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https://www.readbyqxmd.com/read/28651808/addendum-to-weiner-m-l-2016-parameters-and-pitfalls-to-consider-in-the-conduct-of-food-additive-research-carrageenan-as-a-case-study-food-chemical-toxicology-87-31-44
#1
Myra L Weiner, James M McKim, William R Blakemore
This paper is an addendum to a 2016 paper outlining pitfalls and parameters to consider in the conduct of food additive research with carrageenan (Fd. Chem. Tox. 87, 31-44 (2016)). The literature on the food additive, "carrageenan," contains many publications which either erroneously misuses the name, carrageenan, for a sample which is not carrageenan, but "degraded carrageenan" or "poligeenan" and also conduct studies without understanding the physical/chemical properties of carrageenan. Degraded carrageenan and poligeenan are not food additives and have a completely different physical/chemical and toxicological properties from carrageenan...
June 23, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28638728/gene-expression-analysis-in-cutaneous-t-cell-lymphomas-ctcl-highlights-disease-heterogeneity-and-potential-diagnostic-and-prognostic-indicators
#2
Ivan V Litvinov, Michael T Tetzlaff, Philippe Thibault, Pamela Gangar, Linda Moreau, Andrew K Watters, Elena Netchiporouk, Kevin Pehr, Victor G Prieto, Elham Rahme, Nathalie Provost, Martin Gilbert, Denis Sasseville, Madeleine Duvic
Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28571485/continuous-autoregulatory-indices-derived-from-multi-modal-monitoring-each-one-is-not-like-the-other
#3
Frederick Adam Zeiler, Joseph Donnelly, David Menon, Peter Smieleweski, Christian Zweifel, Ken Brady, Marek Czosnyka
We assess the relationships between various continuous measures of autoregulatory capacity in an adult TBI cohort. We assessed relationships between autoregulatory indices derived from intracranial pressure (ICP: PRx, PAx, RAC), Transcranial Doppler (TCD: Mx, Sx, Dx), brain tissue-oxygenation (ORx), and spatially resolved near infrared spectroscopy (NIRS resolved: TOx, THx). Relationships between indices were assessed using Pearson correlation coefficient, Friedman (KW) test, Principle component analysis (PCA), Agglomerative Hierarchal Clustering (AHC) and K-Means Cluster Analysis (KMCA)...
June 1, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28565760/in-silico-insight-into-egfr-treatment-in-patients-with-lung-carcinoma-and-t790m-mutations
#4
Shu-Zhi Zang, Yan-Rong Yang, Sha-Sha Zhao, Yun-Xia Li, Xin-Yuan Gao, Chun-Lei Zhong
The T790M mutational basis of treatment failure, following treatment via alteration of the epidermal growth factor receptor (EGFR) pathway, is a well-known anomaly in patients with non-small cell lung cancer (NSCLC). The T790M mutation activates the kinase domain, causing tyrosine kinase inhibitors, such as gefitinib, to elicit little or no response. To overcome this acquired resistance in NSCLC cells, the present study utilized a structure-based drug designing method to identify a novel lead compound. An in-house traditional Chinese medicinal compound database was used and following initial virtual screening, pre-absorption, distribution, metabolism and excretion/Tox and automated docking analyses, nardosinon was selected as the most appropriate candidate for further analysis...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28554025/assessing-the-toxicity-of-ionic-liquids-application-of-the-critical-membrane-concentration-approach
#5
Kai Bittermann, Kai-Uwe Goss
Charged organic chemicals are a prevailing challenge for toxicity modelling. In this contribution we strive to recapitulate the lessons learned from the well-known modelling of narcosis (or baseline toxicity) of neutral chemicals and apply the concept to charged chemicals. First we reevaluate the organism- and chemical independent critical membrane concentration causing 50% mortality,.cmem(tox), based on a critical revision of a previously published toxicity dataset for neutral chemicals. In accordance to values reported in the literature we find a mean value for cmem(tox) of roughly 100 mmol/kg (membrane lipid) for a broad variety of 42 aquatic organisms (333 different chemicals), albeit with a considerable scatter...
