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https://www.readbyqxmd.com/read/28078656/biosimilars-for-the-treatment-of-cancer-a-systematic-review-of-published-evidence
#1
REVIEW
Ira Jacobs, Reginald Ewesuedo, Sadiq Lula, Charles Zacharchuk
BACKGROUND: Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access. OBJECTIVES: The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer. METHODS: MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015...
January 11, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28075402/comment-on-neiser-et-al-assessment-of-dextran-antigenicity-of-intravenous-iron-preparations-with-enzyme-linked-immunosorbent-assay-elisa-int-j-mol-sci-2016-17-1185
#2
Claes C Strom, Hans B Andreasen
All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s) behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron-carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from randomized clinical trials confirms the method reported by Neiser to be useless to predict reaction risk...
January 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28068087/design-of-a-biased-potent-small-molecule-inhibitor-of-the-bromodomain-and-phd-finger-containing-brpf-proteins-suitable-for-cellular-and-in-vivo-studies
#3
Niall Igoe, Elliott D Bayle, Oleg Fedorov, Cynthia Tallant, Pavel Savitsky, Catherine Rogers, Dafydd R Owen, Gauri Deb, Tim C P Somervaille, David M Andrews, Neil Jones, Anne Cheasty, Hamish Ryder, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The BRPF (bromodomain and PHD finger-containing) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Evaluation of the BRPF family as a potential drug target is at an early stage although there is an emerging understanding of a role in acute myeloid leukemia (AML). We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD of the BRPFs with excellent selectivity over nonclass IV BRD proteins. Evaluation of 13-d in a panel of cancer cell lines showed a selective inhibition of proliferation of a subset of AML lines...
January 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28061744/comprehensive-evaluation-of-extracellular-small-rna-isolation-methods-from-serum-in-high-throughput-sequencing
#4
Yan Guo, Kasey Vickers, Yanhua Xiong, Shilin Zhao, Quanhu Sheng, Pan Zhang, Wanding Zhou, Charles R Flynn
BACKGROUND: DNA and RNA fractions from whole blood, serum and plasma are increasingly popular analytes that are currently under investigation for their utility in the diagnosis and staging of disease. Small non-coding ribonucleic acids (sRNAs), specifically microRNAs (miRNAs) and their variant isoforms (isomiRs), and transfer RNA (tRNA)-derived small RNAs (tDRs) comprise a repertoire of molecules particularly promising in this regard. RESULTS: In this designed study, we compared the performance of various methods and kits for isolating circulating extracellular sRNAs (ex-sRNAs)...
January 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#5
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28053099/hcmv-specific-cd4-t-cells-are-poly-functional-and-can-respond-to-hcmv-infected-dendritic-cells-in-vitro
#6
Sarah E Jackson, George X Sedikides, Gavin M Mason, Georgina Okecha, Mark R Wills
: Human cytomegalovirus (HCMV) infection and periodic re-activation is generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8+ T cell response to HCMV has been extensively studied, the HCMV-specific CD4+ T cell effector response is not as well understood, especially in the context of direct interactions with HCMV infected cells. We screened the IFNγ and IL-10 response to 6 HCMV peptide pools (selected as the most frequently responded to in our previous studies: pp65, pp71, IE1, IE2, gB and US3) in 84 donors, aged 23 - 74 years...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052139/application-of-stochastic-labeling-with-random-sequence-barcodes-for-simultaneous-quantification-and-sequencing-of-environmental-16s-rrna-genes
#7
Tatsuhiko Hoshino, Fumio Inagaki
Next-generation sequencing (NGS) is a powerful tool for analyzing environmental DNA and provides the comprehensive molecular view of microbial communities. For obtaining the copy number of particular sequences in the NGS library, however, additional quantitative analysis as quantitative PCR (qPCR) or digital PCR (dPCR) is required. Furthermore, number of sequences in a sequence library does not always reflect the original copy number of a target gene because of biases caused by PCR amplification, making it difficult to convert the proportion of particular sequences in the NGS library to the copy number using the mass of input DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28045090/mirna-and-mrna-expression-analysis-reveals-potential-sex-biased-mirna-expression
#8
Li Guo, Qiang Zhang, Xiao Ma, Jun Wang, Tingming Liang
Recent studies suggest that mRNAs may be differentially expressed between males and females. This study aimed to perform expression analysis of mRNA and its main regulatory molecule, microRNA (miRNA), to discuss the potential sex-specific expression patterns using abnormal expression profiles from The Cancer Genome Atlas database. Generally, deregulated miRNAs and mRNAs had consistent expression between males and females, but some miRNAs may be oppositely expressed in specific diseases: up-regulated in one group and down-regulated in another...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045081/batch-effects-and-the-effective-design-of-single-cell-gene-expression-studies
