bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of 4MA, a potent inhibitor of 5 alpha‐reductase, on the growth of androgen‐responsive human genitourinary tumors grown in athymic nude mice
Authors: Andriole Gerald L. , Rittmaster Roger S. , Loriaux D. Lynn , Kish Marie L. , Linehan W. Marston 
Published: February 2007

AbstractThe five alpha‐reductase inhibitors are a newly developed family of compounds that block the intracellular conversion of testosterone (T) to dihydrotestosterone (DHT). 17‐β‐N, N‐Diethylcarbamoyl‐4‐methyl‐4‐aza‐5‐alpha‐androstan‐3‐one (4MA), the most widely studied of these compounds, has been shown to inhibit the androgen‐dependent growth of both normal animal tissues and of the Noble tumor, an experimental, hormone‐responsive rat neoplasm. 4MA has been found to inhibit androgen‐dependent growth without altering plasma levels of T or DHT. In the present study, we assessed the efficacy of 4MA in inhibiting the growth of PC‐82 and R198, human androgen‐responsive genitourinary malignancies. In the first experiment, 4MA was administered subcutaneously at a dose of 6 mg/kg/day to castrated and hormonally replaced groups of PC‐82‐bearing male athymic nude mice. 4MA therapy when compared to control therapy caused significant PC‐82 growth inhibition in three different groups of hormonally replaced castrated mice: 1) physiologic T‐replaced (P<.001), 2) supraphysiologic T replaced (P<.001), and 3) supraphysiologic T and DHT replaced (P<.001). There was no difference between the post therapy plasma levels of T or DHT in the control‐treated and 4MA‐treated mice. In the second experiment, the effect of 4MA (6 mg/kg/day S.Q.) was compared to that of castration and control therapy on the growth of R198. Both castration and 4MA therapy effectively inhibited R198 growth when compared to control therapy (P = .01 and .02, respectively), but there was no difference in the degree of growth inhibition seen with 4MA or castration (P = .45). Castration and 4MA‐therapy significantly lowered plasma T levels when compared to control therapy; castration also significantly lowered plasma DHT levels, while 4MA and control therapy did not. These studies suggest that 4MA is effective in inhibiting the growth of human androgen‐responsive tumors grown in athymic nude mice and that further studies with other 5 alpha‐reductase inhibitors are indicated.
Ultrastructure and immunohistochemistry of the lateral prostate in aged rats
Authors: Aumüller Gerhard , Enderle‐Schmitt Ulrike , Seitz Jürgen , Müntzing Jonas , Chandler John A. 
Published: February 2007

AbstractUltrastructural, histological, and immunohistochemical studies were performed on lateral prostates of 1) aged rats from different strains, 2) rats permitted different levels of sexual activity, and 3) castrated rats. Antibodies against the following proteins were used as immunohistochemical markers: SVS II from seminal vesicle, LP 28 from lateral prostate, acid phosphatase isoenzymes from ventral prostate, transglutaminase from coagulating gland, and a commercial monoclonal antibody against cytokeratin. SVS II is a marker of lateral prostatic secretion, while immunoreactions to LP 28 and acid phosphatase (pI 7.1) were cytoplasmic. In aged animals the amount of intracellular secretion is decreased, and focally metaplastic transformation can be visualized by using immunohistochemical markers. Epithelial ultrastructure varied considerably with experimental conditions. Intensive sexual activity resulted in increased polymorphism and increased number of secretory granules within the glandular cells, while castration was followed by a rapid loss of secretory material. Also, in rats older than 10 months, a reduction in the number of secretion granules was common. The epithelium developed a positive immunoreaction to transglutaminase antibodies that were not observed in juvenile glands. Cells, presumably macrophages, which had an intense immunoreactivity for transglutaminase, were increased in number both within and outside the prostatic acini of aged rats. The possible interaction between secretory SVS II, a substrate of transglutaminase, the release of this enzyme from macrophages or its reflux from coagulating glands, the spontaneous cellular exfoliation that is due to decreased androgen levels, and dietary noxae may be of importance in the development of lateral prostatic nonbacterial inflammation in aged rats.
Immunohistochemical demonstration of metallothionein in the rat prostate
Authors: Umeyama Tomokazu , Saruki Kazuhisa , Imai Kyoichi , Yamanaka Hidetoshi , Suzuki Keiji , Ikei Nobuhiro , Kodaira Tsukasa , Nakajima Katsuyuki , Saitoh Hiroshi , Kimura Masami 
Published: February 2007

