bluuebunny/crossref_metadata_2025 huggingface dataset:
Antagonism of androgen action in prostate tumor cells by retinoic acid
Authors: Young Charles Y.‐F. , Murtha Patricia E. , Andrews Paul E. , Lindzey Jonathan K. , Tindall Donald J.
Published: February 2007

Recent studies have demonstrated that retinoic acid (RA) can repress the growth of human prostatic epithelial cells. Since the proliferation of prostate cells is highly dependent on androgen stimulation, presumably via its cognate receptor, we investigated the effects of RA on the expression of the androgen receptor and other androgen‐regulated genes in the human prostatic adenocarcinoma cell line LNCaP. Using a radioligand binding assay, we found that androgen‐binding activity was reduced 30‐40% in cells treated with 10−5 M RA plus 6 nM dihydrotestosterone (DHT), as compared to cells with the androgen alone. Moreover, the reduction of the androgen receptor (AR) was not accompanied by alteration of the ligand‐binding affinity. Concomitant changes in the function of AR were manifested by a dramatic reduction in AR‐mediated transcription activity in a transfection experiment. Androgen‐induced levels of both prostate‐specific antigen (PSA) and human glandular kallikrein‐1 (hKLK2) mRNAs were significantly repressed by RA in a dose‐ and time‐dependent manner. Consistent with this finding, androgen induction of PSA glyco‐protein was also repressed by RA, with maximal inhibition occuring at 10−5 M. These data suggest that the suppression of proliferation and function of prostatic cells by RA may be via modulatory effects on the AR. © 1994 Wiley‐Liss, Inc.
Biosynthesis and secretion of laminin and S‐laminin by human prostate carcinoma cell lines
Authors: Rabinovitz Isaac , Cress Anne E. , Nagle Ray B.
Published: February 2007

Laminin has been previously shown to participate in tumor invasion and metastasis. Tumorigenesis by human prostate cell lines can be influenced by exogenous laminin. We have found that the human prostate tumor cell lines DU145, LNCaP, and PC‐3 produce a variant form of the B1 chain of laminin, known as S‐laminin. DU145 cells produce laminin containing a ratio of A:B1:B2:S of 1.8:1.0:2.5:1.0, respectively, compared to LNCaP cells, which have a ratio of A:B1:B2:S of 1.0:0:10.0:2.5. Kinetic analysis of laminin production showed that LNCaP cells retained most of their laminin production and secreted laminin forms characterized by decreased levels of n‐acetyl glucosamine and sialic acid. In contrast, DU145 cells secreted most of their laminin in mature forms. LNCaP cells bound very little laminin to their surface. These features of LNCaP cells could contribute to their documented low adhesivity in vitro and its nontumorigenic phenotype. © 1994 Wiley‐Liss, Inc.
Bone alkaline phosphatase and prostate‐specific antigen in the monitoring of prostate cancer
Authors: Cooper E. H. , Whelan P. , Purves D.
Published: February 2007

A retrospective study has been made on the interrelationship of serum bone alkaline phosphatase (BAP), measured by the Ostase‐RIA, and prostate‐specific antigen (PSA) in 156 patients with M0 and M1 prostate cancer. BAP is a more sensitive and more specific method of determining osteoblast activity than total alkaline phosphatase (TAP). The main difference between these two assays is seen when the TAP is in the range of normal to twice‐normal.

BAP shows a low intraindividual variation in M0 disease, and was within normal limits in 18 patients following radical prostatectomy with a PSA < 0.1 ng/ml. A raised BAP was observed in 86.4% of M1 disease at diagnosis before treatment. The change of BAP was concordant with PSA in 69% of 49 cases of M1 disease, although there are marked differences in the rates of change of the two markers. A nadir of PSA ⩽ 10 ng/ml after androgen blockade in M1 disease was associated with a high probability of a normal BAP. © 1994 Wiley‐Liss, Inc.
Molecular and cellular changes associated with the acquisition of metastatic ability by prostatic cancer cells
Authors: Rinker‐Schaeffer Carrie W. , Partin Alan W. , Isaacs William B. , Coffey Donald S. , Isaacs John T.
Published: February 2007

Presently, one of every four cancers diagnosed in American males is of prostatic origin. Once prostatic cancer metastasizes, it is a fatal disease for which no therapy presently available is curative. Because of these facts, there is a growing interest in the early detection and screening of men for prostate cancer. Such screening could potentially identify 10 million American men with histological prostatic cancer. It is estimated that approximately 7% (700,000) of these men will eventually die from their disease if left untreated. This raises the critical question of which of the remaining 93% (9,300,000) of men with nonlethal, but potentially life‐altering, histologically detectable prostatic cancer should receive therapy. There is no diagnostic method presently available which allows men with histologically detectable prostatic cancer, whet require immediate therapy, to be distinguished from those requiring either delayed therapy or no treatment. Acquisition of metastatic ability by such histologically detectable prostatic cancer cells is a definitive criterion upon which to base such a diagnostic substaging method. Identification of the cellular and molecular requirements for acquisition of metastatic ability by prostatic cancer cells is needed for the development of such methods. This article will focus on what is known concerning general cellular and specific molecular changes associated with the acquisition of metastatic ability by prostatic cancer cells, and suggested areas for future studies. © 1994 Wiley‐Liss, Inc.
Androgen receptor alterations in prostatic carcinoma
Authors: Klocker Helmut , Culig Zoran , Hobisch Alfred , Cato Andrew C. B. , Bartsch Georg
Published: February 2007

