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Topoisomerase

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https://www.readbyqxmd.com/read/29458004/real-time-analysis-of-cleavage-and-religation-activity-of-human-topoisomerase-1-based-on-ternary-fluorescence-resonance-energy-transfer-dna-substrate
#1
Zhenxing Wang, Hui Ouyang, Cinzia Tesauro, Alessio Ottaviani, Yong He, Paola Fiorani, Hui Xie, Alessandro Desideri, Zhifeng Fu
Human topoisomerase 1B is a ubiquitous and essential enzyme involved in relaxing the topological state of supercoiled DNA to allow the progression of fundamental DNA metabolism. Its enzymatic catalytic cycle consists of cleavage and religation reaction. A ternary fluorescence resonance energy transfer biosensor based on a suicide DNA substrate conjugated with three fluorophores has been developed to monitor both cleavage and religation Topoisomerase I catalytic function. The presence of fluorophores does not alter the specificity of the enzyme catalysis on the DNA substrate...
February 16, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29456350/recurrent-glioblastomas-exhibit-higher-expression-of-biomarkers-with-stem-like-properties
#2
B N Nandeesh, Sharmistha Naskar, Arun H Shashtri, A Arivazhagan, Vani Santosh
Background: Despite advances in the treatment of glioblastoma (GBM), the prognosis of patients continues to remain dismal. This unfavorable prognosis is mainly attributed to the tumor's propensity for progression and recurrence, which in turn is due to the highly aggressive nature of the persisting GBM cells that actively egress from the main tumor mass into the surrounding normal brain tissue. Such a recurrent tumor described to have a more malignant potential is highly invasive and resistant to current therapies, probably due to increased stemness and preferential selection of therapy-resistant clones of tumor cells...
January 2018: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/29455320/elevated-serum-krebs-von-den-lungen-6-in-systemic-sclerosis-a-marker-of-lung-fibrosis-and-severity-of-the-disease
#3
Audrey Benyamine, Xavier Heim, Noémie Resseguier, Daniel Bertin, Carine Gomez, Mikaël Ebbo, Jean-Robert Harlé, Gilles Kaplanski, Pascal Rossi, Nathalie Bardin, Brigitte Granel
OBJECTIVES: We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). METHODS: Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography...
February 17, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29447373/coupling-the-core-of-the-anticancer-drug-etoposide-to-an-oligonucleotide-induces-topoisomerase-ii-mediated-cleavage-at-specific-dna-sequences
#4
Lorena Infante Lara, Sabine Fenner, Steven Ratcliffe, Albert Isidro-Llobet, Michael Hann, Ben Bax, Neil Osheroff
Etoposide and other topoisomerase II-targeted drugs are important anticancer therapeutics. Unfortunately, the safe usage of these agents is limited by their indiscriminate induction of topoisomerase II-mediated DNA cleavage throughout the genome and by a lack of specificity toward cancer cells. Therefore, as a first step toward constraining the distribution of etoposide-induced DNA cleavage sites and developing sequence-specific topoisomerase II-targeted anticancer agents, we covalently coupled the core of etoposide to oligonucleotides centered on a topoisomerase II cleavage site in the PML gene...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29446719/dna-double-strand-breaks-repair-inhibitors-relevance-as-potential-new-anticancer-therapeutics
#5
Paulina Kopa, Anna Macieja, Grzegorz Galita, Zbigniew J Witczak, Tomasz Poplawski
DNA Double-strand breaks are considered one of the most lethal form of DNA damage. Many effective anticancer therapeutic approaches used chemical and physical methods to generate DNA double-strand breaks in the cancer cells. They include: IR and drugs which mimetic its action, topoisomerase poisons, some alkylating agents or drugs which affected DNA replication process. On the other hand, cancer cells are mostly characterized by highly effective systems of DNA damage repair. There are two main DNA repair pathways used to fix double-strand breaks: NHEJ and HRR...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446718/current-trends-and-future-directions-of-fluoroquinolones
#6
Hamada H H Mohammed, Gamal El-Din A A Abuo-Rahma, Samar H Abbas, El-Shimaa M N Abdelhafez
Fluoroquinolones represent an interesting synthetic class of antimicrobial agents with broad spectrum and potent activity. Since the discovery of nalidixic acid, the prototype of quinolones, several structural modifications to the quinolone nucleus have been carried out for improvement of potency, spectrum of activity, and to understand their structure activity relationship (SAR). The C-7 substituent was reported to have a major impact on the activity. Accordingly, Substitution at C-7 or its N-4-piperazinyl moiety was found to affect potency, bioavailability, and physicochemical properties...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29444242/in-vitro-activity-of-zoliflodacin-etx0914-against-macrolide-resistant-fluoroquinolone-resistant-and-antimicrobial-susceptible-mycoplasma-genitalium-strains
#7
A C Damião Gouveia, M Unemo, J S Jensen
Background: Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains. Methods: The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M...
