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https://www.readbyqxmd.com/read/28922853/a-rationale-for-targeting-extracellular-regulated-kinases-erk1-and-erk2-in-glioblastoma
#1
Ricarda Hannen, Maria Hauswald, Joerg Walter Bartsch
Glioblastoma (GBM) is the most common malignant primary brain tumor. It still carries a grim prognosis and new therapies are needed. This review summarizes the current status of mechanistic insights into the function of extracellular regulated kinase (ERK) and its potential as a therapeutic target for patients with GBM. Currently, some promising ERK inhibitors are in clinical trials in tumor entities other than GBM. Here, we provide a comprehensive overview on the functions of ERK1/2 in GBM and a rationale for treatment of GBM with ERK inhibitors...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28922830/connectivity-neurofeedback-training-can-differentially-change-functional-connectivity-and-cognitive-performance
#2
Ayumu Yamashita, Shunsuke Hayasaka, Mitsuo Kawato, Hiroshi Imamizu
Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity...
October 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28922807/tedizolid-is-highly-bactericidal-in-the-treatment-of-pulmonary-mycobacterium-avium-complex-disease
#3
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. Methods: We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922792/breathing-new-life-into-hypoxia-targeted-therapies-for-non-small-cell-lung-cancer
#4
Steven H Lin, Albert C Koong
No abstract text is available yet for this article.
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#5
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922783/targeted-therapy-for-cancer-associated-fibroblasts-are-we-there-yet
#6
Reagan M Barnett, Eduardo Vilar
No abstract text is available yet for this article.
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#7
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922766/altered-accumulation-of-osa-mir171b-contributes-to-rice-stripe-virus-infection-by-regulating-disease-symptoms
#8
Aizi Tong, Quan Yuan, Shu Wang, Jiejun Peng, Yuwen Lu, Hongying Zheng, Lin Lin, Hairu Chen, Yifu Gong, Jianping Chen, Fei Yan
Viral infection affects the pattern of plant miRNA expression. It has been presumed that reduction of miR171 and several other miRNAs influences viral symptoms in plants. We here experimentally demonstrate the association of osa-miR171b with rice stripe virus (RSV) symptoms in rice. Inhibition of osa-miR171b caused stunting with reduced chlorophyll content in leaves similar to viral symptoms. Overexpression of osa-miR171b by an artificial miRNA extended vegetative growth and enhanced chlorophyll accumulation in leaves...
July 10, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28922763/chicory-r2r3-myb-transcription-factors-cimyb5-and-cimyb3-regulate-fructan-1-exohydrolase-expression-in-response-to-abiotic-stress-and-hormonal-cues
#9
Hongbin Wei, Hongbo Zhao, Tao Su, Anja Bausewein, Steffen Greiner, Karsten Harms, Thomas Rausch
In the biennial Cichorium intybus, inulin-type fructans accumulate in the taproot during the first year. Upon cold or drought exposure, fructans are degraded by fructan exohydrolases, affecting inulin yield and degree of polymerization. While stress-induced expression of 1-FEH genes has been thoroughly explored, the transcriptional network mediating these responses has remained unknown. In this study, several R2R3-MYB transcriptional regulators were analysed for their possible involvement in 1-FEH regulation via transient transactivation of 1-FEH target promoters and for in vivo co-expression with target genes under different stress and hormone treatments...
July 10, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28922756/the-meiotic-regulator-jason-utilizes-alternative-translation-initiation-sites-to-produce-differentially-localized-forms
#10
Simon Cabout, Megan P Leask, Shiny Varghese, Jun Yi, Benjamin Peters, Lei Liu Conze, Claudia Köhler, Lynette Brownfield
The JASON (JAS) protein plays an important role in maintaining an organelle band across the equator of male meiotic cells during the second division, with its loss leading to unreduced pollen in Arabidopsis. In roots cells, JAS localizes to the Golgi, tonoplast and plasma membrane. Here we explore the mechanism underlying the localization of JAS. Overall, our data show that leaky ribosom scanning and alternative translation initiation sites (TISs) likely leads to the formation of two forms of JAS: a long version with an N-terminal Golgi localization signal and a short version with a different N-terminal signal targeting the protein to the plasma membrane...
July 10, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28922739/o-glcnac-transferase-regulates-transcriptional-activity-of-human-oct4
#11
Sandii Constable, Jae-Min Lim, Krithika Vaidyanathan, Lance Wells
O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28922737/economic-evaluations-of-internet-and-mobile-based-interventions-for-the-treatment-and-prevention-of-depression-a-systematic-review
#12
REVIEW
Sarah Paganini, Wiebke Teigelkötter, Claudia Buntrock, Harald Baumeister
BACKGROUND: Internet- and mobile-based interventions (IMIs) targeting depression have been shown to be clinically effective and are considered a cost-effective complement to established interventions. The aim of this review was to provide an overview of the evidence for the cost-effectiveness of IMIs for the treatment and prevention of depression. METHODS: A systematic database search was conducted (Medline, PsychInfo, CENTRAL, PSYNDEX, OHE HEED). Relevant articles were selected according to defined eligibility criteria...