Intracellular action of androgens is mediated by the androgen receptor (AR), which is a key element of the androgen signal transduction cascade and a target of endocrine therapy for prostatic carcinoma. Therefore, the qualitative and quantitative alterations of AR expression in prostatic carcinomas and their possible implications for tumor progression and treatment are of great interest. Findings in prostatic tumor cell lines of rat and human origin suggest a reduction of AR protein expression accompanied by an increase in tumor malignancy. However, immunohistochemical studies and binding assays demonstrated presence of ARs in all histological types of prostatic tumors, in therapy‐responsive as well as in therapy‐unresponsive ones. AR content of prostatic tumor specimens did not correlate with outcome of endocrine therapy of advanced prostatic carcinoma in these studies. Solely the degree of heterogeneity of AR expression may be useful as an indicator of responsiveness to therapy. AR mutations have been detected in the LNCaP cell line and in three primary prostatic tumor specimens. Three of them are point mutations in the hormone‐binding domain of the AR, the fourth mutation is a CAG‐microsatellite depression in the N‐terminus. Evidence coming from studies on AR in prostatic cancer highlights the possibility that AR structural alterations may have significance in tumor progression. © 1994 Wiley‐Liss, Inc.
Immunohistochemical localization of estrogen‐specific 17β‐hydroxysteroid oxidoreductase in the human and mouse prostate
Authors: Pylkkänen L. , Santti R. , Salo L. , Mäentausta O. , Vihko R. , Nurmi M.
Published: February 2007

The estrogen‐specific 17β‐hydroxysteroid oxidoreductase (17β‐HSOR) enzyme protein was stained immunohistochemically in the newborn and adult human prostate as well as in the mouse prostate. In the newborn human prostate, ductal and urethral epithelia were faintly stained, whereas in the adult human prostate, intense staining for 17β‐HSOR enzyme antigen could be detected in the epithelium of the collecting ducts and urethral epithelium as well as in the epithelium of the intraprostatic vas deferens and seminal vesicle epithelium. Immunostaining was weak in the prostatic tissues of both newborn and adult prostate. No positive cells were found in stroma. The activity of NADPH‐dependent 3H‐estrone reductase was detectable in cell‐free homogenates prepared from human prostatic tissues. The activities showed a good correlation with immunocytochemical findings.

In the mouse, neonatal estrogenization resulted in intensively stained epithelium of the collecting ducts at the age of 14 days. Moreover, when adult control and neonatally estrogenized mice were implanted with 17β‐estradiol, the metaplastic epithelium of the periurethral collecting ducts of neonatally estrogenized mice was intensively stained with 17β‐HSOR. These findings suggest that metaplastic epithelium rises from 17β‐HSOR‐positive cells.

The similar distributions of 17β‐HSOR‐positive cells confirm the concept of homology in the posterior estrogen‐responsive periurethral region (containing the periurethral ducts and periurethral glands) of the mouse and humans. Our findings further suggest that the 17β‐HSOR‐positive cells may have the same origin and hormonal control in both species. © 1994 Wiley‐Liss, Inc.
Effects of estrogens and progestogens on the membrane permeability and growth of human prostatic carcinoma cells (PC‐3) in vitro
Authors: Widmark Anders , Henriksson Roger , Bergh Anders , Grankvist Kjell , Damber Jan‐Erik
Published: February 2007

The effects of estrogens and progestogens in the management of prostatic adenocarcinoma are generally believed to be related to their suppressive effect on the hypothalamic‐pituitary‐testicular axis, but other mechanisms have also been suggested. The present study was designed to investigate if an androgen‐insensitive human prostatic cancer cell line (PC‐3) is sensitive to estrogens or progestogens and to elucidate possible mechanisms of action. Both estrogens and progestogens in high doses (10−5 M) suppressed tumor cell growth. At these high doses medroxyprogesterone acetate (MPA) most effectively reduced the uptake of 86rubidium chloride, indicating the strongest effect on ion transport and membrane permeability. Effects on rubidium transport were also seen after estrogen treatment. It is suggested that estrogens and progestogens have direct cytotoxic effects on prostatic carcinoma cells in vitro, possibly by an effect on the cell membrane.
A clinical and immunohistochemical study of papillary adenocarcinoma of the prostate
Authors: Ito Takaaki , Furusato Masakuni , Akiyama Akihito , Kato Hiroyuki , Aizawa Shigeo
Published: February 2007

Clinical and immunohistochemical studies were conducted to evaluate prostatic papillary adenocarcinoma and prostatic papillary hyperplasia. Subjects consisted of 5 cases of papillary adenocarcinoma and 2 cases of papillary hyperplasia. There is no conclusive clinical factor for preoperative diagnosis, but we attach importance to endoscopic findings. PSA, PAP, high molecular weight cytokeratin, and PCNA were evaluated immunohistochemically. PSA became positive in every instance but one—a case of papillary adenocarcinoma which became ±. PAP was + in all cases, except for 1 case of papillary adenocarcinoma. Basal cells were positive for high molecular weight cytokeratin in 2 cases of papillary hyperplasia but were missing in papillary adenocarcinoma. Although PCNA was free from positive nuclei in papillary hyperplasia, positive nuclei were found in all cases of papillary adenocarcinoma. Considering these immunohistochemical results, papillary adenocarcinoma can be said to originate in the glandular epithelium of the prostate, as does ordinary prostatic carcinoma.
Transurethral microwave thermal therapy: Pathologic findings in the canine prostate
Authors: Bostwick David G. , Larson Thayne R.
Published: February 2007

