bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of growth of experimental prostate cancer in rats by LH‐RH analogs linked to cytotoxic radicals
Authors: Pinski Jacek , Schally Andrew V. , Yano Tetsu , Szepeshazi Karoly , Halmos Gabor , Groot Kate , Comaru‐Schally Ana Maria , Radulovic Sinisa , Nagy Attila 
Published: February 2007

AbstractThe effects of hybrid cytotoxic LH‐RH analogs, produced by linking anthraquinone or methotrexate to carrier LH‐RH agonist [D‐Lys6]LH‐RH, were evaluated in Copenhagen‐Fisher Fl rats bearing Dunning R‐3327H prostate adenocarcinoma. The two cytotoxic LH‐RH analogs T‐98 [(D‐Lys6)LH‐RH coupled to glutaryl‐2‐(hydroxymethyl)anthraquinone (G‐HMAQ)], and AJ‐04 [(D‐Lys6)LH‐RH linked to methotrexate (MTX)], carrier [D‐Lys6]LH‐RH, or the free cytotoxic compounds MTX and G‐HMAQ were administered from Alzet Osmotic minipumps for 7–8 weeks. The cytotoxic LH‐RH analogs caused somewhat greater tumor growth inhibition than the carrier peptide, while anthraquinone or methotrexate alone, administered in equimolar doses, were ineffective. The inhibition of androgen sensitive organs (testes, ventral prostates, and seminal vesicles) was pronounced with both carrier and cytotoxic analogs, showing the latter to be fully hormonally active in suppressing the pituitary‐gonadal axis. Histological changes were also evaluated. The inhibition of mitosis and the frequency of apoptosis were higher in tumors treated with AJ‐04, T‐98, [D‐Lys6]LH‐RH, or by castration than in those of controls. Serum hormone levels were lowered by both carrier peptide and cytotoxic analogs, LH being substantially depressed, and testosterone not detectable. These results and other findings indicate that LH‐RH analogs containing cytotoxic radicals anthraquinone or methotrexate retain their hormonal activity after administration in vivo, and can effectively inhibit tumor growth. Extensive further studies are required on this new class of compounds, but apparent binding of cytotoxic LH‐RH analogs to tumors such as prostate cancer, which have receptors for LH‐RH, could greatly reduce peripheral toxicity of chemotherapeutic agents. This approach, based on targeted chemotherapy, might be of practical therapeutic importance for the management of advanced prostate cancers, which eventually relapse after palliative hormonal therapy. © 1993 Wiley‐Liss, Inc.
Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP
Authors: Langeler Erna G. , Van Uffelen Connie J. C. , Blankenstein Marinus A. , Van Steenbrugge Gert Jan , Mulder Eppo 
Published: February 2007

AbstractSeveral effects of androgens on LNCaP‐FGC prostate tumor cells showed a biphasic pattern. Stimulation of growth and inhibition of secretion of prostatic acid phosphatase (PAP) was observed at low androgen concentrations (below 1 nM of the synthetic androgen R1881), and inhibition of growth and stimulation of PAP secretion was observed at higher concentrations. In contrast, prostate specific antigen (PSA) secretion did not show this biphasic response pattern. Comparable effects were found for two sublines of the LNCaP‐FGC cells: an early (passage 20, androgen‐dependent) and relatively late (passage 70, androgen‐sensitive) passage of the cells. Culturing of both sublines in the presence of a high concentration of androgens (10 nM R1881) resulted initially in a decrease in growth rate, but the cells started to proliferate within 3 weeks. These cells became less sensitive to androgens, lost their biphasic response pattern, and showed reduced androgen receptor levels. Three weeks after removal of the excess of androgens, the passage 70 cells regained a biphasic growth response to androgens. Culture in medium without steroids but with EGF resulted in a decrease of both androgen sensitivity and androgen receptor level.In conclusion, rapid changes of the androgen sensitivity and receptor level of the LNCaP cells occurred under the influence of culture conditions. These changes were partly reversible and, therefore, were most likely due to adaptation of the cells. © 1993 Wiley‐Liss, Inc.
Comparison of the pathologic features and DNA ploidy value of prostate cancers detectable by sonography and by palpation
Authors: Ohori Makoto , Wheeler Thomas M. , Greene Damian R. , Scardino Peter T. 
Published: February 2007

