bluuebunny/crossref_metadata_2025 huggingface dataset:
Neues Wirkstoff‐Target für die Malaria‐Therapie
Authors: Winckler Thomas
Published: February 2007

Neu entdeckte Inhibitoren der Methionin‐Aminopeptidase 1b von Plasmodium falciparum geben Hoffnung auf eine neue Wirkstoffklasse im Kampf gegen Malaria.
Trivirus – Der Multivirus‐Killer
Authors: Chmiel Nicole , Cugurovic Oliviera , Lange Petra , Zimmermann Anja
Published: February 2007

Immunsupprimierte Patienten sind einem hohen Risiko lebensbedrohlicher Krankheiten, u.a. ausgelöst durch Cytomegalieviren (CMV), Epstein‐Barr‐Viren (EBV) und Adenoviren, ausgesetzt. Bisher existieren auf diesem Gebiet kaum Therapiemöglichkeiten, die vorhandenen Mittel sind – wenn überhaupt – nur gegen CMV wirksam und auch dies wegen Resistenzen in einer höchst unbefriedigenden Weise. Eine aktuelle Publikation macht Hoffnungen, diesen Missstand zu relativieren.
Monomer conversion in a light‐cured dental resin containing 1‐phenyl‐1,2‐ propanedione photosensitizer
Authors: Schroeder Walter , Arenas Gustavo , Vallo Claudia
Published: February 2007

The efficiency of 1‐phenyl‐1,2‐propanedione (PPD) photosensitizer for the photopolymerization of a dental resin based on 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloxyprop‐1‐oxy)phenyl]propane/triethylene glycol dimethacrylate was assessed. Experimental formulations containing PPD or/and camphorquinone (CQ) in combination with dimethylaminoethyl methacrylate (DMAEMA), ethyl‐4‐dimethylaminobenzoate (EDMAB), 4‐(N,N‐dimethylamino)phenethyl alcohol (DMPOH) and N,N‐3,5‐tetramethylaniline (TMA) at different concentrations were studied. The photopolymerization was carried out by means of a commercial light‐emitting diode (LED) curing unit. Near‐infrared spectroscopy was used to follow the consumption of double bonds versus irradiation time. No significant differences in the conversion values among formulations prepared with PPD in combination with DMAEMA, DMPOH and TMA were found. In contrast, the conversion was markedly increased by the presence of EDMAB. At low concentrations of photosensitizer, when used in combination with DMAEMA and EDMAB, PPD resulted in a final conversion equivalent to CQ. However, when DMPOH and TMA were used, PPD was found to be less efficient than CQ. In addition, at high photoinitiator concentration, the effectiveness of PPD was less than that of CQ independently of the co‐initiator used. The replacement of some CQ by an equivalent amount of PPD resulted in similar final monomer conversion as formulations having the same amount of CQ alone. The LED light source employed emitted in the wavelength range 410–490 nm with a peak around 470 nm, whereas the maximum molar absorbance of PPD was in the UV region. However, the small overlap of the spectral distribution of the LED curing lamp and the PPD absorption spectrum was compensated by the large extinction coefficient of PPD. Copyright © 2007 Society of Chemical Industry
Alternating poly(ester amide)s of glycolic acid and ω‐amino acids: Crystalline morphology and main crystallographic data
Authors: Botines Emma , Teresa Casas María , Puiggalí Jordi
Published: February 2007

The unit cell parameters of two alternating poly(ester amide)s constituted by glycolic acid and ω‐amino acid units have been determined by interpretation of X‐ray and electron diffraction patterns. Orthorhombic unit cells containing two chain segments with a nonplanar conformation have been derived. The electron diffraction patterns were rather different from those characteristic of aliphatic polyamides and polyesters with a zig–zag conformation. Chain‐folded lamellar crystals have been obtained by isothermal crystallization of dilute diol or glycerine solutions and the crystalline habit has been studied by means of real space electron microscopy. Polyethylene decoration techniques have been applied to evaluate the regularity of the folding surfaces. Diffraction and morphologic data suggest that hydrogen bonds between amide groups were established along a single direction, which coincides with the preferential crystal growth direction. Spherulites prepared from both evaporation of formic acid solutions and melt crystallization have been also studied. Diffraction data indicate that hydrogen bonds are aligned along the spherulite radius. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 815–825, 2007
Effects of polymerization method on structure and properties of thermoplastic polyurethanes
Authors: Yamasaki Satoshi , Nishiguchi Daisuke , Kojio Ken , Furukawa Mutsuhisa
Published: February 2007

