bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue
Authors: Brolin Jan , Ekman Peter , Skoog Lambert 
Published: February 2007

AbstractThe relative distribution of androgen (AR), progesterone (PR), and estrogen receptors (ER) was localized and estimated in human prostate tissue by immunohistochemistry in five normal tissue samples, in eight benign hyperplastic (BPH) samples, in nine primary cancers, and in seven prostate cancer metastases. Moreover, three prostatic cancer cell lines (LNCaP, DU 145, and PC 3) were analyzed. A comparison between the results obtained by radioligand binding assays and immunohistochemistry was performed for the AR and PR.Using immunohistochemistry, the AR was exclusively detected in the nuclei of both benign and malignant prostatic epithelial cells. The highest proportion of AR‐positive cells was found in BPH and in prostate cancer metastases as compared with normal prostatic tissue. In a majority of the cases, the PR was only present in the nuclei of stromal cells. Benign hyperplastic prostates contained higher proportions of PR‐positive cells as compared with primary carcinoma. PR was sparse in epithelial cells. ER‐positive stromal cell nuclei were only detected in carcinomatous prostates. A few ER‐positive epithelial cell nuclei were found in one sample each of a BPH and normal prostate.All cells from the androgen‐dependent, LNCaP, cell line and a majority of the cells from the androgen‐independent, DU 145, cell line were AR‐positive. In contrast, the cells from the androgen‐independent, PC 3, cell line were all AR‐negative. All three cell lines were PR‐ and ER‐negative.The radioligand binding technique detected the AR in extracts from both the cytosol and the nucleus. Again BPH contained higher amounts of AR as compared with normal prostatic tissue. The LNCaP cells contained high amounts of cytosolic AR while cells from the DU 145 and PC 3 cell lines lacked detectable AR as estimated by biochemical techniques. There seemed to be a discrepancy between biochemically measured and immunohistochemically estimated receptor content.
The relationship between cardiovascular complications of estrogen therapy and fibrinolysis in patients with prostatic cancer
Authors: Hasui Yoshihiro , Nishi Shohei , Kitada Shinichiro , Osada Yukio , Sumiyoshi Akinobu , Marutsuka Kousuke 
Published: February 2007

AbstractTo determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis, fibrinolysis parameters plasminogen, urokinase‐type plasminogen activator (u‐PA), tissue‐type plasminogen activator (t‐PA), and plasminogen activator inhibitor‐1 (PAI‐1), were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy. The levels of plasminogen, u‐PA, and PAI‐1 in the patients treated with the estrogen therapy were significantly higher than those in the patients before the therapy. The t‐PA level in the patients during the therapy was significantly lower than that before the treatment. Cardiovascular complications were found in two patients (16.7%) during estrogen therapy. In the two patients, marked elevation of PAI‐1 and decreased level of t‐PA were observed during the therapy. These results indicate that cardiovascular complications of estrogen therapy in patients with prostatic cancer may be related to hypofibrinolysis resulting from changes of PAI and t‐PA.
Isolation and characterization of transforming growth factor beta response variants from human prostatic tumor cell lines
Authors: Watts Rebecca G. , Ware Joy L. 
Published: February 2007

AbstractIn this study we examined the relation between the response to transforming growth factor beta (TGFβ1) in vitro and the growth in vivo of 1‐LN‐PC3‐1A (1‐LN) human prostatic carcinoma cells. 1‐LN cells resistant to the growth‐inhibitory effects of TGFβ1, were isolated after exposure to 2 ng/ml TGFβ1, in an anchorage‐independent growth assay. Cloning of TGFβ1,‐resistant and ‐sensitive populations produced 2 clones (R2‐6 and 1‐LN clone 4), which maintained relatively stable resistance or sensitivity, respectively, in the absence of TGFβ1, for up to 12 passages. Colony formation by the R2‐6 cells in the presence of TGFβ1, was 2‐10 times greater than that of 1‐LN clone 4, depending upon the TGFβ1, concentration. Injection of 1 × 105 R2‐6 cells into athymic nude mice produced tumors with a significantly shorter latency interval as compared with 1‐LN clone 4 tumors (P < 0.0001). Western immunoblotting showed that higher levels of latent TGFβ1, protein were secreted into the culture medium by 1‐LN clone 4 cells. Acidified conditioned media from both clones inhibited mink lung epithelial cell DNA synthesis. Neutralizing monoclonal antibody to TGFβ1, but not TGFβ2 abrogated this inhibitory effect. Comparison of the different sensitive and resistant clones showed that in vitro sensitivity to TGFβ1, and in vivo tumor latency interval were not invariably correlated. Thus, the TGFβ1, response phenotype in vitro was not always predictive of growth delay in vivo.
The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle
Authors: Shapiro Ellen , Hartanto Victor , Lepor Herbert 
Published: February 2007

