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1.
Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
Beata Filip-Psurska Mateusz Psurski Artur Anisiewicz Patrycja Libako Ewa Zbrojewicz Magdalena Maciejewska Micha Chodyski Andrzej Kutner Joanna Wietrzyk 《International journal of molecular sciences》2021,22(5)
1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. 相似文献
2.
Mauro Zammarano John R. Shields Isaac Leventon Ickchan Kim Shonali Nazare Andre Thompson Rick D. Davis Artur Chernovsky Matthew Bundy 《火与材料》2021,45(1):114-126
Herein, we describe a reduced‐scale test (“Cube” test), measuring the fire performance of specimens including a fire barrier (FB) and a flammable core material, which acts as the main fuel load. The specimen is intended to reproduce a cross‐section of a composite product where heat/mass transfer occurs primarily in a direction perpendicular to the FB. The Cube test procedure and benefits are discussed in this work by adopting residential upholstery furniture as an exemplary study. One flexible polyurethane foam, one polypropylene cover fabric, and 10 commercially available FBs were selected. They were used to compare the fire performance of FBs, measured in terms of peak of heat release rate, in the ASTM E1474‐14 standard test and the newly developed Cube test. Edge effects severely affected the performance of FBs in the ASTM E1474‐14 standard test but not in the Cube test. Furthermore, appropriate test conditions were determined in the Cube test to measure the so‐called “wetting point,” that is, the time and value of heat release rate measured when flammable liquid products were first observed on the bottom of the specimen. The relevance of the “wetting point” in terms of full‐scale fire performance and failure mechanism of FBs is discussed. 相似文献
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Photonic Network Communications - Optical packet switching is a prominent technology proposing not only a reduction in the energy consumption by the elimination of numerous... 相似文献
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We will consider a convex subset of a metric linear space and a certain group of actions G on this set, that allow us to define the notion of Haar zero measure on sets that have zero Haar measure for the translation (by adding) invariant HSY prevalence theory. In this way, we will be able to define the meaning of G-prevalent set according to the pioneering work of Christensen. Our setting considers problems which take into account the convex structure and this is quite different from the previous results on prevalence which consider basically the linear additive structure. In this setting, we will show a kind of quantitative Kupka–Smale theorem, and also we generalize a result about rotation numbers which was first considered by J.-C. Yoccoz (and, also by M. Tsujii). Among other things we present an estimation of the amount of hyperbolicity in a setting that we believe was not considered before. 相似文献
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In this study, the effect of Eucalyptus globulus wood (UE) used as a filler (5–20% w/w) on the physical and thermal properties of high-density polyethylene (HDPE) composites was evaluated. To improve the compatibility with HDPE, the wood was modified (TE) using crude glycerol derived from biodiesel production. The addition of 20% (w/w) of UE or TE led to more rigid and durable composite materials compared to neat HDPE (about 50 or 100% increase in tensile strength, respectively). Composites also revealed 55–75°C higher temperatures at maximal degradation rates. The advantageous behavior of TE over UE in composites was attributed to the improvement of surface morphology of modified wood and it is better compatibility with the HDPE as revealed by surface energy analysis. The changes in wetting behavior of HDPE and ensuing HDPE-TE composites (contact angles of ca 72 and 80°, respectively) explain the matrix-filler interactions. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48619. 相似文献
9.
Bruzda Grzegorz Polkowski Wojciech Polkowska Adelajda Nowak Rafał Kudyba Artur Książek Marzanna Lech Sebastian Karczewski Krzysztof Giuranno Donatella 《Journal of Materials Science》2022,57(28):13724-13735
Journal of Materials Science - Boron-doped molybdenum silicides have been already recognized as attractive candidates for space and ground ultra-high-temperature applications far beyond limits of... 相似文献
10.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds 下载免费PDF全文
Dr. Sandeep Sundriyal Dr. Nicholas A. Malmquist Dr. Joachim Caron Scott Blundell Dr. Feng Liu Xin Chen Nitipol Srimongkolpithak Prof. Jian Jin Prof. Susan A. Charman Prof. Artur Scherf Dr. Matthew J. Fuchter 《ChemMedChem》2014,9(10):2360-2373
Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1 ), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads. 相似文献