AbstractUltrasonography of the prostate detects some cancers that are not palpable, but the pathologic features of such cancers have not been well described. Since screening trials consistently find sonography more sensitive (though less specific) than digital rectal examination, nonpalpable cancers that are visible as hypoechoic lesions on ultrasound have been postulated to be early cancers of limited malignant potential and may not require aggressive treatment.To test this hypothesis, we determined the pathologic features and DNA ploidy value of prostate cancers in 63 radical prostatectomy specimens taken from patients with clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%), the cancer appeared hypoechoic on ultrasound. The median volume of these cancers was 4.19 cm3 (range 0.45–19.22); 80% exhibited extra‐capsular extension (ECE); 30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35 patients, the tumor was palpable, and the pathologic features and DNA ploidy values (94% nondiploid) of these cancers were similar to those of the tumors that were visible on ultrasound. In seven patients, the cancer was visible by ultrasound but not palpable by digital rectal examination. Median tumor volume was 1.72 cm3 (range 0.45–18.98); four patients (57%) had ECE; one (14%) had SVI, and six (86%) had nondiploid cancers.We conclude that most cancers that appear hypoechoic on ultrasound are clinically important and exhibit aggressive pathologic features. Palpable cancers and sonographically visible cancers are similar and should be staged and treated similarly. © 1993 Wiley‐Liss, Inc.
Multivariate analysis of plasma hormones in patients with metastatic prostate cancer receiving combined LHRH‐analog and antiandrogen therapy
Authors: Fiet Jean , Doré Jean‐Christophe , Le Gǒ Alice , Ojasoo Tiiu , Raynaud Jean‐Pierre 
Published: February 2007

AbstractThe following hormones, the plasma protein SHBG, and the tumor markers prostatic acid phosphatase (PAP) and prostate‐specific antigen (PSA) were assayed at 18 time‐points over 1 month during a double‐blind randomized study in 36 stage D2 cancer patients receiving either “buserelin + placebo” or “buserelin + nilutamide (Anandron)”: LH, FSH, estradiol, testosterone, dihydrotestosterone, androstenedione, 5‐androstene‐3,17β‐diol, dehydroepiandrosterone and its sulfate, cortisol, 17α‐hydroxyprogesterone, pregnenolone, 17α‐hydroxypregnenolone, and 3α‐androstanediol glucuronide. Multivariate analysis of the treatment values (over 10,000 assays) by two complementary methods, correspondence factorial analysis (CFA) and the minimum spanning tree (MST) method, identified those variables within the pathways of androgen metabolism that were correlated over time and, in a comparison of the two treatment groups, identified the enzyme targets of nilutamide action in humans. Whereas nilutamide tended to decrease androstenedione slightly, it affected no other variables including cortisol, except for pregnenolone, 17α‐OH‐pregnenolone, and 17α‐OH‐progesterone, which were increased. These increases are indicative of weak inhibition of C17,20 lyase by nilutamide, but, according to the multivariate analysis, are insufficient to account for the more marked and rapid fall in PAP and PSA noted on addition of nilutamide to buserelin that must therefore be explained by another mechanism such as androgen receptor blockade by nilutamide. © 1993 Wiley‐Liss. Inc.
Characterization of a soluble LHRH‐degrading activity in the rat ventral prostate
Authors: Maggi Roberto , Dondi Donatella , Limonta Patrizia , Pimpinelli Federica , Montagnani Marina , Moretti Roberta M. , Motta Marcella 
Published: February 2007