The effects of the dynamic polymerization method and temperature on the molecular aggregation structure and the mechanical and melting properties of thermoplastic polyurethanes (TPUs) were successfully clarified. TPUs were prepared from poly (ethylene adipate) glycol (Mn = 2074), 4,4′‐diphenylmethane diisocyanate and 1,4‐butanediol by the one‐shot (OS) and the prepolymer (PP) methods in bulk at dynamic polymerization temperatures ranging from 140 to 230 °C. Glass‐transition temperatures (Tgs) of the soft segment and melting points (Tms) of the hard segment domains of OS‐TPUs increased and decreased, respectively, with increasing polymerization temperatures, but those of PP‐TPUs were almost independent of the polymerization temperature. Tgs of the soft segment and Tms of the hard segment domains of these TPUs polymerized above 190 °C were almost the same regardless of the polymerization method. Solid‐state nuclear magnetic resonance spectroscopy (NMR) analyses of OS‐ and PP‐TPUs showed that the relative proton content of fast decay components, which corresponds to the hard segment domains, in these TPUs decreased with increasing polymerization temperatures. These results clearly show that the degree of microphase separation becomes weaker with increasing polymerization temperatures. The temperature dependence of dynamic storage modulus and loss tangent of OS‐TPUs coincided with those of PP‐TPUs at polymerization temperature above 190 °C. The apparent shear viscosity for OS‐ and PP‐TPUs polymerized above 190 °C approached a Newtonian behavior at low shear rates regardless of the polymerization method. These results indicate that TPUs polymerized at higher temperatures form almost the same molecular aggregation structures irrespective of the dynamic polymerization method. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 800–814, 2007
Nuclear androgen receptors in the epithelium and stroma of human benign prostatic hypertrophic glands
Authors: Lahtonen Riitta , Bolton Nicholas J. , Vihko Reijo , Kontturi Matti
Published: February 2007

Androgen receptors have been characterized and quantified in nuclear extracts of separated epithelium and stroma from human benign prostatic hypertrophic (BPH) glands. Tritiated dihydrotestosterone was used as the ligand and incubation was carried out at 15°C for 18–20 hr before separation of bound and free ligand using dextran‐coated charcoal. The results were analysed by Scatchard‐type analysis. The concentration of receptor was found to be significantly (p = 0.022) greater in stromal than in epithelial nuclei: 1765 ± 152 vs 1030 ± 227 fmol/mg DNA (SEM, n = 6). Fourteen competitors were tested and the results indicated the presence of specific androgen receptors rather than contaminating sex‐hormone‐binding globulin. This was also borne out by the results of agar gel electrophoresis and sucrose gradient ultracentrifugation studies. The results are in line with current opinion that prostatic stroma is an important androgen‐sensitive tissue, particularly in human BPH.
Fibrillar bodies in human prostate
Authors: Seman Gabriel
Published: February 2007

Electron microscopy was used in an attempt to understand the initial but still obscure steps in the formation of corpora amylacea. To that effect, a specimen of hyperplastic prostate, selected by light microscopy for its abundance in corpora, was examined in the electron microscope. Hitherto unreported, small fibrillar bodies surrounded by glycogen granules were observed free or bound to the surface of acinar cells of the specimen. Fibrils of these bodies were different from amyloid fibrils of corpora. They were thinner, more electron dense, and branching. While the bodies were easily detected in semithin sections of the specimen, as well as in those of two other hyperplastic prostates, they were not seen in sections of their paraffin‐embedded counterparts. Neither were the bodies seen in histological preparations of 18 other prostate specimens (8 hyperplasias, 10 cancers). Whether the fibrillar bodies were precursors of corpora could not be demonstrated.
High‐risk group for benign prostatic hypertrophy
Authors: Araki Hirotaka , Watanabe Hiroki , Mishina Teruo , Nakao Masahiro
Published: February 2007

A case control study was conducted on 100 patients with benign prostatic hypertrophy (BPH) and 100 controls matched by age and residence. Interviews were performed by well‐ trained urologists using an original questionnaire. Matched‐pair analysis revealed the following characteristics and relative risks (RR) as being significantly (P < 0.05) different among the BPH patients versus the controls: higher educational background (RR = 2.77); not engaged in farming, forestry, or fishing (RR = 4.82); no environmental pollution at work (RR = 2.90); a present annual income of more than 2,400,000 yen (RR = 3.84); a previous annual income of more than 2,400,000 yen (RR = 3.82); practice the highest standard of living (RR = 4.24); more than two children (RR = 2.67); experienced first nocturnal emission before reaching the age of 20 (RR = 3.11); expending more than 10 min to complete one act of sexual intercourse (RR = 2.43); having no episode of sexual impotence that lasted more than 1 month (RR = 2.29); no family history of gastric ulcer (RR = 7.98); no family history of breast cancer (RR = 8.25); regular consumption of milk (RR = 2.25); irregular consumption of green and yellow vegetables (RR = 3.91); and pickles not consumed at every meal (RR = 1.99). Characteristics that did not achieve a high level of statistical significance (0.05 < P < 0.10) between cases and controls were as follows: past history of gonorrhea, urethritis, or prostatitis and syphilis (RR = 1.84, 2.76, and 4.26, respectively), and daily meat consumption (RR = 3.18). On the basis of interviews of the patients and cases reported in this study, we conclude that dietaly and sexual habits may be important factors which place individuals at a higher risk for developing BPH.
The etiology of prostate cancer: What does the epidemiology suggest?
Authors: Ross Ronald K. , Paganini‐Hill Annlia , Henderson Brian E.
Published: February 2007

The two most important demographic characteristics of prostate cancer in Los Angeles are the high rates among blacks, which are two times those among whites and four times those among Asians, and the rapid increase in rates with age after age 40. Despite the high rates among blacks, a birth cohort analysis indicates that mortality rates among black men born after 1900 have decreased. In this report, epidemiologic and experimental evidence supporting each of three etiologic hypotheses–industrial exposure to cadmium, sexual transmission by an infectious agent, and endocrine factors–are reviewed. Evidence from descriptive data in Los Angeles suggests that only a small portion of cases might be attributable to industrial exposures. In a cohort study of Catholic priests, we found no deficit of prostate cancer mortality, strong evidence against sexual transmission of the disease. Experimental evidence and a limited amount of human data support an endocrine hypothesis. Preliminary results of a case‐control study of prostate cancer are presented, but these results are unable to distinguish among these hypotheses further. This study finds a substantial protective effect of vasectomy, an event that is accompanied by reduced prostatic function and size, but this result is thus far statistically insignificant.
Prostatic structure and function in relation to the etiology of prostatic cancer
Authors: Isaacs John T.
Published: February 2007

