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https://www.readbyqxmd.com/read/27912880/combination-of-baicalein-and-10-hydroxy-camptothecin-exerts-remarkable-synergetic-anti-cancer-effects
#1
Qin Tang, Fangling Ji, Wenhui Sun, Jingyun Wang, Jianli Guo, Lianying Guo, Yachen Li, Yongming Bao
BACKGROUND: 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy. Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis. The synergistic anti-cancer effect of BA and HCPT has not been reported. PURPOSE: To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. METHODS: Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912094/mre11-is-essential-for-the-removal-of-lethal-topoisomerase-2-covalent-cleavage-complexes
#2
Nguyen Ngoc Hoa, Tsubasa Shimizu, Zhong Wei Zhou, Zhao-Qi Wang, Rajashree A Deshpande, Tanya T Paull, Salma Akter, Masataka Tsuda, Ryohei Furuta, Ken Tsutsui, Shunichi Takeda, Hiroyuki Sasanuma
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#3
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27903656/yeast-hmo1-linker-histone-reinvented
#4
REVIEW
Arvind Panday, Anne Grove
Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p...
March 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/27900038/antitumor-effects-and-mechanisms-of-ganoderma-extracts-and-spores-oil
#5
Chun Chen, Peng Li, Ye Li, Guan Yao, Jian-Hua Xu
Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893431/dysregulated-human-tyrosyl-dna-phosphodiesterase-i-acts-as-cellular-toxin
#6
Selma M Cuya, Evan Q Comeaux, Keith Wanzeck, Karina J Yoon, Robert C A M van Waardenburg
Tyrosyl-DNA phosphodiesterase I (TDP1) hydrolyzes the drug-stabilized 3'phospho-tyrosyl bond formed between DNA topoisomerase I (TOPO1) and DNA. TDP1-mediated hydrolysis uses a nucleophilic histidine (Hisnuc) and a general acid/base histidine (Hisgab). A Tdp1Hisgab to Arg mutant identified in patients with the autosomal recessive neurodegenerative disease SCAN1 causes stabilization of the TDP1-DNA intermediate. Based on our previously reported Hisgab-substitutions inducing yeast toxicity (Gajewski et al. J...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890643/coordination-of-dna-single-strand-break-repair
#7
Rachel Abbotts, David M Wilson
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27889879/plasmid-mediated-quinolone-resistance-in-enterobacteriaceae-a-systematic-review-with-a-focus-on-mediterranean-countries
#8
REVIEW
B Yanat, J-M Rodríguez-Martínez, A Touati
Quinolones are a family of synthetic broad-spectrum antimicrobial drugs. These molecules have been widely prescribed to treat various infectious diseases and have been classified into several generations based on their spectrum of activity. Quinolones inhibit bacterial DNA synthesis by interfering with the action of DNA gyrase and topoisomerase IV. Mutations in the genes encoding these targets are the most common mechanisms of high-level fluoroquinolone resistance. Moreover, three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998 and include Qnr proteins, the aminoglycoside acetyltransferase AAC(6')-Ib-cr, and plasmid-mediated efflux pumps QepA and OqxAB...
November 26, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27884651/analysis-of-mutations-in-dna-gyrase-and-topoisomerase-iv-of-ureaplasma-urealyticum-and-ureaplasma-parvum-serovars-resistant-to-fluoroquinolones
#9
Giorgio Piccinelli, Franco Gargiulo, Valeria Biscaro, Francesca Caccuri, Arnaldo Caruso, Maria Antonia De Francesco
This study aims to determine the prevalence of fluoroquinolone resistance of Ureaplasma biovars and serovars isolated from urogenital clinical samples and determine the underlying molecular mechanism for quinolone resistance for all resistant isolates. Of 105 samples confirmed as positive for U. urealyticum/U. parvum, 85 were resistant to quinolones by the Mycoplasma-IST2 kit. However, only 43 out of 85 quinolone resistant isolates had amino acid substitutions in GyrA, GyrB, ParC and ParE proteins underlining that this assay have mis-identified as fluoroquinolone resistant 42 isolates...
