bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological evaluation of benign prostatic hyperplasia treated by long‐term administration of chlormadinone acetate (CMA)
Authors: Harada Masaoki , Kinoshita Yuzo , Moriyama Masatoshi , Kondo Iichiro , Nakahashi Mitsuru , Kumagai Harumi , Sasaki Koichi , Hosaka Masahiko 
Published: February 2007

AbstractAlthough the clinical effects of attempted nonsurgical treatment of benign prostatic hyperplasia have been well documented, detailed histological evaluation of the effects of treatment appears to be limited. The effect of long‐term administration of an antiandrogen, chlormadinone acetate (CMA), on benign prostatic hyperplasia was evaluated with histological comparison of two biopsy specimens, one before treatment and one after treatment. Secretory epithelium showed obvious regressive changes with occasional basal cell prominence after CMA treatment. Stromal elements, however, did not show any marked changes, except for occasional edematous loosening. Scores of multiple epithelial parameters tended to be correlated with clinical improvement in urinary obstructive symptoms, especially in patients with predominant glandular hyperplasia. These results suggest that long‐term administration of the potent antiandrogen CMA to inhibit dihydrotestosterone‐receptor binding might be a useful therapeutic maneuver in patients with glandular hyperplasia, without any deterioration of the stromal component. © 1994 Wiley‐Liss, Inc.
Synergistic effects of estrogen with androgen on the prostate—effects of estrogen on the prostate of androgen‐administered rats and 5‐alpha‐reductase activity
Authors: Suzuki Kazuhiro , Takezawa Yutaka , Suzuki Takanori , Honma Seijiro , Yamanaka Hidetoshi 
Published: February 2007

AbstractTo clarify the effects of estrogen on the prostate of androgen‐treated rats, we administered estradiol (E2; 0.01 mg/day) to testosterone (T; 1 mg/day)‐treated Wistar rats under various conditions. There were three variable factors: the age of the rat, the untreated period after castration, and the presence of testes. Under all conditions, E2 stimulated the growth of the prostate in T‐treated rats compared with growth in rats in treated with T only.To analyze the mechanism underlying this enhancement of prostate growth by estrogen, we measured 5‐alpha‐reductase activity and calculated its kinetic parameters, i.e., both Vmax and Km. The Vmax of the nuclear fraction was higher in E2‐administered T‐treated rats than in T only‐treated rats. In contrast, the Vmax of the microsomal fraction was lower in E2‐administered rats. Km values in the two groups showed no significant differences. Elevation of the nuclear fraction of 5‐alpha‐reductase activity could explain the synergistic effects of estrogen on the prostate growth of androgen‐treated rats. © 1994 Wiley‐Liss, Inc.
In vivo and in vitro effects of androgen on fibroblast growth factor‐2 concentrations in the human prostate
Authors: Geller Jack , Sionit Lida R. , Baird Andrew , Kohls Matthew , Connors Kenneth M. , Hoffman Robert M. 
Published: February 2007

AbstractProstatic growth is primarily regulated by dihydrotestosterone (DHT). Recent studies have demonstrated that a large number of growth factors are present in the human benign prostatic hyperplasia (BPH) prostate, including epidermal growth factor (EGF), transforming growth factor‐alpha (TGF‐α), transforming growth factor beta (TGF‐β), insulin‐like growth factor (IGF), and basic fibroblast growth factor (bFGF) (FGF‐2). DHT may mediate its mitogenic effects in the prostate by regulating growth factors. To test this hypothesis, we have utilized a histoculture androgen sensitivity assay (HASA) in which 3H‐thymidine incorporation is measured in aliquots of BPH tissue in histoculture with either added DHT or hydroxyflutamide (HF). The resulting DHT/HF ratio is an expression of the androgen sensitivity of the tissue. In this study, we have compared the DHT/HF ratio for 3H‐thymidine incorporation to the DHT/HF ratio for FGF‐2 measured in the histocultured prostates. The DHT/HF ratio for the HASA studies of 3H‐thymidine incorporation averaged 2.68 compared to the DHT/HF ratio for FGF‐2 in the same specimens of 1.01. These values were significantly different, therefore indicating no relationship between DHT stimulation and FGF‐2 levels. In addition, FGF‐2 levels were measured in human BPH prostates from patients medically castrated with megesterol acetate and estradiol 17‐β prior to surgery. These values were not significantly different, and therefore do not suggest any effect of DHT on the concentration of prostatic FGF‐2. Although these studies did not show any effect of DHT on the regulation of prostatic FGF‐2, they do indicate that the HASA assay is feasible and appropriate to use in the study of relationships between DHT and various growth factors. © 1994 Wiley‐Liss, Inc.
Transforming growth factor beta I expression in benign and malignant prostatic tumors
Authors: Glynne‐Jones E. , Harper M. E. , Goddard L. , Eaton C. L. , Matthews P. N. , Griffiths K. 
Published: February 2007

