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https://www.readbyqxmd.com/read/28103614/enrichment-of-putative-pax8-target-genes-at-serous-epithelial-ovarian-cancer-susceptibility-loci
#1
Siddhartha P Kar, Emily Adler, Jonathan Tyrer, Dennis Hazelett, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Natalia Bogdanova, Louise Brinton, Ralf Butzow, Ian Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Jennifer Anne Doherty, Thilo Dörk, Matthias Dürst, Diana Eccles, Peter A Fasching, James Flanagan, Aleksandra Gentry-Maharaj, Rosalind Glasspool, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, David G Huntsman, Allan Jensen, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Douglas A Levine, Qiyuan Li, Jolanta Lissowska, Karen H Lu, Jan Lubiński, Leon F A G Massuger, Valerie McGuire, Iain McNeish, Usha Menon, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, James Paul, Celeste L Pearce, Tanja Pejovic, Jennifer B Permuth, Catherine Phelan, Malcolm C Pike, Elizabeth M Poole, Susan J Ramus, Harvey A Risch, Mary Anne Rossing, Helga B Salvesen, Joellen M Schildkraut, Thomas A Sellers, Mark Sherman, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa Southey, Kathryn L Terry, Shelley S Tworoger, Christine Walsh, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Hannah Yang, Wei Zheng, Argyrios Ziogas, Matthew L Freedman, Simon A Gayther, Paul D P Pharoah, Kate Lawrenson
BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals)...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28103509/3-5-dihydroxy-3-4-7-trimethoxyflavone-induces-er-stress-associated-hct-116-programmed-cell-death-via-redox-signaling
#2
Mahendra Pal Singh, Jaehong Han, Sun Chul Kang
Quercetin, a well cognized bioactive flavone possessing great medicinal value, has limited usage. The rapid gastrointestinal digestion of quercetin is also a major obstacle for its clinical implementation due to low bioavailability and poor aqueous solubility. 3',5-dihydroxy-3,4',7-trimethoxyflavone (DTMF), a novel semi-synthetic derivative of quercetin, is known to modulate several biological activities. Therefore, in the present study we examined the cytotoxic mechanism of DTMF in concentration-dependent manner (25, 50, and 100μM; 24h) against HCT-116 human colon carcinoma cells...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28103505/hesperetin-protects-against-h2o2-triggered-oxidative-damage-via-upregulation-of-the-keap1-nrf2-ho-1-signal-pathway-in-arpe-19-cells
#3
Chao Zhu, Yuchen Dong, Haile Liu, Hua Ren, Zhihua Cui
Age-related macular degeneration (AMD) is an irreversible vision loss disease that primarily results from oxidative stress that causes oxidative damage to the retinal pigment epithelial (RPE) cells. Hesperetin (Hesp) is a common flavanone glycoside compound that has been demonstrated to exhibit a variety of biological and pharmacological properties that include anti-inflammatory and antioxidant properties. The aim of this study is to explore the ability of Hesp to attenuate oxidative damage in hydrogen peroxide (H2O2)-stimulated ARPE-19 cells...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28103441/enantio-specific-allosteric-modulation-of-cannabinoid-1-receptor
#4
Robert B Laprairie, Pushkar M Kulkarni, Jeffrey R Deschamps, Melanie E M Kelly, David R Janero, Maria G Cascio, Lesley A Stevenson, Roger G Pertwee, Terry Kenakin, Eileen M Denovan-Wright, Ganesh A Thakur
The cannabinoid 1 receptor (CB1R) is one of the most widely expressed metabotropic G protein-coupled receptors in brain, and its participation in various (patho)physiological processes has made CB1R activation a viable therapeutic modality. Adverse psychotropic effects limit the clinical utility of CB1R orthosteric agonists and have promoted the search for CB1R positive allosteric modulators (PAMs) with the promise of improved drug-like pharmacology and enhanced safety over typical CB1R agonists. In this study, we describe the synthesis and in vitro and ex vivo pharmacology of the novel allosteric CB1R modulator GAT211 (racemic) and its resolved enantiomers, GAT228 (R) and GAT229 (S)...
