bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear shape and prognosis following orchiectomy in stage D2 prostate cancer
Authors: Miller John , Horsfall David J. , Marshall Villis R. , Skinner John M. , Rao Dora M. , Leong Anthony S. Y.
Published: February 2007

In this study, we have examined whether tumor grade and morphometric nuclear features can predict the outcome of treatment by orchiectomy in patients with stage D2 prostate cancer. Two outcome groups based on duration of survival postorchiectomy were examined, a bad outcome group of 63 patients who died from prostate cancer within 12 months and a good outcome group of 34 patients who survived beyond 5 years. Tumors were histologically classified as well (17%), moderate (17%), or poorly differentiated (66%). Tumor grade and patient outcome were significantly associated (Mann‐Whitney test; P < 0.005), with 76% of poorly differentiated tumors in the bad outcome group, and 65% of well‐differentiated tumors in the good outcome group. Using discriminant function analysis, tumor grade correctly predicted outcome in 70% of cases.

A statistically significant difference was also detected in nuclear shape values between the two outcome groups (P < 0.05) and histological grades (P < 0.05). Using discriminant function analysis, 51% of cases were correctly classified into outcome groups using nuclear shape factors, a figure which rose to 65% when all nuclear morphometric features were used. This demonstrates that nuclear morphometric features are of no clinical value in predicting the outcome of treatment in stage D2 disease. Furthermore, these evaluations cannot select patients who might be spared orchiectomy on the basis of a predicted poor response.

However, nuclear shape and variance measurements of benign glandular epithelial cells within cancerous prostates were significantly different from those of malignant cells (P < 0.005). We conclude that, while video image analysis of prostatic nuclear shape can reliably discriminate between benign and malignant cells, nuclear morphometric features are of minimal prognostic value in men with stage D2 prostate cancer treated by androgen ablation. © 1994 Wiley‐Liss, Inc.
Cathepsin D cytosolic assay and immunohistochemical quantification in human prostate tumors
Authors: Chambon M. , Rochefort H. , Brouillet J. P. , Baldet P. , Maudelonde T. , Rebillard X. , Guiter J.
Published: February 2007

We quantified cathepsin D by immunoradiometric assay (IRMA) and quantitative immunohistochemistry in fifteen human prostate cancers, seventeen BPH, and nine normal prostates. The cytosolic cathepsin D concentration was higher in prostatic carcinoma (mean: 31.5 pmol/mg cytosol proteins; range: 10.2‐66.2) than in normal prostate (16.0 pmol/mg cytosol proteins; 7.2‐25.5; P = 0.01). Prostatic hyperplasia showed intermediate values (20.2 pmol/mg cytosol proteins; 7.6‐33.9). Immunostaining of cathepsin D and prostatic acid phosphatase on serial frozen sections of prostate tissues was only observed in glandular epithelial cells. Immunostaining was quantified by computer‐assisted image analysis as an quantitative immuno‐cytochemical score (QIC score) expressed in arbitrary units (A.U.). QIC scores for cathepsin D were dispersed and had a tendency to be higher in benign prostatic hyperplasia (mean: 178.3 A.U.; range: 95‐297) compared to normal prostate (85.2 A.U.; 2‐173 P < 0.01) and prostatic carcinoma (90.0 A.U.; 21‐179 P = 0.0002). Prostatic cathepsin D levels in cytosols or immunostaining sections were independent of other clinicobiological parameters. © 1994 Wiley‐Liss, Inc.
Estrogen treatment postpones the castration‐induced dedifferentiation of dunning R3327‐PAP prostatic adenocarcinoma
Authors: Landström M. , Damber J.‐E. , Bergh A.
Published: February 2007

Male Copenhagen × Fisher F1 rats, transplanted with the androgen‐sensitive Dunning R3327 PAP rat prostatic adenocarcinoma, were castrated when tumor volumes were approximally 1300 mm3. The rats were thereafter followed with measurements of tumor volume. Castration stopped tumor growth, but some of the tumors started to regrow after 7‐36 weeks. These tumors relapsing from castration treatment were now considered to be androgen‐insensitive. In this study, we defined relapse as the time when the tumor volume had increased to 200% of the volume at the time for castration. At this time, the rats were treated either with estradiol‐17β (E2, 50 μg s.c. daily) or vehicle for 8 weeks. After this period, tumor morphology was examined.

The tumors in the vehicle‐treated group were heterogeneous, and both highly and more dedifferentiated parts were present. The tumor growth rate was correlated to the epithelial cell nuclear size and its variance, and to the mitotic index. In the E2‐treated group, tumor growth rate was retarded throughout the treatment period, and dedifferentiated tumor areas were rare. Estrogen treatment resulted in a reduction of nuclear area and mitotic index, a changed nuclear shape, and an increased apoptotic index compared to that in vehicle‐treated tumors.