Microwave irradiation administered by transurethral transducer to the prostate permits focused hyperthermia with resultant tissue ablation; a cooling system within the catheter allows urethral preservation. We evaluated the effect of microwave hyperthermia in 13 dogs receiving 48–79 min of focused irradiation (16–45 watts, intraprostatic temperature >45°C) delivered by a specially‐designed transducer with an operator‐controlled directional antenna (T3, Urologix Inc., Minneapolis, MN); one other dog had transducer placement without irradiation (sham control). After treatment, the dogs were in good health, voiding well without complications, and were sacrificed after 5–38 days. The prostate and vasa deferentia were removed, fixed in 10% formalin, grossly inspected, cut at 5 mm intervals, and serially sectioned with whole mount sections; representative sections of the adjacent rectum and distal bladder were also obtained. All cases were histologically evaluated with prostatic mapping without knowledge of treatment or time of sacrifice. In the acute phase (5–13 days), the prostate showed sharply circumscribed periurethral coagulative necrosis with hemorrhage; necrosis was also seen in the mucosa and bladder wall of those with transducers placed at the bladder neck. In the subacute phase (17 days), the hemorrhagic necrosis was resolving, often with cystically dilated urethra due to sloughed necrotic tissue; the urothelium was intact. By 24–38 days, the necrosis was in the late stages of resolution, with residual patchy acute and chronic inflammation at the periphery, and frequent persistence of megalourethra. In all cases, the prostatic capsule was intact, the urethral mucosa was preserved, and the vasa deferentia and rectum were normal except for two cases with mild fat necrosis. Microwave irradiation allows precisely localized thermal ablation of prostatic tissue and enlargement of the urethral bore without clinical complications in dogs, offering promise as a therapeutic alternative to surgery in select patients with symptomatic prostatic nodular hyperplasia.
Prolactin specifically increases pyruvate dehydrogenase Elα in rat lateral prostate epithelial cells
Authors: Costello L. C. , Liu Y. , Franklin R. B.
Published: February 2007

Prolactin is an important regulator of prostate citrate production. In rats this regulatory effect of prolactin is specific for lateral prostate, and has no effect on either ventral or dorsal prostate. The mechanisms by which prolactin regulates prostate citrate production have not been elucidated. Two key regulatory enzymes involved in citrate synthesis by prostate epithelial cells are mitochondrial aspartate aminotransferase (mAAT) which provides oxalacetate, and PDH E1α (pyruvate dehydrogenase) which provides acetyl CoA for citrate synthesis. Our previous studies demonstrated that prolactin regulates mAAT. However, an increase in citrate synthesis would require an increase in both oxalacetate and acetyl CoA. Therefore, we investigated the possibility that prolactin might also regulate PDH E1α in LP epithelial cells. The present studies demonstrate that prolactin administration (1 mg/rat) to rats resulted in an increased level of E1α in LP epithelial cells within 6 hr, but had no effect on the E1α level of VP epithelial cells. In vitro studies demonstrated that exposure of freshly prepared LP epithelial cells to prolactin (0.1–1.0 μg/ml) resulted in increased levels of E1α. Prolactin had no effect on either VP or DP epithelial cells. The stimulatory effect of prolactin on E1α was inhibited by actinomycin and cycloheximide, thereby indicating that prolactin stimulated the biosynthesis of E1α. The studies reveal that prolactin specifically stimulates E1α levels of LP epithelial cells, whereas testosterone specifically stimulates E1α levels of VP epithelial cells. At this time, we propose that the effects of prolactin and testosterone involve increased expression of the E1α gene of LP and VP epithelial cells, respectively.
Growth inhibition of androgen‐insensitive human prostate carcinoma cells by a 19‐norsteroid derivative agent, mifepristone
Authors: Lin Ming‐Fong , Kawachi Mark H. , Lin Fen‐Fen , Stallcup Michael R. , Grunberg Steven M.
Published: February 2007

Mifepristone, also known as RU 486, is a 19‐norsteroid derivative. Currently, mifepristone is being tested in clinical trials on meningioma and breast cancer. In this study we analyzed whether mifepristone could inhibit the growth of human prostate cancer cells including androgen‐insensitive (PC‐3 and DU145) and androgen‐sensitive (LNCaP) cell lines. At 1‐nM concentration, mifepristone exhibited a marginal stimulatory action on LNCaP and PC‐3 cells. Nevertheless, a dose‐dependent growth inhibition on those same cell lines was observed at concentrations of 1 μM and 10 μM. Twenty‐day exposure to the clinically achievable concentration of 1 μM mifepristone resulted in consistent inhibition of all three cell lines studied. Furthermore, this in vitro growth inhibition was reflected in an in vivo nude mouse system. Mifepristone at the dosage of 4 mg/100 g body weight completely suppressed the growth of PC‐3 tumors for 21 days, although this was followed by a growth rate similar to that of the control tumor. To understand the possible mechanism of mifepristone inhibition, PC‐3 cells were exposed to mifepristone in comparison with dexamethasone (Dex), progesterone, and 5 alpha‐dihydrotestosterone (DHT), each at 1‐μM concentration. The results demonstrated that while both DHT and Dex alone had essentially no effect on cell growth, progesterone alone resulted in a 20% growth inhibition, while mifepristone had more than 60% inhibition with a 16‐day exposure. At an equal concentration, the degree of growth inhibition of PC‐3 cells by mifepristone or progesterone was partially diminished by simultaneous exposure to Dex. In conclusion, our results demonstrated that the growth of androgen‐insensitive prostate cancer cells can be directly inhibited by mifepristone in cultures. This in vitro inhibition is reflected in xenografted tumors.
Expression of cellular adhesion molecules on human prostate tumor cell lines
Authors: Rokhlin Oskar W. , Cohen Michael B.
Published: February 2007

