bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down‐regulated expression of prostasin in high‐grade or hormone‐refractory human prostate cancers
Authors: Takahashi Satoru , Suzuki Shugo , Inaguma Shingo , Ikeda Yoshihisa , Cho Young‐Man , Hayashi Norio , Inoue Takahiro , Sugimura Yoshiki , Nishiyama Naoki , Fujita Tamio , Chao Julie , Ushijima Toshikazu , Shirai Tomoyuki 
Published: January 2003

AbstractBACKGROUNDWe previously conducted a search for genes which are differentially expressed in hormone‐refractory prostate cancers using cDNA‐representational difference analysis (RDA). The prostasin gene was isolated as one showing down‐regulation in hormone‐refractory cancers. In the present study, linkage to the stage in prostate neoplasia was examined.METHODSProstasin expressions in 54 prostate cancer cases were examined by mRNA in situ hybridization and immunohistochemistry as well as by northern blot analysis.RESULTSExpression levels of prostasin in hormone‐refractory cancers were approximately one‐sixth of those in organ‐confined cancers by northern blotting. Glandular components in benign prostatic hyperplasia and high‐grade prostatic intraepithelial neoplasias tended to exhibit mild to moderate and relatively strong intensities, respectively. Expression levels of both prostasin mRNA and protein were inversely correlated with histological differentiation but not associated with clinical stage of human prostate cancer. Almost all cases of metastatic and hormone‐refractory cancers demonstrated down‐regulation of prostasin expression.CONCLUSIONSThese results suggest that prostasin cannot be regarded as a prognostic indicator for human prostate cancer although it may be a useful marker for tumor differentiation. Prostate 54: 187–193, 2003. © 2002 Wiley‐Liss, Inc.
Quantitation of apoptotic activity following castration in human prostatic tissue in vivo
Authors: Staack Andrea , Kassis Adrienne P. , Olshen Adam , Wang Yuzhuo , Wu David , Carroll Peter R. , Grossfeld Gary D. , Cunha Gerald R. , Hayward Simon W. 
Published: January 2003

AbstractBackgroundAndrogen deprivation induces apoptosis in the prostate. Representative data, quantitating apoptotic activity in human prostatic epithelium following androgen ablation, are lacking.MethodsHuman prostatic tissue was grafted beneath the renal capsule of intact male athymic mice and allowed to become established. The mice were castrated and specimens were harvested on post‐castration day 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 14, 17, 18, and 21. Tissue was immediately fixed and apoptotic epithelial nuclei were identified.ResultsThe percentage of terminal deoxynucleotidyl‐transferase‐mediated dUTP nick end‐labeling (TUNEL) positive epithelial cells increased from a baseline of 0.026%, peaked on post‐castration day 3 (1.54%), and returned to baseline by day 21. Mathematical analysis predicted that the observed apoptotic activity account for the loss of 87% of prostatic epithelial cells in 3 weeks.ConclusionsPost‐castration apoptosis in human prostatic epithelium was low but was sufficient to account for the loss of nearly 90% of epithelial cells. Prostate 54: 212–219, 2003. © 2002 Wiley‐Liss, Inc.
The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer
Authors: Haese Alexander , Graefen Markus , Becker Charlotte , Noldus Joachin , Katz Jared , Cagiannos Ilias , Kattan Michael , Scardino Peter T. , Huland Edith , Huland Hartwig , Lilja Hans 
Published: January 2003

AbstractBackgroundIn recent studies serum levels of human glandular kallikrein 2 (hK2) demonstrated significant differences in pathologically organ‐confined versus non‐organ‐confined prostate cancer (PCa). In this study we investigated whether hK2 adds independent information when considered together with traditionally used parameters to predict organ confined (pT2a/b) PCa.MethodsSerum levels of hK2, total and free prostate‐specific antigens (PSA) were obtained one day before radical prostatectomy in 245 consecutive men. These were included with clinical stage and biopsy Gleason grade into univariate analysis and multivariate logistic regression models.ResultspT2a/b PCa was found in n = 148 patients. In univariate analysis all preoperative parameters demonstrated significant association with the presence of pT2a/b PCa. Using multivariate logistic regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was not. In bootstrap corrected logistic regression based nomograms the addition of hK2 density marginally enhanced predictive accuracy when PSA, PSA density, clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2 density and 0.883 with hK2 density).ConclusionshK2 and hK2 density could independently predict pT2a/b PCa. However, improvement in predictive accuracy was marginal when nomograms based on traditional variables were complemented with this serum marker. Prostate 54: 181–186, 2003. © 2002 Wiley‐Liss, Inc.
Ribozyme‐mediated inhibition of PKCα sensitizes androgen‐independent human prostate cancer cells to cisplatin‐induced apoptosis
Authors: Orlandi Linda , Binda Mara , Folini Marco , Bearzatto Alessandra , Villa Raffaella , Daidone Maria Grazia , Zaffaroni Nadia 
Published: January 2003