AbstractMetallothionein in the rat prostate was demonstrated by using an indirect immunoperoxidase technique. Strong staining was found mainly in the supranuclear area of the cytoplasm of the glandular epithelium in the dorsal and the lateral glands. Diffuse cytoplasmic staining and nuclear staining were found with less frequency. Secretory granules were found in the lumen with various intensities of staining. Most of the epithelial cells in the ventral lobes and the coagulating glands were negatively stained. Immunoreactive cells were found sporadically. Two types of immunoreactive cells, round cells and spindle‐shaped cells, were scattered in the stroma. Vascular endothelial cells, red blood cells, and smooth muscle cells were negatively stained. These results suggest the synthesis and secretion of metallothionein in the rat prostate.
Isolation of a 41 kilodalton cytosol protein from the dunning rat prostatic adenocarcinoma: Characterization as depolymerized actin isomers
Authors: Nishi Nozomu , Matuo Yuhsi , Matsui Sei‐Ichi , Sandberg Avery A. , Isaacs John T. , Wada Fumio 
Published: February 2007

AbstractExcept for albumin, a 41,000‐dalton protein (41K) in the cytosol of the Dunning R‐3327 rat prostatic adenocarcinoma was found to be the most abundant soluble protein. This protein was purified in nearly homogeneous state by conventional chromatographies. After the first chromatography, because of the adhesive nature of the protein, 0.5% SDS and 2 M urea were necessary for subsequent steps of purification. The amino acid composition of the purified 41K was similar to that of actin isolated from rabbit skeletal muscle. Alternatively, 41K could be extracted from the Dunning tumor in the presence of ATP and dithiothreitol, under conditions in which actin molecules are depolymerized, and could be purified by the same method as cytoskeletal actin. The purified protein showed properties similar to rat skeletal muscle actin in amino acid composition and antigenicity. Both 41K proteins were found to be composed of four components having different isoelectric points. These results indicate that most actin exists in a depolymerized form as a cytosol protein of 41,000 daltons in the Dunning tumor and is composed of at least four isomers.
Dihydrotestosterone does not induce prostate adenocarcinoma in L‐W rats
Authors: Pollard Morris , Snyder David L. , Luckert Phyllis H. 
Published: February 2007

AbstractIt has been postulated that dihydrotestosterone (DHT) is the active trophic androgen in initiating pathogenic changes in the prostate gland. Groups of prostate cancer‐susceptible male L‐W rats (age 3 months) were treated with subcutaneous depots of testosterone or of DHT. After 14 months, prostate adenocarcinomas had developed in 24% of the testosteronetreated rats but not in the DHT‐treated rats. In the latter rats, the testes were significantly reduced in weight, there was no evidence of spermatogenesis, and serum testosterone levels were not detectable. It appears that DHT as administered to L‐W rats had an antiandrogenic effect.
Definitive radiotherapy of prostatic cancer: The Norwegian radium hospital's experience (1976‐1982)
Authors: Telhaug Ragnar , Fosså Sophie D. , Ous Sigurd 
Published: February 2007