In this paper, studies by a large series of independent investigators are reviewed with regard to the basic structure and function of the prostate in an attempt to examine their relationship to prostatic cancer etiology. These studies demonstrate that the functional activities of the prostate involve secretion, transport, and reabsorption of a variety of materials into and out of the glandular lumen and that these activities are directly related to the basic structural organization of the gland. These functional activities are constantly occurring in the prostate even under basal (ie, nonejaculating) conditions. Due to these functional activities, the prostatic fluid in the glandular lumen is a complex mixture of a variety of components derived, not only from the synthetic activity of the glandular epithelial cells of the gland itself, but also from the blood serum. The levels of these components are continuously modulated, not only by the frequency of active ejaculation, but also, under basal conditions by the continuous interaction with the glandular prostatic cells lining the acinar lumen and ducts. A concept is presented that the initiation and/or promotion of prostatic carcinogenesis may well involve the chronic modulation/interaction of the prostatic glandular cells with their lumenal fluid.
Effect of castration and steroid treatments on the activity of some hydrolytic enzymes in dog prostate
Authors: Frenette Gilles , Dubé Jean Y. , Tremblay Roland R.
Published: February 2007

Adult mongrel dogs were castrated and treated by intramuscular injections of Sα‐androstane‐3α, 17β‐diol (androstanediol) alone or in combination with estradiol in order to find convenient enzymatic markers of hormone action in prostate. The activities of 15 hydrolytic enzymes were determined. Arginine esterase, acid sulfatase, and acid phosphatase were found to be the most sensitive markers of testicular hormones since they were decreased 18‐, 5‐ and 5‐fold respectively after 1 month of castration. The enzyme activities returned to precastration levels after 2 weeks of injection of androstanediol to castrated animals. The effect of androstanediol on the majority of the remaining enzymes was small. In general, the activities obtained after androstanediol treatment in combination with estradiol were similar to those obtained with androstanediol alone. Finally, β‐glucuronidase and neutral sulfatase were increased after castration, a finding that suggests that these enzymes are constitutents of stromal cells. These studies will provide a basis for future studies of hormone action in the dog prostate.
Course of localized adenocarcinoma of the prostate treated by radical prostatectomy
Authors: Myers Robert P. , Fleming Thomas R.
Published: February 2007

Among 562 patients with histologic stage B‐1, B‐2, or C adenocarcinoma of the prostate treated by radical prostatectomy and pelvic lymphadenectomy, analysis revealed that increasing histologic stage, tumor size, degree of capsular invasion, seminal vesicle involvement, and histologic grade all were highly correlated with both local and systemic progression (log‐rank two‐sided P < 0.0001). No variable correlated with survival–a result that may reflect appropriate adjuvant therapy given at the time of progression. The death rate from prostatic cancer did appear to rise progressively with increase of stage. Overall, the projected 10‐year survival was 76%.
The patient, disease status, and treatment options for prostate cancer: Stages D1 and D2
Authors: Schmidt Joseph D.
Published: February 2007

The treatment of choice for disseminated prostate cancer remains endocrine manipulation, either bilateral orchiectomy or exogenous estrogens. The recommended dose of diethylstilbestrol is I mg tid. Unanswered questions include: When should endocrine manipulation be instituted for the patient with advanced prostatic cancer? At the time of diagnosis, when clinical symptoms occur, or not at all? With few exceptions those patients relapsing after initial endocrine manipulation do not respond to successive attempts at further endocrine therapy. Much of the confusion in this regard relates to the variable response criteria used, inore often subjective than objective. Since the polyclonal theory of prostatic cancer is attractive, its logical extension is the evaluation of combinations of treatments including both endocrine manipulation and cytotoxic agents. Because the currently available antiandrogens and luteinizing hormone‐releasing hormone agonists have mechanisms of action different from conventional estrogens or bilateral orchiectomy, they too may have a role in the multimodal treatment of advanced prostatic cancer.

Therapy for stagc D1 prostatic cancer implies that information Is available either from pelvic lymphadenectomy or from fine‐needle aspiration cytology related to abnormal findings on CT scanning, lymphangiography, or excretory urography. Some evidence exists supporting the case for potential cure by radical prostatectomy when pelvic nodal involvement is minimal. Other options include standard external beam irradiation therapy, endocrine therapy with transurethral prostatic resection, and finally, observation until distant metastases occur. Because of the increased risk of distant metastases in patients with stage D1 prostatic cancer, adjuvant chemotherapy programs are rational with clinical trials now in progress.
Stromal‐epithelial interactions: II. Regulation of prostatic growth by embryonic urogenital sinus mesenchyme
Authors: Chung Leland W. K. , Cunha Gerald R.
Published: February 2007