November 21, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27879063/carbazole-aminoalcohols-induce-antiproliferation-and-apoptosis-of-human-tumor-cells-by-inhibiting-topoisomerase%C3%A2-i
#10
Weisi Wang, Xiao Sun, Deheng Sun, Shizhu Li, Yang Yu, Tingyuan Yang, Junmin Yao, Zhuo Chen, Liping Duan
Novel carbazole aminoalcohols were designed and synthesized as anticancer agents. Among them, alkylamine-chain-substituted compounds showed the most promising antiproliferative activity, with IC50 values in the single-digit micromolar range against two human tumor cell lines. Topoisomerase I (topo I) is likely to be one of the targets of these compounds. Results of comet assays and molecular docking indicate that the representative compounds may act as topo I poisons, causing single-strand DNA damage by stabilizing the topo I-DNA cleavage complex...
November 23, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27877240/ros-responsive-mitochondria-targeting-blended-nanoparticles-chemo-and-photodynamic-synergistic-therapy-for-lung-cancer-with-on-demand-drug-release-upon-irradiation-with-a-single-light-source
#11
Caixia Yue, Yuming Yang, Chunlei Zhang, Gabriel Alfranca, Shangli Cheng, Lijun Ma, Yanlei Liu, Xiao Zhi, Jian Ni, Weihua Jiang, Jie Song, Jesús M de la Fuente, Daxiang Cui
Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for cancer. Here we report, for the first time, synthesis of a new mitochondria-targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel compound, polyethylene glycol was functionalized with thioketal linker-modified camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL-CPT-PEG1K-TPP...
2016: Theranostics
https://www.readbyqxmd.com/read/27875523/a-protein-fragment-derived-from-dna-topoisomerase-i-as-a-novel-tumour-associated-antigen-for-the-detection-of-early-stage-carcinoma
#12
Shang-Mian Yie, Shang-Rong Ye, Xiao-Li Ma, Ke Xie, Jian-Bo Zhang, Mei Cao, Xu He, Zhen-Bo Hu, Cheng-Lu Yang, Jia Zhang, Jie Zeng
BACKGROUND: The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Over the past few decades, a number of different TAAs and their corresponding autoantibodies have been investigated. However, positive frequency of autoantibody detection in cancer patients has been relatively low. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC)...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27872982/interplay-between-top1-and-mms21-nse2-mediated-sumoylation-in-stable-maintenance-of-long-chromosomes
#13
Lakshmi Mahendrawada, Ragini Rai, Deepash Kothiwal, Shikha Laloraya
Genetic information in cells is encrypted in DNA molecules forming chromosomes of varying sizes. Accurate replication and partitioning of chromosomes in the crowded cellular milieu is a complex process involving duplication, folding and movement. Longer chromosomes may be more susceptible to mis-segregation or DNA damage and there may exist specialized physiological mechanisms preventing this. Here, we present genetic evidence for such a mechanism which depends on Mms21/Nse2 mediated sumoylation and topoisomerase-1 (Top1) for maintaining stability of longer chromosomes...
November 21, 2016: Current Genetics
https://www.readbyqxmd.com/read/27872075/pharmacokinetic-pharmacodynamic-evaluation-of-gepotidacin-against-gram-positive-organisms-using-data-from-murine-infection-models
#14
Catharine C Bulik, Ólanrewaju O Okusanya, Elizabeth A Lakota, Alan Forrest, Sujata M Bhavnani, Jennifer L Hoover, David R Andes, Paul G Ambrose
Gepotidacin (formerly GSK2140944) is a novel triazaacenaphthylene bacterial topoisomerase inhibitor with in vitro activity against conventional and biothreat pathogens, including Staphylococcus aureus and Streptococcus pneumoniae Using neutropenic murine thigh- and lung-infection models, the pharmacokinetics-pharmacodynamics (PK-PD) of gepotidacin against S. aureus and S. pneumoniae were characterized. Single dose PK data from uninfected mice (16-128 mg/kg SC) were fit with candidate models. Dose-fractionation studies (one isolate/organism; 2-512 mg/kg/day) and dose-ranging studies (5 isolates/organism; 2-2048 mg/kg/day; MIC ranges: S...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27871039/synthesis-and-antitumor-activity-of-novel-substituted-uracil-1-n-acetic-acid-ester-derivatives-of-20-s-camptothecins
#15
Di-Zao Li, Qiang-Zhe Zhang, Cun-Ying Wang, Yan-Ling Zhang, Xing-Yu Li, Ji-Tao Huang, Hong-Yan Liu, Zhao-Di Fu, Hua-Xian Song, Jin-Ping Lin, Teng-Fei Ji, Xian-Dao Pan
A series of novel substituted uracil-1'(N)-acetic acid esters (6-20) of camptothecins (CPTs) were synthesized by the acylation method. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most of the derivatives exhibited comparable or superior cytotoxicity compare to CPT (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy. Four compounds, 9, 12, 13 and 16, were selected to be evaluated for in vivo antitumor activity against H22, BGC-823 and Bel-7402 in mice...
