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https://www.readbyqxmd.com/read/28735458/the-efficacy-of-lapatinib-and-nilotinib-in-combination-with-radiation-therapy-in-a-model-of-nf2-associated-peripheral-schwannoma
#1
Iddo Paldor, Sara Abbadi, Nicolas Bonne, Xiaobu Ye, Fausto J Rodriguez, David Rowshanshad, MariaLisa Itzoe, Veronica Vigilar, Marco Giovannini, Henry Brem, Jaishri O Blakeley, Betty M Tyler
Neurofibromatosis type 2 (NF2), a neurogenetic condition manifest by peripheral nerve sheath tumors (PNST) throughout the neuroaxis for which there are no approved therapies. In vitro and in vivo studies presented here examine agents targeting signaling pathways, angiogenesis, and DNA repair mechanisms. In vitro dose response assays demonstrated potent activity of lapatinib and nilotinib against the mouse schwannoma SC4 (Nf2 (-/-)) cell line. We then examined the efficacy of everolimus, nilotinib, lapatinib, bevacizumab and radiation (RT) as mono- and combination therapies in flank and sciatic nerve in vivo NF2-PNST models...
July 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28735337/thresholds-of-toxicological-concern-setting-a-threshold-for-testing-below-which-there-is-little-concern
#2
Thomas Hartung
Low dose, low risk; very low dose, no real risk. Setting a pragmatic threshold below which concerns become negligible is the purpose of thresholds of toxicological concern (TTC). The idea is that such threshold values do not need to be established for each and every chemical based on experimental data, but that by analyzing the distribution of lowest or no-effect doses of many chemicals, a TTC can be defined - typically using the 5th percentile of this distribution and lowering it by an uncertainty factor of, e...
2017: ALTEX
https://www.readbyqxmd.com/read/28735239/effects-of-a-glyphosate-based-herbicide-in-pejerrey-odontesthes-humensis-embryonic-development
#3
Yuri Dornelles Zebral, Patrícia Gomes Costa, Bruna de Castro Knopp, Luize Real Lansini, Bruna Zafalon-Silva, Adalto Bianchini, Ricardo Berteaux Robaldo
Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Among them, the Roundup formulations are the most popular. Some aspects of GBH toxicity are well known, such as induction of oxidative stress. However, embryotoxicity is scarcely known. Therefore, the aim of the present study was to evaluate the effect of exposure to different Roundup Transorb R concentrations (0.36, 1.80, 3.62 and 5.43 mg glyphosate a.e./L) on Odontesthes humensis embryonic development. Embryos were sampled at three exposure times (48, 72 and 96 h)...
July 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28735183/reductive-dechlorination-of-trichloroethylene-by-polyvinylpyrrolidone-stabilized-nanoscale-zerovalent-iron-particles-with-ni
#4
Macharla Arun Kumar, Sungjun Bae, Seunghee Han, Yoonseok Chang, Woojin Lee
We developed a novel stabilized nanoscale zerovalent iron (NZVI) particles with Ni using an electron conducting polymer, polyvinylpyrrolidone (PVP), to selectively dechlorinate trichloroethylene (TCE) to non-toxic intermediates. The size of the PVP stabilized NZVI-Ni ((PVP-NZVI-Ni), average diameter: ∼20nm) is smaller than that of bare NZVI (50-80nm) due to the prevention of agglomeration of the resultant iron particles by PVP. PVP-NZVI-Ni showed a complete removal of TCE in 1h with superior dechlorination kinetics (kobs=5...
July 14, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28734790/organ-weights-and-histopathology-of-double-crested-cormorants-phalacrocorax-auritus-dosed-orally-or-dermally-with-artificially-weathered-mississippi-canyon-252-crude-oil
#5
Kendal E Harr, Drury R Reavill, Steven J Bursian, Dave Cacela, Fred L Cunningham, Karen M Dean, Brian S Dorr, Katie C Hanson-Dorr, Kate Healy, Katherine Horak, Jane E Link, Susan Shriner, Robert E Schmidt
A series of toxicity tests were conducted to assess the effects of low to moderate exposure to artificially weathered Deepwater Horizon Mississippi Canyon 252 crude oil on representative avian species as part of the Natural Resource Damage Assessment. The present report summarizes effects of oral exposure (n=26) of double-crested cormorants (DCCO; Phalacrocorax auritus) to 5 or 10ml oil kg(-1) day(-1) for up to 21 days or dermal application (n=25) of 13ml oil to breast and back feathers every three days totaling 6 applications in 21 days on organ weights and histopathology...
July 19, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28734577/characterization-of-a-pvl-negative-community-acquired-methicillin-resistant-staphylococcus-aureus-strain-of-sequence-type-88-in-china
#6
Lu Sun, Dandan Wu, Yan Chen, Qian Wang, Haiping Wang, Yunsong Yu
Sequence type 88 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain SR434, isolated from an outpatient with skin and soft tissue infection, was subjected to whole genome sequencing, antimicrobial susceptibility testing, mouse skin infection model and hemolysis analysis to identify its virulence and resistance determinants. MRSA strain SR434 is resistant to clindamycin, erythromycin and fosfomycin. Four plasmids with resistance genes were identified in this strain, including a 20,658bp blaZ-carrying plasmid, a 2473bp ermC-carrying plasmid, a 2622bp fosB7-carrying plasmid (86% identity with plasmid in a ST2590 MRSA strain) and a 4817bp lnuA-carrying plasmid (99% identity with pLNU4 from bovine coagulase-nagetive Staphylococci)...
