1,720,965 research outputs found
Immunohistochemical quantitation of androgen receptor expression using color video image analysis
No full textBackground: The immunostaining features of the androgen receptor (AR) have been studied in prostate cancer (CaP) to predict the outcome of androgen deprivation therapies. We have developed an automatic video color image analysis system for quantitation of AR expression in large samples of prostatic nuclei. Methods: Essential criteria of immunostaining have been examined to establish a linear relationship between AR protein content and mean optical density (MOD) of the immunoperoxidase-substrate reaction product. Titration of monoclonal AR antibody, F39.4.1, and concentration and reaction time of substrate were optimized using color video image analysis. The methodology was tested twice. First, CWR22 human CaP xenograft specimens, harvested from testosterone (T)-stimulated, castrated and T-resupplemented mice, were immunostained to demonstrate the dependence of AR expression on serum androgen levels. Second, AR expression was measured in archived clinical specimens. Results: In CWR22 tumor-bearing mice castrated for 6 days, AR MOD decreased to 57% of T-stimulated, intact mice. After 72 hrs of T treatment, AR MOD returned to the level measured in T-stimulated, intact mice. Sixteen radical prostatectomy specimens and 16 transurethral resection of prostate (TURP) specimens were double-labeled with F39.4.1 and anti-cytokeratin MAb (13 beta E12) specific for basal epithelial cells. Benign epithelial cells exhibited lower AR MOD in prostatectomy compared to TURF specimens (P < 0.01). Differences in AR immunostaining intensity may have resulted from differences in tissue fixation of whole organ versus small tissue specimens. Conclusions: AR immunostaining can be quantitated accurately using optimized immunohistochemical criteria and video image analysis. Cytometry 35:2-10, 1999. (C) 1999 Wiley-Liss, Inc
Androgen receptor gene amplification and protein expression in recurrent prostate cancer
No full textPurpose: The androgen receptor (AR) is highly expressed in androgen dependent and recurrent prostate cancer, suggesting that it has a role in tumor growth and progression after androgen deprivation. AR amplification may contribute to androgen receptor activation in relative androgen absence. Materials and Methods: Formalin fixed and frozen specimens of recurrent prostate cancer were obtained by transurethral resection from men with increasing serum level of prostate specific antigen in whom urinary retention developed. AR amplification and X-chromosome number were determined by 2-color fluorescence in situ hybridization, and AR protein expression was determined by automated image analysis. We compared clinical characteristics and survival of patients with recurrent prostate cancer whose tumors did or did not exhibit AR amplification and X-chromosome polysomy. Results: Thirty-three percent of the 24 recurrent prostate cancer specimens 8 (33%) showed AR amplification. AR was more intensely immunostained in tumors with amplified (AMP) AR (mean optical density 0.36 +/- 0.07) than in tumors lacking amplification (NO AMP) (mean optical density 0.24 +/- 0.09). No differences were found between the 2 groups when comparing serum levels of prostate specific antigen (AMP 11.9, 14.8; NO AMP 26.0, 60.3), Gleason sum (AMP 9.0, 0.5; NO AMP 9.0, 1.0), clinical TNM stage (AMP 4 cases MO, M1 4; NO AMP 8 MO, 8 M1), race (AMP 6 white and 2 black men, NO AMP white and 7 black men) or survival in months (AMP 47.5, 28.5; NO AMP 33.5, 72.0). Three of the recurrent prostate cancer specimens (13%) demonstrated X-chromosome copy number 2 or greater and no differences were found when comparing clinical characteristics between these groups. Conclusions: AR amplification in recurrent prostate cancer results in higher levels of AR protein expression but does not affect survival
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft
No full textThe insulin-like growth factor (IGF) binding proteins IGFBPs are important modulators of IGF action in many tissues including human prostate. IGFBPs and the androgen receptor (AR) are expressed in CWR22, an androgen-dependent epithelial cell human CaP xenograft that retains biological characteristics of human CaPs, including regression following androgen withdrawal and recurrent growth of AR-containing cells in the absence of testicular androgens beginning several months after castration. Northern blot and in situ hybridization analyses demonstrated that IGFBP-5 is androgen-regulated in CWR22. IGFBP-5 messenger RNA (mRNA) decreased by 90% following castration of tumor-bearing mice compared with noncastrate androgen-stimulated mice. Testosterone treatment of CWR22 tumor-bearing mice 6 or 12 days after castration increased IGFBP-5 mRNA 10- to 12-fold. Levels of other IGFBP mRNAs did not change following androgen withdrawal and replacement. IGFBP-5 protein in tumor extracts bound I-125-labeled IGF-I in ligand blot assays and the amounts of IGFBP-5 measured by immunoblotting paralleled the levels of IGFBP-5 mRNA Androgen-induced expression of IGFBP5 was at a maximum level within 24 h after testesterone replacement, whereas the major increase in cell proliferation as measured by Ki-67 immunostaining occurred between 24-48 h. This time course suggested IGFBP-5 may be a mediator of androgen-induced growth of CWR22. In tumors that recurred several months following castration, IGFBP-5 mRNA and protein increased to levels that approached those in androgen-stimulated CWR22 tumors From noncastrate mice. IGFBP-5 immunohistochemical staining of prostate tissue specimens from patients was stronger in androgen-dependent and androgen-independent CaP than in areas of intraepithelial neoplasia (PIN) or benign prostatic hyperplasia (BPH). IGFBP-5 mRNA in these specimens was localized predominantly to stromal cells and IGFBP-5 protein to epithelial cell membranes
Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes
No full textThe human prostate cancer (CaP) xenograft, CWR22, mimics human Cap, CWR22 grows in testosterone-stimulated nude mice, regresses after castration, and recurs after 5-6 months in the absence of testicular androgen. Like human Cap that recurs during androgen deprivation therapy, the recurrent CWR22 expresses high levels of androgen receptor (AR), Immunohistochemical, Western, and Northern blot analyses demonstrated that AR expression in the androgen-independent CWR22 is similar to AR expression in the androgen-dependent CWR22 prior to castration. Expression of prostate-specific antigen and human kallikrein-2 mRNAs, two well-characterized androgen-regulated genes in human Cap, was androgen dependent in CWR22. Despite the absence of testicular androgen, prostate-specific antigen and human kallikrein-2 mRNA levels in recurrent CWR22 were higher than the levels in regressing CWR22 tumors from 12-day castrate mice and similar to those in the androgen-stimulated CWR22. Other AR-regulated genes followed a similar pattern of expression. Differential expression screening identified androgen regulation of alpha-enolase and alpha-tubulin as well as other unknown mRNAs, Insulin-like growth factor binding protein-5, the homeobox gent Nkx 3.1, the AR coactivator ARA-70, and cell cycle genes Cdk1 and Cdk2 were androgen regulated in CWR22, In recurrent CWR22, the steady-state levels of all these AR-dependent mRNAs were similar to those in the androgen-stimulated CWR22, despite the absence of testicular androgen. Expression of AR and AR-regulated genes in the androgen-deprived recurrent CWR22 at levels similar to the androgen-stimulated CWR22 suggests that AR is transcriptionally active in recurrent CWR22, Induction of these AR-regulated genes may enhance cellular proliferation in relative androgen absence but through an AR-dependent mechanism. Alternatively, in androgen-independent tumors, induced expression of the AR-regulated gene network might result from a non-AR transcription control mechanism common to these genes
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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