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https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#1
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28092765/cytotoxic-genotoxic-and-mutagenic-evaluation-of-surface-waters-from-a-coal-exploration-region
#2
Cynthia Silva Porta, Débora Lemes Dos Santos, Hélio Vieira Bernardes, Bruno Corrêa Bellagamba, Anaí Duarte, Johnny Ferraz Dias, Fernanda Rabaioli da Silva, Mauricio Lehmann, Juliana da Silva, Rafael Rodrigues Dihl
Coal mining generates a considerable amount of waste, which is disposed of in piles or dams near mining sites. As a result, leachates may reach rivers and streams, promoting the wide dispersion of contaminants in solution and as particulate matter. The present study evaluated the cytotoxic, genotoxic, and mutagenic action of surface waters collected around a thermoelectric power plant and the largest mining area in Brazil (Candiota). Four sites in Candiota stream were selected, and samples were collected in winter and summer...
January 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28092007/study-of-the-genotoxicity-of-organic-extracts-from-wastewater-irrigated-vegetables-using-in-vitro-and-in-vivo-biological-tests
#3
Hongxia Gao, Yanhua Cao, Yingli Liu, Nan Liu, Weijun Guan
The purpose of this study was to explore genotoxicity due to organic pollutants in wastewater-irrigated vegetables using biological and chemical analyses. Chinese cabbages from wastewater-irrigated farmland were taken as the research object. For the in vitro test, DNA damage was characterized in rat hepatocytes exposed to organic extracts from the cabbages using the comet assay. For the in vivo tests, mice were exposed to organic extracts from the cabbages. DNA damage was assessed in mouse peripheral blood lymphocytes (PBLs), and chromosome damage was assessed in bone marrow cells using the comet assay and micronucleus test, respectively...
January 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28079919/copper-oxide-nanoparticles-and-copper-sulphate-act-as-antigenotoxic-agents-in-drosophila-melanogaster
#4
Mohamed Alaraby, Alba Hernández, Ricard Marcos
The biological reactivity of metal and metal oxide nanomaterials is attributed to their redox properties, which would explain their pro- or anti-cancer properties depending on exposure circumstances. In this sense, copper oxide nanoparticles (CuONP) have been proposed as a potential anti-tumoral agent. The aim of this study was to assess if CuONP can exert antigenotoxic effects using Drosophila melanogaster as an in vivo model. Genotoxicity was induced by two well-known genotoxic compounds, namely potassium dichromate (PD) and ethyl methanesulfonate (EMS)...
January 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28068603/rational-design-synthesis-and-evaluation-of-novel-2-4-chloro-and-hydroxy-substituted-diphenyl-benzofuro-3-2-b-pyridines-non-intercalative-catalytic-topoisomerase-i-and-ii-dual-inhibitor
#5
Seojeong Park, Til Bahadur Thapa Magar, Tara Man Kadayat, Hwa Jong Lee, Ganesh Bist, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
Novel series of conformationally constrained 2,4-chloro- and hydroxy-substituted diphenyl benzofuro[3,2-b]pyridines were rationally designed and synthesized. Their biological activities were evaluated for topoisomerase I and II inhibitory activity, and antiproliferative activity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds with phenol moiety at 4-position of central pyridine exhibited significant dual topoisomerase I and II inhibitory activities, and strong antiproliferative activity in low micromolar range...
January 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28067798/dark-and-photoinduced-cytotoxic-activity-of-the-new-chlorophyll-a-derivatives-with-oligoethylene-glycol-substituents-on-the-periphery-of-their-macrocycles
#6
Yana I Pylina, Dmitry M Shadrin, Oksana G Shevchenko, Olga M Startseva, Igor O Velegzhaninov, Dmitry V Belykh, Ilya O Velegzhaninov
In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series-pyropheophorbide-a 17-diethylene glycol ester (Compound 21) was performed...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28064118/pb-low-doses-induced-genotoxicity-in-lactuca-sativa-plants
#7
S Silva, P Silva, H Oliveira, I Gaivão, M Matos, O Pinto-Carnide, C Santos
Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used...
