bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of growth factor antagonists on neoplastic and normal prostatic cells
Authors: Morton Ronald A. , Isaacs John T. , Isaacs William B. 
Published: February 2007

AbstractGrowth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen‐dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen‐independent AT‐2 subline of the Dunning R‐3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT‐2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells.
Evaluation of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer
Authors: Juniewicz P. E. , Fetrow N. , Marinelli J. , Wolf M. , Young E. , Lamb J. , Isaacs J. T. 
Published: February 2007

AbstractA series of experiments were conducted to evaluate the effects of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer. In the first experiment, oral administration of Win 49,596 at doses of 30, 100, or 300 mg/kg/day for 28 days inhibited (P <0.05) the growth of the androgen‐sensitive PAP variant of the Dunning R‐3327 prostatic carcinoma in intact male rats relative to intact controls. The degree of inhibition at 100 and 300 mg/kg/day Win 49,596 was similar (P >0.10) to that observed in castrate controls as well as in intact rats administered the nonsteroidal androgen receptor antagonist flutamide orally at 15 mg/kg/day. Castration as well as treatment with either Win 49,596 or flutamide also decreased (P <0.05) the weight of the prostate in tumor‐bearing animals.Additional studies were conducted to determine the effect of Win 49,596 on the growth of the androgen‐dependent PC‐82 human prostatic carcinoma xenografted into athymic nude male mice. Oral administration of Win 49,596 at 30, 100, or 300 mg/kg/day for 35 days inhibited (P <0.05) tumor growth relative to intact controls. The degree of tumor inhibition was similar to that observed in intact male mice administered the nonsteroidal androgen receptor antagonist flutamide orally at 30 mg/kg/day but was less than that observed following castration. Ventral prostate weights were also reduced (P <0.05) in castrate mice as well as in intact mice administered either Win 49,596 or flutamide. In the last experiment, at equivalent total daily dosages of either 150 or 300 mg/kg/day Win 49,596, twice a day (BID) dosing was more effective than once a day (SID) dosing in inhibiting tumor growth. The inhibitory effects of Win 49,596 at 150 mg/kg BID on tumor growth were similar to those observed following castration. Although Win 49,596 treatment reduced (P <0.05) ventral prostate weights relative to intact controls, there was no difference (P >0.10) between SID vs. BID dosing.Based on the results of these studies and subject to further testing, Win 49,596 may have utility in the treatment of hormonally dependent metastatic prostate cancer in humans.
Regional differences in the prostate of the neonatally estrogenized mouse
Authors: Pylkkänen L. , Santti R. , Newbold R. , McLachlan J. A. 
Published: February 2007

AbstractNeonatal estrogenization of the mouse with diethylstilbestrol resulted in time‐of‐exposure and dose‐dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1–6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5α‐dihydrotestosterone in terms of nuclear 3H‐thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma.Secondary estrogen treatment of neoDES mice with 17β‐estradiol did not increase 3H‐thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation.When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship.
H‐ras expression, genetic instability, and acquisition of metastatic ability by rat prostatic cancer cells following v‐H‐ras oncogene transfection
Authors: Ichikawa Tomohiko , Schalken Jack A. , Ichikawa Yayoi , Steinberg Gary D. , Isaacs John T. 
Published: February 2007

AbstractTo study the relationship between metastatic ability, mutated H‐ras expression, and genetic instability, a cloned, nonmetastatic rat prostatic cancer cell line (AT2.1) was transfected with the v‐H‐ras oncogene. The parental AT2.1 clone, 4 control transfectants (Neo/Only), and 9 v‐H‐ras transfectants (Neo/Ras) were characterized with regard to their H‐ras content by using Southern, Northern, and Western blot analysis and their biological behavior in vivo. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors. All 4 (Neo/Only) transfectants like the parental untransfected cell were non‐metastatic. Six of 9 Neo/Ras transfectants were metastatic to the lungs and lymph nodes, while the other 3 Neo/Ras transfectants were not metastatic. There was no simple dose‐response relationship between the level of v‐H‐ras integration, mRNA or p21 protein expression, and the development of metastatic ability by the Neo/Ras transfectants. Cytogenetic analysis demonstrated that the frequency of additional structural and/or additional numerical chromosomal changes among the Neo/Ras transfectants was significantly higher than that in the Neo/Only transfectants (P <0.05). Loss of chromosome 10 was observed in all of the Neo/Ras transfectants, whereas that was observed in only one of the 4 Neo/Only transfectants (P <0.05). There were no specific chromosomal changes, however, which were statistically correlated with the development of metastases in the Neo/Ras transfectants. These results demonstrate that development of the metastatic ability in AT2.1 cells is not a single‐step reaction regulated by the level of H‐ras expression alone, but rather a complex process requiring additional events. One of the additional events appears to be an increase in genetic instability and cytogenetic changes following v‐H‐ras transfection.
Heterogeneity in plasminogen activator (PA) levels in human prostate cancer cell lines: Increased PA activity correlates with biologically aggressive behavior
Authors: Keer Harold N. , Gaylis Franklin D. , Kozlowski James M. , Kwaan Hau C. , Bauer Kenneth D. , Sinha Akhouri A. , Wilson Michael J. 
Published: February 2007