November 8, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27860204/angelman-syndrome-current-and-emerging-therapies-in-2016
#16
REVIEW
Wen-Hann Tan, Lynne M Bird
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a loss of the maternally-inherited UBE3A; the paternal UBE3A is silenced in neurons by a mechanism involving an antisense transcript (UBE3A-AS) at the unmethylated paternal locus. We reviewed all published information on the clinical trials that have been completed as well as the publicly available information on ongoing trials of therapies in AS. To date, all clinical trials that strove to improve neurodevelopment in AS have been unsuccessful...
November 8, 2016: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/27856347/dna-topoisomerase-i-and-dna-gyrase-as-targets-for-tb-therapy
#17
REVIEW
Valakunja Nagaraja, Adwait A Godbole, Sara R Henderson, Anthony Maxwell
Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy...
November 14, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27854277/optimized-detection-of-plasmodium-falciparum-topoisomerase-i-enzyme-activity-in-a-complex-biological-sample-by-the-use-of-molecular-beacons
#18
Asger Givskov, Emil L Kristoffersen, Kamilla Vandsø, Yi-Ping Ho, Magnus Stougaard, Birgitta R Knudsen
The so-called Rolling Circle Amplification allows for amplification of circular DNA structures in a manner that can be detected in real-time using nucleotide-based molecular beacons that unfold upon recognition of the DNA product, which is being produced during the amplification process. The unfolding of the molecular beacons results in a fluorescence increase as the Rolling Circle Amplification proceeds. This can be measured in a fluorometer. In the current study, we have investigated the possibility of using two different molecular beacons to detect two distinct Rolling Circle Amplification reactions proceeding simultaneously and in the same reaction tube by measurement of fluorescence over time...
November 15, 2016: Sensors
https://www.readbyqxmd.com/read/27852749/quantitative-proteomic-analysis-of-replicative-and-non-replicative-forms-reveals-important-insights-into-chromatin-biology-of-trypanosoma-cruzi
#19
Teresa Cristina Leandro de Jesus, Simone Guedes Calderano, Francisca Nathalia de Luna Vitorino, Ricardo Pariona Llanos, Mariana de Camargo Lopes, Christiane Bezerra de Araújo, Otavio Henrique Thiemann, Marcelo da Silva Reis, Maria Carolina Elias, Julia Pinheiro Chagas da Cunha
Chromatin associated proteins are key regulators of many important processes in the cell. Trypanosoma cruzi, a protozoa flagellate that causes Chagas disease, alternates between replicative and non-replicative forms accompanied by a shift on global transcription levels and by changes in its chromatin architecture. Here, we investigated the T. cruzi chromatin proteome using three different protocols and compared it between replicative (epimastigote) and non-replicative (trypomastigote) forms by high-resolution mass spectrometry...
November 16, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27852319/inhibitory-effects-of-lapachol-on-rat-c6-glioma-in-vitro-and-in-vivo-by-targeting-dna-topoisomerase-i-and-topoisomerase-ii
#20
Huanli Xu, Qunying Chen, Hong Wang, Pingxiang Xu, Ru Yuan, Xiaorong Li, Lu Bai, Ming Xue
BACKGROUND: Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms. METHODS: The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexin V-FITC/PI staining, and comet assay...
November 16, 2016: Journal of Experimental & Clinical Cancer Research: CR
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