AbstractThe expression of transforming growth factor beta 1 (TGF‐β1) in prostate specimens obtained from patients with benign prostatic hyperplasia (BPH, n = 32) and prostate carcinoma (n = 66) was investigated using Northern blot analysis and immunohistochemistry. Northern blot analysis revealed TGF‐β1 message (2.5 kb) in virtually all of the samples examined, reflecting the ubiquitous nature of this growth factor. No statistical difference was found between the levels of mRNA detected in benign and malignant tissues due, in part, to the inherent heterogeneity of prostate tissue. Immunohistochemical methods using an antibody to native TGF‐β1 revealed a novel pattern of immunoreactivity. Staining observed only in certain epithelial cells of benign glands was associated with areas of infection rather than tumorigenesis. Interestingly, intense staining was also seen in polymorphonuclear leukocytes. No correlation was found with the mRNA results, suggesting that this antibody is binding to TGF‐β1 activated in response to infection rather than detecting sites of synthesis of latent TGF‐β. © 1994 Wiley‐Liss, Inc.
Loss and gain of chromosomes 1, 18, and Y in prostate cancer
Authors: König Josée J. , Teubel Wilma , Van Dongen Jan Willem , Romijn Johannes C. , Hagemeijer Anne , Schröder Fritz H. 
Published: February 2007

AbstractNuclear suspensions of 42 prostate carcinoma specimens obtained at surgery were used to investigate loss and gain of chromosomes 1, 18, and Y by fluorescence in situ hybridization (FISH) with centromere‐specific probes. The outcome of FISH analysis was correlated with clinical parameters and the relationship between DNA‐FCM (ploidy at cellular level) and FISH (ploidy of individual chromosomes) was assessed.Significant loss of chromosomes 1 and 18 was infrequent (respectively, three and five cases), but 53% of the tested specimens showed loss of Y. Loss was not correlated with DNA ploidy. Significant gain occurred in 36% (chromosome 1), 63% (chromosome 18), and 28% (Y) of the specimens. Gain of chromosome 18 was shown in DNA diploid (7/14) and aneuploid tumors (18/26), while gain of chromosomes 1 and Y was nearly restricted to DNA aneuploid specimens. Significant unbalance between these chromosomes occurred in 11 cases. Most cases which had significant gain of chromosome 1 or 18 showed trisomic as well as tetrasomic cells. Simultaneous loss of some and gain of other investigated chromosomes is suggestive of clonal heterogeneity and/or multiclonality. This was observed in eight tumors.Correlation between DNA‐FCM and FISH was best for the Y chromosome. DNA‐FCM showed more aberrant histograms with increasing stage and grade of tumors. The presence of numerical aberrations of the investigated chromosomes however, seemed independent of clinical grade or stage. © 1994 Wiley‐Liss, Inc.
Inhibition of growth and increase of acid phosphatase by testosterone on androgen‐independent murine prostatic cancer cells transfected with androgen receptor cDNA
Authors: Suzuki Hiroyoshi , Nihei Naoki , Sato Naohide , Ichikawa Tomohiko , Mizokami Atsushi , Shimazaki Jun 
Published: February 2007

AbstractMost androgen‐unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen‐dependent to androgen‐unresponsive tumor, the AR gene was transfected into an AR‐negative rat prostatic cancer cell line CUB‐II. AR‐transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR‐transfectant cells by histochemical examination. Therefore, AR‐transfectant cells were considered to contain functional AR. The growth of AR‐transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR‐transfectant cells in male mice showed much slower growth than those in females. The tumors of AR‐transfectant cells in mice consisted of slightly larger spindle‐shaped cells when compared to those of CUB‐II cells. Moreover, AR‐transfectant cells contained a few polynuclear giant cells. Since CUB‐II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR‐transfectant cells. It is concluded that resumption of androgen‐dependent processes reduces the growth rate accompanying changes of phenotype. © 1994 Wiley‐Liss, Inc.
Analysis of prostatic fluid: Evidence for the presence of a prospective marker for prostatic cancer
Authors: Grover Phulwinder K. , Resnick Martin I. 
Published: February 2007