By flow cytometric analysis we have examined the expression of cellular adhesion molecules (CAMs) on the surface of four different human prostate tumor cell lines: DU 145, from a brain metastasis; PC 3, from a bone metastasis; LNCaP.FGC, from a lymph node metastasis; and a primary tumor cell line, ND 1. The corresponding ligands for the expressed CAMs were, by and large, extracellular matrix proteins. We detected high‐level expression of ICAM‐1 on three of the four prostate cell lines, whereas LNCaP cells were negative. We observed unstable, heterogeneous expression of E‐cadherin in the cell lines DU 145, PC 3, and ND 1. Flow cytometric cell sorting enabled us to divide PC 3 cells into negative and bright positive subpopulations but, after several cell divisions in culture, sorted cells returned to the original heterogeneous phenotype. The laminin‐specific α6β4 integrin was not expressed by LNCaP, and was expressed at a low level and heterogeneously on DU 145 and PC 3 cell lines. In contrast, ND 1 cells, derived from a primary tumor, showed homogeneous and high‐level expression of the α6β4 integrin. All of the prostate cell lines expressed the RGD‐dependent binding of α3β1 and α5β1 integrins and did not reveal non‐RGD‐dependent α4β1 integrin expression. This finding provides a stimulus to investigate the inhibition capacity of RGD‐containing peptides on the metastatic behavior of prostate tumor cells.
Spontaneous metastasis of PC‐3 cells in athymic mice after implantation in orthotopic or ectopic microenvironments
Authors: Waters David J. , Janovitz Evan B. , Chan Thomas C. K.
Published: February 2007

The ability of subcutaneous, prostatic, and nonprostatic intraabdominal organ microenvironments to influence local tumor growth and metastasis of PC‐3 human prostate carcinoma cells in athymic mice was determined. Tumorigenesis and metastasis of PC‐3 were evaluated 60 days after subcutaneous and intraprostatic (orthotopic) implantation of 5 × 105 PC‐3 cells in 6‐week‐old, male athymic mice. Intraprostatic implantation of PC‐3 cells resulted in paraaortic lymph node metastases in 10 of 10 (100%) mice with prostatic tumors, whereas metastases were present in only 2 of 9 (22%) mice after subcutaneous implantation. Next, we determined whether the urinary bladder (nonprostatic, urogenital microenvironment) or stomach (nonurogenital, intraabdominal microenvironment) would facilitate the metastasis of PC‐3 cells in athymic mice. Tumorigenesis and metastasis were 100% after subserosal implantation of PC‐3 cells within the wall of the urinary bladder (n = 6 mice). Subserosal implantation of PC‐3 cells into the stomach wall (n = 7 mice) also resulted in tumor formation and metastasis to regional lymph nodes in 100% of mice. In all experiments, regional lymph nodes were the most frequent site of metastasis, regardless of implantation site. We conclude that tumor microenvironment factors responsible for the metastasis of PC‐3 cells in athymic mice may not be organ‐specific, since nonprostatic visceral microenvironments are sufficient for predictable metastasis. Use of these models may further our understanding of how tumor microenvironment modulates expression of the metastatic phenotype by human prostate carcinoma cells.
Pathology review in an early prostate cancer detection program: Results from the american cancer society‐national prostate cancer detection project
Authors: Mostofi F. K. , Murphy G. P. , Mettlin C. , Sesterhenn I. A. , Batsakis J. G. , Khaliq S. U. , Nadimpalli V. , Tahan S. , Siders D. B. , Kollin J. , Marsh W. , Owings M. , Sweet J.
Published: February 2007

Biopsy materials obtained in the American Cancer Society National Prostate Cancer Detection Project were reviewed at the Central Pathology Laboratory at the Armed Forces Institute of Pathology. Of 265 cases submitted, 177 were diagnosed as prostatic carcinoma, 7 as prostatic intraepithelial neoplasia (PIN), 13 as atypical glands or atypical hyperplasia, and the remaining 68 were benign hyperplasias. Irrespective of the means of detection or the grading system used (Gleason or WHO‐Mostofi), a large majority of the cancers were detected as low‐grade tumors. Of 27 cases of PIN reported, 20 were associated with cancer, leaving 7 cases with the sole diagnosis of PIN. These data may indicate the increased use of prostate‐specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS) in the United States is shifting the spectrum of prostate cancer pathology toward early low‐grade tumors. © 1995 Wiley‐Liss, Inc.
Immunocytochemical characterization of explant cultures of human prostatic stromal cells
Authors: Kooistra Anko , Elissen Nancy M. J. , König Josée J. , Vermey Marcel , Van Kwast Theodorus H. Der , Romijn Johan C. , Schröder Fritz H.
Published: February 2007

The study of stromal‐epithelial interactions greatly depends on the ability to culture both cell types separately, in order to permit analysis of their interactions under defined conditions in reconstitution experiments. Here we report the establishment of explant cultures of human prostatic stromal cells and their immunocytochemical characterization. As determined by antibodies to keratin and prostate specific acid phosphatase, only small numbers (<5%) of epithelial cells were present in primary cultures; subsequent passaging further reduced epithelial cell contamination. Antibodies against intermediate filament proteins (keratins, vimentin, and desmin) and smooth muscle actin microfilaments demonstrated that stromal cells from benign prostatic hyperplasia and prostate carcinoma differed in regard to their differentation markers. Two contrasting phenotypes were identified in cultures derived from these two different lesions: One, exhibiting fibroblastic features, was predominant in cultures derived from benign lesions and a second, showing varying degrees of smooth muscle differentiation, was more abundant in carcinoma‐derived cultures. These findings are indicative of a remarkable divergence in the stromal‐epithelial relationships associated with these pathological conditions and may provide us with a potential tool for studying these processes. © 1995 Wiley‐Liss, Inc.
Rat prostatic inhibin: Less than 35 kDa protein(s)
Authors: Kharbanda Kusum , Ramakrishnan P. R. , Duraiswami S.
Published: February 2007