#9
Po-Yuan Tung, John D Blischak, Chiaowen Joyce Hsiao, David A Knowles, Jonathan E Burnett, Jonathan K Pritchard, Yoav Gilad
Single-cell RNA sequencing (scRNA-seq) can be used to characterize variation in gene expression levels at high resolution. However, the sources of experimental noise in scRNA-seq are not yet well understood. We investigated the technical variation associated with sample processing using the single-cell Fluidigm C1 platform. To do so, we processed three C1 replicates from three human induced pluripotent stem cell (iPSC) lines. We added unique molecular identifiers (UMIs) to all samples, to account for amplification bias...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042823/identification-and-analysis-of-rna-editing-sites-in-the-chloroplast-transcripts-of-aegilops-tauschii-l
#10
Mengxing Wang, Hui Liu, Lingqiao Ge, Guangwei Xing, Meng Wang, Song Weining, Xiaojun Nie
RNA editing is an important way to convert cytidine (C) to uridine (U) at specific sites within RNA molecules at a post-transcriptional level in the chloroplasts of higher plants. Although it has been systematically studied in many plants, little is known about RNA editing in the wheat D genome donor Aegilops tauschii L. Here, we investigated the chloroplast RNA editing of Ae. tauschii and compared it with other wheat relatives to trace the evolution of wheat. Through bioinformatics prediction, a total of 34 C-to-U editing sites were identified, 17 of which were validated using RT-PCR product sequencing...
December 30, 2016: Genes
https://www.readbyqxmd.com/read/28039018/estrogen-regulated-stat1-activation-promotes-tlr8-expression-to-facilitate-signaling-via-microrna-21-in-systemic-lupus-erythematosus
#11
Nicholas A Young, Giancarlo R Valiente, Jeffrey M Hampton, Lai-Chu Wu, Craig J Burd, William L Willis, Michael Bruss, Holly Steigelman, Maya Gotsatsenko, Stephanie A Amici, Mary Severin, Lucila Marino Claverie, Mireia Guerau-de-Arellano, Amy Lovett-Racke, Stacy Ardoin, Wael N Jarjour
Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation...
December 27, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28032755/ambipolar-small-molecule-polymer-blend-semiconductors-for-solution-processable-organic-field-effect-transistors
#12
Minji Kang, Hansu Hwang, Won-Tae Park, Dongyoon Khim, Jun-Seok Yeo, Yunseul Kim, Yeon-Ju Kim, Yong-Young Noh, Dong-Yu Kim
We report on the fabrication of an organic thin-film semiconductor formed using a blend solution of soluble ambipolar small molecules and an insulating polymer binder that exhibits vertical phase separation and uniform film formation. The semiconductor thin films are produced in a single step from a mixture containing a small molecular semiconductor, namely, quinoidal biselenophene (QBS), and a binder polymer, namely, poly(2-vinylnaphthalene) (PVN). Organic field-effect transistors (OFETs) based on QBS/PVN blend semiconductor are then assembled using top-gate/bottom-contact device configuration, which achieve almost four times higher mobility than the neat QBS semiconductor...
January 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28032594/structurally-related-odorant-ligands-of-the-olfactory-receptor-or51e2-differentially-promote-metastasis-emergence-and-tumor-growth
#13
Guenhaël Sanz, Isabelle Leray, Denise Grébert, Sharmilee Antoine, Adrien Acquistapace, Adeline Muscat, Abdelhak Boukadiri, Lluis M Mir
Olfactory receptors are G protein-coupled receptors. Some of them are expressed in tumor cells, such as the OR51E2 receptor overexpressed in LNCaP prostate cancer cells. It is considered a prostate tumor marker. We previously demonstrated that this receptor is able to promote LNCaP cell invasiveness in vitro upon stimulation with its odorant agonist β-ionone, leading to increased generation of metastases in vivo. In the present study, we show that even a relatively short exposure to β-ionone is sufficient to promote metastasis emergence...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029251/diversity-of-secondary-structure-in-catalytic-peptides-with-%C3%AE-turn-biased-sequences
#14
Anthony J Metrano, Nadia C Abascal, Brandon Q Mercado, Eric K Paulson, Anna E Hurtley, Scott J Miller
X-ray crystallography has been applied to the structural analysis of a series of tetrapeptides that were previously assessed for catalytic activity in an atroposelective bromination reaction. Common to the series is a central Pro-Xaa sequence, where Pro is either l- or d-proline, which was chosen to favor nucleation of canonical β-turn secondary structures. Crystallographic analysis of 35 different peptide sequences revealed a range of conformational states. The observed differences appear not only in cases where the Pro-Xaa loop-region is altered, but also when seemingly subtle alterations to the flanking residues are introduced...