AbstractThe objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long‐acting selective alpha, blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer‐assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonre‐sponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle.
Immunohistochemical evidence of the existence and localization of aromatase in human prostatic tissues
Authors: Matzkin Haim , Soloway Mark S. 
Published: February 2007

AbstractEstrogens may be involved in normal growth of the prostate and the development of benign prostatic hyperplasia (BPH). The location of estrogen production is still unclear, and there has never been a direct evidence for the existence of the aromatase system, which converts androgens to estrogens, in the prostate. Using an avidin‐biotin technique with a polyclonal anti‐human placental aromatase, we demonstrated the existence of aromatase in normal prostates of young men and BPH tissue from elderly men. The staining is more pronounced in the stroma. However, positive stains were also seen in the glandular epithelium. While evidence of the existence of an enzyme system does not equal demonstration of its activity in a specific tissue site, our findings suggest that local estrogen production in the stroma and/or epithelium of the prostate may play a role in the maintenance of normal growth and development Of BPH.
DNA sequence of the androgen receptor in prostatic tumor cell lines and tissue specimens assessed by means of the polymerase chain reaction
Authors: Culig Zoran , Klocker Helmut , Eberle Johannes , Kaspar Felizia , Hobisch Alfred , Cronauer Marcus V. , Bartsch Georg 
Published: February 2007

AbstractEssentially all prostatic carcinomas relapse to an androgen‐independent stage during androgen ablation therapy. The underlying genetic changes are still unclear. Such changes are suspected to affect the androgen‐signalling pathway as well as growth promoting and inhibiting factors. This study was undertaken to test for structural changes of the androgen receptor in prostatic tumor cell lines and primary tumors. Complementary DNA (cDNA) fragments of the androgen receptor (AR) were isolated from the cell lines LNCaP, PC‐3, and DU 145, ten tissue specimens obtained by radical prostatectomy, and five fine‐needle biopsies by means of the polymerase chain reaction (PCR) technique. Fragments encoding the hormone‐and DNA‐binding domains were analyzed by DNA sequencing. The PCR technique is highly sensitive and especially recommended for the analysis of small tissue samples, such as those obtained by fine‐needle aspiration.No alterations were detected in the tissue specimens and the five fine‐needle aspirates. In the three tumor cell lines that represent late stages of prostatic tumor, different findings were obtained. The androgen‐independent DU 145 cells did not express androgen receptors, whereas the PC‐3 cells, which are also androgen‐independent, expressed very low levels of normal AR. In contrast to this, the androgen‐dependent LNCaP cells expressed high levels of structurally abnormal androgen receptors. These results suggest that androgen receptor mutations are probably uncommon molecular events in the early stages of prostatic cancer. Qualitative and quantitative changes, however, seem to occur in advanced prostatic cancer. © 1993 Wiley‐Liss, Inc.
The effect of finasteride on prostate‐specific antigen in men with benign prostatic hyperplasia
Authors: Guess H. A. , Heyse J. F. , Gormley G. J. 
Published: February 2007

AbstractFinasteride is a specific 5‐α‐reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was −50% (5–95% range: −81% to + 20%). At baseline 72% had PSA ⩽ 4.0 ng/ml and 93% had PSA ⩽ 10.0 ng/ml. After 12 months on finasteride, 75% had PSA ⩽ 2.0 ng/ml and 95% had PSA ⩽ 5.0 ng/ml. Thus, the proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml. Among the 10 men in these trials subsequently diagnosed with prostate cancer while on long‐term finasteride therapy (5 mg/day), the median percentage change in PSA was −26% (range: −48% to + 12%). Limited experience with finasteride in men with prostate cancer suggests that the reduction in PSA of malignant origin appears to be no greater than the percentage reduction in PSA of benign origin. These effects on PSA have not been shown to confer any therapeutic benefit. Physicians using finasteride should be aware of its effect on PSA levels. © 1993 Wiley‐Liss, Inc.
Growth of an androgen‐sensitive human prostate cancer cell line, LNCaP, in nude mice
Authors: Lim David J. , Liu Xiang‐Lin , Sutkowski Debra M. , Braun Eva J. , Lee Chung , Kozlowski James M. 
Published: February 2007