An attempt was made to purify and physicochemically characterize the inhibin‐like activity of rat ventral prostate based on the technique of immunosorption. It was possible to partially purify prostatic inhibin by affinity chromatography and the molecular size of inhibin‐like material was shown to be less than 35 kDa. © 1995 Wiley‐Liss, Inc.
Binding of estradiol to whole prostatic DU‐145 cells in the presence and absence of tamoxifen and acetylsalicylic acid
Authors: Viljoen Theo C. , van Aswegen Casper H. , du Plessis Dion J.
Published: February 2007

Conflicting results have been obtained with regard to the estradiol receptor (ER) capacity of human prostatic tissue. Human prostatic DU‐145 cells have been found to be ER‐negative with immunohistochemical assays. The object of this investigation was to determine if whole DU‐145 cells, which had been grown in monolayer culture, have ER and, if so, to confirm the finding with antiestrogens. After cells had been lysed, a Bmax of 44.7 ± 4.0 fmol/mg (Kd = 0.6 ± 0.6 nM) was obtained. Subcellular localization studies showed that the estrogen receptor level in the cytoplasmic fraction was approximately 10 times higher than in the nuclear fraction. Competitive binding studies showed that tamoxifen, DES, and acetylsalicylic acid decreased estradiol binding. The dissociation constants and relative affinities for tamoxifen, DES, and acetylsalicylic acid were 0.2 nM (281.7%), 0.2 nM (224.0%), and 0.8 nM (78.43%), respectively. However, 5α‐dihydrotestosterone and metabolites of acetylsalicylic acid had no effect in competitive binding studies. These results may contribute to a better understanding of prostatic carcinogenesis, which may in turn lead to more effective treatment. © 1995 Wiley‐Liss, Inc.
Commentary on maximal androgen blockade in prostate cancer: A theory to put into practice?
Authors: Denis L.
Published: February 2007

The population at risk of prostate cancer is on the increase, and so is public awareness of this disease. There has been an unresolved controversy surrounding the benefits of maximal androgen blockade (MAB) as a valid approach to treatment of non‐curative prostate cancer since it was first proposed in 1945. How are we to interpret the data on MAB in order to give each patient the best advice on treatment? Studies of MAB using medical castration (luteinizing hormone‐releasing hormone [LHRH] analogue plus antiandrogen) vs. LHRH analogues alone are inconclusive when viewed collectively, although the largest showed objective benefits for MAB. The remaining studies have insufficient power to show the expected effect size. Studies of MAB using surgical castration plus antiandrogen vs. surgical castration alone also gave inconsistent results, although a meta‐analysis is in favor of MAB on objective criteria of response. Among trials of MAB using an LHRH analogue vs. surgical castration alone, one is positive and the remaining two are neutral for MAB. No study shows MAB to be worse than either medical or surgical castration alone. An overall meta‐analysis shows a trend for benefit with MAB but is not statistically significant. The existing data have strongly suggested that there may be a particular benefit for certain subgroups of patients (including those with minimal disease) but numbers studied have been too small to allow valid conclusions. The INT 0105 trial in progress may permit firmer conclusions to be drawn on this and other questions. In the meantime one of the drawbacks to current MAB regimens is the exchange of modest clinical advantages for the side effects of nilutamide and flutamide. Given that the disease is noncurative, improved quality of life is the main goal of therapy, and excellent tolerability of treatment is fundamental to this. In a comparative trial, bicalutamide (Casodex) was more effective than flutamide (each in combination with an LHRH analogue) in terms of time to treatment failure and produced a significantly lower incidence of diarrhoea. In conclusion, the evidence supports early use of adequate hormonal treatment, and this should mean either medical or surgical castration, ideally augmented by an antiandrogen. Tolerability of the antiandrogen is a key consideration in gaining an improvement in quality of life with MAB. © 1995 Wiley‐Liss, Inc.
Prostate specific antigen in a community‐based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism
Authors: Bosch J. L. H. Ruud , Hop Wim C. J. , Bangma Chris H. , Kirkels Wim J. , Schröder Fritz H.
Published: February 2007

The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation.

PSA and PSAD did not correlate with the body mass index. Weak correlations were found between PSA and age (r = 0.25; P < 0.001), PSAD and age (r = 0.17; P < 0.001) and between PSA and the total prostate volume (r = 0.58; P < 0.001). PSA did not correlate independently with age after adjustment for volume (P = 0.22). The finding that PSAD correlates with age (r = 0.17; P < 0.001) is partly explained by the incomplete volume adjustment of PSAD which is proved by the positive correlation between PSAD and prostate volume (r = 0.26; P < 0.001).

