that reverses drug resistance in tumor cells, stimulated the growth of PAIII‐DMSOr cells in the presence of 2.5% DMSO, but was inhibitory in the absence of DMSO. Growth of PAIII cells was inhibited by the differentiating agents sodium butyrate and retinoic acid and by the ionophore monensin. Interestingly, growth of PAIII‐DMSOr cells in the presence of 2.5% DMSO was largely unaffected by sodium butyrate or retinoic acid. The results suggest that (1) PAIII‐DMSOr cells arise from the induction of a compensation mechanism to DMSO effects in a preexisting population of cells; (2) there is a correlation between GAG synthesis and cell proliferation; and (3) further study of the verapamil effect may help elucidate the mechanism of the DMSO‐induced differentiation of cancer cells.
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

There 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

During 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

At 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

Androgen‐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

Seven 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

A 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

The 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

Proteinase 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

A 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

Human 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

The 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

In 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

Pentosan 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

The 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

Previous 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.
Interaction of epidermal growth factor and transforming growth factor beta in human prostatic epithelial cells in culture
Authors: Sutkowski Debra M. , Fong Chau‐Jye , Sensibar Julia A. , Rademaker Alfred W. , Sherwood Edward R. , Kozlowski James M. , Lee Chung
Published: February 2007

The present study was conducted to study the interaction between epidermal growth factor (EGF) and transforming growth factor‐β (TGF‐β) in benign human prostatic epithelial cells in culture. Primary cultures of human prostatic epithelial cells were grown in complete WAJC, which consisted of WAJC‐404 medium and, in addition to other defined additives, EGF and bovine pituitary extract (BPE). Incomplete WAJC contained the same composition except EGF and BPE were deleted. TGF‐β was added into media at concentrations of 0, 0.1, and 1.0 ng/ml. When cells were grown in complete WAJC, they proliferated rapidly. Cell proliferation was greatly suppressed when incomplete WAJC was used. Addition of TGF‐(β to these cultures caused a significant reduction in the final cell number when either complete WAJC or incomplete WAJC was used. In additional experiments, cells were prelabeled with 3H‐thymidine for 72 hr prior to treatment with TGF‐β. The percentage of radioactivity released into the medium at the end of a 6‐day culture was used as an indication of the extent of cell death. Trypan blue exclusion test was also used to assess the extent of cell death. Addition of TGF‐β into complete WAJC did not significantly affect the extent of cell death beyond what was considered as the result of normal cellular turnover. Addition of TGF‐β into incomplete WAJC, however, caused a significant increase in the percent of cell death in the culture. These results demonstrated an interaction between EGF and TGF‐β in proliferation and cell death in human prostatic epithelia in culture. In the presence of EGF alone in the culture medium, prostatic epithelial cells were stimulated to proliferate. The rate of proliferation was greatly diminished when EGF was deleted from the medium or when TGF‐β was added in the presence of EGF. Finally, cell death was induced when TGF‐β was added into the medium in the absence of EGF.
Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas
Authors: Sarkar Fazlul H. , Sakr Wael , Li Yi‐Wei , Macoska Jill , Ball Daniel E. , Crissman John D.
Published: February 2007

The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short‐sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma.

We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short‐sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short‐sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA‐PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.
Correlation between the prostatic vein and vertebral venous system under various conditions
Authors: Suzuki Takanori , Kurokawa Kohei , Okabe Kazuhiko , Ito Kazuto , Yamanaka Hidetoshi
Published: February 2007

In dogs, the venous blood from the prostate gland was observed under X‐ray fluoroscopy to drain into the vertebral venous system under conditions of abdominal compression, the addition of various intraabdominal pressures, and occlusion of the inferior vena cava by a balloon catheter. Pressure in the inferior vena cava and abdominal cavity were measured simultaneously. The venous blood draining from the prostate gland started to flow from the inferior vena cava into the vertebral veins at more than 25 mmHg of intraabdominal pressure with the animal in the supine position. The average pressure of the inferior vena cava draining into the vertebral veins was 12.8±1.3 mmHg in the supine position and 21.1 ± 2.7 mmHg in the standing position. The average intraabdominal pressures were 35.5± 3.9 mmHg and 30.1 ± 2.8 mmHg, respectively. Under conditions of abdominal compression and balloon occlusion of the inferior vena cava, the materials flowed into the vertebral venous system from various routes, such as the internal iliac vein, common iliac vein, and inferior vena cava. It was suggested that the inferior vena caval blood easily enters the vertebral venous system in the standing position by adding high intraabdominal pressure, and that the vertebral venous system may be useful for experimental study of drug administration in bone metastasis of prostate cancer.
Amino acid concentrations in serum and urine after intravenous infusion of 1.5% glycine in prostatectomy patients
Authors: Hahn Robert G.
Published: February 2007

Glycine 1.5% was given by intravenous infusion at a rate of 50 mg/min over 20 min to 10 patients (aged 57‐79 years) scheduled for transurethral prostatectomy. The concentrations of amino acids in serum and urine were measured at 0, 10, 20, 50, 80, and 140 min in the experiments in order to study how elderly men handle a glycine load. The results show an increase in the serum concentrations of alanine, proline, glutamine, glycine, serine, and threonine. The apparent distribution volume for the excess glycine was 33 ±9 L, the half‐life was 41 ±7 min, and the total body clearance was 0.56 ±0.08 L/min, while the renal clearance for glycine was 36 ±14 ml/min (mean ±SD). There was an increase in the excretion of all amino acids that could be detected in the urine. The renal clearances of urea and creatinine was reduced in some of the patients. The absence of toxic symptoms is consistent with unchanged serum concentrations of ammonia and glutamate.
Estrogen‐induced morphological and immunohistochemical changes in stroma and epithelium of rat ventral prostate
Authors: Zhao G. Q. , Holterhus P. M. , Dammshäuser I. , Hoffbauer G. , Aumüller G.
Published: February 2007

Prostatic smooth muscle cells have been regarded to play a major pathogenetic role during the development of benign prostatic hyperplasia (BPH) in elderly men. Altered hormonal signals (increased estrogen) have been made responsible for the “metabolic” transformation of prostatic smooth muscle cells, which were thought to produce increased amounts of connective tissue fibers observed in BPH. In order to find out the role of metabolically “activated” smooth muscle cells, hormone stimulation experiments were performed in male rats. The effects of androgen deprivation and estrogen stimulation were recorded by semiquantitative analysis of intermediate and myofilament proteins in stromal smooth muscle cells. In castrated or estrogen‐treated or estrogen‐treated and castrated animals, the reduction of the glandular lumen is the most obvious morphological alteration, accompanied by an increase in connective tissue. Regressive changes occurred most rapidly in castrated animals (already within the first week), slower in castrated estrogen‐treated animals and still slower in normal estrogen‐treated animals. Regression of the epithelium was accompanied by a marked decrease in immunoreactivity for prostatic binding protein (PBP) in castrated animals, while PBP immunoreactivity in estrogenized animals was retained for up to 6 weeks. Smooth muscle cells became atrophic in castrated animals. This effect was attenuated in estrogen‐treated animals. There was no indication for enhanced collagen synthesis by smooth muscle cells. Actin and desmin‐immunoreactivity were only slightly altered in experimental animals and showed a changed distribution pattern. Prostatic smooth muscle cells respond less markedly to hormonal alterations than do the fibroblasts.