AbstractBACKGROUNDTherapeutic strategies to target the molecular basis of hormone and drug resistance of prostate cancer cells are needed. Since protein kinase Cα (PKCα) is thought to have a role in the development of the androgen‐independent phenotype of prostate cancer cells and in apoptosis suppression, the objective of the present study was to test whether specific inhibition of PKCα by a hammerhead ribozyme was able to sensitize androgen‐independent prostate cancer cells the effects of apoptosis‐inducing anticancer drugs.METHODSAn active ribozyme (PKCαRZ) targeting codon 4 in human PKCα mRNA was synthesized by in vitro transcription. A mutant ribozyme (PKCαmutRZ) was also made by deleting G12 from the catalytic core of the active ribozyme and used as a control throughout the study. The double‐stranded, ribozyme‐encoding sequences were then inserted into an expression vector under the control of the cytomegalovirus promoter and delivered to growing prostate cancer cells (DU145 and PC‐3) by a DOTAP‐mediated transfer. A neomycin resistance gene on the vector was used to select ribozyme‐expressing clones. The clones were analyzed for PKCα expression, sensitivity to anticancer drugs and ability to undergo drug‐induced apoptosis.RESULTSTwo DU145‐derived cell clones expressing the active ribozyme (DURZ 2 and DURZ 12) and one clone expressing the catalytically inactive ribozyme (DUmutRZ) were selected for the study. DURZ 2 and DURZ 12 were characterized by a markedly (about 40–50%) lower PKCα protein level than parental DU145 cells, whereas no reduction in PKCα expression was observed in DUmutRZ cells. Results of cytotoxicity experiments indicated that DURZ 2 and DURZ 12 but not DUmutRZ cells were significantly more sensitive than parental DU145 cells to a 1 hr exposure to the mononuclear platinum compounds (cisplatin and oxaliplatin) and showed an increased susceptibility to undergo cisplatin‐induced apoptosis. A significantly enhanced apoptotic response to cisplatin was also observed in a PC‐3‐derived polyclonal cell population endogenously expressing the active ribozyme.CONCLUSIONSResults of the study highlight the importance of PKCα in the response of prostate cancer cells to mononuclear platinum compounds and indicate specific inhibition of the enzyme as a potential therapeutic strategy to sensitize androgen‐independent prostate cancer cells to these drugs. Prostate 54: 133–143, 2003. © 2002 Wiley‐Liss, Inc.
Serum human glandular kallikrein (hK2) and insulin‐like growth factor 1 (IGF‐1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA
Authors: Scorilas Andreas , Plebani Mario , Mazza Saverio , Basso Daniela , Soosaipillai Antoninus R. , Katsaros Nikos , Pagano Francesco , Diamandis Eleftherios P. 
Published: January 2003

AbstractBACKGROUNDThere is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities.METHODSHuman glandular kallikrein 2 (hK2), insulin‐like growth factor‐1 (IGF‐1), free and total PSA concentrations were measured with non‐competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP.RESULTShK2 and IGF‐1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF‐1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 μg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the “gray zone” (4–10 μg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF‐1/free PSA and hK2/free PSA as independent predictors of CaP.CONCLUSIONShK2/free PSA and IGF‐1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy. Prostate 54: 220–229, 2003. © 2002 Wiley‐Liss, Inc.
Experimental therapy of human prostate cancer by inhibiting MDM2 expression with novel mixed‐backbone antisense oligonucleotides: In vitro and in vivo activities and mechanisms
Authors: Wang Hui , Yu Dong , Agrawal Sudhir , Zhang Ruiwen 
Published: January 2003