By castration, it is possible to induce an alteration of the androgen‐sensitive Dunning R3327 PAP tumor phenotype to an androgen‐insensitive tumor with an altered morphology. Estradiol‐17β apparently inhibits not only the growth, but also postpones the castration‐induced dedifferentiation of the tumor. © 1994 Wiley‐Liss, Inc.
Magnetic resonance spectroscopy detects metabolic differences between seven dunning rat prostate tumor sublines with different biological behavior
Authors: Cornel E. B. , Heerschap A. , Smits G. A. H. J. , Oosterhof G. O. N. , Debruyne F. M. J. , Schalken J. A.
Published: February 2007

In this study, it was investigated whether prostate tumor biological parameters correlate with metabolic profiles. 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of seven Dunning R‐3327 prostate tumor sublines. Several metabolic ratios, for example, phosphocholine/total phosphate, choline/total creatine, and inositol/total creatine, did not correlate specifically with one biological characteristic but, based on each of these ratios, the well‐differentiated, nonmetastatic, and hormone‐dependent sublines could be discriminated from the poorly differentiated or anaplastic, metastatic, and hormone‐independent sublines. The glycerophosphoethanolamine/total phosphate, glycerophosphocholine/total phosphate, and phosphocreatine/total phosphate ratios correlated with differentiation grade, and the differences in glycerophosphorylglycerol/total phosphate ratio between metastatic and nonmetastatic sublines was highly significant. No correlation for hormonal sensitivity with any of the metabolites measured could be found, neither by 31P nor by 1H MRS. © 1994 Wiley‐Liss, Inc.
Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia
Authors: Hasui Yoshihiro , Marutsuka Kousuke , Asada Yujiro , Ide Hisamitsu , Nishi Shohei , Osada Yukio
Published: February 2007

The relationship between the serum values of prostate specific antigen (PSA) and the extent of histological prostatitis was investigated in 42 patients undergoing transurethral resection of the prostate for benign hyperplasia (BPH) without clinical evidence of prostatitis. Histological prostatitis was divided into three groups: acute, chronic‐active, and chronic‐inactive inflammation. The extent of histological prostatitis was expressed as the number of prostatic acinar and ductal glands with inflammatory infiltrate per total number of glands (%). The serum PSA values significantly correlated with the extent of acute and chronic‐active prostatitis (correlation coefficient r = 0.765 and 0.656, P < 0.01). A relationship between PSA values and the extent of chronic‐inactive prostatitis was not found. In the immunohistochemical study, prostatic epithelial cells with acute and chronic‐active inflammation showed negative staining for PSA antigen. These results indicate that histological acute and chronic‐active prostatitis is considered an important factor for inducing the high increase in serum PSA values via the leak phenomenon. © 1994 Wiley‐Liss, Inc.
Bioenergetic theory of prostate malignancy
Authors: Costello L. C. , Franklin R. B.
Published: February 2007

Normal and benign prostate hyperplasia (BPH) prostate is characterized by the presence of extraordinarily high levels of citrate. Presumably, this results from the inability of the prostate epithelial cells to oxidize citrate due to a limiting mitochondrial (m‐) aconitase. In contrast, prostate carcinoma (CA) is not characterized by high citrate levels. Malignant prostate epithelial cells apparently undergo a metabolic transformation from citrate‐producing to citrate‐oxidizing cells. A consequence of citrate production in normal and BPH cells is an inefficient and low level of ATP production. It is proposed that the process of malignancy necessitates an energy production that cannot be provided by citrate‐producing cells. Consequently, the transformation of prostate epithelial cells to citrate‐oxidizing cells which increases the energy production capability is essential to the process of malignancy and metastasis. The metabolic transformation likely occurs as a premalignant or early malignant stage. This bioenergetic theory of prostate malignancy, if correct, will provide new approaches to the diagnosis and treatment of CA. © 1994 Wiley‐Liss, Inc.
DNA ploidy measurements in prostate cancer: Differences between image analysis and flow cytometry and clinical implications
Authors: Pindur A. , Chakraborty S. , Welch D. G. , Wheeler T. M.
Published: February 2007

The relationship between DNA ploidy and prognostic parameters has been established in prostate cancer. However, comparison of various techniques used for DNA ploidy analysis has not been sufficiently addressed in prostate carcinoma. In the present study, grossly identified discrete carcinoma foci from 48 consecutive radical prostatectomy specimens were analyzed by flow cytometry and image analysis using both imprints and tissue sections. Correlations with other prognostically important pathological findings such as grade, size, extracapsular extension, positive surgical margin, and seminal vesicle and lymph node involvement were done. Image analysis detected 26 (54.2%) nondiploid tumors compared to 15 (31.3%) nondiploid tumors by flow cytometry. No significant differences were demonstrated between imprints and tissue sections. DNA ploidy status showed a good correlation with most other pathological findings listed above. In conclusion, DNA ploidy status determination gives clinically useful information which correlates well with the other useful pathological parameters of prognostic importance. Image analysis may be more sensitive than flow cytometry in detecting nondiploid populations. Tissue sections appear to be as reliable as imprints when properly controlled. © 1994 Wiley‐Liss, Inc.
Two‐phase short‐term culture method for cytogenetic investigations from human prostate carcinoma
Authors: Szücs Sandor , Zitzelsberger Horst , Breul Jürgen , Bauchinger Manfred , Höfler Heinz
Published: February 2007

