bluuebunny/crossref_metadata_2025_split huggingface dataset:
Danazol treatment of advanced prostate cancer: Clinical and hormonal effects
Authors: Cole R. M. , Raghavan D. , Caterson I. , Pearson Bruce , Boulas John , Teriana Nory , Rosen M. 
Published: February 2007

AbstractDanazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15–18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.
Two‐dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid
Authors: Lee Chung , Tsai Yvonne , Sensibar Julia , Oliver Lyda , Grayhack John T. 
Published: February 2007

AbstractSpecimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two‐diemnsional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two‐dimensional gels, those that are related to prostate‐associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase‐antiperoxidase as the staining reagent. Each protein spot in the two‐dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2–8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6–6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum‐related proteins by an extensive absorption with anti‐human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non‐serum proteins. These non‐serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two‐dimensional gels should be considered as the characteristic property of the prostatic secretions.
Design of cytotoxic steroids for prostate cancer
Authors: Petrow Vladimir , Padilla George M. 
Published: February 2007

AbstractOur object was to determine 1) if the aromatic nucleus of estramustine (I) is optimal for binding affinity to prostate cytosolic proteins, and 2) if C3 is the preferred position for the N‐mustard carbamate moiety. To this end we have submitted 34 steroids for in vitro assay of binding affinity to total prostate cytosolic proteins. Our structures included aromatic and hydroaromatic steroids containing N‐mustard carbamate and other substituents at C3, C6, C11, C16, C17, C20, and C21. Our results show that binding affinity to prostate proteins is optimally present in C3‐nitrogen mustard carbamates attached directly to a totally planar aromatic ring as in (IV). Partial deviation from total planarity as in enol‐carbamates (V) leads to some loss of binding affinity, which largely disappears in hydroaromatic structures (VI). Thus, our data lead to the Ring A aromatic structure (X) as a basis for the design of steroidal N‐mustard carbamates with prostate selectivity.Preliminary in vivo studies using the Dunning R3327AT prostatic adenocarcinoma implanted in the Copenhagen rat generally support our in vitro data.
Role of adrenal androgens in prostate regression in rats treated with an antiandrogen and an lhrh agonist
Authors: Foldesy Robin G. , Vanderhoof Mary M. , Canton Lucila E. , Hahn Do Won 
Published: February 2007

AbstractHistrelin, a potent luteinizing hormone releasing hormone (LHRH) agonist, and flutamide, an antiandrogen, were administered to intact and adrenalectomized rats to determine the role of adrenal androgens in the additive effects of the two drugs on prostate regression. Each compound, given separately, was effective in decreasing prostate weights in intact rats. When given together, additive effects were demonstrated by even greater atrophy of the prostates. It has previously been proposed that this additive effect may be primarily attributed to the ability of the antiandrogen to block the action of adrenal androgens. However, in adrenalectomized rats, the combination of histrelin and flutamide still produced a greater reduction in prostate weights than did either drug alone, indicating that the role of adrenal androgens in this effect is negligible. This experiment also was repeated with castrate, androgen‐supplemented rats, and the additive effects previously described were not observed. In a final experiment, prostatic atrophy in castrate rats was not enhanced by either adrenalectomy or flutamide treatment. Thus, the additive effects of histrelin and flutamide appear to focus on testicular rather than adrenal androgens.
Androgen and estrogen effect on guinea pig seminal vesicle muscle: A combined stereological and biochemical study
Authors: Bruengger A. , Mariotti A. , Rohr H. P. , Stahel W. , Wiederkehr P. , Bartsch G. , Carmichael S. W. , Mawhinney M. G. 
Published: February 2007

