1,721,274 research outputs found
[Sabahaddin Ergi tarafından Sabiha Bozcalı'ya gönderilen mektup]
No full textTaha Toros Arşivi, Dosya No: 8-Sabiha Bozcalı.
Not: Ekte fotoğraflar ve kartpostallar bulunmaktadır.İstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033
New Selective Inhibitors of ERG Positive Prostate Cancer: ERGi-USU6 Salt Derivatives
No full textProstate
cancer is among the leading causes of cancer related death
of men in the United States. The ERG gene fusion
leading to overexpression of near full-length ERG transcript and protein represents most prevalent (50–65%)
prostate cancer driver gene alterations. The ERG oncoprotein overexpression
persists in approximately 35% of metastatic castration resistant prostate
cancers. Due to the emergence of eventual refractoriness to second-
and third-generation androgen axis-based inhibitors, there remains
a pressing need to develop drugs targeting other validated prostate
cancer drivers such as ERG. Here we report the new and more potent
ERG inhibitor ERGi-USU-6 developed by structure–activity studies
from the parental ERGi-USU. We have developed an improved procedure
for the synthesis of ERGi-USU-6 and identified a salt formulation
that further improves its activity in biological assays for selective
targeting of ERG harboring prostate cancer cells
Abstract 1183: Structure-activity studies and biological evaluations of ERGi-USU, a highly selective inhibitor for ERG-positive prostate cancer cells
No full textAbstract
Introduction and objectives: While new prostate cancer (CaP) treatments (Abiraterone and Enzalutamide) have improved survival in castration-resistant prostate cancer (CRPC), their benefits are short-lived and drug resistance develops likely due to numerous adaptive mutations. Therefore it is a critical to develop effective novel inhibitors to target other signaling pathways that promote or contribute to prostate tumorigenesis. Accumulating evidence has established the androgen regulated TMPRSS2-ERG fusion as a common oncogenic driver that contributes to the early development and progression of over half of CaP. Therefore, ERG oncoprotein and ERG dependent pathways are promising targets for CaP therapy in early stages when cancer is most responsive to treatment. We previously identified a small molecule inhibitor, ERGi-USU, which selectively inhibits ERG protein and cell growth in ERG positive tumor cell lines and mouse xenograft models. In an effort to further develop ERGi-USU with enhanced efficacy we performed detailed structure-activity relationship (SAR) evaluation of ERGi-USU core structure and developed new derivatives.
Methods: Based on SAR of the core structure of ERGi-USU, 48 new derivatives were designed and synthesized by substitutions with alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or hydroxyl groups. The new ERGi-USU derivatives were evaluated for inhibition of cell growth and ERG protein levels in the TMPRSS2-ERG fusion harboring CaP cell line, VCaP. Four of these compounds have been selected for evaluation of ERG selectivity by defining IC50 in ERG positive malignant cells (VCaP, KG1, MOLT-4 and COLO320), ERG negative CaP cell line (LNCaP) or ERG positive normal primary endothelium-derived cells (HUVEC).
Result: Like parental compound, four new ERGi-USU derivatives exhibited inhibition of cell growth and ERG protein levels in ERG positive VCaP, KG1, MOLT-4 and COLO320 cell lines, with no or minimal effects on LNCaP and HUVEC cells. One of the new derivatives (ERGi-USU#6) showed increased efficacy for cell growth inhibition (IC50=0.074µM) compared to the parental ERGi-USU (IC50=0.200µM). Other three new compounds showed similar IC50 as the ERGi-USU.
Conclusion: Comprehensive evaluation of ERGi-USU derivatives along with parental compound has continued to underscore selective inhibition of ERG positive tumor cells by these small molecules.
Citation Format: Ahmed A. Mohamed, Charles P. Xavier, Gauthaman Sukumar, Samuel D. Banister, Vineet Kumar, Shyh-Han Tan, Shilpa Katta, Lakshmi Ravindranath, Muhammad Jamal, Taduru Sreenath, David G. McLeod, Gyorgy Petrovics, Albert Dobi, Meera Srivastava, Sanjay Malhotra, Clifton Dalgard, Shiv Srivastava. Structure-activity studies and biological evaluations of ERGi-USU, a highly selective inhibitor for ERG-positive prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1183. doi:10.1158/1538-7445.AM2017-1183</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Jafnsnjallr sem geit, es í augu leit. Um Bjarnar sögu Hítdælakappa, aldur, ástir, níð og ergi
No full textÞessi ritgerð er lögð fram til B.A.- prófs í íslensku við Hugvísindasvið Háskóla Íslands. Umfjöllunarefni ritgerðarinnar er Bjarnar saga Hítdælakappa.
Aldur Bjarnar sögu Hítdælakappa hefur lengi verið deiluefni fræðimanna. Margir hafa talið hana til elstu Íslendinga sagna, þar á meðal Sigurður Nordal sem álítur hana eina af þeim þremur elstu. Í ritgerðinni er fjallað um aldurinn og þær kenningar sem settar hafa verið fram til að aldursgreina ekki bara Bjarnar sögu heldur Íslendinga sögur almennt. Því verður haldið fram að vísurnar séu sennilega eldri en sagan eins og hún er varðveitt. Í ritgerðinni eru vísurnar í brennidepli. Það eru nokkrar ástarvísur í Bjarnar sögu og verða þær skoðaðar, því það er ástarþríhyrningur þriggja aðalpersóna sögunnar, sem hrindir af stað atburðarás sögunnar. Ástarþríhyrningurinn verður til þess að aðalkarlpersónurnar þeir Björn Arngeirsson og Þórður Kolbeinsson takast á með vísnagerð sinni. Þessar vísur eru uppfullar af níði og ásökunum um ergi en hvort tveggja verður sérstaklega skoðað og reynt að varpa ljósi á það. Umfjöllunin um níð og ergi er í þrennu lagi. Fyrst verður fjallað almennt um þau og sagt frá rannsóknum á þeim en síðan rætt um valdar vísur
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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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