Embryonic urogenital sinus mesenchyme (UGM) has been demonstrated previously to be a potent inductor of prostatic morphogenesis and functional differentiation when associated with either embryonic urogenital sinus epithelium (UGE) or urothelium derived from adult urinary bladder (ABLE) and grown in male hosts. To determine the role of mesenchyme in prostatic acinar growth, homotypic tissue recombinants of 16‐day‐old embryonic mouse urogenital sinus mesenchyme and epithelium (UGMmouse + UGEmouse) were prepared in which the relative amounts of UGM to UGE were varied from approximately 0.1:1 to 100: 1. Recombinants were grown for 1 month in intact male hosts after which the amount of acinar growth was assessed by histological analysis and by determination of wet weight and DNA content. The latter criteria are valid measures of acinar content of histologically normal prostatic tissue because the rodent prostate is composed of greater than 80% ductalacinar tissue. From this analysis the amount of acinar growth was found to be determined by the amount of mesenchymal tissue and was independent of the amount of epithelium utilized to prepare the tissue recombinants. Similarly, the magnitude of growth in heterospecific rat‐mouse tissue recombinants prepared with urogenital sinus epithelium or adult bladder epithelium (ABLE) and urogenital sinus mesenchyme (UGMmouse + UGErat, UGMmouse + ABLErat UGMrat + UGEmouse, or UGMrat + ABLEmouse) is determined by the source of UGM. Although the initial DNA content per UGM is comparable between mouse and rat, the overall acinar growth induced by UGMrat is about 10‐fold greater than that induced by UGMmouse when recombined reciprocally with UGEmouse and UGErat, respectively. These results suggest that UGM is of fundamental importance as a regulator of prostatic epithelial growth. The relevance of this finding to the development of human benign prostatic hyperplasia is discussed.
Gonadotropin‐releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma
Authors: Koutsilieris M. , Tolis G.
Published: February 2007

Orchiectomy or chronic administration of the gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly‐NH210 ethylamide (HOE 766) were employed as therapeutic maneuvers in 25 patients with advanced prostatic carcinoma. HOE 766 administration effectively suppressed plasma testosterone to castrate levels that persisted for as long as treatment continued. Surgical and medical castration resulted in a significant decrease in prostatic size; this became evident earlier for surgically than medically treated patients (P <.05), but no difference existed after the third month of treatment. Symptoms and signs of prostatism improved in practically all the patients. Among patients with stage D2 disease, there was an improvement in five as far as bone radiological assessment was concerned. Alkaline phosphatase levels did not show appreciable changes in patients showing objective stable disease or partial response according to National Prostatic Cancer Project criteria. Radioimmunoassayable prostatic acid phosphatase levels became normal in two of two stage C, five of five stage D1, and eight of seventeen patients with stage D2 disease, a rise in prostatic acid phosphatase (PAP), in alkaline phosphatase, and deterioration in bone radiology were associated with clinical evidence of relapse; this occured despite persistently low levels of plasma testosterone. Serum thyroxine, cortisol, and prolactin levels remained unchanged following orchiectomy or chronic administration of HOE 766. Practically all patients complained of hot flashes and experienced a decrease in libido and potency, but none developed gynecomastia or thromboembolic episodes. The data indicate that HOE 766 can be used safely as an alternative to castration or estrogens for the treatment of patients with androgen‐dependent prostatic cancer.
Preliminary results on the clinical efficacy and safety of androgen inhibition by an LHRH agonist alone or combined with an antiandrogen in the treatment of prostatic carcinoma
Authors: Faure N. , Lemay A. , Laroche B. , Robert G. , Plante R. , Jean C. , Thabet M. , Roy R. , Fazekas A. T. A.
Published: February 2007

We have used the paradoxical antigonadal effects of LHRH agonists as a chemical castration in advanced prostatic cancer. We report early results of a phase II study on the clinical efficacy of the LHRH agonist D‐Ser (TBU)6, des‐Gly‐NH210 LHRH administered to patients with stage D prostatic carcinoma. Following dose‐range finding studies using either intranasal (IN) (200 μg twice/day or 500 μg twice/day) or subcutaneous (SC) administration (50 μg once/day, we developed a sequential combination of SC (500 μg three times/day for seven days) and IN regimen that was administered for 3 to 16 months to a group of 23 patients with stage D prostatic carcinoma. Initiation of therapy was associated with a clinical flare in one patient during the first week of treatment. Mean serum testosterone levels were already decreasing at one week and remained inhibited to levels inferior to 1 ng/ml after the first four weeks of treatment. Overall assessment shows that within the first six months of treatment, 26% patients were improved, 39% were stabilized, and 35% were nonresponders. Fourteen patients were followed during the next six months: 29% continued to respond, 29% escaped, 21% remained stable, and 21% were nonresponders. Histologic studies from castrated patients showed changes in spermatogenesis correlating to the degree and duration of suppression of testicular steroidogenesis without signs of toxicity. Preliminary observations on the combination of the pure antiandrogen RU 23908 with Buserelin (n = 5 ) or castration (n = 3) suggest that the addition of an antiandrogen does not seem to improve the patients nonresponding to other hormonal suppressive therapy (Buserelin) administered before (n = 3) or concomitantly with the antiandrogen (n = 2). Three relapsing castrate patients responded to the antiandrogen, but the response was temporary in two (eight to nine months of therapy). No side effects other than hot flashes and decreased potency are related to LHRH agonist alone or to the low‐dose antiandrogen. Multicenter trials will be necessary to delineate the place of LHRH agonist alone or LHRH agonist combined with an antiandrogen in the treatment of prostatic cancer.
Chemotherapy principles in the treatment of prostatic cancer
Authors: Könyves I. , Müntzing J. , Rozencweig M.
Published: February 2007

