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https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#1
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28917173/synthetic-iron-hydr-oxide-glucose-associations-in-subsurface-soil-effects-on-decomposability-of-mineral-associated-carbon
#2
R C Porras, C E Hicks Pries, M S Torn, P S Nico
Soils are a globally important reservoir of organic carbon. There is a growing understanding that interactions with soil mineral phases contribute to the accumulation and retention of otherwise degradable organic matter (OM) in soils and sediments. However, the bioavailability of organic compounds in mineral-organic-associations (MOAs), especially under varying environmental conditions is not well known. To assess the impact of mineral association and warming on the decomposition of an easily respirable organic substrate (glucose), we conducted a series of laboratory incubations at different temperatures with field-collected soils from 10 to 20cm, 50-60cm, and 80-90cm depth...
September 13, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28914193/chalcone-derivatives-anti-inflammatory-potential-and-molecular-targets-perspectives
#3
Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Vivek Asati
Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold has gained considerable scientific interest in medicinal chemistry owing to its simple chemistry, ease in synthesizing a variety of derivatives and exhibiting a broad range of promising pharmacological activities by modulating several molecular targets. A number of natural and (semi-) synthetic chalcone derivatives have demonstrated admirable anti-inflammatory activity due to their inhibitory potential against various therapeutic targets like cyclooxygenase (COX), lipooxygenase (LOX), interleukins (IL), prostaglandins (PGs), nitric oxide synthase (NOS), leukotriene D4 (LTD4), nuclear factor-κB (NF-κB), intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and TLR4/MD-2, etc...
September 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28903093/chlorination-chloramination-and-ozonation-of-carbamazepine-enhance-cytotoxicity-and-genotoxicity-multi-endpoint-evaluation-and-identification-of-its-genotoxic-transformation-products
#4
Yingnan Han, Mei Ma, Na Li, Rui Hou, Chao Huang, Yoshimitsu Oda, Zijian Wang
Investigations have focused on the removal and transformation of pharmaceuticals during drinking water and wastewater treatment. In the present study, we investigated for the first time the changes of the cytotoxicity and genotoxicity based on different modes of action (MoAs) during chlorination, chloramination and ozonation processes of the anti-epileptic drug carbamazepine (CBZ). The results illustrated that ozonation enhanced the cytotoxicity and the chromosome damage effects on CHO-K1 cells detected by cytokinesis-block micronucleus (CBMN) assay based on high-content screening technique, though ozonation showed the highest removal efficiency for CBZ...
September 1, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28886135/differential-regulation-of-innate-immune-cytokine-production-through-pharmacological-activation-of-nuclear-factor-erythroid-2-related-factor-2-nrf2-in-burn-patient-immune-cells-and-monocytes
#5
Timothy K Eitas, Wesley Stepp, Lucas Sjeklocha, Clayton Long, Caitlin Riley, James Callahan, Yolanda Sanchez, Peter Gough, Laquanda Knowlin, David van Duin, Shiara Ortiz-Pujols, Samuel Jones, Robert Maile, Zhi Hong, Scott Berger, Bruce Cairns
Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients...
2017: PloS One
https://www.readbyqxmd.com/read/28885868/evaluating-the-moa-human-relevance-framework-for-f-344-rat-liver-epithelioid-granulomas-with-mineral-oil-hydrocarbons
#6
David Adenuga, Katy Goyak, R Jeffrey Lewis
Toxicology feeding studies of mineral oil hydrocarbons (MOHs), within the carbon number range C22-C28, results in species-specific epithelioid granulomas in the liver of F-344 rats but not in other rat strains, or species. While MOH has been detected, and some pathological effects have been shown to occur in other organs/tissues of F-344 rats and other rat strains/species, it is generally accepted that the effect of toxicological concern is species-specific inflammatory liver granuloma. As oil retention and other MOH-related nontoxic pathological changes in the liver are observed in humans, some have hypothesized that the potential for oil accumulation over a lifetime, through dietary sources, may predispose humans to similar liver effects as observed in F-344 rats...