January 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28103248/effect-of-the-latent-reservoir-on-the-evolution-of-hiv-at-the-within-and-between-host-levels
#5
Hilje M Doekes, Christophe Fraser, Katrina A Lythgoe
The existence of long-lived reservoirs of latently infected CD4+ T cells is the major barrier to curing HIV, and has been extensively studied in this light. However, the effect of these reservoirs on the evolutionary dynamics of the virus has received little attention. Here, we present a within-host quasispecies model that incorporates a long-lived reservoir, which we then nest into an epidemiological model of HIV dynamics. For biologically plausible parameter values, we find that the presence of a latent reservoir can severely delay evolutionary dynamics within a single host, with longer delays associated with larger relative reservoir sizes and/or homeostatic proliferation of cells within the reservoir...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28103242/genome-wide-binding-of-posterior-hoxa-d-transcription-factors-reveals-subgrouping-and-association-with-ctcf
#6
Ivana Jerković, Daniel M Ibrahim, Guillaume Andrey, Stefan Haas, Peter Hansen, Catrin Janetzki, Irene González Navarrete, Peter N Robinson, Jochen Hecht, Stefan Mundlos
Homeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox genes are expressed in overlapping patterns and function in a partially redundant manner. In vitro biochemical screens probing the HOX-TF sequence specificity revealed largely overlapping sequence preferences, indicating that co-factors might modulate the biological function of HOX-TFs. However, due to their overlapping expression pattern, high protein homology, and insufficiently specific antibodies, little is known about their genome-wide binding preferences...
January 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28103115/involvement-of-autophagy-in-nk-cell-development-and-function
#7
Alejandro López-Soto, José Manuel Bravo-San Pedro, Guido Kroemer, Lorenzo Galluzzi, Segundo Gonzalez
Natural killer (NK) cells are the prototypical members of the recently identified family of innate lymphoid cells (ILCs). Thanks to their cytotoxic and secretory functions, NK cells play a key role in the immune response to cells experiencing various forms of stress, including viral infection and malignant transformation. Autophagy is a highly conserved network of degradative pathways that participate in the maintenance of cellular and organismal homeostasis as they promote adaptation to adverse microenvironmental conditions...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28103033/design-synthesis-and-biological-evaluation-of-small-high-affinity-siglec-7-ligands-toward-novel-inhibitors-of-cancer-immune-evasion
#8
Horst Prescher, Martin Frank, Stephan Gütgemann, Elena Kuhfeldt, Astrid Schweizer, Lars Nitschke, Carsten Watzl, Reinhard Brossmer
Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28103008/quantitative-tracking-of-combinatorially-engineered-populations-with-multiplexed-binary-assemblies
#9
Ramsey Zeitoun, Gur Pines, William C Grau, Ryan T Gill
Advances in synthetic biology and genomics have enabled full-scale genome engineering efforts on laboratory timescales. However, the absence of sufficient approaches for mapping engineered genomes at system-wide scales onto performance has limited the adoption of more sophisticated algorithms for engineering complex biological systems. Here we report on the development and application of a robust approach to quantitatively map combinatorially engineered populations at scales up to several dozen target sites...
January 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28102829/absorbed-dose-evaluation-of-auger-electron-emitting-radionuclides-impact-of-input-decay-spectra-on-dose-point-kernels-and-s-values
#10
Nadia Falzone, Boon Lee, José Fernández-Varea, Christiana Kartsonaki, Andrew Stuchbery, Tibor Kibedi, Katherine Vallis
AIM: The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model <i>BrIccEmis</i> on dose point kernels (DPKs- radial dose distribution around a unit point source) and <i>S</i>-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely <sup>67</sup>Ga, <sup>80m</sup>Br, <sup>89</sup>Zr, <sup>90</sup>Nb, <sup>99m</sup>Tc, <sup>111</sup>In, <sup>117m</sup>Sn, <sup>119</sup>Sb, <sup>123</sup>I, <sup>124</sup>I, <sup>125</sup>I, <sup>135</sup>La, <sup>195m</sup>Pt and <sup>201</sup>Tl...
January 19, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28102757/dysbiosis-in-crohn-s-disease-joint-action-of-stochastic-injuries-and-focal-inflammation-in-the-gut
#11
Ludovica F Buttó, Dirk Haller
Gut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets...