The efficacy of chemotherapy for prostatic cancer is difficult to evaluate owing to the low incidence of measurable indicator lesions and the resulting need for indirect response criteria. Although complete regressions remain exceptional, a number of agents, eg, doxorubicin and cisplatin have been shown to be effective in the treatment of this disease. So far, combinations of effective agents with or without concomitant hormone therapy have not proven to be more effective than single agents. Androgen priming has considerable theoretical appeal and deserves further consideration. A higher effectiveness of chemotherapeutic agents might be obtained by linkage to various carriers. Estramustine phosphate is an example of such a complex that has a cytotoxic effect in test systems in which estrogen has no effect and in patients with hormone‐refractory prostatic cancer. The use of hormonal and other carriers that could increase the specificity of chemotherapeutic agents deserves extensive exploration.
In vitro synthesis and glycosylation of androgen‐dependent secretory proteins of rat dorsal prostate and coagulating gland
Authors: Bartlett Richard J. , French Frank S. , Wilson Elizabeth M.
Published: February 2007

The two major androgen‐dependent secretory proteins of rat dorsal prostate and coagulating gland, DP I and DP II, were compared by in vitro translation of total poly(A)RNA and by pulse‐chase techniques by means of [35S]methionine and tissue minces of coagulating gland. DP I is a major in vitro translation product of isolated poly(A)RNA, whereas DP II is undetectable in a mouse embryo fibroblast cell‐free system where glycosylation does not occur. DP I is synthesized within 20 min in minces of coagulating gland incubated in the presence of [35S]methionine and is secreted in 40 min. DP II is detectable in the medium only after 8 hr of labeling. Inhibition of asparagine‐linked protein glycosylation with tunicamycin (10 μg/ml) blocked the synthesis and secretion of DP II with an apparent increase in DP I secretion. Inhibition of DP II synthesis by monensin implicates the Golgi in the processing of DP II oligosaccharides. The data are consistent with the proposal that DP I enters a pathway of rapid secretion that is enhanced by the absence of core glycosylation, whereas DP II follows a slow pathway through the Golgi that involves extensive glycosylation.
Dimethylsulphoxide stimulation of dome formation in cultured rat prostate epithelial cells
Authors: Bologna Mauro , Festuccia Claudio , Napolitano Tiziano , Angeletti Pietro Ubaldo
Published: February 2007

Primary cultures of normal rat prostate produce cells with epithelial characteristics that may be useful in the study of cell differentiation and prostate physiology. These epithelial cells, grown in DME plus 10% FCS, 10% HS, and 50 ng/ml each of hydrocortisone and insulin, can be induced to differentiate into dome (hemicyst) forming cells by 250 mM DMSO, a molecule that acts as a differentiation inducer in Friend erythroleukemia cells, Madin‐Darby canine kidney cells, and in mouse and rat mammary epithelial cells. Dome formation in cell culture is the consequence of transepithelial transport of water and ions, resulting in fluid accumulation between the culture dish and the cell layer. Dome formation in prostate epithelial cells, besides representing an example of induction of differentiation in a cell culture system, suggests that prostate (ductal?) epithelial cells have fluid reabsorption capabilities.
Cooperative clinical trials of the national prostatic cancer project: Protocol 900
Authors: Schmidt Joseph D.
Published: February 2007

In May 1978, the National Prostatic Cancer Project Treatment Subgroup activated its first clinical trial evaluating adjuvant chemotherapy (Protocol 900). This protocol is a comparison of long‐term adjuvant chemotherapy with cyclophosphamide, estramustine phosphate, or no additional treatment in patients with definitive surgical therapy for adenocarcinoma of the prostate. To date, 128 patients have been entered with an entry rate of approximately 2.2 patients per month. One hundred five patients form the basis of this report, with 96 patients still on active therapy. Estramustine phosphate has been administered at a dose of 600 mg/m2 orally daily in three divided doses. The cyclophosphamide is administered 1 g/m2 intravenously every 3 weeks. Results are still preliminary; only two evaluable patients have died. Approximately two‐thirds of patients entered have had negative lymph nodes. Recurrent disease has been documented in 15 patients, including eight receiving cyclophosphamide, three receiving estramustine phosphate, and four on the no‐treatment arm. The recurrence rate has been disproportionately high (50%) in patients receiving cryosurgery rather than radical prostatectomy (12%). Maximum survival has reached 241 weeks. Side effects have consisted of leukopenia in patients receiving cyclophosphamide (56%), and nausea and vomiting with cyclophosphamide (85%), and estramustine phosphate (36%). This study continues with patient entries now over one‐half of the number anticipated in the original study design.
Stable versus partial response in advanced prostate cancer
Authors: Slack Nelson H. , Brady Mark F. , Murphy Gerald P.
Published: February 2007