AbstractThis study was undertaken to establish an androgen‐sensitive model of human prostatic carcinoma in nude mice. The androgen‐sensitive prostatic carcinoma cell line, LNCaP, was suspended in reconstituted basement membrane (Matrigel) and injected subcutaneously into nude mice. The LNCaP cell line was chosen for the study, because the cell line is androgen‐sensitive and secretes prostate specific antigen (PSA) into culture media. Following injection of 1 × 106 LNCaP cells with 0.25 ml of Matrigel, 88. of mice exhibited palpable tumor burdens after 12 weeks of observation. In addition, significant levels of PSA were observed in the serum of LNCaP‐bearing mice. Bilateral orchiectomy of mice resulted in tumor regression and stabilization of serum PSA levels, compared to testis‐intact controls. A significant correlation of PSA to tumor volume and weight was observed. The castrate level of testosterone was confirmed by radioimmunoassay and was similar to testosterone levels in female nude mice. Matrigel allows for a conducive environment to propagate LNCaP cells in nude mice. Furthermore, the growth can be manipulated by castration, leading to involution of tumor and stabilization of serum PSA level. This in vivo model of hormone‐sensitive human prostate cancer cell line will serve as a model for the study of prostate tumor biology and treatment. © 1993 Wiley‐Liss, Inc.
Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR)
Authors: Sarkar Fazlul H. , Sakr Wael A. , Li Yi‐Wei , Sreepathi Prabhakar , Crissman John D. 
Published: February 2007

AbstractHuman papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60–100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate.We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16 and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6‐E7. The areas of PIN and cancer in 6 p.m H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P‐labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P‐labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators. © 1993 Wiley‐Liss, Inc.
Finasteride (MK‐906) in the treatment of benign prostatic hyperplasia
Authors:   The Finasteride Study Group
Published: February 2007

AbstractThe effects of finasteride, a potent 5α‐reductase inhibitor, were assessed in 750 patients with benign prostatic hyperplasia (BPH) in a multicenter, double‐blind, placebo‐controlled study. Patients were randomized to finasteride, 1 or 5 mg, or placebo, daily for 12 months. The following changes were seen with finasteride 5 mg after 12 months: (1) Serum dihydrotestosterone decreased by 62% compared to no change with placebo (P < 0.001); (2) serum prostate‐specific antigen (PSA) decreased by 46% compared to no change with placebo (P < 0.001); (3) prostate volume was reduced by 22% compared to a 5% decrease with placebo (P < 0.001); (4) maximum urinary flow rate increased by 1.7 ml/sec compared to a 0.4 ml/sec increase with placebo (P < 0.025); (5) total urinary symptom scores decreased by 3.3 points compared to a 2.0 point decrease with placebo (P = 0.005), and (6) obstructive symptom scores decreased by 2.1 points compared to a 1.4 point decrease with placebo (P = 0.017). The effects of finasteride 1 mg were similar to 5 mg, except in urinary symptoms, where no significant differences between 1 mg and placebo were seen. Patients treated with 5 mg finasteride demonstrated significantly greater improvements in urological status (assessed by the investigator) and the troublesome symptom score, compared to placebo. Treatment with finasteride was well tolerated. We conclude that finasteride is an effective medical therapy for a significant proportion of patients with BPH. © 1993 Wiley‐Liss, Inc.
Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation
Authors: Peterson Greg , Barnes Stephen 
Published: February 2007

AbstractThe effect of the isoflavones, genistein, daidzein, and biochanin A on the growth of the LNCaP and DU‐145 human prostate cancer cell lines has been examined. Genistein and biochanin A, but not daidzein, inhibit both serum and EGF‐stimulated growth of LNCaP and DU‐145 cells (IC50 values from 8.0 to 27 μg/ml for serum and 4.3 to 15 μg/ml for EGF), but have no significant effect of the EGF receptor tyrosine autophosphorylation. In contrast, tyrphostin 25, a specific EGF receptor tyrosine kinase inhibitor, inhibits EGF‐stimulated growth and EGF receptor tyrosine autophosphorylation in these whole cells, but does not inhibit serum‐stimulated growth. These data suggest that the mechanism of action of genistein and biochanin A does not depend on inhibition of EGF receptor tyrosine autophosphorylation, but on a more distal event in the EGF receptor‐mediated signal transduction cascade. © 1993 Wiley‐Liss, Inc.
A common set of nuclear matrix proteins in prostate cancer cells
Authors: Pienta Kenneth J. , Lehr Jeffrey E. 
Published: February 2007