AbstractDuring the years 1976 to 1982 definitive curatively aimed radiotherapy to the primary tumor was given to 53 patients with prostatic cancer confined to the true pelvis (T0, 2; T1‐2, 19; T3, 24; T4, 8; N0, 18; N+, 2; Nx, 33); all patients were of the M0‐category. The pelvic lymph nodes received a total dose of 2 Gy × 25 by means of an anterior and posterior radiation field. The prostatic gland was irradiated by an additional booster dose of 2 Gy × 10 given to a perineal field. Twenty‐four patients have relapsed after their prostatic radiotherapy, only three of them within the irradiated area. For the patients with T0‐T2 tumors, the 5‐year crude survival was 69%, whereas it was only 37% for patients with T3 tumors. Thirty‐five patients developed intestinal (26 patients) and/or urogenital (23 patients) radiation side effects. In three patients a colostomy had to be performed owing to rectal stricture or fistula. The poor survival after radiotherapy in the present series is probably due to a high incidence of unrecognized pelvic lymph node metastases. In the future only prostatic cancer patients without pelvic lymph node spread will be considered candidates for definitive radiotherapy. An optimal radiation technique is mandatory in order to avoid major radio‐therapy‐induced toxicity.
Morphological studies on the effect of taxol on cultured human prostatic cancer cells
Authors: Röyttä Matias , Laine Kirsi‐Marja , Härkönen Pirkko 
Published: February 2007

AbstractThe effect of taxol, an experimental antitumor drug, was studied in vitro on human prostatic cancer cells. Different concentrations of taxol, varying from 5μM to 0.01 nM, were used. The effect of taxol was examined by light and electron microscopy. Taxol had a marked cytotoxic effect on prostatic cancer cells down to a 10 nM concentration of taxol when observed by light microscopy. However, by electron microscopy, the specific effect of taxol was seen even with a 1 nM concentration of taxol. Taxol induced the appearance of numerous round cells after a few days and, subsequently, progressive death of the tumor cells. Among the surviving tumor cells, large tumor cells were noted as well as many multinucleated tumor cells. By electron microscopy, the round tumor cells showed mitotic figures with a high amount of cytoplasmic microtubules. Nonmitotic cells were often multinucleated and contained a high number of cytoplasmic microtubules and microtubule‐related structures. The results show that taxol, even at very low concentrations, has a highly cytotoxic effect on prostatic cancer cells; and when a very low concentration of taxol is used with no obvious cytotoxic effect at the light microscopic level, specific taxol‐induced ultrastructural alterations can be observed.
Immunocytochemical localization of estrogen receptors in spontaneous and experimentally induced canine benign prostatic hyperplasia
Authors: Schulze Harald , Barrack Evelyn R. 
Published: February 2007

AbstractEstrogens are believed to play a critical role in the etiology of canine benign prostatic hyperplasia (BPH); however, the mechanism has not been elucidated. To gain insight into this problem, we investigated the immunocytochemical localization of estrogen receptors (ER) in normal prostates, spontaneous BPH, and experimentally induced BPH by using a monoclonal ER antibody (H222). In all canine prostates the majority of ER was localized in nuclei of the same histological components: (1) transitional epithelium and subjacent stroma of the prostatic urethra, (2)periurethral prostatic ductal epithelium, and (3) prostatic stroma. ER content in the stroma was highest in the periurethral region of the prostate. Among the different groups of dogs, differences in ER location were seen only in the glandular epithelium. No ER was found in the glandular epithelium of normal prostates of young untreated dogs. In striking contrast, glandular epithelium of spontaneous BPH contained specific nuclear ER staining, though this staining was heterogeneous and was observed in only a minority (<10%) of the acinar epithelial cells. ER‐positive acini in BPH were located predominantly in the periurethral region. These data demonstrate anatomical and biochemical heterogeneity of prostatic components and indicate that the estrogen sensitivity of prostatic cells is heterogeneous. If estrogen does play a role in BPH, it appears to act selectively rather than uniformly throughout the prostate. We reasoned that if glandular epithelial ER are involved in the development of spontaneous BPH, one might expect to find the same location of ER in BPH that was induced experimentally by specific types of treatment with androgens ± estradiol. However, among hormone‐treated dogs the presence of ER‐positive prostatic glandular epithelium varied with the type of hormonal treatment but did not correlate with the experimental induction of glandular BPH. Some treatment groups with induced BPH had ER‐positive prostatic glandular epithelial nuclei (with the same extent and pattern of ER localization as in spontaneous BPH); however, other treatment groups with induced BPH had ER‐negative glandular epithelium. These data indicate either that glandular epithelial ER may not be involved in the pathogenesis of canine BPH or that there may be different types of BPH that have different etiologies. Possible mechanisms by which estrogen may affect the canine prostate are discussed in light of these new data on ER location.
Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement
Authors: English Hugh F. , Santen Richard J. , Lsaacs John T. 
Published: February 2007