AbstractBACKGROUNDMDM2 oncogene is overexpressed in many human cancers including prostate cancer and MDM2 levels are associated with poor prognosis. This study was undertaken to investigate the functions of MDM2 oncogene in prostate cancer growth and the value of MDM2 as a drug target for prostate cancer therapy by inhibiting MDM2 expression.METHODSAntisense anti‐human‐MDM2 mixed‐backbone oligonucleotide and its mismatch control were tested in in vitro and in vivo human prostate cancer models (LNCaP, DU 145, and PC‐3) for anti‐tumor activity. Targeted gene products and related proteins were analyzed and the anti‐tumor activity was determined when the oligonucleotides were used alone or in combination with cancer therapeutics.RESULTSThe antisense oligonucleotide specifically inhibited MDM2 expression in a dose‐ and time‐dependent manner, resulting in significant anti‐tumor activity in vitro and in vivo. In LNCaP cells, p53 and p21 levels were elevated. The antisense oligonucleotide also potentiated the effects of p53 activation and p21 induction by chemotherapeutic agents 10‐hydroxycamptothecin, adriamycin, 5‐fluorouracil, and paclitaxel. In DU145 cells, following inhibition of MDM2 expression, p21 levels were elevated although p53 levels remained unchanged. In both cell lines, the antisense oligonucleotide inhibited tumor cell growth and induced apoptosis in vitro. In a dose‐dependent manner, the antisense oligonucleotide showed anti‐tumor activity in nude mice bearing DU145 or PC‐3 xenografts. It significantly increased therapeutic effectiveness of the chemotherapeutic agent irinotecan and slightly improved the effects of paclitaxel and Rituxan.CONCLUSIONSThese results indicate that MDM2 has a role in prostate tumor growth through both p53‐dependent and p53‐independent mechanisms, indicating that MDM2 inhibitors have a broad spectrum of anti‐tumor activities in human prostate cancers regardless of p53 status. Prostate 54: 194–205, 2003. © 2002 Wiley‐Liss, Inc.
Bioequivalence and the pharmaceutical industry
Authors: Patterson Scott D. , Jones Byron 
Published: January 2003

AbstractSince the early 1990s, average bioequivalence (ABE) studies have served as the international regulatory standard for demonstrating that two formulations of drug product will provide the same therapeutic benefit and safety profile when used in the marketplace. Population (PBE) and individual (IBE) bioequivalence have been the subject of intense international debate since methods for their assessment were proposed in the late 1980s and since their use was proposed in United States Food and Drug Administration guidance in 1997.Guidance has since been proposed and finalized by the Food and Drug Administration for the implementation of such techniques in the pioneer and generic pharmaceutical industries. The current guidance calls for the use of replicate design and of cross‐over studies (cross‐overs with sequences TRTR, RTRT, where T is the test and R is the reference formulation) for selected drug products, and proposes restricted maximum likelihood and method‐of‐moments techniques for parameter estimation. In general, marketplace access will be granted if the products demonstrate ABE based on a restricted maximum likelihood model. Study sponsors have the option of using PBE or IBE if the use of these criteria can be justified to the regulatory authority. Novel and previously proposed SAS®‐based approaches to the modelling of pharmacokinetic data from replicate design studies will be summarized.Restricted maximum likelihood and method‐of‐moments modelling results are compared and contrasted based on the analysis of data available from previously performed replicate design studies, and practical issues involved in the application of replicate designs to demonstrate ABE are characterized.It is concluded that replicate designs may be used effectively to demonstrate ABE for highly variable drug products. Statisticians should exercise caution in the choice of modelling procedure. Copyright © 2002 John Wiley & Sons, Ltd.
Dealing with selective dropout in clinical trials
Authors: Möcks Joachim , Köhler Walter , Scott Martin , Maurer Joerg , Budde Michael , Givens Sam 
Published: January 2003