Stable response to therapy in patients with advanced prostate cancer, as experienced in clinical trials of the National Prostatic Cancer Project (NPCP), has been reexamined. Data from ten complete trials totaling over 1,300 patients have been examined for survival patterns within categories of response to therapy. Survival patterns, both for all patients and for those alive at 12 weeks, were significantly poorer for patients categorized as progressors after 12 weeks on treatment than for those categorized as stable or as partial regressions. Furthermore, comparisons of survival patterns for those patients categorized as stable or partial regression revealed no statistically significant differences between them. The similarity of survival for the stable and partial regression categories indicates that the stable category represents more than a segment of the population with slowly progressing disease and can be taken as an indicator of response to therapy.
Nonsteroidal serum factors involved in the regulation of the proliferation of canine prostatic epithelial cells in culture
Authors: Chevalier Simone , Bleau Gilles , Roberts Kenneth D. , Chapdelaine Alcide
Published: February 2007

Canine prostatic epithelial cells were cultured in primary monolayers in order to define those factors that induce a proliferative response at the cellular level. Cultures were performed in a serum‐free medium or in a medium supplemented either with fetal bovine serum or dog serum in the presence or absence of several sex steroids (androstenedione, testosterone, dihydrotestosterone, 3α‐ and 3β‐androstanediols, epitestosterone, epidihydro‐testosterone, estrone, estradiol, and progesterone). Cell proliferation was observed in the absence of serum and exogenous steroids. The rate of cell division was serum dependent and steroid independent. Pretreatment of sera with charcoal had no effect on their mitogenic activities. Cells maintained in an endocrine milieu prior to tissue dispersion and throughout the whole procedure proliferate to the same extent as those deprived of hormones, whether free of serum or added supplements. The addition of insulin (2 μg/ml), dog prolactin (up to 25 ng/ml) and zinc (10−8 to 10−2 M) in a serum‐free medium did not induce cell responsiveness to steroids. Dihydrotestosterone, 3α‐androstanediol, and estradiol alone or in combinations known to induce the growth of the canine prostate in vivo were ineffective in vitro. The proliferative responses to sera were time and concentration dependent, and dog serum was more potent than fetal bovine serum. Thus, humoral factors other than steroids, prolactin, insulin, or zinc may be of importance in the activation of epithelial cells involved in the development of prostatic hyperplasia and adenocarcinoma.
Effects of prostatic secretion on reduced sugars in human seminal plasma
Authors: Montagnon D. , Clavert A. , Cranz C.
Published: February 2007

Glucose and fructose levels were determined enzymatically in liquefied human seminal plasma (whole or collected in three fractions) and in preparations obtained by DEAE ion‐exchange chromatography on whole seminal plasma. When these secretions or DEAE‐extracted preparations were overloaded with fructose, the level of glucose increased. This increase is greater in fraction I of split ejaculates than in fractions II and III, and is greater in solutions containing elements of prostatic secretion obtained chromatographically than in whole seminal plasma. Using increasing quantities of fructose in the overloading test, glucose levels reached a maximum, suggesting that the process of conversion of fructose into glucose appears to be related to an enzymatic process. Other experiments suggest that the sperm‐free fraction I of split ejaculates and compounds obtained from seminal plasma by ion‐exchange chromatography contain enzymes of prostatic origin that are involved in the conversion of fructose to glucose.
A histochemical comparison of acid phosphatase activity in human bph and rat ventral prostate
Authors: Buchanan Lynn J. , Riches Andrew C.
Published: February 2007

Acid phosphatase activity and its sensitivity to formalin inhibition were compared histo‐chemically in cryostat sections of human BPH and rat ventral prostate. While the glandular epithelium in both human and young adult rat ventral prostate exhibits positive acid phosphatase activity, the intensity of the reaction is greater in human tissue. Moreover, human prostatic tissue remains acid phosphatase positive following 24 hours immersion in formalin, whereas the enzyme reaction in young adult rat ventral prostate disappears after 5 hours of formalin treatment. Unlike both human and young adult rat ventral prostate, sites of acid phosphatase activity in aged rat ventral prostate are not homogeneously distributed throughout the glandular epithelium but, rather, appear as large clumps, which persist after 5 hours of formalin treatment. Procedures used for the histochemical demonstration of formalin‐resistant human prostatic acid phosphatase are not, therefore, directly applicable to rat ventral prostate.
Antagonistic effect of androgen on prostatic cell death
Authors: Isaacs John T.
Published: February 2007

Androgen, besides having the well‐established agonistic ability to stimulate prostate cell proliferation, also has an antagonistic ability to inhibit prostatic cell death. This statement is based upon the observations that 1) only 2.1% of the total prostatic cells die per day when serum testosterone level is sufficient for chronic maintenance of the gland; 2) 3 days following castration, when serum testosterone level is less than 10% of the intact value, the percentage of total prostatic cells now dying per day is increased tenfold to a value of 20.8%; and 3) this high rate of prostatic cell death can be inhibited following castration if serum androgen level is appropriately maintained by exogenous testosterone treatment. The serum testosterone level needed to antagonistically inhibit prostatic cell death (ie, 1.4 ± 0.1 ng/ml) is more than twofold lower than that needed to antagonistically stimulate prostatic cell proliferation (3.3 ± 0.4 ng/ml). Due to this dose difference, it is experimentally possible in castrated rats to inhibit prostatic cell death selectively without simultaneously stimulating cell proliferation and still completely prevent the rapid involution of the prostate following castration. These results suggest that the rapid involution of the prostate following castration is predominantly due to a decreased antagonistic effect of androgen on prostatic cell death rather than to a decreased agonistic effect of androgen on prostatic cell proliferation and that these two androgenic effects are distinct processes in the prostate.
Animal models and treatment of prostate cancer
Authors: Pollard Morris , Luckert P. H.
Published: February 2007