AbstractLight microscope autoradiography was utilized to investigate the separate proliferative activities of the basal and glandular cell types during androgen‐mediated restoration of the ventral prostatic epithelium in castrated rats. Our objective was to determine whether the proliferative population of the prostatic epithelium is restricted to the basal cell subtype under these experimental conditions. In the intact animal, substantial numbers of basal as well as glandular cells were found to be proliferating. The basal cell labeling index (LI) was 3.75%±0.3% or 1.85±0.4 × 105 labeled cells per prostate. For the glandular cells the comparable figures were 0.38% and 3.32±1.5 × 105. Seven days after surgical castration, both subtypes persisted. However, only the numbers of glandular cells were found to be significantly reduced (66% decrease). When androgens were replaced by daily subcutaneous injection (testosterone propionate, 2 mg/0.2 ml sesame oil), both cell types responded with significantly increased proliferation. The temporal pattern of response displayed by each cell type was very similar. A greater proportion of basal than glandular cells responded, ie, 28% vs 11% LI. However, in terms of approximate numbers of cells labeled during the peak response, the value for the glandular cells was larger, ie, 2.4 vs 1.1 × 106 labeled cells. These data clearly indicate that under normal conditions as well as during testosterone stimulation, basal cells are not the sole population of proliferating cells in the prostatic epithelium. Thus, basal cells, as a distinct morphologic population, are not homogeneously undifferentiated stem cells which give rise to differentiated and nonproliferating glandular epithelial cells. Aspects of these data can nevertheless be interpreted to support the idea that the prostatic epithelium is maintained by a single cell lineage system in which the stem cells comprise a subpopulation of the basal cells. Alternatively, the two populations may be separate and distinct as no data are presented which unequivocally links the two cell types in a precursor‐progeny relationship.
Long‐term results with a long‐acting formulation of D‐TRP‐6 LH‐RH in patients with prostate cancer: An Italian prostatic cancer project (P.O.N.CA.P.) study
Authors: Boccardo F. , Decensi A. , Guarneri D. , Rubagotti A. , Massa T. , Santi L. , Martorana G. , Giberti C. , Giuliani L. , Cerruti G. B. , Tani F. , Zanollo A. , Germinale T. , Borzone C. , Perri F. , Usai E. 
Published: February 2007

AbstractNinety‐five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D‐TRP‐6 LH‐RH (“Decapeptyl”) for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn‐RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down‐regulation of testicular LH receptors. Of 88 patients evaluable for response, about one‐half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D‐TRP‐6 LH‐RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.
Xenografted small cell undifferentiated cancer of prostate: Possible common origin with prostatic adenocarcinoma
Authors: van Haaften‐Day Caroline , Raghavan Derek , Russell Peter , Wills Edward J. , Gregory Patricia , Tilley Wayne , Horsfall David J. 
Published: February 2007

AbstractThe first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU‐PR‐2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone‐specific enolasè. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor‐bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.
Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate
Authors: De Voogt H. J. , Rao B. R. , Geldof A. A. , Gooren L. J. G. , Bouman F. G. 
Published: February 2007

AbstractThe effect of androgen blockade on the normal human prostate was studied in 16 healthy volunteers opting for male‐to‐female gender reassignment. Their ages ranged from 19 to 27 years. After 8 weeks of treatment with Anandron, serum hormone levels indicated antiandrogenic action and physical signs of feminization appeared. Prostate volumes (measured by ultrasound) before and following Anandron treatment remained the same. After 18 months of treatment with cyproterone‐acetate and ethinyl estradiol, prostate volumes again were not changed. However, histology revealed glandular atrophy and an increase in stromal tissue. The significance of these findings is discussed.
Immunohistochemical distribution of the three predominant secretory proteins in the parenchyma of hyperplastic and neoplastic prostate glands
Authors: Abrahamsson P.‐A. , Lilja H. , Falkmer S. , Wadströ L. B. 
Published: February 2007