AbstractIn an endeavor to identify marker(s) for prostatic cancer, proteins in prostatic fluids were analyzed by two‐dimensional (2‐D) gel electrophoresis. The fluids were obtained from five males who had no prostate lesions and five patients each with benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCA). The specimens were collected directly over a mixture of protease inhibitors and centrifuged, and the supernatants were lyophilized and solubilized in sodium dodecyl sulfate mix. Identical amounts of proteins were pooled according to donors' prostate disease and the resulting samples were subjected to 2‐D gel analysis employing the ISO‐DALT system. The electrophoretograms were developed by silver or double stain.The samples of each group exhibited distinctive profiles with the exception of similar relative positions of major protein spots. A predominant protein occurring as several charge variants was consistently present in prostatic fluids of patients with PCA. This protein appeared to be a previously unknown constituent that we have called protein D (molecular weight ∼︁22 kDa and isoelectric point ∼︁4), and was undetectable in the fluids of “normal” men and patients with BPH. An analysis of pooled, unprocessed urine from PCA patients revealed that perhaps this protein is excreted in urine in very low quantities.These results strongly suggest that the potential of this protein as a marker for prostatic cancer should be further explored.
Effects of prostatectomy on testicular androgenesis and serum levels of gonadotropins in mature albino rats
Authors: Ghosh Pradip Kumar , Ghosh D. , Ghosh P. , Chaudhuri A. 
Published: February 2007

AbstractThe effects of prostatectomy on testicular steroidogenic enzymes, and on serum levels of gonadotropins, prolactin, and testosterone were studied. Adult male rats were prostatectomized and sacrificed after 14 and 21 days. There was augmentation of both Δ5‐3β‐hydroxysteroid dehydrogenase (Δ5‐3β‐HSD) and 17β‐hydroxysteroid dehydrogenase (17β‐HSD) activities in the testes along with increased levels of FSH, prolactin, and testosterone in the serum, while no changes were observed in serum levels of LH. Hence it may be concluded that the prostate gland has an inhibitory effect on testicular androgenesis and can exert some influence in the regulation of FSH and prolactin secretion.
6‐methylene progesterone is cytotoxic to human cancer cell lines independent of its 5‐α‐reductase activity
Authors: Roberson Kathryn M. , Robertson Cary N. , Padilla George M. , Schmidt James Malcolm , Petrow Vladimir 
Published: February 2007

AbstractThis investigation examined the effects of 6‐methylene progesterone (6MP), an irreversible inhibitor of 5‐α‐reductase, on prostatic cancer (PC) cell lines. Dose titration microculture tetrazolium assays were used to evaluate cytotoxicity in cultures treated for 72 hr with 6MP (0–20 μg/ml). An androgen‐sensitive cell line, LNCaP, was drug‐sensitive with a mean 50% lethal dose value (LD50) of 2.632 ± 0.103. Hormone‐resistant PC cell lines 1‐LN, DU 145, and PC3 also demonstrated sensitivity with LD50 values between 0.8579–1.110 μg/ml with a group average of 1.023 ± 0.082 μg/ml. Increasing dosages of dihydrotestosterone in the growth media did not alter 6MP cytotoxicity in androgen‐insensitive prostatic cancer cell lines. No correlation between androgen‐responsiveness and 6MP‐induced cytotoxicity was observed. In nonprostatic malignancies, 6MP inhibited adenocarcinoma cell lines with a mean group LD50 value of 0.7772 μg/ml ± 0.110. J82, a transitional cell carcinoma cell line of bladder origin, exhibited an average LD50 value of 1.041 ± 0.260. In an epidermoid cervical cancer cell line, ME180, an LD50 value of 0.5356 μg/ml ± 0.010 was noted. In a melanoma cell line, Du Mel 6, a mean LD50 of 0.7428 ± 0.023 μg/ml was achieved with 6MP. We conclude that 6MP, a novel 5‐α‐reductase inhibitor, has potential as a cytotoxic agent in prostatic carcinoma and additional human malignancies. Further study is justified.
Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas
Authors: Brooks James D. , Steven Bova G. , Isaacs William B. 
Published: February 2007

AbstractInactivation of the retinoblastoma (Rb) gene has been implicated in the genesis and progression of a number of tumor types, including prostatic adenocarcinomas. We have analyzed a series of 46 surgically‐resected human prostatic adenocarcinomas for allelic loss of the Rb gene with PCR amplification of a highly polymorphic region of the gene. 41 of 46 tumors (89%) were informative and 11 of these (27%) had lost one Rb allele. The relative frequency of this occurrence suggests that inactivation of the retinoblastoma gene may be an important event in prostate carcinogenesis.
A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia
Authors: Gann Peter H. , Hennekens Charles H. , Grodstein Francine , Stampfer Meir J. , Longcope Christopher , Verhoek‐Oftedahl Wendy 
Published: February 2007