AbstractRecent evidence supports the hypothesis of a direct action of LHRH at the level of the prostate. Since peptidases able to degrade the hormone are present in several LHRH target structures, it was deemed of interest to investigate whether the prostate of adult normal male rats might possess LHRH degrading activities (LHRH‐DA). Through the use of RP‐HPLC, it has been observed that LHRH‐DA is present in the soluble fraction of the rat ventral prostate homogenate, and is able to hydrolyze synthetic LHRH and to generate fragments 1–3 and 1–5 of the decapeptide. The degradation of [pGlu‐3H]LHRH is inhibited by LHRH itself, and affected by several LHRH agonists and antagonists with different kinetics and potencies. TRH, the enkephalin analog [D‐Ala2‐D‐Leu5]enkephalin and rat prolactin do not inhibit the degradation of [pGlu‐3H]LHRH by the soluble fraction of prostate homogenate; on the contrary, this is inhibited by graded doses of somatostatin. The prostatic LHRH‐DA is also inhibited, in a dose dependent manner, by bacitracin, serine protease inhibitors (diisopropylfluorophosphate and phenylmethansulfonylfluoride), the metal chelating agent EDTA, HgCl2, and dithiothreitol. No inhibitory effect on [pGlu‐3H]LHRH hydrolysis was observed after incubation of the prostatic extract in the presence of captopril. The prostatic LHRH‐DA seems to be different from that present in other tissues of the rat (e.g., hypothalamus, pituitary, gonads), and to be decreased by castration performed 3 weeks before. These results suggest that (1) an LHRH‐DA is found in the soluble fraction of rat prostate homogenate; (2) this enzymatic activity exhibits the characteristics of a metallo‐ and thioldependent neutral endopeptidase; (3) it appears to be different from similar hydrolytic activities found in other tissues; and (4) it is influenced by the hormonal milieu, since castration causes a significant decrease of its activity. © 1993 Wiley‐Liss, Inc.
Nuclear casein kinase 2 (CK‐2) activity in human normal, benign hyperplastic, and cancerous prostate
Authors: Yenice Sedef , Davis Alan T. , Goueli Said A. , Akdas Atif , Limas Catherine , Ahmed Khalil 
Published: February 2007

AbstractIn previous work, we had observed that chromatin‐associated nonhistone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples [Rayan et al: Cancer Res 45:2277‐2282, 19851]. The properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). By employing the specific synthetic substrate for casein kinase 2 (CK‐2) for assays in cellular fractions, we have shown that this protein kinase is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25‐fold, as compared with its activity in the normal prostate chromatin. This suggests that CK‐2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK‐2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the en‐zymic data. However, sections from prostatic carcinoma samples appeared to show differential staining, depending on the Gleason's grade of the sample. The samples with higher Gleason's grade showed less intense immunostain in the nucleus, compared with samples of lower Gleason's grade. Further, regions of sections in samples with higher Gleason's grade did not show any immunostaining. These differences in the characteristics of CK‐2 expression in prostatic carcinoma samples may be potentially significant, but need to be evaluated further for their significance to the pathobiology of prostatic neoplasia. © 1994 Wiley‐Liss, Inc.
Age‐related changes of the prostate gland in the senescence‐accelerated mouse
Authors: Sugimura Yoshiki , Sakurai Masaki , Hayashi Norio , Yamashita Atsushi , Kawamura Juichi 
Published: February 2007

AbstractAging is of utmost importance in the pathogenesis of the prostate gland (i.e., benign prostate hyperplasia or prostatic carcinoma). The object of this study was to examine the morphological and histological changes of the aging prostate of the so‐called senescence‐accelerated mouse (SAM). Ventral and dorsolateral lobes of prostate glands of SAM were microdissected into two‐dimensional ductal arrays. Gross morphology, ductal branching patterns, and histology were examined in these microdissected specimens. Wet weight and numbers of ductal tips in ventral and dorsolateral prostate glands in senescence accelerated‐prone (SA‐P) mice were significantly smaller than those of senescence accelerated‐resistant (SA‐R) mice, although the changes of patterns of gross ductal morphology were virtually identical in these groups. High incidence of stromal hyperplasia with fibrosis and inflammation was observed in the dorsal lobe of the aged SA‐P mouse. Atypical glandular epithelial cells and cribriform glandular deformity were observed in the dorsal and lateral lobe of aged SA‐P mice. Marked heterogeneity in age‐related pathological changes was observed between prostatic lobes. These data suggest that the aging process occurs heterogeneously within the prostate gland, and that SA‐P mice may be an important model for the study of age‐related changes in the prostate gland. © 1994 Wiley‐Liss, Inc.
The proliferative function of basal cells in the normal and hyperplastic human prostate
Authors: Bonkhoff Helmut , Stein Ute , Remberger Klaus 
Published: February 2007