December 27, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28059653/sulforaphane-suppresses-the-growth-of-glioblastoma-cells-glioblastoma-stem-cell-like-spheroids-and-tumor-xenografts-through-multiple-cell-signaling-pathways
#8
Khadijeh Bijangi-Vishehsaraei, M Reza Saadatzadeh, Haiyan Wang, Angie Nguyen, Malgorzata M Kamocka, Wenjing Cai, Aaron A Cohen-Gadol, Stacey L Halum, Jann N Sarkaria, Karen E Pollok, Ahmad R Safa
OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28058665/oxidative-stress-and-genotoxicity-of-zinc-oxide-nanoparticles-to-pseudomonas-species-human-promyelocytic-leukemic-hl-60-and-blood-cells
#9
Deepika Soni, Deepa Gandhi, Prashant Tarale, Amit Bafana, R A Pandey, Saravanadevi Sivanesan
In the present study, toxicity of commercial zinc oxide nanoparticles (ZnO NPs) was studied on the bacterium Pseudomonas sp., human promyelocytic leukemia (HL-60) cells, and peripheral blood mononuclear cells (PBMC). The toxicity was assessed by measuring growth, cell viability, and protein expression in bacterial cell. The bacterial growth and viability decreased with increasing concentrations of ZnO NP. Three major proteins, ribosomal protein L1 and L9 along with alkyl hydroperoxides reductase, were upregulated by 1...
January 5, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28054742/evaluation-of-dna-damage-in-hepg2-cells-and-mutagenicity-of-garcinielliptone-fc-a-bioactive-benzophenone
#10
Lismare da Silva Prado, Juliana da Silva, Ana Letícia Hilario Garcia, Fernanda Brião Menezes Boaretto, Ivana Grivicich, Lucas Umpierre Conter, Aguisson de Oliveira Salvi, Flávio Henrique Reginatto, Suele Bierhals Vencato, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Garcinielliptone FC (GFC) is a polyprenylated benzophenone isolated from the hexanic extract of Platonia insignis seeds with potential pharmacological effects on the central nervous system. In a pre-clinical study, this compound showed anticonvulsant action, becoming a candidate to treat epilepsy disorders. However, genotoxicological aspects of GFC should be known to ensure its safe use. This study investigated the cytotoxic, genotoxic and mutagenic effects of GFC. Cytotoxicity was evaluated using the colourimetric assay of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) in human hepatoma cells (HepG2) (2 - 100 μg/mL) for 3, 6 and 24 hr...
January 5, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28053116/dna-dependent-protease-activity-of-human-spartan-facilitates-replication-of-dna-protein-crosslink-containing-dna
#11
Mónika Mórocz, Eszter Zsigmond, Róbert Tóth, Márton Zs Enyedi, Lajos Pintér, Lajos Haracska
Mutations in SPARTAN are associated with early onset hepatocellular carcinoma and progeroid features. A regulatory function of Spartan has been implicated in DNA damage tolerance pathways such as translesion synthesis, but the exact function of the protein remained unclear. Here, we reveal the role of human Spartan in facilitating replication of DNA-protein crosslink-containing DNA. We found that purified Spartan has a DNA-dependent protease activity degrading certain proteins bound to DNA. In concert, Spartan is required for direct DPC removal in vivo; we also show that the protease Spartan facilitates repair of formaldehyde-induced DNA-protein crosslinks in later phases of replication using the bromodeoxyuridin (BrdU) comet assay...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#12
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28050721/titanium-dioxide-nanoparticles-an-in-vitro-study-of-dna-binding-chromosome-aberration-assay-and-comet-assay
#13
Suhani Patel, Palak Patel, Sonal R Bakshi
Engineered titanium dioxide nanoparticles (TiO2 NPs) are extensively used in cosmetic, pharmaceutical and other industries globally due to their unique properties, which has raised concern for biosafety. Genotoxicity assessment is an important part of biosafety evaluation; we report in vitro cytogenetic assays for NPs considering their unique physicochemical characteristics to fill the gap of laboratory data regarding biological safety along with mechanistic study for mode of interaction of NP with genetic material...