AbstractA combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone‐ or estradiol‐treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels. The estrogen‐induced increase in muscle weight and DNA content appeared to be due only to hyperplasia of muscle cells and not to a proliferation of fibroblasts or to infiltration by inflammatory cells. In all treatment groups, including the estrogen‐treated castrates, more than 95% of the cells in the tissue were smooth muscle cells, and there was no evidence that polyploidy contributed to changes in DNA levels. In addition, in the estrogen‐treated muscles, DNA concentration remained high, and the stereologically determined cell size remained low. Therefore, both morphological and biochemical evidence indicate that androgen induces hypertrophy, whereas estrogen induces hyperplasia of muscle cells.The correction of stereological and biochemical data validates the application of stereological cell size determination for smooth muscle cells in organs that hardly can be separated into stromal and epithelial components; eg, the prostate.
Complete response of lung metastases caused by prostatic cancer after chronic administration of a gonadotropin‐releasing hormone analog, buserelin (HOE 766)
Authors: Koutsilieris Michael , Ackmanr C. F. Douglas 
Published: February 2007

AbstractA stage D2 prostate cancer patient with biopsy‐proven lung metastases and negative work‐up for metastases is discussed. Treatment consisted of hormonai therapy in the form of chronic administration of an analog of gonadotropin‐releasing hormone (GnRH‐A), Buserelin, with follow‐up for 24 months. The complete response of the patient to GnRH‐A therapy provides an interesting and unusual case in the understanding of the biological behavior of prostate cancer.
Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue
Authors: Hulka Barbara S. , Beckman William C. , Checkoway Harvey , Diferdinando George , Hammond John E. , Fried Floyd A. , Mickey Don D. , Stumpf Walter E. , Clark Terry D. 
Published: February 2007

AbstractAndrogen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.
Evolution of fetal and adult thymidine kinase isoenzymes in rat ventral prostates during development
Authors: Derré P. , Samperez S. , Jouan P. 
Published: February 2007

AbstractThymidine kinase activity exhibited important changes during prostate growth. It increased considerably during the prepubertal period and reached a maximum level on day 55 of age. Then, it decreased gradually to the low values observed on and after day 90. Changes in enzyme activity were due mainly to variations in the activity of the fetal isoenzyme, which was maximum from day 45 to day 55 and decreased to undetectable levels on and after day 90 of life. The low thymidine kinase activity observed at the same time was due to the adult isoenzyme alone. Administration of 5α‐dihydrotestosterone to animals resulted in the considerable increase in fetal thymidine kinase activity. The stimulation of the fetal isoenzyme by androgens was maximum during the prepubertal period and decreased thereafter.
Interaction of sex steroids and prolactin on phosphatases, transaminases, and citric acid in the ventral prostate of male albino rats
Authors: Srinivasan N. , Aruldhas M. Michael , Govindarajulu P. 
Published: February 2007

AbstractThe interaction of androgens, testosterone propionate (TP), and dihydrotestosterone (DHT) with prolactin (PRL) and estradiol‐17β (E2) on phosphatases, transaminases, and citric acid were studied in the ventral prostate of prepubertal and adult intact and castrated rats. None of the secretory products studied were affected by androgens or their combinations with E2/PRL in prepubertal rats except for the increase observed in organ weight and DNA content. However, in adults the hormonal combinations produced some significant changes. Among the secretory products, phosphatases, glutamate oxaloacetic transaminase (GOT), and citric acid increased significantly in adult rats after the administration of TP/DHT. Glutamate pyruvic transaminase (GPT) required PRL along with TP/DHT to show an appreciable increment in intact adult rats. The synergistic effect of PRL with androgens was observed in the adult ventral prostatic secretory acid phosphatase and citric acid. Unlike PRL, E2 in combination with androgens produced an antagonistic effect in intact adult rats, which was well pronounced in the case of prostatic weight, DNA content secretory acid phosphatase, and citric acid. None of the androgens or their combination with PRL produced any significant change in DNA content compared to intact controls.
Quantal relationship between prostatic dihydrotestosterone and prostatic cell content: Critical threshold concept
Authors: Kyprianou Natasha , Isaacs John T. 
Published: February 2007