AbstractTo obtain more insight into the proliferative function of basal and secretory cell types in human prostate, we studied the immunoprofile of three well‐characterized proliferation‐associated antigens (Ki‐67, PCNA, MIB 1) in normal and hyperplastic prostate tissue. Distinction between labeled basal and secretory cell types was made by simultaneous demonstration of the proliferation‐associated antigens and basal cell‐specific cytokeratins in identical sections. In normal and hyperplastic acini, approximately 70% of labeled cells were of the basal cell phenotype. These data clearly suggest that the proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. Compared to normal and hyperplastic conditions, severe proliferative abnormalities were detected in high‐grade prostate intraepithelial neoplasias (PIN), as documented by the extension of the proliferative compartment up to the luminal border. Conversely, approximately 70% of proliferating cells detected in atypical hyperplasias that progressed in invasive carcinomas were localized in the remaining basal cell layer.These findings may indicate the proliferative role of basal cells in the epithelial renewal, and the development of hyperplastic and neoplastic disorders in the human prostate. © 1994 Wiley‐Liss, Inc.
Effect of early exposure of flutamide on subsequent growth of transplantable rat prostatic tumor (dunning R‐3327)
Authors: Lee Sue Zen , Sato Naohide , Suzuki Hiroyoshi , Watabe Yoshio , Masai Motoyuki , Shimazaki Jun 
Published: February 2007

AbstractRat transplantable prostatic tumors (Dunning R‐3327) were treated with flutamide before tumors grew palpable, in order to examine the effect of short term treatment of antiandrogen for prostatic cancer in latent period on the growth after appearance of tumor. Flutamide delayed an appearance of the tumor nodule and retarded the growth rate in proportion as treatment began earlier. Flutamide also reduced final tumor volume. Flutamide‐treated tumors histologically consisted of small or dilated glandular structure with an increase in stromal area, but androgen receptors were preserved. Flutamide‐treated tumor showed slow growth with androgen sensitivity when transplanted to intact rats, showing prolonged influences of antiandrogen on tumor growth. There was no significant difference between flutamide‐treated and control groups in weight of accessory sex organs and serum androgen or estrogen levels. In conclusion, flutamide treatment may retard an appearance of prostatic cancer concomitant in benign prostatic hyperplasia. © 1994 Wiley‐Liss, Inc.
Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells
Authors: Harris Stephen E. , Harris Marie A. , Mahy Patrick , Feng Jian Q. , Mundy Gregory R. , Wozney John 
Published: February 2007

AbstractHuman prostate cancer cells are known to produce several growth regulatory factors, including transforming growth factor β (TGFβ) and heparin‐binding fibroblast growth factors (FGFs), which may play as‐yet‐undefined roles in prostate gland morphogenesis, as well as in prostate cancer cell behavior. Recently, a family of proteins in the extended TGFβ family, the bone morphogenetic proteins (BMPs), has been identified which stimulates bone formation in vivo, and in which, the proteins are likely involved in a variety of morphogenetic processes during embryogenesis. These powerful morphogenetic factors are capable of redirecting muscle mesenchyme cells to differentiate along the lines of bone tissue. We examined a number of well‐characterized rat and human prostate cancer cell lines for the expression of BMP 2, 3, 4, and 6 messenger RNA. Poly(A + )‐RNA was isolated from normal human and rat ventral prostate, from the rat prostate adenocarcinoma PAIII tumor and cultured cells derived from it, and from human prostate cancer cell lines PC‐3, LNCaP, and DU‐145. BMP mRNA levels were measured using BMP 2, 3, 4 and Vgr‐1 (BMP 6) cDNA probes. Both normal and neoplastic prostate tissue expressed these BMP mRNAs, although the level of expression varied from tumor to tumor. Normal human prostate expressed BMP 4 mRNA predominantly, as did the human prostate cancers PC‐3 and DU‐145. PC‐3 also expressed BMP 2 mRNA and BMP 3 mRNA in large amounts. Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate adenocarcinoma PAIII expressed predominantly BMP 3 mRNA. The reason that different BMPs are expressed in varying amounts by these normal and neoplastic cells is unknown. However, if these BMPs are expressed in biologically active form, they could be responsible for important effects on normal prostate growth and morphogenesis, on neoplastic prostate cell behavior, and could even contribute to the capacity of prostatic cancer cells to stimulate new bone formation at metastatic tumor sites in bone. © 1994 Wiley‐Liss, Inc.
Detection of prostatic‐inhibin‐like peptide in the cytoplasm of LNCaP cells, a human prostatic adenocarcinoma cell line
Authors: Hurkadli Kalpana S. , Sheth Anil R. , Lokeshwar Balakrishna , Block Norman L. 
Published: February 2007