September 8, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28871279/longitudinal-changes-in-absolutevo2peak-physical-activity-level-body-mass-index-and-overweightedness-among-adolescents-in-vocational-and-non-vocational-studies
#7
Pål Lagestad, Oddbjørn Floan, Ivar Fossland Moa
The purpose of the study was to examine differences in physical activity level, physical fitness, body mass index, and overweight among adolescents in vocational and non-vocational studies, at the age of 14, 16, and 19, using a 5-year longitudinal design. Students in sport studies had the highest absoluteVO2peak and higher physical activity levels, than students in vocational subjects and students with a specialization in general studies. However, there were no significant differences between students in vocational subjects and students with a specialization in general studies according to absoluteVO2peak and physical activity levels...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28869848/discriminating-modes-of-toxic-action-in-mice-using-toxicity-in-balb-c-mouse-fibroblast-3t3-cells
#8
Tao Huang, Lichen Yan, Shanshan Zheng, Yue Wang, Xiaohong Wang, Lingyun Fan, Chao Li, Yuanhui Zhao, Christopher J Martyniuk
The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R(2) = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R(2) = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds...
August 26, 2017: Chemosphere
https://www.readbyqxmd.com/read/28868669/attributes-of-bio-oss-%C3%A2-and-moa-bone-%C3%A2-graft-materials-in-a-pilot-study-using-the-sheep-maxillary-sinus-model
#9
M M Smith, W J Duncan, D E Coates
BACKGROUND AND OBJECTIVE: The aim of this pilot study was to characterize surface morphology and to evaluate resorption and osseous healing of two deproteinated bovine bone graft materials after sinus grafting in a large animal model. MATERIAL AND METHODS: Surfaces of a novel particulate bovine bone graft, Moa-Bone(®) were compared with Bio-Oss(®) using scanning electron microscopy. Six sheep then had maxillary sinus grafting bilaterally, covered with BioGide(®) ...
September 4, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28861278/comparing-structural-and-transcriptional-drug-networks-reveals-signatures-of-drug-activity-and-toxicity-in-transcriptional-responses
#10
Francesco Sirci, Francesco Napolitano, Sandra Pisonero-Vaquero, Diego Carrella, Diego L Medina, Diego di Bernardo
We performed an integrated analysis of drug chemical structures and drug-induced transcriptional responses. We demonstrated that a network representing three-dimensional structural similarities among 5452 compounds can be used to automatically group together drugs with similar scaffolds, physicochemical parameters and mode-of-action. We compared the structural network to a network representing transcriptional similarities among a subset of 1309 drugs for which transcriptional response were available in the Connectivity Map data set...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28860722/patient-and-oncologist-preferences-for-attributes-of-treatments-in-advanced-melanoma-a-discrete-choice-experiment
#11
Frank Xiaoqing Liu, Edward A Witt, Scot Ebbinghaus, Grace DiBonaventura Beyer, Reshma Shinde, Enrique Basurto, Richard W Joseph
PURPOSE: To examine and compare patient and oncologist preferences for advanced melanoma treatment attributes and to document their trade-offs for benefits with risks. MATERIALS AND METHODS: A discrete choice experiment (DCE) was conducted among advanced melanoma patients and oncologists. Qualitative pilot testing was used to inform the DCE design. A series of scenarios asked stakeholders to choose between two hypothetical medications, each with seven attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (MDT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AEs)...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28858244/andrographolide-suppresses-mv4-11-cell-proliferation-through-the-inhibition-of-flt3-signaling-fatty-acid-synthesis-and-cellular-iron-uptake
#12
Xiao Chen, Jianbin Zhang, Lixia Yuan, Yifei Lay, Yin Kwan Wong, Teck Kwang Lim, Chye Sun Ong, Qingsong Lin, Jigang Wang, Zichun Hua
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR's anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system...
August 31, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28856597/chemical-genetics-based-development-of-small-molecules-targeting-hepatitis-c-virus
#13
REVIEW
Guanghai Jin, Jisu Lee, Kyeong Lee
Hepatitis C virus (HCV) infection is a major worldwide problem that has emerged as one of the most significant diseases affecting humans. There are currently no vaccines or efficient therapies without side effects, despite today's advanced medical technology. Currently, the common therapy for most patients (i.e. genotype 1) is combination of HCV-specific direct-acting antivirals (DAAs). Up to 2011, the standard of care (SOC) was a combination of peg-IFNα with ribavirin (RBV). After approval of NS3/4A protease inhibitor, SOC was peg-IFNα and RBV with either the first-generation DAAs boceprevir or telaprevir...
August 30, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28841366/mortality-and-transcriptional-effects-of-inorganic-mercury-in-the-marine-copepod-calanus-finmarchicus
#14
Knut Erik Tollefsen, You Song, Tore Høgåsen, Ida Beathe Øverjordet, Dag Altin, Bjørn Henrik Hansen
Inorganic mercury (Hg) is highly toxic to organisms including crustaceans and displays multiple toxic modes of action (MoA). The main aim of this investigation was to assess the acute and sublethal toxicity mediated by mercury chloride (HgCl2) in the marine copepod Calanus finmarchicus. A combination of short-term static studies to determine acute toxicity and a transcriptional investigation to characterize the sublethal MoA of HgCl2 were conducted with an in-house continuous culture of C. finmarchicus. Transcriptional changes were determined by a custom 6...