AbstractClinical trials in severely diseased populations often suffer from a high dropout rate that is related to the investigated target morbidity. These dropouts can bias estimates and treatment comparisons, particularly in the event of an imbalance. Methods to describe such selective dropout are presented that use the time in study distribution to generate so‐called population evolution charts. These charts show the development of a distribution of a covariate or the target morbidity measure as it changes as a result of the dropout process during the follow‐up time. The selectiveness of the dropout process with respect to a variable can be inferred from the change in its distribution. Different types of selective dropout are described with real data from several studies in metastatic bone disease, where marked effects can be seen. A general strategy to cope with selective dropout seems to be the inclusion of dropout events into the endpoint. Within a time‐to‐event analysis framework this simple approach can lead to valid conclusions and still retains conservative elements. Morbidity measures that are based on (recurrent) event counts react differently in the presence of selective dropout. They differ mainly in the way dropout is included. One simple measure achieves good performance under selective dropout by introducing a non‐specific penalty for premature study termination. The use of a prespecified scoring system to assign a weight for each works well. This simple and transparent approach performs well even in the presence of unbalanced selective dropout. Copyright © 2002 John Wiley & Sons, Ltd.
Changing times in pharmaceutical statistics: 2000‐2020
Authors: Day Simon 
Published: January 2003

AbstractIn a previous paper we considered how pharmaceutical statistics had changed between 1980 and 2000. In this paper we go on to consider some of the likely influences and changes in the world of pharmaceutical statistics over the next twenty years. Statistical research by pharmaceutical companies is supported, although its direct value in boosting company profits is challenged. The duality between fraud and conflict of interest is explored, particularly with regard to data and safety monitoring boards. Political correctness within clinical trials and (allegedly) better patient‐oriented outcomes is questioned and the whole notion of intention‐to‐treat and per‐protocol analyses is rejected in favour of pragmatic trials and explanatory trials. The dominance of SAS software within the industry is explored and the possibility for change considered. Finally, whilst the future of pharmaceutical companies is not addressed, the impact of future mergers, collaborations and take‐overs between clinical research organizations is considered. Copyright © 2002 John Wiley & Sons, Ltd.
Low‐energy electron diffraction study of atomic structure of Sc–O/W(100) surface acting as Schottky emitter at high temperatures
Authors: Iida S. , Tsujita T. , Nagatomi T. , Takai Y. 
Published: January 2003

AbstractLow‐energy electron diffraction (LEED) was used to investigate the atomic structure of an Sc–O/W(100) surface acting as a Schottky emitter in order to elucidate a marked reduction in the work function of the Sc–O/W(100) Schottky emitter surface. The results of our LEED observation of the Sc–O/W(100) surface at room temperature revealed that a p(2 × 1) and p(1 × 2) double‐domain structure is formed on the surface. This reconstructed structure exhibited no changes when heated to 1400 K, and continued to remain stable even when held at 1400 K. These results strongly suggest that the p(2 × 1) and p(1 × 2) double‐domain structure is formed by scandium–oxygen electric dipoles on the W(100) surface, leading to a marked reduction in the work function of the Sc–O/W(100) surface at the operating temperature of the Sc–O/W(100) Schottky emitter. Copyright © 2003 John Wiley & Sons, Ltd.
Electron emission characteristics of ZrO/W electron sources with a wide range of tip radii
Authors: Sakawa Seiichi , Tsunoda Katsuyoshi , Terui Yoshinori 
Published: January 2003

AbstractEmitters of ZrO/W with a wide range of tip radii (0.43–4.2 µm) were prepared and evaluated. A unique tip‐forming method using local Joule heating was developed to make the tip radii >2 µm. The tip radius dependency of the energy spread agrees qualitatively with the energy spread calculated by Knauer's formula when evaluating the Boersch effect. Emitters with tip radii >2 µm show their energy spread to be close to the theoretically predicted energy spread without the Boersch effect. Even at 400 µA sr−1 operation, the emitter with a 4.2 µm tip radius shows a 0.47 eV full width at half‐maximum (FWHM) energy spread and the emitter with a 0.43 µm tip radius shows a 0.98 eV FWHM energy spread. Emitters with tip radii >2 µm, fabricated by local Joule heating, are expected to suppress chromatic aberration in low beam voltage application and thus would be helpful for industrial uses such as critical dimension and defect review SEM. Copyright © 2003 John Wiley & Sons, Ltd.
Structural characterization of randomly and vertically oriented carbon nanotube films grown by chemical vapour deposition
Authors: Ikuno Takashi , Furuta Hiroshi , Yamamoto Tetsuro , Takahashi Syunji , Kamizono Motoki , Honda Shin‐ichi , Katayama Mitsuhiro , Hirao Takashi , Oura Kenjiro 
Published: January 2003