AbstractWe assessed the relation of plasma hormone levels and nonhormonal factors with subsequent occurrence of surgical treatment for benign prostatic hyperplasia (BPH) among participants in the Physicians' Health Study. Frozen plasma samples, collected at the study onset, were available for 320 men who developed surgically treated BPH up to 9 years later and for 320 age‐matched controls. Plasma testosterone (T), dihydrotestosterone (DHT), androstenedione, estradiol (E2), and estrone (E1) were measured for each case‐control pair. In unadjusted analyses, none of the hormones or hormone ratios were associated with BPH; for example, for T and E2 the odds ratios (OR) comparing the highest quintile (Q5) with the lowest (Q1) were 0.74 (95% CI = 0.42, 1.30) and 1.07 (95% CI = 0.51, 2.22), respectively. However, in multivariate analyses controlling diastolic blood pressure, exercise, alcohol, E1, and DHT:T ratio, we observed a strong trend for increasing risk across quintiles for E2 (Q5 vs. Q1 OR = 3.56, P trend = 0.009), and a weak inverse trend for E1 (Q5 vs Q1 OR = 0.51, P trend = 0.07). The excess risk associated with E2 was confined to men with relatively low androgen levels. Three nonhormonal factors previously suspected as risk factors were independently associated with surgical BPH in these data. The OR for a 1‐mm Hg difference in diastolic blood pressure was 1.04 (95% CI = 1.01, 1.07). Alcohol use and infrequent exercise were inversely associated with risk of BPH surgery; however, risk estimates were not consistent across categories of exercise and alcohol frequency. Our results indicate that normal variation in circulating androgen levels does not influence development of BPH, but that variation in estrogen levels might be important.
Comparison of the effects of new specific azasteroid inhibitors of steroid 5α‐reductase on canine hyperplastic prostate: Suppression of prostatic DHT correlated with prostate regression
Authors: Cohen S. M. , Werrmann J. G. , Rasmusson G. H. , Tanaka W. K. , Malatesta P. F. , Harris G. , Prahalada S. , Jacobs J. G. , Nett T. M. 
Published: February 2007

AbstractFour new azasteroid inhibitors of steroid 5α‐reductase were compared to the benchmark compound finasteride, each at a dose level of 1 mg/kg/day, as well to placebo and to castration, in seven groups of mature male beagle dogs with enlarged prostates. Prostate volumes were measured repetitively by a volume MRI method over 15 weeks of treatment. The study probed the obverse of the familiar relation between DHT and prostate growth, and provides the first documentation of a tight negative correlation between prostate regression and the prostatic concentration of DHT across a range of treatment regimens (r = −0.982). In this first direct comparison study of structure vs. in vivo activity for several azasteroids in the dog model of BPH, relative efficacy for induction of shrinkage of the dog prostate did not correlate at all with the inhibitor's relative activity against the dog 5α‐reductase in vitro. On the basis of the relative IC50 values it would not have been predicted that, at the dose tested, the analogue MK‐434 (17β‐benzoyl‐4‐aza‐5α‐androst‐1‐en‐3‐one) was distinguished from the other inhibitors with respect to the induction of faster and more complete regression (69%) as well as greater reduction in prostatic DHT (95%), both of which approached the castrated dog levels of 75% prostatic shrinkage and >98% reduction in DHT. Treatment with any one of the five azasteroids induced two‐ to five‐fold increases in prostatic testosterone. However, total androgen was conserved at the placebo control level. Despite the differences noted, each azasteroid tested induced a highly significant decrease in prostatic volume that correlated tightly with a decreased prostatic DHT level in canine spontaneous BPH.
Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki‐67 and PCNA expression
Authors: Cher Michael L. , Carroll Peter R. , Chew Karen , Rosenau Werner 
Published: February 2007