AbstractPlasminogen activators (PA), particularly the lower Mr urokinase (u‐PA) type, have been associated with tumor cell invasion and metastasis. We have examined the expression of PA by two human prostate cancer cell lines (PC‐3 and DU‐145) using functional and immunologic techniques. The culture media and cell extracts of the more aggressive PC‐3 cell line contained more than two‐fold greater PA activity than the relatively indolent DU‐145 cell line. Zymographic studies identified the PA expressed as u‐PA. PC‐3 cells expressed an additional lower molecular weight form of u‐PA not noted in DU‐145 cells. Heterogeneity in u‐PA expression was shown by the fibrin lysis assay, immunohistochemistry, and dual parameter flow cytometry indicating the presence of phenotypically divergent cell populations. Increased u‐PA expression may identify those tumor cells that possess aggressive biological potential.
Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines
Authors: Rose David P. , Connolly Jeanne M. 
Published: February 2007

AbstractDietary Fatty acids (FAs) may be involved in the carcinogenic process within the prostate gland and progression to clinically manifest disease. We have shown that growth of the androgen‐unresponsive PC‐3 human prostate cancer cell line is stimulated in vitro by the presence of linoleic acid (LA), an omega‐6 polyunsaturated FA. The response was positively related to the FA concentration over the entire range examined (5–750 ng/ml). Conversely, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega‐3 FAs present in fish oils, inhibited PC‐3 cell growth in a dose‐dependent manner; both were equally effective, with an approximately 65% reduction in growth occurring at a concentration of 2.0 μg/ml (P < 0.001). The DU 145 human prostate cancer cell line, which is also androgen‐unresponsive, showed no growth response to LA and was less susceptible to growth inhibition when cultured in the presence of omega‐3 FAs. Growth experiments with indomethacin, esculetin, and piroxicam, pharmacological inhibitors of eicosanoid biosynthesis with differing sites of action, indicated that human prostate cancer cell growth requires intact metabolic pathways for both leukotriene and prostaglandin production.
Prostate—an extrapituitary source of follicle‐stimulating hormone (FSH): Occurrence, localization, and de novo biosynthesis and its hormonal modulation in primates and rodents
Authors: Garde Seema V. , Sheth Anil R. , Shah Madhavi G. , Kulkarni Sujata A. 
Published: February 2007

AbstractA comparative study on the immunocytochemical localization, de novo biosynthesis, and hormonal modulation of follicle‐stimulating hormone (FSH) was carried out in the prostates of man, monkey, dog, guinea pig, hamster, rat, and mouse. FSH was localized in the cytoplasm of the prostatic epithelial cells. In some specimens, staining was also observed in the nucleus. Both pituitary as well as prostatic FSH were coeluted on a Sephadex G‐100 column and high‐performance liquid chromatography (HPLC) indicating physicochemical similarities of FSH in both the tissues. Surprisingly, the modulation of pituitary and prostatic FSH by inhibin and its related peptides were comparable. The intensity and grandularity of FSH staining was stronger in the case of benign prostatic hyperplasia as compared with normal prostatic specimens. In view of the well‐known effects of FSH on the cellular growth, differentiation, and function of gonadal tissues, a similar role for FSH in pathophysiology of prostate is postulated.
Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate
Authors: Sherwood Edward R. , Theyer Gerhard , Steiner Georg , Berg Lori A. , Kozlowski James M. , Lee Chung 
Published: February 2007