AbstractThe shape of the prostatic dihydrotestosterone (DHT) dose vs prostatic cell number response curve can be used to determine if the androgen‐induced increase in prostatic cell number occurs as a continuous graded process increasing with all levels of prostatic DHT, or whether the process is quantal, beginning to occur only when a critical threshold of prostatic DHT is reached. To make this determination, castrated‐adrenalectomized rats, castrated rats given no treatment, and castrated rats given testosterone‐filled silastic implants of varying lengths were used to construct such a prostatic DHT dose/prostatic cell number response curve ranging from undetectable to pharmacologically high levels of prostatic DHT. The shape of this dose‐response curve was found not to be continuously hyperbolic, but instead, to be discontinuously sigmoidal. This demonstrates that, in the rat, androgen‐induced increase in prostatic cell number occurs as a quantal process which can only begin when the concentration of prostatic DHT is above a critical threshold value (ie, 0.4 ng/108 cells for the rat ventral prostate). Thus, in order to completely prevent this androgenic stimulation of prostatic cell number, the prostatic DHT level has to be lowered to below this critical threshold but does not have to be completely eliminated.
Immunoscintigraphic evaluation of lymph node involvement in prostatic carcinoma
Authors: Vihko Pirkko , Kontturi Matti , Lukkarinen Olavi , Martikainen Paula , Pelliniemi Lauri , Heikkilä Juhani , Vihko Reijo 
Published: February 2007

AbstractFive patients who were candidates for radical prostatectomy were investigated. One milligram of diethylene triamine pentaacetic acid derivatives of purified F(AB′)2 fragments of monoclonal antibodies against prostatic acid phosphatase, labeled with 99mTc, were bilaterally injected into the periprostatic space. The amount of radioactivity injected varied between 3 and 7 mCi. Imaging took place dynamically for the first hour following injection, then at 6 and 24 hr. In one patient, lymph node metastases were detected in the left paraaortic, iliac, and obturator lymph nodes by this technique. The lesions incorporating radioactivity were confirmed to be metastases of prostatic cancer following staging pelvic lymphadenectomy. Immunolabeling electron microscopy studies revealed internalized antibody in prostatic cancer cells. In the four other patients, radioimaging did not show any lymph node metastases, and this negative finding was confirmed at surgery. These early data indicate the possibility of preoperative staging of prostatic cancer using radiolabeled derivatives of monoclonal antibodies raised against prostatic acid phosphatase and injected into the periprostatic area.
Synergic inhibitory effects of the aromatase inhibitor 1‐methyl‐androsta‐1, 4‐diene‐3, 17‐dione and the antiandrogen cyproterone acetate on androstenedione‐ induced hyperplastic effects in the prostates of castrated dogs
Authors: Habenicht Ursula‐F. , El Etreby M. Fathy 
Published: February 2007

AbstractWe examined whether the induction of estrogen‐related hyperplastic changes in the prostate (ie, activation and stimulation of the stroma, especially of the smooth muscle) of castrated beagle dogs was reproducible. The effectiveness of the aromatase inhibitor 1‐methyl‐androsta‐1, 4‐diene‐3, 17‐dione (1‐Methyl‐ADD) in antagonizing such estrogen‐related alterations was investigated in comparison with a combined treatment of 1‐Methyl‐ADD and the antiandrogen CPA. These studies have demonstrated the suitability of the androstenedione model for testing the efficacy of aromatase inhibitors. In addition, it has been demonstrated that an aromatase inhibitor in combination with an antiandrogen can synergically inhibit the glandular and stromal components of the prostate.
Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue
Authors: Van Steenbrugge G. J. , Van Dongen J. J. W. , Reuvers P. J. , De Jong F. H. , Schroeder F. H. 
Published: February 2007

AbstractThis paper is the first part of a series of three describing a number of observations made on the PC‐82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen‐dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1‐90 nmol/liter) has been levelled out by the use of T‐containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC‐82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC‐82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC‐82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC‐82 tumor tissue. Androgen withdrawal from T‐implanted, tumor‐bearing female mice caused a rapid reduction (90% within one day) of the tissue‐T and a slower decline (up to 90% within seven to ten days) of tissue‐DHT concentrations.
Pharmacologically induced ultrastructural and lmmunohistochemical changes in the prostate of the castrated dog
Authors: Aumüller G. , Habenicht U. F. , El Etreby M. F. 
Published: February 2007