AbstractWe have investigated the structures of randomly and vertically oriented carbon nanotubes grown by thermal chemical vapour deposition and dual‐r.f.‐plasma‐enhanced chemical vapour deposition, respectively. The randomly oriented carbon nanotubes have a bamboo‐like structure, whereas the vertically oriented carbon nanotubes have a multi‐shell shape. Both types of nanotubes have a metal nanoparticle at the tip. The field emission property of the randomly oriented nanotube films was better than that of the vertically oriented nanotube films. This result indicates that more emission sites exist at the body than at the tip of the nanotubes. Copyright © 2003 John Wiley & Sons, Ltd.
High‐resolution AES study of Ar+‐irradiated graphite
Authors: Hashimoto Hiroyuki , Watanabe Masatoshi , Nishiuma Satoru , Nakamura Kumi , Yoshida Shigeki 
Published: January 2003

AbstractHigh‐resolution AES (HR‐AES) has been used to study the electronic state of Ar+‐irradiated graphite in which the increase in the partial charge density caused by the lattice damage has been indicated. At doses of <5 × 1011 Ar+ cm−2, which was reported as a maximum value to avoid the overlapping cascades, neither plasmon energies nor the work function in highly oriented pyrolytic graphite (HOPG) was changed. Increase in the work function was observed in Ar+‐irradiated graphite with doses in the range of ∼1 × 1013 to 1 × 1015 ions cm−2, and Ar+ at a dosage of 3 × 1014 ions cm2 increased the work function of HOPG by ∼0.2 eV. This implies an increase in the average electron density at the surface or an increase in the local electron density at a torn graphite edge. The π plasmon energy was decreased by an irradiation of >1 × 1014 Ar+ cm−2 and the π + σ plasmon energy was decreased slightly at >1 × 1015 Ar+ cm−2. The difference in the two energy variations in the range of 1 × 1014 to 1 × 1015 Ar+ cm−2 shows that the possibility of changes in the resonance energy and/or the lattice parameters is present if the π/σ electron ratio does not change. Copyright © 2003 John Wiley & Sons, Ltd.
Copper nanostructure formation and structure analysis on hydrogen‐terminated Si(111) surface
Authors: Kuroiwa N. , Fukushima Y. , Rajasekar P. , Neddermeyer H. , Jalochowski M. , Bauer E. , Yasue T. , Koshikawa T. 
Published: January 2003

AbstractThe growth of Cu nanostructures on the hydrogen‐terminated Si(111) surface was studied by scanning tunnelling microscopy (STM). On the hydrogen‐terminated Si(111) surface, small Cu nanostructures scatter mainly on the terraces and a few structures along the steps and domain boundaries at a deposition temperature of ∼310°C: the shape of the nanostructure is round or triangular, and the face is not clear. At ∼340°C, the Cu nanostructures form preferentially at steps and domain boundaries of the substrate: the shape is triangular with truncated corners and the nanostructures have some facets. The top face has an inclination angle of ∼6° and the side face has one of ∼35°. On the top face, mono‐atomic steps can be seen ∼0.8 nm apart. From these results, it is concluded that the Cu nanostructure has a {554} facet on top and a {110} facet on the side. Copyright © 2003 John Wiley & Sons, Ltd.
Formation of promising Co–C nanocompositions
Authors: Lavrentiev V. , Abe H. , Yamamoto S. , Naramoto H. , Narumi K. 
Published: January 2003

AbstractEncapsulation of Co nanoparticles ∼20 nm in size by C60‐based substances has been realized by simultaneous deposition of cobalt (electron beam evaporation) and C60 fullerene (thermal sublimation) on (0001) α‐Al2O3 and (001) NaCl substrates at room temperature under 10−5 Pa. Sharp hills 20 nm above the film surface were detected by atomic force microscopy and scanning electron microscopy. Electron diffraction analysis revealed the existence of diamond near distorted fcc Co crystals. Graphite, Co2C and Co3C carbides also have been found. Raman spectra confirm the appearance of diamond and graphite in an as‐deposited Co + C60 mixed film. The behaviour of the main Raman modes reflects the formation of Co–C60 polymeric chains during co‐deposition. Analysis of Raman spectra discovered a pronounced growth of diamond and single‐wall carbon nanotubes during annealing of the Co + C60 mixed film even at 300°C. The formation of these promising nanostructures is discussed. Copyright © 2003 John Wiley & Sons, Ltd.