In the main target age‐range for prostate cancer screening there is a poor basis for the use of age‐specific reference values or volume adjustment for PSA levels in order to increase the clinical usefulness of this serum marker. Comparison of the results of the present study and studies conducted in others regions shows that there may be significant differences in PSA values per age stratum. Further studies are needed to clarify the reasons for these differences. © 1995 Wiley‐Liss, Inc.
Induction of urinary plasminogen activator by retinoic acid results in increased invasiveness of human prostate cancer cells PC‐3
Authors: Liu Dong F. , Rabbani Shafaat A.
Published: February 2007

Overproduction of uPA by prostate cancer cells in vivo results in tumor invasiveness and osteoblastic skeletal metastasis due to its mitogenic actions in osteoblasts. In the present study we have examined the effect of several growth factors and steroid hormones on regulating uPA gene expression in the human prostate cancer cell line (PC‐3). Treatment of these cells with dexamethasone (Dex) caused a decrease, whereas epidermal growth factor (EGF) and fetal bovine serum (FBS) increased uPA expression in a dosedependent manner. Trans retinoic acid (RA) also induced uPA mRNA and protein production in a dose‐dependent manner (10−6 to 10−9 M). This increase was seen as early as 2 hr of treatment until 48 hr. Dex treatment resulted in decreased tumor cells invasiveness, whereas exposure to EGF and RA caused an increase in the invasive capacity of PC‐3 cells. These studies should help to better understand the control mechanism of uPA expression in prostate cancer, where uPA has been implicated as a major pathogenetic factor. © 1995 Wiley‐Liss, Inc.
Retinoblastoma gene mutations in primary human prostate cancer
Authors: Kubota Yoshinobu , Fujinami Kiyoshi , Uemura Hiroji , Dobashi Yasushi , Miyamoto Hiroshi , Iwasaki Yoshiko , Kitamura Hitoshi , Shuin Taro
Published: February 2007

Structural alterations in the entire coding regions (exons 1 to 27) of the retinoblastoma (RB) gene in primary human prostate cancers were investigated, using polymerase chain reaction and single strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, four (16.4%) were found to have RB alterations. DNA sequencing of the PCR products revealed point mutations resulting in single amino‐acid substitutions of exons 6 and 19 in two cases, and base deletions of exons 8 and 17 in two cases. Two of four cases with RB mutations were moderately differentiated localized tumors and other two with RB mutations were poorly differentiated tumors with metastases. Our results suggest that RB gene mutation is involved in progression steps of prostate carcinogenesis. © 1995 Wiley‐Liss, Inc.
Dna heterogeneity determined by flow cytometry in prostatic adenocarcinoma—necessitating multiple site analysis
Authors: Warzynski Michael J. , Soechtig C. Eugene , Maatman Thomas J. , Goldsmith Larry C. , Grobbel Mary Ann , Carothers George G. , Shockley Kenneth F.
Published: February 2007

Although DNA ploidy analysis of prostate cancer is generally associated with grade, stage, clinical outcome, and responsiveness to androgen therapy, one possible reason cited for contrary reports may be tumor heterogeneity. A preliminary report using flow cytometric analysis of punch biopsies demonstrated DNA heterogeneity in five of nine patients. We evaluated 75 patients by cutting whole mounts of formalin fixed prostatectomy tissue every 0.6 cm. All malignant areas and a selected normal area were circumscribed, excised, remounted, and 1–3 50 μ thick sections removed. The nuclei were extracted by a Hedley technique and the DNA stained with propidium iodide. Each whole mount had an average of 1 distinct malignant area (range of 1–6 areas per whole mount block). Nuclei were analyzed on a Becton Dickinson (San Jose, CA) FACScan flow cytometer equipped with RFIT DNA software program. After excluding histograms with CVs > 8.0% and/or “suspicious” diploid histograms having a right “shoulder,” 75 or 87 patients still had ≥2 malignant sites available for analysis (average 4, range 2–9 malignant sites/patient). The 322 histograms had an average CV of 4.4%. Thirty of 75 patients (40%) showed DNA heterogeneity in multiple samples taken from the same prostate. There were 37 prostates with only diploid (D), 1 with only tetraploid (T), 7 with only aneuploid (A), 20 with D plus A, 7 with D plus T, 2 with D plus T plus A, and 1 with a D plus suspected hypodiploid DNA content. Exclusion of the tetraploid and “near diploid aneuploid” cases still resulted in 16% (12/75) of the patients having a diploid versus aneuploid DNA content heterogeneity. Because 40% of the prostates contained a different ploidy depending on which area was sampled, this report suggests multiple sites of malignancy must be analyzed to more accurately assess the ploidy status of prostatic adenocarcinoma. © 1995 Wiley‐Liss, Inc.
Detection and characterisation of strong resistance to phosphine in Brazilian Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae)
Authors: Lorini Irineu , Collins Patrick J , Daglish Gregory J , Nayak Manoj K , Pavic Hervoika
Published: February 2007

As failure to control Rhyzopertha dominica (F.) with phosphine is a common problem in the grain‐growing regions of Brazil, a study was undertaken to investigate the frequency, distribution and strength of phosphine resistance in R. dominica in Brazil. Nineteen samples of R. dominica were collected between 1991 and 2003 from central storages where phosphine fumigation had failed to control this species. Insects were cultured without selection until testing in 2005. Each sample was tested for resistance to phosphine on the basis of the response of adults to discriminating concentrations of phosphine (20 and 48 h exposures) and full dose–response assays (48 h exposure). Responses of the Brazilian R. dominica samples were compared with reference susceptible, weak‐resistance and strong‐resistance strains from Australia in parallel assays. All Brazilian population samples showed resistance to phosphine: five were diagnosed with weak resistance and 14 with strong resistance. Five samples showed levels of resistance similar to the reference strong‐resistance strain. A representative highly resistant sample was characterised by exposing mixed‐age cultures to a range of constant concentrations of phosphine for various exposure periods. Time to population extinction (TPE) and time to 99.9% suppression of population (LT99.9) values of this sample were generally similar to those of the reference strong‐resistance strain. For example, at 0.1, 0.5 and 1.0 mg L−1, LT99.9 values for BR33 and the reference strong‐resistance strain were respectively 21, 6.4 and 3.7 days and 17, 6.2 and 3.8 days. With both strains, doubling phosphine concentrations to 2 mg L−1 resulted in increased LT99.9 and TPE. High level and frequency of resistance in all population samples, some of which had been cultured without selection for up to 12 years, suggest little or no fitness deficit associated with phosphine resistance. The present research indicates that widespread phosphine resistance may be developing in Brazil. Fumigation practices should be monitored and resistance management plans implemented to alleviate further resistance development. Copyright © 2007 Society of Chemical Industry
The storage and provenance of fine sediment on the channel bed of two contrasting lowland permeable catchments, UK
Authors: Collins A. L. , Walling D. E.
Published: February 2007