July 13, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28734221/treatment-of-highly-toxic-cardboard-plant-wastewater-by-a-combination-of-electrocoagulation-and-electrooxidation-processes
#7
Erhan Gengec
The objective of this study was to investigate the removal efficiencies of the electrochemical treatment systems as an alternative for the treatment of cardboard plant wastewater (CPW). In accordance with this purpose, CPW was treated by electrocoagulation (EC) with Al electrodes and the effects of current density (CD), operating time (t), and initial pH (pHi) were investigated. The results showed that EC at optimum treatment conditions (CD: 7.5mA/cm(2), pHi: 7.0 and t: 60min) have limited removal efficiencies for total organic carbon (TOC; 17...
July 19, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28734219/acute-toxicity-of-cadmium-in-anisops-sardeus-heteroptera-notonectidae-effects-on-adult-and-nymphal-survival-and-swimming-behavior
#8
Chongtham Memtombi Chanu, Susmita Gupta, Abhik Gupta
Adult female and male, and final instar nymph of Anisops sardeus (Heteroptera: Notonectidae) were exposed to graded concentrations of cadmium in 96h static-with-renewal acute toxicity tests, which were conducted in dry (March) and wet (May-June) seasons. The 96h LC50 values for instar V nymph, adult female and male were found to be 0.9, 0.59 and 0.51mgL(-1) Cd, respectively, in wet season, while these were 26.7 and 20.2mgL(-1) Cd for adult female and male, respectively, in dry season. Adult males were most sensitive to Cd, followed by females in both seasons, while highest tolerance in wet season was observed in instar V nymph...
July 19, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28733784/environmental-impact-of-coal-mining-and-coal-seam-gas-production-on-surface-water-quality-in-the-sydney-basin-australia
#9
A Ali, V Strezov, P Davies, I Wright
The extraction of coal and coal seam gas (CSG) will generate produced water that, if not adequately treated, will pollute surface and groundwater systems. In Australia, the discharge of produced water from coal mining and related activities is regulated by the state environment agency through a pollution licence. This licence sets the discharge limits for a range of analytes to protect the environment into which the produced water is discharged. This study reports on the impact of produced water from coal mine activities located within or discharging into high conservation environments, such as National Parks, in the outer region of Sydney, Australia...
August 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28733528/analyses-of-selected-safety-endpoints-in-phase-1-and-late-phase-clinical-trials-of-anti-pd-1-and-pd-l1-inhibitors-prediction-of-immune-related-toxicities
#10
Ricardo Costa, Rubens B Costa, Sarah M Talamantes, Irene Helenoswki, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Razelle Kurzrock, Francis J Giles
PURPOSE: Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. METHODS: PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733192/pharmacological-evaluation-of-phytochemicals-from-south-indian-black-turmeric-curcuma-caesia-roxb-to-target-cancer-apoptosis
#11
K S Mukunthan, R S Satyan, T N Patel
Curcuma caesia Roxb. (Black turmeric), a perennial herb of the family Zingiberaceae is indigenous to India. C. caesia is used as a spice, food preservative and coloring agent commonly in the Indian subcontinent. Functional parametric pharmacological evaluations like drug ability and toxicity profile of this endangered species is poorly documented. In our present study, among all the extracts of dried C. caesia rhizome viz- hexane, ethyl acetate, methanol and water tested for free radical scavenging capacity by total antioxidant activity (TAO) method, Hexane Rhizome Extract (HRE) wzs found to possess remarkable activity (1200mg ascorbic acid equivalent/100g)...
July 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28733131/preclinical-studies-for-a-phase-1-clinical-trial-of-autologous-hematopoietic-stem-cell-gene-therapy-for-sickle-cell-disease
#12
Fabrizia Urbinati, Jennifer Wherley, Sabine Geiger, Beatriz Campo Fernandez, Michael L Kaufman, Aaron Cooper, Zulema Romero, Filippo Marchioni, Lilith Reeves, Elizabeth Read, Barbara Nowicki, Elke Grassman, Shivkumar Viswanathan, Xiaoyan Wang, Roger P Hollis, Donald B Kohn
BACKGROUND AIMS: Gene therapy by autologous hematopoietic stem cell transplantation (HSCT) represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials. METHODS: Data are shown to evaluate and establish the feasibility of isolating, transducing with the Lenti/β(AS3)-FB vector and cryopreserving CD34(+) cells from human bone marrow (BM) at clinical scale...