May 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28547769/evaluation-of-piggybac-mediated-cho-pools-to-enable-material-generation-to-support-glp-toxicology-studies
#6
Yashas Rajendra, Sowmya Balasubramanian, Neil A McCracken, Dawn L Norris, Zhirui Lian, Matthew G Schmitt, Christopher C Frye, Gavin C Barnard
Generating purified protein for GLP toxicology studies (GLP-Tox) represents an important and often rate limiting step in the biopharmaceutical drug development process. Toxicity testing requires large amounts of therapeutic protein (>100g), typically produced in a single 500L - 2,500L bioreactor, using the final CHO clonally-derived cell line (CDCL). One approach currently used to save time is to manufacture GLP-Tox material using pools of high-producing CHO CDCLs instead of waiting for the final CDCL. Recently, we reported CHO pools producing mAb titers >7 g/L using piggyBac-mediated gene integration (PB CHO pools)...
May 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28531557/characterization-of-dissolved-organic-carbon-leached-from-a-woodchip-bioreactor
#7
Ibrahim Abusallout, Guanghui Hua
Woodchip bioreactors are increasingly being applied to remove nitrate from agricultural subsurface drainage. However, dissolved organic carbon (DOC) released from woodchips may negatively affect the aquatic ecosystems and drinking water supplies. The objective of this study was to evaluate the leaching characteristics, disinfection byproduct (DBP) formation potentials, and treatability of DOC derived from a laboratory woodchip bioreactor. Initial flush of woodchips resulted in the release of high organic content from woodchips...
May 13, 2017: Chemosphere
https://www.readbyqxmd.com/read/28489605/genetic-rearrangements-result-in-altered-gene-expression-and-novel-fusion-transcripts-in-s%C3%A3-zary-syndrome
#8
Katarzyna Iżykowska, Grzegorz K Przybylski, Claudia Gand, Floriane C Braun, Piotr Grabarczyk, Andreas W Kuss, Karolina Olek-Hrab, Armando N Bastidas Torres, Maarten H Vermeer, Willem H Zoutman, Cornelis P Tensen, Christian A Schmidt
Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480263/diagnosis-in-france-of-a-non-toxigenic-tox-gene-bearing-strain-of-corynebacterium-diphtheriae-in-a-young-male-back-from-senegal
#9
Typhaine Billard-Pomares, Cécile Rouyer, Violaine Walewski, Edgar Badell-Ocando, Marc Dumas, Coralie Zumelzu, Françoise Jaureguy, Sylvain Brisse, Frédéric Caux, Olivier Bouchaud, Etienne Carbonnelle
Cutaneous diphtheria is uncommon in Europe. In this study, we report a case of imported cutaneous infection due to a non-toxigenic but tox gene-bearing (NTTB) strain of Corynebacterium diphtheriae. The NTTB strains are recognized as emerging pathogens across Europe, and physicians and bacteriologists should be aware of the circulation of these strains.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28469408/modification-of-s-adenosyl-l-homocysteine-as-inhibitor-of-nonstructural-protein-5-methyltransferase-dengue-virus-through-molecular-docking-and-molecular-dynamics-simulation
#10
Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami
Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test...
2017: Drug Target Insights
https://www.readbyqxmd.com/read/28464377/bile-salts-and-alkaline-ph-reciprocally-modulate-the-interaction-between-the-periplasmic-domains-of-vibrio-cholerae-toxr-and-toxs
#11
Charles R Midgett, Salvador Almagro-Moreno, Maria Pellegrini, Ronald K Taylor, Karen Skorupski, F Jon Kull
ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood...