An improved technique for primary short‐term culture of prostate carcinoma cells in two phases, with and without serum, for subsequent cytogenetic analysis is reported and compared with four other methods. After mechanical disaggregation and a brief collagenase treatment of tumor specimens, cell clusters were seeded in RPMI 1640 and 15% fetal calf serum (FCS) without any other supplement in the first phase. The culture medium was changed to a serum‐free medium supplemented with bovine pituitiary extract (BPE) and epidermal growth factor (EGF) when the first outgrowth became apparent. During this second phase, fibroblast growth could be virtually abolished within 48 hr. The epithelial and prostatic origin of the cultured cells was confirmed by immunocytochemical methods in each culture. Metaphase analysis revealed chromosome aberrations in over 80% of cases (both clonal and nonclonal alterations) indicating the presence of neoplastic cells. Clonal numerical chromosome aberrations, found by conventional cytogenetic analysis, were used to provide the reliability of the culture system in interphase nuclei of corresponding uncultured tumor tissue by fluorescence in situ hybridization (FISH). The main points of the described method are: 1) combined mechanical/enzymatic disaggregation, 2) seeding of the disaggregated cell clumps rather than of single cells, 3) initialization of the cultures in RPMI 1640 medium with 18% FCS without any other supplements, and (4) stimulating of selective epithelial proliferation by changing the culture conditions through serum‐free medium. © 1994 Wiley‐Liss, Inc.
Fresh tissue harvest for research from prostatectomy specimens
Authors: Wheeler Thomas M. , Lebovitz Russell M.
Published: February 2007

As a consequence of molecular biological and genetic techniques, the demand for fresh tissue for basic research has increased dramatically at academic medical centers. Because of the extreme lability of many biological macromolecules, tissue must be harvested with the least possible delay from the time of removal. This necessity for quick action, frequently under less than optimal circumstances, along with the obvious loss of tissue available for diagnostic purposes, presents a daunting challenge to the pathologist responsible for accurate grading and staging of the cancer. A novel approach is described for the procurement of fresh and freshly frozen prostatic tissue with acceptable limitations on subsequent morphological analysis. © 1994 Wiley‐Liss, Inc.
Inhibition of prostatic epithelial cell proliferation by a factor secreted specifically by prostatic stromal cells
Authors: Kooistra Anko , J. König Josée , Keizer Diederick M. , Romijn Johan C. , Schröder Fritz H.
Published: February 2007

Stromal cells from the prostate were recently shown to inhibit clonal growth of the prostatic carcinoma cell lines PC‐3 (hormone‐independent) and LNCaP (hormone‐sensitive) in coculture. Our study revealed that stromal cell‐conditioned medium strongly inhibited proliferation of PC‐3 and LNCaP cells when grown in monolayer culture. Antiproliferative activity was found to be reversible, and was produced specifically by prostatic stromal cells and not by stromal cells derived from skin, foreskin, uterus, kidney, and Wilms' tumor. Inhibition was not species‐specific, since the cell lines AT‐2.1 and MATLyLu, derived from the Dunning rat prostate tumor, were also sensitive. No inhibition, however, occurred on breast and renal carcinoma cell lines, suggesting a prostate‐specific action. The putative inhibiting factor(s) could be concentrated and partially purified by ammonium sulfate precipitation. The possible role in stromal control of epithelial cell proliferation is discussed.
Comparison of prostate specific antigen, prostate specific membrane antigen, and LNCaP‐based enzyme‐linked immunosorbent assays in prostatic cancer patients and patients with benign prostatic enlargement
Authors: Murphy Gerald. P. , Holmes E. H. , Boynton A. L. , Kenny G. M. , Erickson S. J. , Barren R. J. , Ostenson R. C.
Published: February 2007

Serum assays for prostate specific antigen (PSA; monoclonal), for prostate specific membrane antigen (PSM; Western blot), and a LNCaP/7E11.C5‐based competitive enzyme‐linked immunosorbent assay (ELISA) were evaluated in a small number of prostate cancer patients with localized or disseminated disease, and judged to be in clinical progression or remission based on National Prostate Cancer Project (NPCP) criteria. PSA values recognized the presence of clinical progression in localized disease (B1‐C) and to a lesser degree disseminated disease (D1‐D2). In contrast, to a limited degree the ELISA test recognized clinical progression mainly in disseminated disease and chiefly in stage D2. PSM values were elevated in both D1 and D2 but not in a linear fashion as observed with PSA. The ELISA and PSM results may be assessing a different clinical response to prostatic cancer than that recognized by PSA. This could reflect a developing clone of resistant prostatic cells as previously postulated. To further pursue this possibility a secondary generation of monoclonal antibodies to PSM is being developed. The ELISA levels for benign prostatic enlargement were not elevated above normal. In contrast both with PSA and PSM the assays reflected levels significantly above the normal range in benign prostatic hypertrophy (BPH).
Immunohistochemical localization of cathepsin B in neoplastic human prostate
Authors: Sinha Akhouri A. , Wilson Michael J. , Reddy Pratap K. , Gleason Donald F. , Sameni Mansoureh , Sloane Bonnie F.
Published: February 2007

