bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stromal‐epithelial interactions: II. Regulation of prostatic growth by embryonic urogenital sinus mesenchyme
Authors: Chung Leland W. K. , Cunha Gerald R. 
Published: February 2007

AbstractEmbryonic 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

AbstractOrchiectomy 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

AbstractWe 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

AbstractThe 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

AbstractThe 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

AbstractPrimary 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

AbstractIn 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

AbstractStable 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

AbstractCanine 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

AbstractGlucose 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

AbstractAcid 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

AbstractAndrogen, 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

AbstractModel 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

AbstractWhether 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

AbstractAndrogen‐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.