May 2, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28441483/discovery-of-a-novel-class-of-survival-motor-neuron-2-splicing-modifiers-for-the-treatment-of-spinal-muscular-atrophy
#12
Emmanuel Pinard, Luke Green, Michael Reutlinger, Marla Weetall, Nikolai A Naryshkin, John Baird, Karen S Chen, Sergey V Paushkin, Friedrich Metzger, Hasane Ratni
Spinal muscular atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene, resulting in low levels of functional SMN protein. We have reported recently the identification of small molecules (coumarins, iso-coumarins and pyrido-pyrimidinones) that modify the alternative splicing of SMN2, a paralogous gene to SMN1, restoring the survival motor neuron (SMN) protein level in mouse models of SMA. Herein, we report our efforts to identify a novel chemotype as one strategy to potentially circumvent safety concerns from earlier derivatives such as in vitro phototoxicity and in vitro mutagenicity associated with compounds 1 and 2 or the in vivo retinal findings observed in a long-term chronic tox study with 3 at high exposures only...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28395759/a-multicenter-phase-ii-study-of-personalized-folfiri-cetuximab-for-safe-dose-intensification
#13
MULTICENTER STUDY
Michèle Boisdron-Celle, Jean Philippe Metges, Olivier Capitain, Antoine Adenis, Jean Luc Raoul, Thierry Lecomte, You Heng Lam, Roger Faroux, Claude Masliah, Anne Lise Poirier, Virginie Berger, Alain Morel, Erick Gamelin
We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU(ODPM Tox)) followed by PK-guided dose optimization (5-FU(ODPM Protocol))...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28395758/prevention-of-5-fluorouracil-induced-early-severe-toxicity-by-pre-therapeutic-dihydropyrimidine-dehydrogenase-deficiency-screening-assessment-of-a-multiparametric-approach
#14
RANDOMIZED CONTROLLED TRIAL
Michele Boisdron-Celle, Olivier Capitain, Roger Faroux, Christophe Borg, Jean Philippe Metges, Marie Pierre Galais, Mehdi Kaassis, Jaafar Bennouna, Karine Bouhier-Leporrier, Eric Francois, Isabelle Baumgaertner, Véronique Guerin-Meyer, Oana Cojocarasu, Celia Roemer-Becuwe, Claire Stampfli, Ludovic Rosenfeld, Thierry Lecompte, Virginie Berger, Alain Morel, Erick Gamelin
5-Fluorouracil (5-FU)-based treatments can lead to early-onset severe (4%-5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28371489/a-strategy-to-accelerate-protein-production-from-a-pool-of-clones-in-chinese-hamster-ovary-cells-for-toxicology-studies
#15
Zhilan Hu, Wendy Hsu, Abby Pynn, Domingos Ng, Donna Quicho, Yilma Adem, Zephie Kwong, Brad Mauger, John Joly, Bradley Snedecor, Michael W Laird, Dana C Andersen, Amy Shen
In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for Investigational New Drug (IND)-enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND-enabling toxicology studies ("Pool for Tox strategy") during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately four months at Genentech), leading to a potential acceleration of four months for the IND submission...
April 3, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28350787/quality-adjusted-survival-with-combination-nal-iri-5-fu-lv-vs-5-fu-lv-alone-in-metastatic-pancreatic-cancer-patients-previously-treated-with-gemcitabine-based-therapy-a-q-twist-analysis
#16
Uwe Pelzer, Jean-Frédéric Blanc, Davide Melisi, Antonio Cubillo, Daniel D Von Hoff, Andrea Wang-Gillam, Li-Tzong Chen, Jens T Siveke, Yin Wan, Caitlyn T Solem, Marc F Botteman, Yoojung Yang, Floris A de Jong, Richard A Hubner
BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST)...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28337503/gut-microbiome-related-metabolic-changes-in-plasma-of-antibiotic-treated-rats
#17
C Behr, H Kamp, E Fabian, G Krennrich, W Mellert, E Peter, V Strauss, T Walk, I M C M Rietjens, B van Ravenzwaay
The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites...
March 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28327672/tox-and-adipoq-gene-polymorphisms-are-associated-with-antipsychotic-induced-weight-gain-in-han-chinese
#18
Shen Li, Chengai Xu, Yuan Tian, Xueshi Wang, Rui Jiang, Miaomiao Zhang, Lili Wang, Guifu Yang, Ying Gao, Chenyu Song, Yukun He, Ying Zhang, Jie Li, Wei-Dong Li
To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#19
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295221/regosarc-regorafenib-versus-placebo-in-doxorubicin-refractory-soft-tissue-sarcoma-a-quality-adjusted-time-without-symptoms-of-progression-or-toxicity-analysis
#20
Vincent Berry, Laurent Basson, Emilie Bogart, Olivier Mir, Jean-Yves Blay, Antoine Italiano, François Bertucci, Christine Chevreau, Stéphanie Clisant-Delaine, Bernadette Liegl-Antzager, Emmanuelle Tresch-Bruneel, Jennifer Wallet, Sophie Taieb, Emilie Decoupigny, Axel Le Cesne, Thomas Brodowicz, Nicolas Penel
BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse...
March 10, 2017: Cancer
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