AbstractProstatic acid phosphatase (PAP), prostate‐specific antigen (PSA), and β‐microseminoprotein (β‐MSP) were regularly localized immunohistochemically to the epithelium of the acini and that of the ducts in the nodules of 24 cases of benign prostatic hyperplasia.The immunohistochemical distribution of these three prostatic‐secreted proteins was also examined, with monoclonal antisera against PAP and PSA and with polyclonal antisera against PAP, PSA, and β‐MSP, in a series of 40 cases of prostatic adenocarcinomas graded according to the WHO classification. Highly differentiated (grade I) carcinomas showed a high incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. As in the normal and hyperplastic prostate parenchyma, highly differentiated (grade I) carcinomas were found to contain an almost equal number of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. When semiquantitatively assessed, the incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells was found to be lower in the moderately and poorly differentiated (grades II and III) tumors than in the highly differentiated ones; they also showed greater staining variability. Tumor cells immunoreactive with a monoclonal antiserum raised against PAP in carcinomas of grades II and III were less frequent than tumor cells immunoreactive with antisera against PSA, β‐MSP, and a polyclonal antiserum against PAP. The almost identical distribution of PSA and β‐MSP in carcinomas of grades II and III suggests that PSA and β‐MSP are not less sensitive tumor markers than PAP for the monitoring of the course and the treatment of prostatic carcinomas.
Treatment of metastatic prostate carcinoma with the depot LRH analog zoladex
Authors: Holdaway I. M. , Ibbertson H. K. , Croxson M. S. , Harvey V. , Boulton J. , List A. , Rutland M. , Knox B. S. 
Published: February 2007

AbstractA long‐acting LRH agonist (ICI 118630, Zoladex) was given by monthly subcutaneous injection to 25 patients with previously untreated symptomatic advanced prostatic carcinoma. The medication was well tolerated with the only side effect being hot flushes in 15 patients. Subjective improvement occurred in 22 patients, and disease remission or stabilization judged by objective criteria was seen in 21 and 18 patients from the total group at 3 and 6 months of treatment, respectively. Twelve of 18 patients followed for 1 year were still in objective remission/stabilization. Prostate volume measured by ultrasound decreased by a mean value of 75% and urine flow increased significantly. There were significant falls in serum testosterone and gonadotrophin levels and significant although lesser reductions in serum androstenedione and dehydroepiandrosterone. These changes were accompanied by significant reductions in serum acid and alkaline phosphatase and a rise in serum osteocalcin. Four patients (16%) experienced an initial tumor flare. Although only a small number of patients were studied, Zoladex appeared to be a well‐tolerated agent for treatment of prostatic carcinoma, with an initial clinical response similar to that seen with standard endocrine therapy.
Growth of a spontaneous canine prostatic adenocarcinoma in vivo and in vitro: Isolation and characterization of a neoplastic prostatic epithelial cell line, CPA 1
Authors: Eaton C. L. , Pierrepoint C. G. 
Published: February 2007

AbstractNeoplastic epithelium derived from a spontaneous canine prostatic adenocarcinoma has been maintained and grown in cell culture and as xenografts in athymic mice. An epithelial cell line (CPA 1) has been isolated from primary cultures and has been partially characterized in vitro. The growth of this cell line was not modified by either androgens or estrogens, and high‐affinity receptors for these steroids could not be demonstrated in these cells'. Xenografts were serially transplantable, with growth being similar in both sexes. Receptors for androgens and estrogens could not be detected in homogenates of xenografts or primary tumor. The histological appearances of serially transplanted tumors, and of xenografts generated by inoculation of the cell line (CPA 1) and several cloned substrains, were very similar to that of the primary tumor and were judged to be well differentiated. The characteristics of this neoplastic cell type have been compared with those of normal prostatic epithelium.