August 25, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28832191/if-there-were-a-vaccine-against-acute-myocardial-infarction-would-you-use-it
#15
C Raina MacIntyre, Aye M Moa
No abstract text is available yet for this article.
August 23, 2017: Future Cardiology
https://www.readbyqxmd.com/read/28830741/effects-of-omega-3-in-the-treatment-of-violent-schizophrenia-patients
#16
Yi Qiao, Yi Mei, Huiqin Han, FengJu Liu, Xiao Min Yang, Yang Shao, Bin Xie, Bin Long
OBJECTIVE: This study was designed to explore the relationship in between the daily consumption of fish oil (360mg DHA+540mg EPA), and reduction of symptoms and violent behavior among patients with schizophrenia. METHOD: Fifty inpatients meeting ICD-10 criteria for schizophrenia and scoring more than four of Modified Overt Aggression Scale (MOAS) with antipsychotics treatment were randomly assigned to receive either fish oil (N=28) or a placebo (N=22) in a twelve week, double-blind supplementation trial...
August 19, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28827284/rhinovirus-infection-of-ormdl3-transgenic-mice-is-associated-with-reduced-rhinovirus-viral-load-and-airway-inflammation
#17
Dae Jin Song, Marina Miller, Andrew Beppu, Peter Rosenthal, Sudipta Das, Maya Karta, Christine Vuong, Amit Kumar Mehta, Michael Croft, David H Broide
Orosomucoid like 3 (ORMDL3), a gene localized to chromosome 17q21, has been linked in epidemiologic studies to childhood asthma and rhinovirus (RV) infections. As the single nucleotide polymorphisms linking ORMDL3 to asthma are associated with increased expression of ORMDL3, we have used hORMDL3(zp3-Cre) mice (which have universal increased expression of human ORMDL3) to determine whether infection of these transgenic mice with RV influences levels of airway inflammation or RV viral load. RV infection of hORMDL3(zp3-Cre) mice resulted in reduced RV viral load assessed by quantitative real-time PCR (lung and airway epithelium), as well as reduced airway inflammation (total bronchoalveolar lavage cells, neutrophils, macrophages, and lymphocytes) compared with RV-infected wild-type mice...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28813645/lat-is-essential-for-the-mast-cell-stabilising-effect-of-thga-in-ige-mediated-mast-cell-activation
#18
Ji Wei Tan, Daud Ahmad Israf, Nur Fariesha Md Hashim, Yoke Kqueen Cheah, Hanis Hazeera Harith, Khozirah Shaari, Chau Ling Tham
Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28806050/linking-high-throughput-screens-to-identify-moas-and-novel-inhibitors-of-mycobacterium-tuberculosis-dihydrofolate-reductase
#19
John P Santa Maria, Yumi Park, Lihu Yang, Nicholas Murgolo, Michael D Altman, Paul Zuck, Greg Adam, Chad Chamberlin, Peter Saradjian, Peter Dandliker, Helena I M Boshoff, Clifton E Barry, Charles Garlisi, David B Olsen, Katherine Young, Meir Glick, Elliott Nickbarg, Peter S Kutchukian
Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for a mechanism of action (MoA) and reveal actionable chemical matter. Here, we describe a framework for identifying efficacy targets of bioactive compounds. High throughput biophysical profiling against a broad range of targets coupled with machine learning was employed to identify chemical features with predicted efficacy targets for a given phenotypic screen...
August 29, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28804988/patterns-of-systemic-treatment-for-psoriatic-arthritis-in-the-united-states-2004-2015
#20
Moa P Lee, Joyce Lii, Yinzhu Jin, Rishi J Desai, Daniel H Solomon, Joseph F Merola, Seoyoung C Kim
OBJECTIVE: To examine trends in use of systemic disease-modifying antirheumatic drugs (DMARD) among patients with psoriatic arthritis (PsA) in the U.S. METHODS: Using claims data (2004-2015) from a large U.S. commercial healthplan, we identified patients with PsA who initiated DMARDs. We examined baseline patient characteristics and initial treatment patterns. We then assessed changes in the DMARD regimen over the 12-month period after the 1(st) DMARD initiation date...
August 13, 2017: Arthritis Care & Research
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