December 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28028226/single-pixel-interior-filling-function-approach-for-detecting-and-correcting-errors-in-particle-tracking
#15
Stanislav Burov, Patrick Figliozzi, Binhua Lin, Stuart A Rice, Norbert F Scherer, Aaron R Dinner
We present a general method for detecting and correcting biases in the outputs of particle-tracking experiments. Our approach is based on the histogram of estimated positions within pixels, which we term the single-pixel interior filling function (SPIFF). We use the deviation of the SPIFF from a uniform distribution to test the veracity of tracking analyses from different algorithms. Unbiased SPIFFs correspond to uniform pixel filling, whereas biased ones exhibit pixel locking, in which the estimated particle positions concentrate toward the centers of pixels...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28024368/breaking-degeneracy-of-tautomerization-metastability-from-days-to-seconds
#16
Jens Kügel, Aimee Sixta, Markus Böhme, Andreas Krönlein, Matthias Bode
We present a detailed study of the tautomerization, that is, the switching of hydrogen protons, between different sites in the molecular frame of phthalocyanine (H2Pc) on a Ag(111) substrate by means of scanning tunneling microscopy (STM) and STM-based pump-and-sample techniques. Our data reveal that the symmetry mismatch between the substrate and the molecular frame lifts the energetic degeneracy of the two H2Pc tautomers. Their energy difference is so large that only one tautomer can be found in the ground state...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/28024121/sodium-binding-sites-and-permeation-mechanism-in-the-nachbac-channel-a-molecular-dynamics-study
#17
Carlo Guardiani, P Mark Rodger, Igor A Khovanov
NaChBac was the first discovered sodium voltage dependent channel, yet computational studies are still limited due to the lack of a crystal structure. In this work a pore-only construct built using the NavMs template was investigated using unbiased Molecular Dynamics and Metadynamics. The Potential of Mean Force (PMF) from the unbiased run features four minima, three of which correspond to sites IN, CEN and HFS discovered in NavAb. During the run the Selectivity Filter (SF) is spontaneously occupied by two ions and frequent access of a third one is often observed...
December 26, 2016: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28017791/conditions-to-minimize-soft-single-biomolecule-deformation-when-imaging-with-atomic-force-microscopy
#18
Christian Godon, Jean-Marie Teulon, Michael Odorico, Christian Basset, Matthieu Meillan, Luc Vellutini, Shu-Wen W Chen, Jean-Luc Pellequer
A recurrent interrogation when imaging soft biomolecules using atomic force microscopy (AFM) is the putative deformation of molecules leading to a bias in recording true topographical surfaces. Deformation of biomolecules comes from three sources: sample instability, adsorption to the imaging substrate, and crushing under tip pressure. To disentangle these causes, we measured the maximum height of a well-known biomolecule, the tobacco mosaic virus (TMV), under eight different experimental conditions positing that the maximum height value is a specific indicator of sample deformations...
December 22, 2016: Journal of Structural Biology
https://www.readbyqxmd.com/read/28009170/modulation-of-molecular-flux-using-a-graphene-nanopore-capacitor
#19
Manish Shankla, Aleksei Aksimentiev
Modulation of ionic current flowing through nanoscale pores is one of the fundamental biological processes. Inspired by nature, nanopores in synthetic solid-state membranes are being developed to enable rapid analysis of biological macromolecules and to serve as elements of nanofludic circuits. Here, we theoretically investigate ion and water transport through a graphene-insulator-graphene membrane containing a single, electrolyte-filled nanopore. By means of all-atom molecular dynamics simulations we show that the charge state of such a graphene nanopore capacitor can regulate both the selectivity and the magnitude of the nanopore ionic current...
December 23, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28001386/assessment-and-optimization-of-configurational-bias-monte-carlo-particle-swap-strategies-for-simulations-of-water-in-the-gibbs-ensemble
#20
Peng Bai, J Ilja Siepmann
Particle swap moves between phase are usually the rate-limiting step for Gibbs ensemble Monte Carlo (GEMC) simulations of fluid phase equilibria at low reduced temperatures because the acceptance probabilities for these moves can become very low for molecules with articulated architecture and/or highly directional interactions. The configurational-bias Monte Carlo (CBMC) technique can greatly increase the acceptance probabilities, but the efficiency of the CBMC algorithm is influenced by multiple parameters...
December 21, 2016: Journal of Chemical Theory and Computation
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