February 12, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29439406/site-specific-cleavage-by-topoisomerase-2-a-mark-of-the-core-centromere
#8
Walter E Mills, Jennifer M Spence, Tatsuo Fukagawa, Christine J Farr
In addition to its roles in transcription and replication, topoisomerase 2 (topo 2) is crucial in shaping mitotic chromosomes and in ensuring the orderly separation of sister chromatids. As well as its recruitment throughout the length of the mitotic chromosome, topo 2 accumulates at the primary constriction. Here, following cohesin release, the enzymatic activity of topo 2 acts to remove residual sister catenations. Intriguingly, topo 2 does not bind and cleave all sites in the genome equally; one preferred site of cleavage is within the core centromere...
February 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29438989/mitotic-phosphorylation-of-senp3-regulates-de-sumoylation-of-chromosome-associated-proteins-and-chromosome-stability
#9
Bo Wei, Chao Huang, Bin Liu, Yang Wang, Nansong Xia, Qiuju Fan, Guo-Qiang Chen, Jinke Cheng
Progression of mitotic cell cycle as well as chromosome condensation and segregation are controlled by posttranslational protein modifications such as phosphorylation and SUMOylation. However, how SUMO isopeptidases (SENP) regulate cell mitotic procession is largely unknown. Here we demonstrate that precise phosphorylation of SENP3 during mitosis suppresses SENP3 de-SUMOylation activity towards chromosome-associated proteins including Topoisomerase IIα (Topo IIα). Cyclin B-dependent kinases 1 (CDK1) and protein phosphatase 1α (PP1α) were identified as the kinase and phosphatase in control of mitotic SENP3 phosphorylation, respectively...
February 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29434976/prediction-of-long-term-survival-rates-in-patients-undergoing-curative-resection-for-solitary-hepatocellular-carcinoma
#10
Yi Cao, Zhelong Jiang, Shaohu Wang, Haoyang Zhang, Yi Jiang, Lizhi Lv
The present study developed a novel laboratory-based algorithm to predict long-term survival rates in patients undergoing curative resection for solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The present study included 426 patients with solitary HBV-related HCC who underwent surgery for primary tumors at a single center between 2003 and 2012. Demographic characteristics, laboratory analysis, clinical pathology and immunohistochemistry of topoisomerase II-a and Ki67 were analyzed. A simple prognostic risk calculator was developed using regression coefficients from multivariate models...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434938/genetic-characterization-and-in-vitro-activity-of-antimicrobial-combinations-of-multidrug-resistant-acinetobacter-baumannii-from-a-general-hospital-in-china
#11
Fang Chen, Ling Wang, Min Wang, Yixin Xie, Xiaomeng Xia, Xianping Li, Yanhua Liu, Wei Cao, Tingting Zhang, Pengling Li, Min Yang
The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434373/author-correction-sister-chromatid-resolution-is-an-intrinsic-part-of-chromosome-organization-in-prophase
#12
Kota Nagasaka, M Julius Hossain, M Julia Roberti, Jan Ellenberg, Toru Hirota
In the version of this Letter originally published, the authors omitted a citation of an early study demonstrating topoisomerase-II-dependent sister chromatid resolution. This reference has now been added to the reference list as reference number 28, and the relevant text has been amended as follows to include its citation: 'Resolution must reflect the removal of sister-sister contacts, and we show here that Topo-IIα-mediated release of DNA catenation plays a major role (Fig. 4), in agreement with previous findings28, whereas, surprisingly, cohesin dissociation is not strictly required (Fig...