Cathepsin B (CB) has been shown to degrade extracellular matrix (ECM) proteins, and has been reported to be involved in invasion and metastasis of several types of solid organ tumors in human and animals, but CB has not been studied in human prostate cancer (CAP). Our objective was to determine the CB protein immunostaining pattern in CAP and to correlate the immunostaining with the degree of malignancy as reflected in the Gleason grading system. We used two types of CB antibodies (namely, monospecific, polyclonal antibodies to human liver CB prepared in rabbits, and polyclonal antibody produced in sheep) to establish CB localization patterns in neoplastic prostate. Our analysis showed a heterogeneous CB immunostaining pattern in the neoplastic human prostate. CB immunostaining occurred in many, but not all, of the neoplastic columnar/cuboidal cells of acini and isolated cells, i.e., in small ragged glands and clusters (groups) of invasive cells in the prostatic stroma. We have shown that, in general, there was a positive correlation of the intensity of CB immunostaining with the Gleason histologic score (or Gleason grade sum) tumors, i.e., from the lowest scores through score 8, but many of the tumors with scores 9 and 10 showed little CB immunostaining. Our study indicated that the increased CB immunostaining in the Gleason grade sum 5–8 tumors may be associated with increased degradation of ECM, but not in 9 and 10 despite the fact that the latter tumors are more malignant clinically. In well‐differentiated tumors, fewer CB immunostaining cells were present than the moderately‐differentiated tumors. In other words, most of the stromal invasion of the prostatic ECM occurred in tumors of Gleason grade sums 5–8. We suggest that CB immunostaining might be a useful method to assess stromal invasion of prostatic carcinoma, especially in the higher grade tumors.
Growth inhibition of human prostate tumor cells by an agonist of gonadotrophin‐releasing hormone
Authors: Loop Stephen M. , Gorder Christine A. , Lewis Suzanne M. , Saiers Joseph H. , Drivdahl Rolf H. , Ostenson Richard C.
Published: February 2007

The effect of [D‐Leu6, des‐Gly‐NH210, Proethylamide9]‐GnRH, leuprolide, was determined for the human primary prostate tumor cell line ALVA‐31 by in vitro mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by leuprolide. Inhibition was not observed in parallel cultures treated with other low molecular weight bioactive peptides. The incorporation and metabolic reduction of testosterone was not affected by concentrations of leuprolide that were inhibitory in the mitogenic assay. Specific high‐affinity binding of 125I‐labeled leuprolide was also demonstrated on intact tumor cells with an estimated effective median dose (ED50) of <1 × 10–9M. Inhibition of prostate tumor growth was further demonstrated in Balb/c athymic intact and castrate male mice bearing ALVA‐31 tumor xenografts following chronic administration of leuprolide. These data clearly demonstrate that leuprolide can inhibit the growth of a human prostate carcinoma cell line. Studies conducted in castrate animals further suggest an alternative mechanism of growth inhibition that appears to be independent of the suppression of steroid hormone biosynthesis by LHRH analogues.
Isolation of cDNAs that are differentially expressed between androgen‐dependent and androgen‐independent prostate carcinoma cells using differential display PCR
Authors: Blok Leen J. , Vijay Kumar M. , Tindall Donald J.
Published: February 2007

In the development of prostate cancer there is an important transition from androgen‐dependent growth (which can be treated) to androgen‐independent growth (which is beyond medical control). This transition is probably accompanied by genetic changes, resulting in the activation of oncogenes or the inactivation of tumor suppressor genes. In the present manuscript, the isolation of genes that may be involved in advanced, androgen‐independent prostate cancer growth is described.

Using differential display PCR, 13 cDNAs were isolated representing genes that are differentially expressed between the androgen‐dependent prostate carcinoma cell line LNCaP and the androgen‐independent prostate carcinoma cell lines PC‐3 and DU 145. These clones were divided into four groups: androgen‐responsive genes (TL5, TL25, TL32, and TL35); genes with a marked decreased expression in one of the prostate cancer cell lines (TL27); genes with a marked, increased expression in one or more of the prostate cancer cell lines (TL4, TL16, TL21, and TL22); and genes with minor (but repeatable) changes in expression between prostate cancer cell lines (TL7, TL15, TL18, and TL33). The 13 genes were analyzed for their sequence information, tissue specificity, and androgen responsiveness in order to identify genes of interest.

In summary, differential display PCR appears to provide an attractive alternative to existing molecular techniques to screen for differentially expressed genes in prostate cancer cells.
Inhibition of tumor angiogenesis and the therapeutic ability of linomide against rat prostatic cancers
Authors: Vukanovic Jasminka , Isaacs John T. , Hartley‐Asp Beryl
Published: February 2007

Linomide, a quinoline‐3‐carboxamide, has growth‐inhibitory effects against a series of Dunning R‐3327 rat prostatic cancers in vivo [Ichikawa et al.: Cancer Res 52:3022–3028, 1992]. In addition, we have demonstrated that daily linomide treatment can inhibit angiogenic responses in nontumor‐bearing rats and reduce tumor blood flow in tumor‐bearing rats [Vukanovic et al.: Cancer Res 53:1833, 1993]. In the present study we have demonstrated that the reduced tumor blood flow is due to linomide's ability to inhibit tumor angiogenesis, as documented by decreased number of blood vessels in prostatic carcinomas growing in rats treated daily with linomide. Due to linomide's ability to inhibit tumor angiogenesis, and since tumor angiogenesis is required not only for the growth of the primary cancer but also for its ability to metastasize, the effect of linomide on metastasis was directly tested using a quantitation metastasis assay. These in vivo experiments demonstrated that daily linomide treatment decreased by 3‐fold the extent of dissemination of cancer cells to the lungs.