Fine sediment (<63 µm) storage in river channels frequently represents a significant term in catchment sediment budgets and plays an important role in diffuse pollution problems. A combination of a sediment remobilization technique and the fingerprinting approach was used to examine the storage and provenance of fine sediment on the channel bed of two contrasting lowland permeable catchments in the UK. In the upper Tern (∼231 km2) study catchment, estimates of mean fine sediment storage on the channel bed ranged between 860–5500 g m−2, with an overall average of 2391 g m−2, compared to 470–2290 g m−2 and 1065 g m−2 in the Pang (∼166 km2) and 770–1760 g m−2 and 1255 g m−2 in the Lambourn (∼234 km2) sub‐catchments. Mean total fine sediment storage on the bed of the main channel was equivalent to 37% (upper Tern), 38% (Pang) and 21% (Lambourn) of the mean annual suspended sediment loads measured at the catchment outlets. Over the study period, the total gain (1427 t) and loss (1877 t) to fine sediment storage on the channel bed in the upper Tern catchment were equivalent to 82% and 108% of the mean annual suspended sediment load, respectively, compared to 149% (740 t) and 136% (678 t) in the Pang sub‐catchment, and 39% (422 t) and 49% (528 t) in the Lambourn sub‐catchment. The source of the fine sediment stored on the channel bed within each study area varied. In the upper Tern catchment, the weighted mean relative contributions from individual source types were estimated to be 35 ± 5% (pasture), 51 ± 5% (cultivated) and 14 ± 3% (channel banks and subsurface sources). The corresponding estimates were 49 ± 8%, 33 ± 5% and 18 ± 5% for the Pang sub‐catchment, compared to 19 ± 6%, 64 ± 5% and 17 ± 5% for the Lambourn sub‐catchment. These sediment source estimates have important implications for the design and implementation of targeted sediment control policies within the study areas. Copyright © 2007 John Wiley & Sons, Ltd.
Strategic purity: A multi‐industry evaluation of pure vs. hybrid business strategies
Authors: Thornhill Stewart , White Roderick E.
Published: February 2007

Twenty‐five years of empirical research has failed to resolve a basic strategy question. Does strategic purity pay? Most theorists believe strategic purity—the extent to which a business pursues one type of generic strategy over another—contributes to better performance. By defining the strategy space consistent with the theory, and employing improved design and methods, our study of 2,351 businesses finds a significant relationship between strategic purity and performance. Purity does appear to pay. Some variations in strategic purity and performance relationship were observed across four major industry sectors: manufacturing, construction, retail, and business services. But in all instances pure strategies never did less well, and often did better than hybrid strategies. Copyright © 2007 John Wiley & Sons, Ltd.
Prevalence and prognostic impact of bundle branch block in patients with heart failure: Evidence from the CHARM programme
Authors: Hawkins Nathaniel M. , Wang Duolao , McMurray John J.V. , Pfeffer Marc A. , Swedberg Karl , Granger Christopher B. , Yusuf Salim , Pocock Stuart J. , Östergren Jan , Michelson Eric L. , Dunn Francis G. ,   CHARM Investigators and Committees
Published: February 2007

Background

Bundle branch block (BBB) is a powerful independent predictor of cardiovascular mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The prognostic implications in HF with preserved systolic function (HF–PSF) are less well understood.

Methods

The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic HF to receive candesartan or placebo. The primary outcome comprised cardiovascular death or HF hospitalisation. The relative risk conveyed by BBB relative to a normal electrocardiogram was examined.

Results

The prevalence of BBB was significantly lower in patients with preserved compared with reduced systolic function (CHARM‐Preserved 14.4%, Alternative 29.6%, Added 30.5%), p<0.0001. Overall, the adjusted hazard ratio for the primary outcome was 1.48 (95% confidence interval 1.22–1.78), p<0.0001, reflecting increased risk in patients with reduced LVEF (1.72 [1.28–2.31], p=0.0003). The apparently more modest risk among patients with HF–PSF was significant in unadjusted (1.80 [1.37–2.37], p<0.0001) but not adjusted analysis (1.16 [0.88–1.54], p=0.2897). However, no formal statistical difference was observed between the two cohorts, and interpretation is limited by the unknown prevalence of left and right BBB morphologies in each. Comparing BBB presence with absence yielded qualitatively similar results.