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The “Pollard tumors” provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.
Familial factors affecting prostatic cancer risk and plasma sex‐steroid levels
Authors: Wayne Meikle A. , Smith Joseph A. , West Dee W.
Published: February 2007

Whether familial factors affect the frequency of prostatic cancer and the plasma content of sex‐steroids was investigated. Brothers (n = 257) of probands (n = 150) diagnosed with prostatic cancer before age 62 years had a fourfold higher risk for developing the disease than men in the general population in the State of Utah and their brothers‐in‐law (n = 202). Familial factors markedly affected the plasma content of sex steroids (testosterone, dihydro‐testosterone, the ratio of testosterone to DHT, sex‐hormone binding globulin, and the free fraction of testosterone) in nonendocrinologically treated probands and their brothers and sons and in normal men in the general populations. Index cases and their brothers and sons had a significantly lower mean plasma testosterone content than controls of comparable age. Preliminary data suggest that the metabolic clearance rate of testosterone and the conversion ratio of testosterone to estradiol are relatively high in probands. The observations indicate that familial factors are potent risk factors for the development of prostatic cancer. They also suggest that plasma androgen values in families with prostatic cancer cluster in the lower range of normal and that plasma sex‐steroid content is more similar in each brothers with or without prostatic cancer than among nonbrothers.
Approaches to prostatic cancer chemotherapy using the dunning R3327H prostatic adenocarcinoma
Authors: Padilla George M. , Petrow Vladimir , Marts Sherry A. , Mukherji Suresh
Published: February 2007

Androgen‐responsive cells: To determine if testosterone or dihydrotestosterone is the main trophic hormone of prostatic adenocarcinoma, we have treated Dunning R3327H prostatic adenocarcinoma‐bearing rats with 6‐methylene progesterone, which blocks conversion of testosterone to dihydrotostesterone. Copenhagen‐Fisher rats were treated with steroid (20 mg/Kg daily) immediately following implantation of tumor and thereafter for 117 days. There was a 92% inhibition of growth of tumors and a lesser effect upon prostate and seminal vesicles. Tumor‐free body weights remained unchanged. Both treated and untreated tumors had equivalent DNA content on a per weight basis. This result supports the thesis that prostatic adenocarcinoma requires dihydrotestosterone for growth.

Androgen‐insensitive cells: Advanced prostate cancer does not respond to endocrine therapy but is temporarily controlled by the cytotoxic steroid estramustine. The latter shows significant selective binding to prostatic protein.

To develop chemotherapeutic agents that will control androgen‐insensitive cells and possess improved selectivity for prostatic protein, we have studied a number of steroids for their ability to displace 3H‐labeled estramustine from prostatic cytosolic proteins. Surprisingly, a carbamide substituent at the C17 position was found to confer significant binding affinity for prostatic estramustine‐binding protein. Extension of this structural characteristic to the estramustine type of molecule is being studied.
Sex steroid receptors in normal and hyperplastic human prostate
Authors: Robel Paul , Eychenne Bernard , Blondeau Jean‐Paul , Baulieu Etienne‐Emile , Hechter Oscar
Published: February 2007

The concentrations of sex steroid receptors (per unit DNA) were measured in normal periurethral and peripheral prostatic tissue samples from seven men (mean age 64 years; range 54–71 years) undergoing cystectomy for bladder cancer, and in hyperplastic nodules from 15 men with BPH (mean age 69 years; range 60–89). Occupied androgen (AR) and estrogen (ER) receptors were measured with an improved exchange procedure, where receptor‐binding sites were stabilized by a combinatorial procedure involving (1) careful washout of extracellular secretory products (including proteases) prior to homogenization, (2) inclusion of 0.5 mM phenylmethyl sulfonylfluoride (PMSF) and 20 mM molybdate in the exchange medium, and (3) long‐term incubation at 0–4°C. Bound radioligands were separated by a hydroxylapatite (HAP) batch adsorption procedure. Maximal specific exchange binding of 3H‐R 1881 or 3H‐estradiol in total homogenates of human prostate samples was achieved after incubation periods of about 72 hat 0–4°C. In contrast, progestin receptors (PR) were readily available for binding 3H‐R 5020; thus overnight binding at 0–4°C was routinely used to measure PR. Binding specificities and equilibrium binding constants (calculated from 8‐point Scatchard plots, correcting for nonsaturable binding) were found to be characteristic for AR, PR, and ER, respectively. The receptor results obtained in this study demonstrate that (1) no significant differences existed in total AR per unit DNA between hyperplastic and either central or peripheral prostatic tissue samples; (2) PR was present in both zones of normal prostatic tissue as often as in BPH samples, with PR concentrations significantly lower in hyperplastic samples; and (3) ER was irregularly detected in both normal and hyperplastic tissue in low concentration relative to AR and PR; the frequency of ER detection was much lower in BPH than in normal prostate tissue. Studies of steroid receptor content relative to enzyme markers specific for epithelial and stromal cells in BPH samples showed a positive correlation between acid phosphatase activity (a specific marker for epithelial cells) and both AR and PR. No correlation was observed between AR or PR with either prolyl hydroxylase or myosin ATPase (specific markers for stromal cells). These observations suggest that PR, as well as AR, is primarily associated with the epithelial elements of prostate. Because of the relative infrequency of ER, similar correlation of ER with enzyme markers was not possible.
Radioactive iodine‐125 implantation for cancer of the prostate
Authors: Nag Subir
Published: February 2007