To test if this antimetastatic response is due to direct effects of linomide on the metastatic cells themselves as well as an induced effect upon inhibition of tumor angiogenesis, additional studies were performed. These studies demonstrated that linomide is not converted in vivo to metabolite(s) which are directly cytotoxic or cytostatic to the prostatic cancer cells themselves. These studies also demonstrated that linomide does not decrease the attachment, migration, or invasive abilities of metastatic cancer cells. These results suggest that the major mechanism for the antitumor and antimetastatic effects of linomide is via its inhibition of tumor angiogenesis. Additional studies have demonstrated that in vivo linomide treatment results in the apoptotic death of thymocytes. This cytotoxic effect is not required for linomide's antitumor effect, nor is it due to elevated plasma levels of glucocorticoid.
Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer
Authors: Meikle A. W. , McWhorter W. P. , Stephenson R. A. , Middleton R. G. , Skolnick M. H.
Published: February 2007

Benign prostatic hyperplasia (BPH) and prostate cancer commonly occur together. This suggests that common familial, hormonal, and environmental factors contribute to their development. In men at risk for the development of prostate cancer (at 40 men in 19 families) and aged‐matched unrelated controls (n = 46), we have determined whether familial factors, age, and blood hormone concentrations are related to the transition zone (TZ), peripheral zone (PZ), or total volume of the prostate measured by transrectal ultrasound (TRUS). We determined that the influences of age, prostate cancer (n = 15), and familial status did not significantly affect the relationships reported. Therefore, data from all groups were combined for this study. TZ correlated positively with age (P = 0.003) after controlling for family status, but total prostate volume correlated insignificantly with age (P = 0.08). In addition, the ratio of TZ to PZ volumes also correlated significantly with age in the control group (r = 0.27, P = 0.014). Both TZ and PZ volumes correlated highly (r = 0.91, P < 0.0001, n = 86) with total volume. In addition, total volume correlated significantly (r = 0.71, P < 0.001) with the ratio of the TZ/PZ volumes, which also correlated significantly with each other (r = 0.61, P < 0.0001, n = 86). In contrast to the increase of TZ volume related to total prostate volume, PZ volume declined compared with total volume. Prostate volumes up to 50 ml are predominated by the PZ and above 50 ml by the TZ, which may compress and shrink the PZ. Both TZ and total prostate volume correlated positively with serum estrone concentrations (P = 0.04 and P = 0.003, respectively). These results suggest that the risk of prostate cancer does not contribute to generalized overgrowth of the prostate, including the TZ. However, estrogens and age strongly influence TZ but not PZ volume. Both PZ and TZ volumes rise together until the prostate exceeds 50 ml, when the growth of the TZ appears to exceed the PZ and then to compress it.
Mediation of glucocorticoid receptor function by transforming growth factor beta I expression in human PC‐3 prostate cancer cells
Authors: Reyes‐Moreno Carlos , Frenette Gilles , Boulanger Jocelyn , Lavergne Eliane , Govindan Manjapra V. , Koutsilieris Michael
Published: February 2007

We investigated the role of glucocorticoids in controlling the proliferation of androgen‐independent PC‐3 human prostate cancer cells via the action of transforming growth factor beta 1 (TGF β1). The presence of glucocorticoid receptor (GR) in PC‐3 cells was detected by immunoblotting analysis using a rabbit anti‐GR polyclonal antibody against the synthetic human GR peptide (hGR383–393). In PC‐3 cells, GR bound radiolabeled dexamethasone with an affinity similar to wild‐type GR. In addition, GR‐ligand complex bound radiolabeled DNA as detected by DNA band‐shift analysis on gel electrophoresis and trans‐activated the mouse mammary tumor virus‐thymidine kinase‐chloramphenicol acetyltransferase chimeric gene in transiently transfected PC‐3 cells. Dexamethasone (0.1 up to 100 nM) and TGF β1 (0.5 up to 50 ng/ml) inhibited PC‐3 cell proliferation. TGF β1 and dexamethasone both increased the distribution of PC‐3 cells into the G1/G0 phase of the cell cycle. Platelet‐derived growth factor (PDGF) stimulated the proliferation of PC‐3 cells and overcame dexamethasone's inhibition of PC‐3 cell growth. Dexamethasone's inhibition (10–7M) of PC‐3 cell growth was completely neutralized by RU 486 (10–6M) and partly neutralized by anti‐TGF β1 polyclonal antibody. Furthermore, dexamethasone up modulated the expression of TGF β1 mRNA in PC‐3 cells. Because dexamethasone's inhibition was neutralized at least in part by an anti‐TGF β1 polyclonal antibody and dexamethasone up modulated the expression of TGF β1 mRNA in PC‐3 cells, we conclude that GR function in human PC‐3 prostate cancer cells is mediated at least in part by TGF β1 expression.
In vitro proton magnetic resonance spectroscopy of four human prostate cancer cell lines
Authors: Cornel E. B. , Smits G. A. H. J. , De Ruijter J. E. , Oosterhof G. O. N. , Debruyne F. M. J. , Schalken J. A. , Heerschap A.
Published: February 2007

There is accumulating evidence that some biochemical pathways observable by magnetic resonance spectroscopy, e.g., citrate acid and phospholipid metabolism, are altered in human prostate cancer. Four well‐established human prostate cancer cell lines were therefore studied with magnetic resonance spectroscopy to compare differences in metabolic content with tumor biological behavior. Herein we demonstrate that, although each cell line has its own metabolic profile, relative creatine and citrate levels can be used to discriminate the androgen‐dependent LNCaP cell line from the androgen‐independent DU‐145, TSU, and PC‐3 cell lines.
Cost‐effectiveness analysis in early detection of prostate cancer: An evaluation of six screening strategies in a randomly selected population of 2,400 men
Authors: Gustafsson Ove , Norming Ulf , Nyman Claes R. , Carlsson Per , Svensson Helene
Published: February 2007

Based on the findings in an early detection study for prostate cancer [Gustafsson et al.: J Urol 148:1827–1831, 1992] using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate‐specific antigen (PSA), a cost‐effectiveness analysis was performed based on 6 screening strategies, namely: 1) DRE of all individuals; 2) TRUS of all individuals; 3) DRE, TRUS, and PSA analysis followed by reexamination of individuals with PSAs ≥7 ng/ml; 4) DRE of individuals with PSAs of ≥4 ng/ml; 5) TRUS of individuals with PSAs of ≥4 ng/ml; 6) DRE and PSA analysis followed by TRUS on individuals with PSAs ≥4 ng/ml.