AbstractThe effects of an aromatase inhibitor and of an antiandrogen on the ultrastructure and the expression of a secretory protein (acid phosphatase) and marker proteins for basal cells (keratin) and fibroblasts (vimentin) were studied in the prostate of castrated, androstenedi‐one‐treated dogs. Androstenedione treatment partially restored the normal appearance of the gland and also some secretory activity. In the central portion of the gland, basal cell hyperplasia developed instead of secretory activity after androstenedione treatment. Administration of the aromatase inhibitor reduced the number of secretory cells but did not completely suppress the latter. There was some proliferation of the connective tissue surrounding the atrophic acini. Combined treatment with aromatase inhibitor and antiandrogen resulted in a general atrophy of prostatic acini that was less intense relative to the changes observed after castration. Resi dual secretory activity, detected in specimens treated exclusively with aromatase inhibitor, were lacking after combined treatment. The influence of all regimens on the ultrastructure of smooth muscle cells was comparably discrete, whereas regional differences in the arrangement pattern of the epithelium and the fibromuscular stroma were impressive. The ultrastructural findings support previous results of a synergic inhibitory effect of aromatase inhibitor and antiandrogens on the canine prostate.
Autochthonous prostate adenocarcinomas in Lobund‐Wistar rats: A model system
Authors: Pollard Morris , Luckert Phyllis H. 
Published: February 2007

AbstractAn experimental model system for autochthonous prostate adenocarcinoma (PA) has been developed in Lobund‐Wistar (L‐W) rats. Large primary PAS were induced in 31 of 40 (77.5%) L‐W rats within an average of 10.7 months after a single dose of methylnitrosourea (MNU) and subcutaneous implants of testosterone. Metastatic tumors had developed in over 60% of the tumor‐bearing rats. In addition, localized in situ PAs had developed in 5 of the 40 test rats. At 14 months 50 untreated L‐W rats were free of demonstrable PAs. Two of 20 (10%)L‐W rats developed PA at 14 months after inoculation of MNU alone. Six of 42 (14%) L‐W rats developed PAs within 14 months after s.c. administration of testosterone implants. Thus, testosterone acted as a tumor promoter of PA for cells that had been initiated by MNU. The manifestations of the PAs in the L‐W rats resembled many aspects of the counterpart disease in man.
Interaction of male and female sex hormones in cultured rat prostate
Authors: Mäkelä Sari I. , Santti Risto S. S. , Härkönen Pirkko L. , Suominen Jyrki J. O. , Martikainen Paula M. 
Published: February 2007

AbstractThe organ culture of the rat ventral prostate was chosen as a model to determine whether any of the estrogen effects in vivo on the prostate are direct and expressed at the hormone concentrations normally found in the male. During 2 weeks of culture, estradiol at the high concentration of 10−5 M blocked the androgenic activation of [3H]thymidine incorporation into DNA. The inhibition was localized in epithelium. Protein content of testosteronetreated explants and the accumulation of prostatein in the medium were considerably decreased, indicating inhibition of secretion. Antiandrogenic effects were not seen in morphology of estrogen‐treated explants. The lower concentrations (from 10−9 M to 10−6) of estradiol increased the volume density of epithelium from day 7 onwards. The height of epithelium was concomitantly increased. The volume density of epithelium as well as the percentage of acini with metaplastic changes were significantly increased. These epithelial changes were less pronounced in the presence of androgen, suggesting that physiological concentrations of androgen prevent the expression of estrogen action in the morphology of the prostate. A change in staining with peanut (PNA)‐ and wheat germ agglutinin (WGA)‐ lectins indicated defective secretory capacity in metaplastic epithelium. In spite of the increased protein content in the explants, no constant pattern of the changes in prostatein accumulation could be recorded. Although the concentrations of estrogen required to induce squamous metaplasia were still unphysiological, the occurrence of this abnormal differentiation of the prostatic epithelium suggests that the cooperative action of estrogen is involved in androgen‐dependent normal epithelial growth and possibly also in promoting growth of prostatic neoplasia.