January 3, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28046013/homologous-recombination-defective-arabidopsis-mutants-exhibit-enhanced-sensitivity-to-abscisic-acid
#14
Sujit Roy, Kali Pada Das
Abscisic acid (ABA) acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB) repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28040247/spermatozoa-a-relevant-biological-target-for-genotoxicity-assessment-of-contaminants-in-the-estuarine-bivalve-scrobicularia-plana
#15
Amélie Châtel, Mélanie Bruneau, Clémence Lièvre, Astrid Goupil, Catherine Mouneyrac
Evaluation of DNA quality of gametes is a relevant method to predict potential consequences of pollutants in the next generations, as it allows to define adverse outcome pathways implicated in pollutant-mediated toxicity for risk assessment. In the present study, a comet assay was developed for the spermatozoa of Scrobicularia plana exposed to 10 and 100μg/L of benzo[a]pyrene (B[a]P) for 24h and 5days. The induction of apoptosis and repair mechanisms was assessed by determining caspase-3 activity and polymerase cell nuclear antigen (PCNA) mRNA expression level...
December 28, 2016: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28039958/human-papillomavirus-status-and-the-relative-biological-effectiveness-of-proton-radiotherapy-in-head-and-neck-cancer-cells
#16
Li Wang, Xiaochun Wang, Yuting Li, Shichao Han, Jinming Zhu, Xiaofang Wang, David P Molkentine, Pierre Blanchard, Yining Yang, Ruiping Zhang, Narayan Sahoo, Michael Gillin, Xiaorong Ronald Zhu, Xiaodong Zhang, Jeffrey N Myers, Steven J Frank
BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown. METHODS: Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks...
December 30, 2016: Head & Neck
https://www.readbyqxmd.com/read/28039529/genotoxicity-assessment-of-volatile-organic-compounds-in-landfill-gas-emission-using-comet-assay-in-higher-terrestrial-plant
#17
Veerapas Na Roi-Et, Wilai Chiemchaisri, Chart Chiemchaisri
Genotoxicity model is developed to assess the individual subacute toxicity of benzene, toluene, ethylbenzene, and xylene (BTEX) at very low levels as in a landfill gas. Golden Pothos (Epipremnum aureum), a higher plant, was tested under variation of benzene 54-5656 ng/L, toluene 10-4362 ng/L, ethylbenzene 28-4997 ng/L, xylene 53-4845 ng/L, for 96 h. DNA fragmentation in plant leaves were investigated via comet assay. The results show that DNA migration ratio increased with the BTEX concentrations, but at different rates...
December 30, 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28039056/dna-loop-domain-organization-in-nucleoids-from-cells-of-different-types
#18
Katerina Afanasieva, Marianna Chopei, Alexandra Lozovik, Anastasia Semenova, Lyubov Lukash, Andrei Sivolob
The loop domain organization of chromatin plays an important role in transcription regulation and thus may be assumed to vary in cells of different types. We investigated the kinetics of DNA loop migration during single cell gel electrophoresis (the comet assay) for nucleoids obtained from human lymphocytes, lymphoblasts and glioblastoma T98G cells. The results confirm our previous observation that there are three parts of DNA in nucleoids: DNA on the nucleoid surface, loops up to ∼150 kb inside the nucleoid, and larger loops that cannot migrate...
December 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28039000/moving-into-advanced-nanomaterials-toxicity-of-rutile-tio2-nanoparticles-immobilized-in-nanokaolin-nanocomposites-on-hepg2-cell-line
#19
Maria João Bessa, Carla Costa, Julian Reinosa, Cristiana Pereira, Sónia Fraga, José Fernández, Miguel A Bañares, João Paulo Teixeira
Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO2 NPs(1)), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocomposites. The present work intended to evaluate the hepatic toxicity of nanocomposites (C-TiO2(2)), constituted by rutile TiO2 NPs immobilized in nanokaolin (NK(3)) clay, and its individual components...
December 28, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28035959/mobilization-of-nuclear-copper-by-green-tea-polyphenol-epicatechin-3-gallate-and-subsequent-prooxidant-breakage-of-cellular-dna-implications-for-cancer-chemotherapy
#20
Mohd Farhan, Mohammad Oves, Sandesh Chibber, Sheikh Mumtaz Hadi, Aamir Ahmad
Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA...
December 26, 2016: International Journal of Molecular Sciences
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