AbstractThe purpose of the present study was to identify cytokeratin polypeptides that are specifically associated with the basal and luminal epithelia of the human prostate. This aim was accomplished by immunohistochemical and immunoblot analysis of human prostate using cytokeratin‐specific monoclonal antibodies. In immunohistochemical studies, monoclonal anticytokeratin 8.12 exhibited immunoreactivity with the basal, but not luminal, epithelial cells of fetal, juvenile, normal adult, and hyperplastic prostate. The 8.12 antibody did not stain prostate cancer tissues. Epithelia of 30 and 36 week fetal prostate contained only basal cells whereas both luminal and basal cells were noted in 7 month and 1 year old juvenile prostate. This finding suggests a stem cell function for the prostatic basal cells. Immunoblot analysis of proteins separated by two‐dimensional electrophoresis showed that cytokeratins 5 and 15 were basal‐cell‐specific cytokeratins that were absent from prostatic carcinoma while cytokeratins 8 and 18 appear to be luminal‐cell‐specific. These results indicate that antibodies to specific cytokeratin polypeptides can be used not only to differentiate between prostatic basal and luminal cells but also to study the biological processes of prostatic organogenesis and carcinogenesis.
The in vivo effect of regional hyperthermia on dunning R3327 prostatic tumor
Authors: Tucker Robert D. , Loening Stefan A. , Landas Steve , Mardan Ali H. , Zong‐Ying Ren , Lubaroff David M. 
Published: February 2007

AbstractThis report describes the in vivo effect of regional hyperthermia on male Copenhagen rats implanted with Dunning R3327 prostatic carcinoma. In six rats, a 22‐gauge 1.5‐cm needle was inserted into the tumor and heated to 46.5%C for 2 hr. Two hyperthermia treatments were administered 48 hr apart. In a separate group of six rats, the needle was inserted into the tumor, but not heated. After treatment, serial measurements of tumor volume and body weight were made twice a week for 4 weeks. From the first day of measurement to day 22, the tumor size in the treated group compared to control was significantly smaller, P = 0.02. In the first 12 days following treatment, the mean value of body weight in the treated and control groups decreased 7% and 3%, respectively. Following this, body weights increased to baseline levels by the end of the study. No other side effects related to hyperthermia were observed and no immediate mortality occurred. In the control group, two rats died from lung metastasis of the prostatic carcinoma after day 22. In the treated group, no lung metastases were found and no rats died before being sacrificed on day 29. Our experiments show that local elevation of the temperature of the Dunning tumor results in the deam of tumor cells; at 46.5°C for 2 hr there is marked tumor damage while the rats tolerated the hyperthermia well.
Differential antiproliferative activities of alpha‐ and gamma‐interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice
Authors: Van Moorselaar Reindert J. A. , Van Stratum Peter , Borm George , Debruyne Frans M. J. , Schalken Jack A. 
Published: February 2007

AbstractWe have investigated the antiproliferative effects of recombinant human alpha‐ and gamma‐Interferon (IFN) and recombinant human Tumor Necrosis Factor alpha (TNF) against the hormone‐independently growing PC3 and DU145 prostatic tumor lines. Subcutaneous, peritumoral administration of the drugs was started 24 hours after subcutaneous implantation of 1–2 mm3 tumor pieces. IFN was given three times per week and TNF five times per week. IFN‐alpha (dose‐range 0.5–5 ng/gram bodyweight) had significant growth‐inhibiting effects against the PC3 tumor, but showed no significant antitumor effects against the DU145 tumor. IFN‐gamma monotherapy (dose‐range 8–80 ng/gram bodyweight) was less effective than IFN‐alpha. 500 ng/gram TNF produced growth inhibition of both tumors, whereas the lower dose (50 ng/g) was only effective against the PC3 tumor. IFN‐alpha and ‐gamma combination treatment had significant antiproliferative effects against the PC3 tumor, but not against the DU145 tumor. Combinations of IFN‐alpha and TNF were very effective against both xenografts; some combinations resulted in complete growth inhibition. IFN‐gamma and TNF combinations also showed significant antitumor effects against both tumor lines. We therefore conclude that cytokine combination treatment may provide a new approach in the treatment of hormone‐escaped prostatic tumors.
Investigation on serum neurone‐specific enolase in prostate cancer diagnosis and monitoring: Comparative study of a multiple tumor marker assay
Authors: Tarle Marko , Radoś Nikola 
Published: February 2007