Localized cancer of the prostate can be treated by radical prostatectomy, external beam irradiation, or radioactive implantation with similar survival results. Radical prostatectomy, however, almost universally results in impotency, although a new, nerve‐sparing procedure may preserve potency in B1 patients. External beam irradiation radiates a large volume of tissue with significant rectal and bladder morbidity, 23–47% risk of impotency, and requires prolonged treatment (6–8 weeks). Radioactive implantation may be done suprapubically or transperineally using iodine‐125, gold‐198, or radon‐222 permanent implantation techniques and iridium‐192 or radium‐226 removable implantation techniques. Interstitial iodine‐125 implantation is frequently employed since it is a short procedure and limits the morbidity to a 7% incidence of impotency, 20% urinary complications, and 5% rectal complications. The overall 5‐year survival of patients with iodine‐125 is 79%, the survival rate decreasing with increasing T or N stage or increasing grade of tumor.
Testosterone‐induced decrement of prostatic vascular resistance in rats is reversed by estrogens
Authors: Daehlin Lars , Damber Jan‐Erik , Selstam Gunnar , Bergman Bo
Published: February 2007

The function and growth of the rat prostate are stimulated by androgens and inhibited by estrogens. To study the influence of these hormones on the prostatic blood flow, prostatic vascular resistance was measured in castrated adult rats, which were testosterone supplemented and treated with different estrogenic substances. Prostatic blood flow was measured using the microsphere technique. Testosterone supplementation for 8–9 days after castration resulted in decreased vascular resistance in both the ventral and dorsolateral prostates. In testosterone‐supplemented rats, treatment for the same period of time with estradiol benzoate, ethinyl estradiol, and diethylstilbestrol induced increased vascular resistance in both the ventral and dorsolateral prostates. However, treatment with estromustine or estramustine did not change prostatic vascular resistance significantly. It was concluded that the testosterone‐induced decrease of prostatic vascular resistance was reversed by estradiol, ethinyl estradiol, and diethylstilbestrol, possibly by a direct effect on the prostate.
Prostatic calculi: A review
Authors: Klimas Richard , Bennett Betsy , Gardner William A.
Published: February 2007

Prostatiac calculi are rare in children, infrequent below age 40, and common in males over 50. They may be solitary but usually occur in clusters and are associated with some other disease process (nodular hyperplasia, prostatic carcinoma, metabolic abnormalities). They are most often asymptomatic; however, symptoms that may be attributable to prostatic calculi include reduction of the urinary stream, prostatism, and intense lower back and leg pain. Treatment may be accomplished by transurethral resection, but prostatectomy is the best means to insure complete removal.

Prostatic calculi may form by two related mechanisms with obstruction and stasis of prostatic fluid as central entities in both. These mechanisms are calcification of corpora amylacea and simple precipitation of prostatic secretion. They may arise spontaneously, initiating an inflammatory reaction that contributes to their growth, or they may arise as the consequence of another pathologic situation producing acinar obstruction. It appears that infection probably occurs secondary to stone formation.
Transrectal ultrasound in the diagnosis of prostate cancer: Location, echogenicity, histopathology, and staging
Authors: Lee F. , McLeary R. D. , Kumasaka G. H. , Borlaza G. S. , Straub W. H. , Gray J. M. , Meadows T. R. , Lee F. , Solomon M. H. , McHugh T. A. , Wolf R. M.
Published: February 2007

Adenocarcinoma of the prostate produces specific ultrasonic findings that can be used in diagnosis. We have examined 211 patients using transrectal ultrasound in both the sagittal and axial planes. Thirty‐three carcinomas were detected, and 31 histologically confirmed; 24 by needle biopsy, six by transurethral resection, one by total prostatectomy, and two by the demonstration of distant metatases. On ultrasound, all of the carcinomas were less echogenic than normal prostate. All appeared to originate in the peripheral zone of the prostate and produced asymmetry of the gland. The majority of carcinomas in this series showed capsular involvement and ten penetrated and extended beyond the prostatic capsule.

The results of this series indicate that transrectal ultrasound can be used to detect cancer of the prostate gland. Ultrasound demonstrated the extent of tumor involvement and enabled accurate staging of these cancers.
Proteins of the rat prostate: I. Preliminary characterization by two‐dimensional electrophoresis
Authors: Lee Chung , Tsai Yvonne , Sensibar Julia , Harrison Harold H.
Published: February 2007

The rat prostate consists of three distinct lobes: the ventral, lateral, and dorsal. Proteins in the three lobes of the prostate were studied with the ISO‐DALT system for high‐resolution two‐dimensional electrophoresis. Proteins were detected with ammoniacal silver stain. Comparison of patterns from the three lobes of the prostate of control, noncastrated rats revealed that while there was a remarkable overall similarity, six groups of proteins showed lobe‐specific differences. When prostatic regression was induced by castration, androgen‐dependent proteins showed a decrease in staining intensity. A group of proteins, with pI 5.0–6.0 and MW 65,000–70,000, was consistently observed only during the active phase of prostatic regression (days 3–7 postcastration). Their presence during this specific interval may play a role in tissue involution.