AbstractProstatic inhibin peptide (PIP) is a 94‐amino acid peptide involved in various cellular functions. The concentration of this peptide changes with prostatic pathophysiology suggesting a role in various disease conditions; present study was undertaken to investigate the presence of this peptide in two human prostatic cell lines: LNCaP and PC3 cells. The LNCaP cells showed an intense intracellular fluorescence pattern after staining with rabbit‐anti‐PIP antiserum and FITC conjugated goat antirabbit‐IgG, while the PC3 cells did not exhibit any fluorescence. There was no alteration in the concentration of PIP in LNCaP cells with or without supplementation of steroids in culture medium. Immunoblot analysis indicates similarities between PIP from LNCaP cells and that from the human seminal plasma. Thus, present study demonstrates the presence of PIP in a human prostatic cell line, i.e., LNCaP cells. Its intracellular concentration is androgen independent, and has a close similarity with PIP isolated from the human seminal plasma. © 1994 Wiley‐Liss, Inc.
N‐(4‐hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells
Authors: Igawa Mikio , Tanabe Tetsuyuki , Chodak Gerald W. , Rukstalis Daniel B. 
Published: February 2007

AbstractThe synthetic retinoid N‐(4‐hydroxyphenyl) retinamide (4‐HPR) has been demonstrated to inhibit the development of primary and metastatic neoplasms in several animal models. In order to investigate the effect of 4‐HPR on human prostate adenocarcinoma, we designed a series of in vitro experiments with the PC3 cell line to evaluate effects on proliferation, cell cycle kinetics, and c‐myc mRNA expression. 4‐HPR demonstrated cytoxicity only at the supraphysiologic concentration of 10.0 μM. However, asynchronously growing cells exposed to 1 μM 4‐HPR demonstrated a 51% reduction in proliferation rate, associated with an accumulation of cells in the G0/G1 phase of the cell cycle. PC3 cells synchronized with serum deprivation or aphidicoline exhibited significant decreases in DNA synthesis when treated with 1 μM 4‐HPR. Additionally, these cells were found to accumulate in G0/G1 and S phase. Northern blots indicated a significant decrease in c‐myc mRNA expression in asynchronously growing cells with continuous administration of 1 μM 4‐HPR for 6 days. These data suggest that 4‐HPR can inhibit growth of PC3 cells as a consequence of a block in cell cycle transition from G1 to S phase at a concentration of 1 μM, and that this inhibition is associated with a suppression of c‐myc gene expression. © 1994 Wiley‐Liss, Inc.
DNA analysis by flow cytometry of paraffin embedded core biopsies of the prostate
Authors: Warzynski Michael J. , Soechtig C. Eugene , Goldsmith Larry C. , Maatman Thomas J. , Carothers George G. 
Published: February 2007

AbstractThe majority of literature concerning DNA analysis of prostate cancer involves testing formalin‐fixed prostatectomy tissue, fresh or formalin‐fixed transurethral resections of the prostate (TURP), or fresh core biopsies. We were interested if flow cytometry could analyze the DNA of formalin‐fixed, paraffin‐embedded, core biopsies separated into normal versus malignant segments.Of the 50 potentially available samples for analysis representing 11 controls of normal core tissue and 39 core biopsies from the 11 patients, one patient had no normal tissue, one core had no malignancy, and three cores had no tissue visibly remaining in the paraffin blocks for analysis. Therefore, of 45 actual samples available for processing, sometimes representing segments as small as 0.2 cm, separate segments containing malignant glands or normal glands were excised from the blocks, and processed separately by the Hedley technique. Forty‐four of the 45 available samples produced interpretable DNA histograms as defined by discernible G0/G1 peaks, a calculable cell cycle analysis, and the qualitative appearance of a “smooth” histogram appearance, reflecting sufficient nuclei were analyzed. This is the first report to our knowledge where flow cytometry has successfully been used to analyze paraffin blocks of core biopsies which were, in addition, separated into malignant versus normal enriched segments. © 1994 Wiley‐Liss, Inc.