AbstractProstatic carcinomas vary in their biological potential, even when stratified by grade and stage. Measurement of cellular proliferation by various methods has been shown to correlate with outcome for several human cancers, including prostatic carcinoma. Uptake of bromodeoxyuridine (BrdUrd), a thymidine analogue, has been accepted as a measure of cellular proliferative rate. However, the technique is somewhat complex, requiring incubation with fresh tissue. We compared cellular proliferation as measured by BrdUrd uptake with two more simple immunohistochemical methods in 44 prostatic adenocarcinoma specimens and correlated the results with standard clinical parameters. The tissue was obtained via needle biopsy, channel transurethral resection, and radical prostatectomy. Specimens were incubated in vitro with BrdUrd and then fixed and paraffin embedded. Sections were immunohistochemically stained with antibodies to BrdUrd, proliferating cell nuclear antigen (PCNA), and Ki‐67. At least 1,000 cells were scored, and a labeling index (LI) was calculated (number of positive cells/total number of cells). The mean LI determined by all three indices was low (BrdUrd = 3.0, PCNA = 7.0, Ki‐67 = 3.4), consistent with the knowledge that prostatic tumors grow slowly. In 36 patients who had not been treated at the time of analysis, the LI as determined by all three methods correlated well with clinical stage and pathological grade. Furthermore, the LIs discriminated between those with tumor confined to the prostate and those with extension to the seminal vesicles, lymph nodes, or bone (P = 0.003, 0.004, 0.008 for BrdUrd, PCNA, and Ki‐67, respectively). The LIs for PCNA and Ki‐67 correlated well with that for BrdUrd (r = 0.84; r = 0.85), while the LIs for Ki‐67 and PCNA correlated slightly less well with each other (r = 0.78). PCNA and Ki‐67 expression appear to reflect essentially the same biological process as BrdUrd uptake. Either can substitute for BrdUrd as a measure of cellular proliferation, and Ki‐67 seems to offer the fewest technical problems.
Differential expression of uPA in an aggressive (DU 145) and a nonaggressive (1013L) human prostate cancer xenograft
Authors: Billström Anita , Dahllöf Björn , Hartley‐Asp Beryl , Lecander Ingegerd , Dagnaes‐Hansen Frederik , Stenram Unne 
Published: February 2007

AbstractProstate cancer has a slow growing noninvasive phase, but, in general, is invasive on diagnosis. An initial step in the invasion of surrounding normal tissue is the activity of proteolytic enzymes such as components of the plasminogen activator system (PA). In cell culture, the primary human prostate cancer cell line 1013L expressed no urokinase type‐PA (uPA), while DU 145, a cell line derived from a metastatic lesion, expressed high levels of uPA. The DU 145 cells grew easily as xenografts but the establishment of 1013L in the SCID mice was possible only with the aid of a gelatin sponge (Spongostan). The latency period was 42–64 days, followed by a slow growth phase before a fast growth phase occurred. This fast growth phase was characterized by rapid degeneration of tumor tissue, while high proliferation occurred around the blood vessels. On serial transplantation of tumor material, the growth pattern was similar. Furthermore, the 1013L tumor was encapsulated by connective tissue and no invasiveness could be detected. We found that 1013L tumor homogenates had hardly detectable levels of uPA, i.e., 300‐fold lower than we found in the invasive prostate xenograft DU 145. In addition, no expression of uPA was found in the plasma of 1013L tumor‐bearing mice whilst uPA antigen was detected in the plasma of DU 145 tumor‐bearing mice. In conclusion, the 1013L cell line, which exhibits a nonaggressive pattern, could be a good model for studying progression of prostate cancer to a more aggressive phenotype in vivo and in vitro.
Microvascularity in benign prostatic hyperplasia
Authors: Deering Robert E. , Bigler Steven A. , Brown Marianne , Brawer Michael K. 
Published: February 2007

AbstractThe vascular density of benign prostatic hyperplasia (BPH) has not been characterized. Previously we reported vessel density (vv/mm2) in prostatic carcinoma was twice that of normal prostate [Bigler et al.: Hum Pathol 24:220–226 1993]. To further characterize vessel density in benign prostate tissue we examined 15 cases of BPH obtained by open prostatectomy. Vessels were stained with antibodies to Factor VII‐related antigen, and vessel density was measured using computer‐assisted image analysis.Vessel density was analyzed between various histologic tissue types. Mean vessel density in all transition zone tissue was 70.2 vv/mm2. Vessel density in epithelial hyperplastic nodules (mean 99.3, SD 40.7) exhibited density levels similar to those found in prostatic carcinoma (mean 101.4, SD 35.6). Vessel density in epithelial nodules was significantly higher than in non‐nodular epithelial tissue (mean 76.7, SD 23.1; P < 0.001, ratio = 1.3). Higher vessel densities were found in hypercellular stromal nodules (mean 64.7, SD 19.1) than in adjacent stromal areas (mean 36.5, SD 15.3; P < 0.001, ratio = 1.8). Overall, vessel density in BPH was higher than previously found in benign tissue measured in radical prostatectomy specimens, especially in areas of nodular morphology.