July 18, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28732990/combination-of-sonodynamic-with-temozolomide-inhibits-c6-glioma-migration-and-promotes-mitochondrial-pathway-apoptosis-via-suppressing-nhe-1-expression
#13
Lei Chen, Damin Cong, Yongzhe Li, Dan Wang, Qingsong Li, Shaoshan Hu
Temozolomide (TMZ) was used for clinical postoperative or non-surgical chemotherapy patients. However, its effect remains unsatisfactory and gradually discovered that the presence of chemoresistance. To explore more effective therapy using TMZ, we investigate the effects of combination of application of TMZ together with Sonodynamic therapy (SDT), which is based on the ultrasonic activation of a sonosensitizer, with low toxicity, noninvasive, deeper penetrability and a promising approach for treating malignant glioma by inducing apoptosis on glioma cells in vitro...
November 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28732404/influence-of-the-stabilizers-on-the-toxicity-of-metallic-nanomaterials-in-aquatic-organisms-and-human-cell-lines
#14
Tatiana Andreani, Verónica Nogueira, Vera V Pinto, Maria José Ferreira, Maria Graça Rasteiro, Amélia M Silva, Ruth Pereira, Carlos M Pereira
In this study, following a systematic approach, we used aquatic species (bacteria Vibrio fischeri and microalgae Raphidocelis subcapitata) and different human cell lines (Caco-2, HepG2, SV-80 and HaCaT) representing different tissues and exposure pathways, to investigate how two organic stabilizers (PVA and DMSO) used for NMs dispersion influence their physicochemical properties, the persistence of metals in suspension and the toxicity/ecotoxicity of two metallic NMs (nano-Ag and nano-Cu). Although the stabilizers are expected to contribute to improve the dispersion and stability of NMs, the results obtained clearly showed that no similar changes in toxicity and morphological properties of the nano-Ag can be expected after its stabilization with PVA...
July 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28732336/using-machine-learning-to-identify-air-pollution-exposure-profiles-associated-with-early-cognitive-skills-among-u-s-children
#15
Jeanette A Stingone, Om P Pandey, Luz Claudio, Gaurav Pandey
Data-driven machine learning methods present an opportunity to simultaneously assess the impact of multiple air pollutants on health outcomes. The goal of this study was to apply a two-stage, data-driven approach to identify associations between air pollutant exposure profiles and children's cognitive skills. Data from 6900 children enrolled in the Early Childhood Longitudinal Study, Birth Cohort, a national study of children born in 2001 and followed through kindergarten, were linked to estimated concentrations of 104 ambient air toxics in the 2002 National Air Toxics Assessment using ZIP code of residence at age 9 months...
July 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#16
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28732306/photostability-testing-using-online-reactor-hplc-hyphenation-and-mass-spectrometric-compound-identification-illustrated-by-ketoprofen-as-model-compound
#17
Jaber Assaf, Diego Zulkiewicz Gomes, Bernhard Wuest, Maria Kristina Parr
Investigations on the photochemical stability of pharmaceutical substances are mandatory in drug development and licensing as photo-induced degradation of an active pharmaceutical ingredient (API) may not only lead to decreased API concentrations but also to toxic or reactive products. Thus, the US Food and Drug Administration (FDA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) issued Guidance for Industry Q1B "Photostability Testing of New Drug Substances and Products" for testing of pure but also packed drugs...
July 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28731685/lipophilic-polycation-vehicles-display-high-plasmid-dna-delivery-to-multiple-cell-types
#18
Yaoying Wu, Adam E Smith, Theresa M Reineke
A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731627/his-tag-immobilization-of-cutinase-1-from-thermobifida-cellulosilytica-for-solvent-free-synthesis-of-polyesters
#19
Alessandro Pellis, Marco Vastano, Felice Quartinello, Enrique Herrero Acero, Georg M Guebitz
For many years, lipase B from Candida antarctica (CaLB) was the primary biocatalyst used for enzymatic esterification and polycondensation reactions. More recently, the need for novel biocatalysts with different selectivity has arisen in the biotechnology and biocatalysis fields. The present work describes how the catalytic potential of Thermobifida cellulosilytica cutinase 1 (Thc_Cut1) was exploited for polyester synthesis. in a first step, Thc_Cut1 was immobilized on three different carriers, namely Opal, Coral and Amber, using a novel non-toxic His-tag method based on chelated Fe(iii) ions (>99% protein bounded)...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28731393/the-impact-of-decompression-with-instrumentation-on-local-failure-following-spine-stereotactic-radiosurgery
#20
Jacob A Miller, Ehsan H Balagamwala, Camille A Berriochoa, Lilyana Angelov, John H Suh, Edward C Benzel, Alireza M Mohammadi, Todd Emch, Anthony Magnelli, Andrew Godley, Peng Qi, Samuel T Chao
OBJECTIVE Spine stereotactic radiosurgery (SRS) is a safe and effective treatment for spinal metastases. However, it is unknown whether this highly conformal radiation technique is suitable at instrumented sites given the potential for microscopic disease seeding. The authors hypothesized that spinal decompression with instrumentation is not associated with increased local failure (LF) following SRS. METHODS A 2:1 propensity-matched retrospective cohort study of patients undergoing SRS for spinal metastasis was conducted...
July 21, 2017: Journal of Neurosurgery. Spine
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