The detection rates of prostate cancer using these 6 strategies were 2.4%, 3.3%, 3.6%, 2.0%, 2.6%, and 3.2%, respectively. Except for costs per detected cancer, costs were also calculated per detected small cancer (≤1.5 cm) and per detected cancer treated for cure. The cost calculations were based on total costs, i.e., direct plus indirect costs.

When the 6 strategies were compared, taking into account the detection rate of cancers treated for cure and cost‐effectiveness with respect to cancers treated for cure, strategies 1), 2), 3), and 4) were ruled out as less favorable than the remaining 2 strategies.

TRUS of individuals with PSAs ≥4 ng/ml (strategy 5) was the most cost‐effective strategy and detected 80% of the cancers actually treated for cure. Screening with DRE and PSA analysis followed by TRUS of individuals with PSAs ≥4 ng/ml (strategy 6) had a somewhat lower cost‐effectiveness, but detected 90% of the cancers treated for cure.
Survival of patients with localized prostate cancer treated with percutaneous transperineal placement of radioactive gold seeds: Stages A2, B, and C
Authors: Hochstetler Jerald A. , Kreder Karl J. , Loening Stefan A. , Brown C. Kice
Published: February 2007

Between 1984 and 1991, a total of 177 patients with adenocarcinoma of the prostate were treated with transcutaneous, transperineal radioactive gold seeds. Of these 177 patients, 20 were determined to have pelvic lymph node involvement and were excluded from this review. The remaining 157 patients received a median radioactivity dose of 164 mCi with a median follow‐up of 48 months. Cancer‐specific survival at 5 years was 100% for stage A2 and B1, 90% for stage B2, and 76% for stage C cancer. Covariates of grade, total radioactivity administered, age of the patient, and number of seeds implanted did not influence disease‐free survival in a statistically significant manner. Significant complications were observed in two patients.

The survival rates of patients treated with 198Au seed implanation for localized cancer are equivalent or better when compared to historical data of patients treated with 125I implantation, external beam radiotherapy, combination radioactive gold seed implantation and external irradiation, and radical prostatectomy. In addition, these comparable survival rates using intersitial 198Au seeds may be achieved with less morbidity.
Prognostic significance of capsular invasion and capsular penetration in patients with clinically localized prostate cancer undergoing radical prostatectomy
Authors: Theiss Matthias , Wirth Manfred P. , Manseck Andreas , Frohmüller Hubert G. W.
Published: February 2007

One hundred thirty patients with an observed follow‐up of more than 10 years after radical prostatectomy were restaged with regard to local extent of the tumor in relation to the prostate capsule. Of 112 patients with surgically staged negative pelvic lymph nodes, 62 had a tumor‐free prostate capsule, 24 had capsular invasion without penetration, and 26 had tumors extending through the capsule of the prostate.

Observed overall and disease‐free 10‐year‐survival rates were 79% and 69.4%, respectively, in patients with absence of capsular involvement and 70.8% and 66.7%, respectively, in patients with capsular invasion alone. In patients with capsular penetration, however, the survival rates significantly decreased to 57.7% (P= 0.018) and to 38.5 (P= 0.017), respectively.

The overall progression rate was found to be significantly higher in patients with tumors extending through the prostatic capsule (46.2%), as compared to those with absence of capsular involvement (21%;P= 0.014) as well as to those with capsular invasion alone without penetration (25%;P= 0.034).

Thus, in contrast to capsular invasion alone, capsular penetration means a poor prognostic indicator, which accounts for a reduced survival expectancy and a higher progression rate following radical prostatectomy. Therefore, tumors with capsular invasion and those with capsular penetration should not be grouped together in the same tumor stage as done in the 1987 edition of the TNM tumor clasification system. © 1995 Wiley‐Liss, Inc.
Tumor suppressor gene P53 mutations in human prostate cancer
Authors: Kubota Yoshinobu , Shuin Taro , Uemura Hiroji , Fujinami Kiyoshi , Miyamoto Hiroshi , Torigoe Soichiro , Dobashi Yasushi , Kitamura Hitoshi , Iwasaki Yoshiko , Danenberg Kathleen , Danenberg Peter V.
Published: February 2007

The genetic background underlying the growth and development of human prostatic cancer is not yet clear. Here we searched for possible mutations in the entire coding region of tumor suppressor gene p53 in primary human prostatic carcinomas, using polymerase chain reaction and single‐strand conformational polymorphism analysis of RNA.

We found p53 gene mutations in 4 of 21 cases (19%). DNA sequencing of the polymerase chain reaction products revealed missense point mutations that resulted in amino acid changes in exon 5 or 3 in three cases and single base deletions in exon 7 in two cases. One case contained both a missense point mutation and a single base deletion. Three of these four cases were pathologically diagnosed as poorly differentiated adenocarcinomas, and three of the four cases were clinically localized to stage C or D. None of seven noncancerous prostate tissues nor three well‐differentiated adenocarcinoma tissues showed any mutations.