AbstractA quadruple tumor marker serotest assay (neurone‐specific enolase, NSE, prostate‐specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino‐embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28,6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonre‐sponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE‐positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE‐positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision‐making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.
Immunohistochemical study of metallothionein in normal and benign prostatic hyperplasia of human prostate
Authors: Suzuki Takanori , Umeyama Tomokazu , Ohma Chikako , Yamanaka Hidetoshi , Suzuki Keiji , Nakajima Katsuyuki , Kimura Masami 
Published: February 2007

AbstractMetallothionein (MT) in the human prostate gland was examined. Prostatic tissues were obtained from patients of urinary bladder cancer who had received radical cystoprostatectomy. MT content was 99.3 μg/g wet tissue (w.t.) in the peripheral zone (PZ), 12.0 μg/g w.t. in the preprostatic region (PR), 7.3 μg/g w.t. in the central zone (CZ), 6.8 μg/g w.t. in the anterior fibromuscular stroma, and 29.5 μg/g w.t. in benign nodular hyperplasia (adenoma) by radioimmunoassay. Immunohistochemical study demonstrated that MT was localized in the cytoplasm, nuclei of glandular epithelia, and secretory products. In general, a positive immunoreaction was strong in PZ and weak in CZ. It is considered that glandular epithelial cells in PZ, PR, CZ, and adenoma may react differently to heavy metals, e.g., zinc and cadmium.
Effect of etidronate disodium on the development of bone lesions in an animal model of bone metastasis using the human prostate cancer cell line PC‐3
Authors: Shevrin Daniel H. , Gorny Kathleen I. , Rosol Thomas J. , Kukreja Subhash C. 
Published: February 2007

AbstractWe have established an animal model of bone metastasis using the PC‐3 human prostate tumor cell line. In order to assess whether inhibition of bone resorption would prevent the development of bone metastasis, the diphosphonate etidronate (EHDP) was administered to 20 mice at a dose of 30 mg/kg subcutaneously daily starting 2 days prior to injection of tumor cells. Control mice received daily injections of the saline vehicle. In the EHDP‐treated mice, there was no significant reduction in the incidence of bone metastasis, the size of the lesions, or the number of bone lesions per mouse. Approximately 50% of the mice developed bone metastasis, which was similar to the control group and similar to what was observed in earlier studies with this animal model. Histomorphometric analysis of bones showed marked inhibition of mineralization in EHDP‐treated mice, thus indicating biological effect on the bone. Therefore, the use of EHDP in biologically effective doses failed to reduce the incidence, size, or number of bone metastases in this animal model.
Reconstituted basement membrane promotes morphological and functional differentiation of primary human prostatic epithelial cells
Authors: Fong Chau‐Jye , Sherwood Edward R. , Sutkowski Debra M. , Abu‐Jawdeh Graziella M. , Yokoo Hidejiro , Bauer Kenneth D. , Kozlowski James M. , Lee Chung 
Published: February 2007

AbstractProstatic epithelial cells undergo rapid proliferation and lose their ability to synthesize and secrete prostate‐specific antigen (PSA) and prostatic acid phosphatase (PAP) under standard tissue culture conditions. Herein, we compared the morphology, growth, secretory activity, and intermediate filament expression of human prostatic epithelial cells cultured on either standard tissue culture plastic or reconstituted basement membrane. Epithelial cells grown on plastic exhibited a 10‐fold increase in proliferation and a higher percentage of cells in the S‐phase of the cell cycle compared to cells cultured on basement membrane. However, cells grown on basement membrane secreted markedly higher levels of PSA and PAP. The basement membrane‐induced enhancement of secretory activity was potentiated by dihydrotestosterone (DHT) and prostate stromal cell conditioned medium. Morphological studies showed that cells plated on basement membrane formed organoid‐like clusters and maintained several aspects of differentiated epithelium including abundant secretory vesicles, microvilli, and desmosomes with associated cytoskeletal elements. Cultivation of epithelial cells on basement membrane components also suppressed the expression of vimentin, a mesenchymal intermediate filament polypeptide. However, cytokeratin expression was abnormal in cells grown on either surface. These results indicate that the differentiated properties of prostatic epithelial cells are promoted by cultivation on reconstituted basement membrane in the presence of DHT and stromal cell conditioned medium.