| 1. |
- Simões, Bruno M, et al.
(författare)
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Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity.
- 2015
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 12:12, s. 1968-1977
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancers (BCs) typically express estrogen receptors (ERs) but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC) activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX) tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.
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| 2. |
- Buyukeksi, Sebile Isik, et al.
(författare)
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Electron/energy transfer studies on hybrid materials based on dinuclear coordination compounds of twisted perylene diimide
- 2019
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Ingår i: Journal of Photochemistry and Photobiology A: Chemistry. - : Elsevier BV. - 1010-6030. ; 372, s. 226-234
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Tidskriftsartikel (refereegranskat)abstract
- To understand the influence of transition metal ion coordination on the properties and performance of the triads, the symmetric bridging ligand, 1,10-phenanthroline-perylene diimide-1,10-phenanthroline, 1,10-Phen-PDI-1,10-Phen (1) comprising four electron-donating 4-methoxyphenoxy bulky groups at bay-positions and its corresponding square-planar coordination compounds with dichloroplatinum(II), [{PtCl2}(2)-1] (2) and palladium(II) [{PdCl2}(2)-1] (3) were prepared in order to tune the photochemical and optical properties of these hybrid materials. These triads show strong electronic absorption bands attributed to the PDI and M(II)(1,10-Phen)Cl-2 moieties in DMSO. UV-vis absorption spectra of the compounds were calculated using Time-Dependent Density Functional Theory (TDDFT) for the ground state optimized structures in DCM. Current results indicate that 2 has the lowest HOMO-LUMO gap (2.29 eV in DCM) among the investigated molecules. The energy and charge transfer processes with tailoring molecular structures are one of the important strategies for the design of future functional triads based on donor and acceptor moieties for hybrids optoelectronic devices. Thus, we studied linear absorption, fluorescence, and ultrafast transient absorption spectra measurements for the triads in DCM to investigate the impact of different functionalization strategies on the optical characteristics, photo-stability, and photo-induced charge-transfer (CT) processes. The observed ultrafast intramolecular charge transfer from donor units to acceptor part of 1-3 is related to fluorescence quenching and faster singlet state decay on transient absorption measurements. The intramolecular charge transfer mechanism was also compared with the unsymmetrical counterparts that were investigated previously. Symmetrical compounds exhibit faster charge transfer in comparison with the unsymmetrical compounds.
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| 3. |
- Huri, Emre, et al.
(författare)
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Evaluation of Residencies in Turkey The First Report of the ESRU Questionnaire in the Europe Home Version
- 2009
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Ingår i: UROLOGIA INTERNATIONALIS. - : S. Karger AG. - 0042-1138 .- 1423-0399. ; 83:2, s. 206-210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to evaluate the general status of last-year residents in Turkey by filling in the questionnaire Evaluation of Residencies in Europe. Subjects and Methods: The questionnaire `Evaluation of Residencies in Europe, designed by the European Society of Residents in Urology (ESRU), was applied to 91 last-year urology residents. It consisted of 7 sections; Introduction, Membership, Residency, Life and Financial Conditions, Future Practice, Training and Research Activities and Contribution to Scientific Literature. The results were determined and reviewed as well. Statistical analysis was performed using ANOVA and the Kruskal-Wallis Test. Results: More than 40 parameters were evaluated. The level of English was average or good for 86%. Half of the residents were aware of ESRU activities, 91% knew national ESRU representatives. Fifty-seven percent of the residents wanted to subspecialize in urology, nephrectomy or andrology, and general urology procedures had a high rate being performed by a first surgeon. Transurethral prostate resection, transurethral resection of bladder and extracorporeal shock wave lithotripsy were well known, with a rate of 76%. Conclusions: Although the Turkish resident number is one of the most excessive in Europe, we have a well-trained homogenous resident group especially in the field of endourology; most of those in the last year of their training period were satisfied with their general condition.
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