The present results suggest that p53 gene mutation is involved in the late progression steps of human prostate carcinogenesis. © 1995 Wiley‐Liss, Inc.
In vivo and in vitro complex formation of prostate specific antigen with αi‐anti‐chymotrypsin
Authors: Huber Peter R. , Mattarelli Gianfranco , Strittmatter Bernadette , van Steenbrugge Gert Jan , Schmid Hans‐Peter , Maurer Andreas
Published: February 2007

Complex formation of prostate specific antigen (PSA) with its inhibitor α1‐anti‐chymotrypsin (ACT) in vivo and in vitro was studied. Patients with benign prostatic hyperplasia (BPH) were treated with the computer assisted device “Prostatron ®.” This instrument acts by means of thermal destruction of prostatic tissue. The effect of the treatment was followed by measurement of serum PSA concentrations using commercially available immunoassays from Roche (Cobas® Core), Wallac (Delfia®) and Abbot (IMx®) and Hybritech Tandem®. Serum samples were further analyzed by molecular sieving on S.300 (Pharmacia) and analyzed for PSA by immuno assay. The complex formation of PSA with ACT in serum was studied, demonstrating this process to be influenced by external stimulus. Patient sera revealing initially normal PSA levels (3 to 5 ng/ml) were stimulated to very high levels of PSA (≥ 140 ng/ml) by Prostatron® treatment. The absolute PSA level depends on the assay system and not only on the staging of the prostate tumor. In addition, complex formation was studied in athymic nude mice and in vitro revealing the possible pathways of PSA release. PSA from LNCAP cells kept in vitro show predominantly uncomplexed (free) PSA, whereas PSA from LNCAP cells injected into nude mice appears in the serum of the animals in complexed form. This demonstrates how in the immunization process free and complexed PSA serve as antigens in the standard procedure for the production of antisera for PSA. This model system also can be used for studies of the release mechanism of PSA into blood circulation. © 1995 Wiley‐Liss, Inc.
Protein kinase c regulation of the adenylyl cyclase system in rat prostatic epithelium
Authors: Carmena María J. , García‐Paramio Pilar , Solano Rosa M. , Prieto Juan C.
Published: February 2007

In the context of the crosstalk between transmembrane signalling pathways, we studied the loci within the stimulatory receptor/Gs protein/adenylyl cyclase system at which protein kinase C (PKC) exerts regulatory effects in rat prostatic epithelial cells. The treatment of cells with the PKC activator phorbol 12‐myristate 13‐acetate (PMA) resulted in an impairment of the stimulation of adenylyl cyclase activity in terms of both potency, as seen with both vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase‐activating peptide (PACAP‐27), and efficacy, as seen with the β‐adrenergic agonist isoproterenol. This inhibitory effect of PMA could be prevented by cell incubation with pertussis toxin but not with cholera toxin, pointing to a Gi‐but not Gs‐dependent mechanism. This hypothesis was reinforced by ADP‐ribosylation experiments that showed a low extent of αi with pertussis toxin but no change of αs with cholera toxin, as well as by the observation of the loss of the ability of low Gpp[NH]p doses to inhibit forskolin‐stimulated adenylyl cyclase activity (a measure of Gi function) after cell treatment with PMA. However, the phorbol ester did not modify the adenylyl cyclase catalytic subunit, as shown by experiments on direct stimulation of the enzyme by forskolin. Whatever the exact mechanisms, the results support a crosstalk between the PKC and the adenylyl cyclase systems in rat prostatic epithelial cells in terms of an impairment of adenylyl cyclase stimulation, due presumably to phosphorylation of both membrane receptors (coupled to Gs) and Gi protein, but not of Gs protein or the adenylyl cyclase itself. © 1995 Wiley‐Liss, Inc.
Work environment and prostate cancer risk
Authors: van der Gulden J. W. J. , Kolk J. J. , Verbeek A. L. M.
Published: February 2007

A case‐referent study of 345 prostate cancer cases and 1,346 referents was carried out in the Netherlands to investigate the relationship between work environment and prostate cancer risk. Cases were selected from the Cancer Registry of the Comprehensive Cancer Centre IKO. Referents (men diagnosed with benign prostate hyperplasia) were recruited with assistance of the pathology laboratories in the IKO region. Questionnaires were mailed to all subjects to obtain information on their work history and occupational exposure. Moreover, workers in farming (n = 323), and in metal work and maintenance (n = 340), were requested to complete short supplements to the questionnaire inquiring in more detail into specific types of exposure. Significantly elevated risks were found for work in food manufacturing and for bookkeepers. Significantly elevated odds ratios (OR) were also observed for jobs held between 1960 and 1970 in administration, in storage, or as farm laborer. In addition, a statistically significant excess risk was found for subjects who reported frequent occupational exposure to cadmium. Cases who worked in farming applied pesticides during significant more days per year than the referents did. A nonsignificantly elevated OR was found for maintenance of tractors and agricultural machinery. Among metal workers, mechanics, and repairmen, nonsignificantly increased ORs were observed with regard to the use of acids, solvents, iron, and steel, and for welding and maintenance of machinery. © 1995 Wiley‐Liss, Inc.
Effects of a new steroidal antiandrogen, TZP‐4238 (17 α‐acetoxy‐6‐chloro‐2‐oxa‐4, 6‐pregnadiene‐3, 20‐dione), on spontaneously developed canine benign prostatic hyperplasia
Authors: Takezawa Yutaka , Ito Kazuto , Suzuki Kazuhiro , Fukabori Yoshitatsu , Yamanaka Hidetoshi , Honma Seijiro , Mieda Mamoru , Hamataki Nobutoshi , Kushitani Masayuki
Published: February 2007