Conclusion

The simple clinical finding of BBB is a powerful independent predictor of worse clinical outcomes in patients with HF and reduced LVEF. It is less frequent, with a more modest predictive effect, in patients with preserved systolic function.
Development of and recovery from short‐ and long‐term low back pain in occupational settings: A prospective cohort study
Authors: Gheldof Els L.M. , Vinck Jan , Vlaeyen Johan W.S. , Hidding Alita , Crombez Geert
Published: February 2007

Using the data of the EuroBack Unit prospective cohort study, this paper investigated the role of work‐related physical factors and psychological variables in predicting the development of and recovery from short‐term and long‐term LBP. At baseline, 1294 predominantly male industrial workers from 10 companies in Belgium and the Netherlands filled in questionnaires. At follow‐up, data from 812 employees were available. Odds ratios (ORs) were calculated using simple and multiple logistic regression analyses. For those workers reporting 0 days LBP in the year prior to baseline, negative affectivity (OR 1.06, 95% CI 1.01–1.11) was a risk factor for thedevelopment of short‐term LBP(=1–30 days total of LBP in the year prior to follow‐up). For those who reported 1–30 days total of LBP in the year prior to baseline, only high fear of (re)injury due to movement (OR 1.07, 95% CI 1.02–1.12) increased the risk for failure torecovery from short‐term LBP. For thedevelopment of long‐term LBP(=more than 30 days total of LBP in the year prior to follow‐up), a significant increased risk was observed among workers with high pain severity (OR 1.19, 95% CI 1.01–1.40) and with pain referred to the ankles or feet (OR 2.92, 95% CI 1.09–7.83). The risk was reduced by social support of co‐workers (OR 0.73, 95% CI 0.59–0.92) and by manual handling of materials (OR 0.63, 95% CI 0.46–0.85). For those who reported more than 30 days total of LBP in the year prior to baseline, high pain severity (OR 1.18, 95% CI 1.04–1.34) increased the risk for failure torecovery from long‐term LBP. Results are compared to the baseline study (Gheldof et al., 2005) and discussed in relation with prospective studies.
Carbon inhibits vascular endothelial growth factor‐ and fibroblast growth factor‐promoted angiogenesis
Authors: Murugesan Saravanababu , Mousa Shaker A. , O’Connor Laura J. , Lincoln David W. , Linhardt Robert J.
Published: February 2007

Angiogenesis is important for normal growth and wound healing processes. An imbalance of the growth factors involved in this process, however, causes the acceleration of several diseases including malignant, ocular, and inflammatory diseases. Inhibiting angiogenesis through interfering with its pathway is a promising methodology to hinder the progression of these diseases. Herein, we studied the anti‐angiogenic effects of various carbon materials such as graphite, multiwalled carbon nanotubes and fullerenes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2)‐induced angiogenesis evaluated in the chick chorioallantoic membrane (CAM) model. All the carbon materials tested showed substantial anti‐angiogenic activity against either FGF2‐ or VEGF‐induced angiogenesis in the CAM model. Those carbon materials did not have any significant effects on basal angiogenesis in the absence of the added growth factors.
Three‐dimensional hysterosonography versus hysteroscopy for the detection of intracavitary uterine abnormalities
Authors: Makris N. , Kalmantis K. , Skartados N. , Papadimitriou A. , Mantzaris G. , Antsaklis A.
Published: February 2007

Objective: To compare 3‐dimentional hysterosonography (3‐DHS) and diagnostic hysteroscopy for the evaluation of intrauterine lesions. Methods: In this prospective study 124 women with suspected intrauterine abnormality on 2‐D ultrasonography or on hysterosalpingography were scheduled to undergo hysteroscopy, 3‐DHS, and 3‐D power Doppler (3‐DPD) examination. However, 3‐DHS could not be performed in 3 of the women because of cervical stenosis. The sensitivity and specificity of 3‐DHS and 3‐DPD were compared with those of hysteroscopy. Results: Of the 121 women found to have an intracavitary abnormality, 20 had polyps, 11 had myomas, 2 had Müllerian duct anomalies, and 6 had synechiae on hysteroscopy. There was agreement between hysteroscopy and 3‐DHS in 19 of the polyp cases, 11 of the myoma cases, 2 of the Müllerian anomaly cases, and 4 of the synechiae cases. Examination with 3‐DHS and 3‐DPD reached a sensitivity of 91.9% and specificity of 98.8%, with a positive predictive value of 97.1% and a negative predictive value of 96.5%, respectively. Conclusions: Examination with 3‐DHS and 3‐DPD both allows for accurate assessment of intrauterine abnormalities.
Cervical ripening with the Foley catheter
Authors: Cromi A. , Ghezzi F. , Tomera S. , Uccella S. , Lischetti B. , Bolis P.F.
Published: February 2007

Objective: To evaluate maternal and neonatal outcomes in a large series of patients undergoing cervical ripening with a Foley catheter. Methods: The database of the Labor and Delivery Unit of the University of a teaching hospital in Italy was used to identify consecutive patients with a Bishop score (BS) of 4 or less who underwent pre‐induction cervical ripening with a Foley catheter. The main outcome measures were clinical chorioamnionitis, endometritis, and suspected and culture‐proven neonatal sepsis. Results: Of 602 women undergoing cervical ripening with a Foley catheter, 160 (26.6%) went into active labor without additional interventions. Oxytocin was administered immediately after removal of the Foley catheter in 188 (31.2%) of the women, and 254 (42.2%) required an application of prostaglandin E2 vaginal gel. The cesarean delivery rate was 25.6%. The median time to delivery was 1469 min (range, 94–3350 min). Of the women who gave birth vaginally, 225 (50.2%) were delivered within 24 h. Clinical chorioamnionitis and postpartum endometritis occurred in 3 (0.5%) and 6 (1.0%) of the women, respectively. Neonatal sepsis was suspected in 4 (0.7%) of the newborns but blood culture results were negative in all cases. Conclusion: Transcervical use of the Foley catheter is safe for pre‐induction cervical ripening, and the associated risk of maternal or perinatal infections is negligible.