January 19, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#12
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#13
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102666/a-simulation-approach-for-timing-analysis-of-genetic-logic-circuits
#14
Hasan Baig, Jan Madsen
Constructing genetic logic circuits is an application of synthetic biology, where parts of the DNA of a living cell are engineered to perform a dedicated Boolean function triggered by appropriate concentration levels of certain proteins or by different genetic components. These logic circuits work in a manner similar to electronic logic circuits, but are much more stochastic and hence much harder to characterize. In this paper, we introduce an approach to analyze the threshold value and timing of genetic logic circuits...
January 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28102575/bcl-2-family-in-non-small-cell-lung-cancer-its-prognostic-and-therapeutic-implications
#15
Ping-Li Sun, Hironobu Sasano, Hongwen Gao
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Despite significant advances in its research of tumor biology and therapy, the prognosis for this neoplasm has still remained poor. The great majority of anticancer agents, regardless of their mechanisms of action, exert their lethal actions on cancer cells by inducing apoptosis following drug-induced cellular damage. Many reported studies have evaluated the prognostic and therapeutic implications of apoptosis in lung cancer, but their exact clinical value has remained unclear...
January 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28102565/development-of-novel-sers-probe-for-selective-screening-of-healthy-prostate-from-malignant-prostate-cancer-cells-using-zn-ii
#16
Paresh Chandra Ray, Avijit Pramanik, Suhash Reddy Chavva, Bhanu Priya Viraka Nellore, Kelli May, Tejus Matthew, Stacy Jones, Aruna Vangara
Even in 21st century, prostate cancer remains the second leading cause of cancer death for men. Since normal prostate gland contains the most Zn(II) and there are huge differences in Zn(II) content between the healthy and malignant prostate cancer cells, mobile zinc can be used as a biomarker for prostate cancer prediction. Current article reports the design of novel and highly efficient surface enhanced Raman spectroscopy (SERS) probe using p-(imidazole)azo) benzenethiol attached gold nanoparticle as a Raman reporter, which has the capability to identify prostate cancer cells based on Zn(II) sensing...
January 19, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28102523/the-effect-of-superparamagnetic-iron-oxide-nanoparticle-surface-charge-on-antigen-cross-presentation
#17
Yongbin Mou, Yun Xing, Hongyan Ren, Zhihua Cui, Yu Zhang, Guangjie Yu, Walter J Urba, Qingang Hu, Hongming Hu
Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28102341/lasing-in-live-mitotic-and-non-phagocytic-cells-by-efficient-delivery-of-microresonators
#18
Marcel Schubert, Klara Volckaert, Markus Karl, Andrew Morton, Philipp Liehm, Gareth B Miles, Simon J Powis, Malte C Gather
Reliable methods to individually track large numbers of cells in real time are urgently needed to advance our understanding of important biological processes like cancer metastasis, neuronal network development and wound healing. It has recently been suggested to introduce microscopic whispering gallery mode lasers into the cytoplasm of cells and to use their characteristic, size-dependent emission spectrum as optical barcode but so far there is no evidence that this approach is generally applicable. Here, we describe a method that drastically improves intracellular delivery of resonators for several cell types, including mitotic and non-phagocytic cells...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102324/antiproliferative-and-apoptosis-inducing-effect-of-exo-protoporphyrin-ix-based-sonodynamic-therapy-on-human-oral-squamous-cell-carcinoma
#19
Yanhong Lv, Jinhua Zheng, Qi Zhou, Limin Jia, Chunying Wang, Nian Liu, Hong Zhao, Hang Ji, Baoxin Li, Wenwu Cao
Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3-4 times more cell apoptosis compared to sonocation alone...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102269/from-morphogen-to-morphogenesis-and-back
#20
Darren Gilmour, Martina Rembold, Maria Leptin
A long-term aim of the life sciences is to understand how organismal shape is encoded by the genome. An important challenge is to identify mechanistic links between the genes that control cell-fate decisions and the cellular machines that generate shape, therefore closing the gap between genotype and phenotype. The logic and mechanisms that integrate these different levels of shape control are beginning to be described, and recently discovered mechanisms of cross-talk and feedback are beginning to explain the remarkable robustness of organ assembly...
January 18, 2017: Nature
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