The effects of the new steroidal antiandrogen, TZP‐4238 on spontaneouslydeveloped canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5–9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP‐4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP‐4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP‐4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP‐4238 also appeared to reduce 5α‐reductase activity by prevention of the androgen action in prostate as described above. © 1995 Wiley‐Liss, Inc.
Data structure and algorithm for large‐scale generalized assignment problem which considers priority orders
Authors: Nishikori Akimine
Published: February 2007

In this paper, the author proposes a data structure and approximate solution for solving a large‐scale generalized assignment problem, being a constraint satisfaction problem. To find a desired solution from among many executable solutions, the proposed algorithm sets a priority order for resources and repeatedly solves an integer programming problem in order to reduce the nonexecutable sum of constraints. This study is an analysis of what type of data structure may be effective in raising the cache memory hit rate when a two‐dimensional matrix 0–1 assignment variable xij, which frequently crops up in the field of operations research, has large‐scale sparsity. The proposed algorithm constructs multiple search trees, makes searches and examines which resource assignments must be changed, and retains information from the search as an arc. Two‐fold “garbage collection” is performed to avoid the fragmentation of the memory necessary for the search, when performing a state space search using multiple search trees. Furthermore, a data structure necessary for the searches, in order to apply the proposed algorithm to a real large‐scale problem, is described. © 2007 Wiley Periodicals, Inc. Syst Comp Jpn, 38(3): 83–91, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10272
Combination of GMM‐based speech estimation method and temporal domain SVD‐based speech enhancement for noise robust speech recognition
Authors: Fujimoto Masakiyo , Ariki Yasuo
Published: February 2007

This study proposes a speech recognition method which is made robust to noise by combining speech signal estimation based on GMM and speech enhancement based on SVD in the temporal domain. Conventional speech signal estimation based on GMM has the problems that the time dependence of the noise is not considered and the performance is degraded in a low‐SNR environment. As regards the first problem, successive updating of the mean noise vector is performed in this study to follow the time variation of the noise. As regards the second problem, an attempt is made to improve performance by improving the SNR beforehand by means of speech enhancement based on SVD in the time domain. Furthermore, in speech enhancement based on SVD in the time domain, the over‐subtraction factor for the noise component is introduced in order to minimize the effect of noise, and adaptive determination of the factor is considered. The proposed method is evaluated using the AURORA2 database, and it is shown that the speech recognition accuracy is improved compared to conventional speech signal estimation based on GMM. © 2007 Wiley Periodicals, Inc. Syst Comp Jpn, 38(3): 23–38, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20487
Probabilistic ISC for matching images of objects having individual difference
Authors: Mita Takeshi , Kaneko Toshimitsu , Hori Osamu
Published: February 2007

This paper considers image matching for objects with individual differences and deformations, such as the human face, and proposes the concept of probabilistic increment sign correlation (ISC) as a new statistic suited to the purpose. Probabilistic ISC is a statistic based on the probability of occurrence of incremental signs calculated from multiple reference images. Since matching is sought considering only the increase or decrease of the spatial brightness, it is less affected by changes of illumination and other factors. In matching, the variation of the incremental sign produced by changes of the object shape and other factors is represented by a probability, and high matching accuracy is achieved by assigning larger weights to features with smaller variation. The computation cost is as low as that of increment sign correlation, and the method is also suited to hardware implementation. It is possible to set the matching threshold analytically on the basis of statistical properties. In order to verify the effectiveness of the proposed method, an experiment was performed to detect a face from 2420 images, and higher detection accuracy was obtained than by methods based on correlation, such as normalized correlation and increment sign correlation, or the subspace method. © 2007 Wiley Periodicals, Inc. Syst Comp Jpn, 38(3): 12–22, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20613
Alliance networks and firm performance: The impact of repeated partnerships
Authors: Goerzen Anthony
Published: February 2007

A phenomenon that has become the focus of recent research on interorganizational alliance network growth is that firms often enter into repeated relationships with prior partners. The implications of this tendency on corporate performance, however, are not well understood. From transaction cost and network perspectives, I test competing hypotheses on a large sample of multinational corporations. My results indicate clearly that firms not only often do enter into repeated equity‐based partnerships but also that those with a greater propensity to do so experience inferior economic performance. Further, statistical tests indicate that the negative effect of repeated partnerships on performance is particularly strong in environments of greater technological uncertainty. Copyright © 2007 John Wiley & Sons, Ltd.
Choice, chance, and inevitability in strategy
Authors: de Rond Mark , Thietart Raymond‐Alain
Published: February 2007

We propose a theory to manage the uneasy relation between strategic choice, chance, and determinism (or inevitability). To do so, we locate arguments in intellectual history that have a clear bearing on this relation. We introduce and defend four conjectures that outline the relationship between each of them and their comparative significance. The paper thus aims at achieving three objectives: (a) to articulate a philosophically sustainable theory of strategic choice that corroborates experience (without being induced by it); (b) to synthesize what remains one of the most sustained debates in strategy, namely the nature, role, and relation of choice, chance and determinism; and (c) to contribute to developing a foundation for multilevel research. Copyright © 2007 John Wiley & Sons, Ltd.