July 18, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28922698/survival-improvements-with-adjuvant-therapy-in-patients-with-glioblastoma
#13
Dasantha Jayamanne, Helen Wheeler, Raymond Cook, Charles Teo, David Brazier, Geoff Schembri, Marina Kastelan, Linxin Guo, Michael F Back
BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28922688/medium-term-outcomes-of-fenestrated-endovascular-repair-of-juxtarenal-abdominal-aortic-aneurysms
#14
Timothy P Shiraev, Trevor M Y Kwok, Steven R Dubenec
BACKGROUND: Abdominal aortic aneurysms pose a substantial clinical burden, and a significant proportion are not anatomically suitable for open repair or standard endovascular aneurysm repair (EVAR), instead requiring fenestrated EVAR (fEVAR). We sought to compare clinical outcomes and trends over time in patients undergoing fEVAR in Australia. METHODS: We conducted a retrospective analysis of all patients undergoing fEVAR at a tertiary referral centre between 2010 and 2015, including outcomes and complications, both as inpatients and after discharge...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28922655/zymosan-a-protects-the-hematopoietic-system-from-radiation-induced-damage-by-targeting-tlr2-signaling-pathway
#15
Jicong Du, Ying Cheng, Suhe Dong, Pei Zhang, Jiaming Guo, Jiaqi Han, Fu Gao, Hainan Zhao, Ding Sun, Jianguo Cui, Jianming Cai, Cong Liu
BACKGROUND/AIMS: The hematopoietic system is vulnerable to ionizing radiation and is often severely damaged by radiation. Molecules affecting radioresistance include Toll-like receptor 2. We investigated whether Zymosan-A, a novel TLR2 agonist, can protect the hematopoietic system from radiation-induced damage after total body irradiation. METHODS: Mice were exposed to total body radiation after treatment with Zymosan-A or normal saline, and their survival was recorded...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28922629/new-indole-based-chalconoids-as-tubulin-targeting-antiproliferative-agents
#16
Hassan Mirzaei, Mohammad Shokrzadeh, Mona Modanloo, Ali Ziar, Gholam Hossein Riazi, Saeed Emami
Tubulin-targeting compounds have a broad anticancer spectrum and are an important class of chemotherapeutic agents. Due to the importance of 3-bromo-3,5-dimethoxyphenyl scaffold in the anticancer activity of microtubule inhibitors such as crolibulin (EPC2407), we introduced this functionality into the indole-derived chalcones. Thus, we describe here the synthesis and biological evaluation of new indole-based chalconoids as tubulin-targeting antiproliferative agents. The best result was obtained by compound 9b against A549 cell with IC50 of 4...
September 7, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28922618/an-electromagnetic-system-for-inducing-a-localized-force-gradient-in-an-ecm-and-its-influence-on-hmvec-sprouting
#17
Hian Hian See, Sahan C B Herath, Rerngchai Arayanarakool, Yue Du, Evan Tan, Ruowen Ge, Harry Asada, Peter C Y Chen
Mechanical properties of the extracellular matrix (ECM) have been observed to influence the behavior of cells. Investigations on such an influence commonly rely on using soluble cues to alter the global intrinsic ECM properties in order to study the subsequent response of cells. This article presents an electromagnetic system for inducing a localized force gradient in an ECM, and reports the experimentally observed effect of such a force gradient on in vitro angiogenic sprouting of human microvascular endothelial cells (HMVECs)...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28922609/serum-proteomic-variability-associated-with-clinical-phenotype-in-familial-transthyretin-amyloidosis-attrm
#18
Gloria G Chan, Clarissa M Koch, Lawreen H Connors
Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues. Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated. ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) which arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP) reflecting the clinical phenotype...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28922598/proteolytic-unlocking-of-ultra-stable-twin-acylhydrazone-linkers-for-lysosomal-acid-triggered-release-of-anticancer-drugs
#19
Yiwu Zheng, Jing Ren, Yaqi Wu, Xiaoting Meng, Yibing Zhao, Chuanliu Wu
Targeted prodrugs exploiting cleavable linkers capable of responding to endogenous stimuli have increasingly been explored for cancer therapy. Successful application of these prodrug designs relies on the manipulation of both stability and responsiveness of the cleavable linkers, which, however, are difficult to be finely regulated, particularly for acid-responsive acylhydrazone bonds. Here we developed a new class of peptide-bridged twin-acylhydrazone linkers (PTA linkers) displaying both an ultrahigh stability and a rapid responsiveness-highly stable in neutral and acidic conditions due to effect of cooperativity between the two acylhydrazone bonds, easily cleavable in acidic conditions after enzymatically-triggered unlocking of the two bonds...
September 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28922596/privileged-substructures-to-modulate-protein-protein-interactions
#20
Nicolas Bosc, Mélaine A Kuenemann, Jérome Bécot, Marek Vavrusa, Adrien H Cerdan, Olivier Sperandio
Given the difficulties to identify chemical probes that can modulate protein-protein interactions (PPIs), actors in the field start to agree on the necessity to use PPI-tailored screening chemical collections. However, which type of scaffolds may promote the binding of compounds to PPI targets remains unclear. In this big data analysis, we have identified a list of privileged chemical substructures that are most often observed within inhibitors of PPIs. Using molecular frameworks as a way to perceive chemical substructures with the combination of an experimental and a machine-learning based predicted dataset of iPPI compounds, we propose a list of privileged substructures in the form of scaffolds and chemical moieties that can be substantially chemically functionalized and do not present any toxicophore nor Pan-assay interference (PAINS) alerts...
September 18, 2017: Journal of Chemical Information and Modeling
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