AbstractThe nuclear matrix is the RNA‐protein network which forms the skeleton of the nucleus, and participates in DNA organization as well as in multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific, as well as to reflect the state of cell differentiation and/or transformation. Previously, common nuclear matrix proteins were demonstrated between the rat prostate and the Dunning rat prostate adenocarcinoma cell lines. This study demonstrates that nuclear matrices derived from Dunning rat and human prostate cancer cell lines, as well as human tumors, share several common proteins. These common proteins suggest that alterations which occur in the nuclear matrix with prostate cell transformation may share a common basis. © 1993 Wiley‐Liss, Inc.
Vitamin A regulates proliferation and differentiation of human prostatic epithelial cells
Authors: Peehl Donna M. , Wong Stephen T. , Stamey Thomas A. 
Published: February 2007

AbstractThe response of cultured human prostatic epithelial cells to vitamin A was measured by clonal growth assay in serum‐free medium. Retinoic acid at 3 nM or higher inhibited the proliferation of cell strains derived from normal, benign hyperplastic and malignant tissues, while lower levels (0.03 nM) were stimulatory. Reduced proliferation induced by retinoic acid was accompanied by a marked change in morphology, as intercellular adhesion decreased. In conjunction, the expression of keratins 8 and 18, associated with the differentiated luminal phenotype of prostatic epithelia, was increased. In post‐confluent cultures, retinoic acid prevented the appearance of keratin 1, which accompanied the development of a squamous phenotype by cells maintained under these conditions. The findings of this study indicate a role for vitamin A as a modulator of the growth and differentiation of prostatic epithelial cells. © 1993 Wiley‐Liss, Inc.
Castration‐induced changes in morphology, androgen levels, and proliferative activity of human prostate cancer tissue grown in athymic nude mice
Authors: Van Weerden W. M. , Van Kreuningen A. , Elissen N. M. J. , Vermeij M. , De Jong F. H. , Van Steenbrugge G. J. , Schröder F. H. 
Published: February 2007

AbstractThe transplantable human prostate tumor lines PC‐82 and PC‐EW regress after androgen depletion. The castration‐induced decline in tumor volume was faster in the PC‐EW tumor (half‐life 6 days) than in the PC‐82 tumor (half‐life 18 days), despite similar castrate androgen levels of less than 3 pmollg tissue. Androgen ablation of the PC‐82 tumor induced a wave of apoptosis, whereas in the PC‐EW tumor, necrotic cell death was predominantly observed. The proliferative activity (BrdU index) of PC‐82 and PC‐EW tumor tissue declined from 3% to less than 1% after castration. After androgen depletion, some proliferative activity remained, the major part of which was localized in the (murine) stromal compartment of the tumors. In contrast to the PC‐EW tumors, regrowth of androgen‐ablated PC‐82 tumors was rapidly induced by androgen resubstitution. The differences in response of these tumor models to androgen depletion and repletion appear to be related to the putative involvement of different cell death pathways. The role of the stroma in these processes is unclear. © 1993 Wiley‐Liss, Inc.
Presence of 11 β‐hydroxysteroid dehydrogenase enzyme in the human prostate tumor cell line LNCaP
Authors: Nath Nagendra , Lakshmi Vijaya , Rosenthal Julian C. 
Published: February 2007

Abstract11 β‐Hydroxysteroid dehydrogenase (11β‐HSD) is the enzyme that catalyzes the reversible oxidation of the biologically active steroid cortisol and corticosterone to their inactive metabolites cortisone and dehydrocorticosterone. We report its presence in significant levels in the human prostate carcinoma cell line LNCaP cultured in medium RPMI‐1640 with 10% fetal calf serum (FCS). The 11‐dehydrogenase activity of 11β‐HSD is present, while the 11‐reductase activity is undetectable in these tumor cells under the present culture conditions. The enzyme activity is found to be linear with time of incubation, and is proportional to plated cell density. The enzymatic activity can be determined in cultures maintained for longer times. Carbenoxolone, the potential inhibitor of the 11β‐HSD, inhibits 95% of the dehydrogenase activity of the tumor cells when used in nM concentration. The presence of this enzyme in tumor cell line indicates that 11β‐HSD plays an important role in maintaining the active glucocorticoid levels in the prostate. © 1993 Wiley‐Liss, Inc.