February 12, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29432724/guanabenz-promotes-neuronal-survival-via-enhancement-of-atf4-and-parkin-expression-in-models-of-parkinson-disease
#13
Xiaotian Sun, Pascaline Aimé, David Dai, Nagendran Ramalingam, John F Crary, Robert E Burke, Lloyd A Greene, Oren A Levy
Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes eIF2α dephosphorylation...
February 9, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29431122/poly-adp-ribose-polymerase-1-regulates-fibroblast-activation-in-systemic-sclerosis
#14
Yun Zhang, Sebastian Pötter, Chih-Wei Chen, Ruifang Liang, Kolja Gelse, Ingo Ludolph, Raymund E Horch, Oliver Distler, Georg Schett, Jörg H W Distler, Clara Dees
OBJECTIVES: The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) transfers negatively charged ADP-ribose units to target proteins. This modification can have pronounced regulatory effects on target proteins. Recent studies showed that PARP-1 can poly(ADP-ribosyl)ate (PARylate) Smad proteins. However, the role of PARP-1 in the pathogenesis of systemic sclerosis (SSc) has not been investigated. METHODS: The expression of PARP-1 was determined by quantitative PCR and immunohistochemistry...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29429988/the-deubiquitylase-usp15-regulates-topoisomerase-ii-alpha-to-maintain-genome-integrity
#15
Andrew B Fielding, Matthew Concannon, Sarah Darling, Emma V Rusilowicz-Jones, Joseph J Sacco, Ian A Prior, Michael J Clague, Sylvie Urbé, Judy M Coulson
Ubiquitin-specific protease 15 (USP15) is a widely expressed deubiquitylase that has been implicated in diverse cellular processes in cancer. Here we identify topoisomerase II (TOP2A) as a novel protein that is regulated by USP15. TOP2A accumulates during G2 and functions to decatenate intertwined sister chromatids at prophase, ensuring the replicated genome can be accurately divided into daughter cells at anaphase. We show that USP15 is required for TOP2A accumulation, and that USP15 depletion leads to the formation of anaphase chromosome bridges...
February 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29425806/hyperactivated-m-calpain-affects-acquisition-of-doxorubicin-resistance-in-breast-cancer-cells
#16
Kyung-Hwa Jeon, Han Vit Yu, Youngjoo Kwon
BACKGROUND: Doxorubicin is commonly using chemotherapeutic agents for breast cancer. However, doxorubicin has limitations in clinical use because of dose-dependent cardiotoxicity and drug resistance. Despite of previously reported studies about mechanisms of doxorubicin resistance including overexpression of P-gp and abnormal expression and mutation of topoisomerase IIα, resistance to this agent still abundantly occur and is regarded as a major obstacle to successful treatment. METHODS: We have established doxorubicin resistant T47D cells...
February 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29421698/design-synthesis-characterization-antimicrobial-evaluation-and-molecular-modeling-studies-of-some-dehydroacetic-acid-chalcone-1-2-3-triazole-hybrids
#17
Kashmiri Lal, Pinki Yadav, Ashwani Kumar, Anil Kumar, Avijit Kumar Paul
A series of new dehydroacetic acid chalcone-1,2,3-triazole hybrids as potential antimicrobial agents was designed, synthesized and characterized by FTIR, NMR and HRMS spectral techniques. All the synthesized compounds were screened in vitro against four bacterial strains (Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and two fungal strains (Aspergillus niger and Candida albicans). The antimicrobial results indicated that some of the compounds showed remarkable activities comparable to the standard drugs...
January 11, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29412654/activity-of-topotecan-towards-the-dna-topoi-complex-a-theoretical-rationalization
#18
Semiha Kevser Bali, Antoine Marion, Ilke Ugur, Ayse Kumru Dikmenli, Saron Catak, Viktorya Aviyente
Topotecan (TPT) is a non-toxic anti-cancer drug characterized by a pH dependent lactone/carboxyl equilibrium. TPT acts on the covalently bonded DNA/Topoisomerase I (DNA/TopoI) complex by intercalating between two DNA bases at the active site. This turns TopoI into a DNA-damaging agent and inhibits supercoil relaxation. Although only the lactone form of the drug is active and effectively inhibits TopoI, both forms have been co-crystalized at the same location within the DNA/TopoI complex. To gain further insights into the pH dependent activity of TPT, the differences between two TPT:DNA/TopoI complexes presenting either the lactone (acidic pH) or the carboxyl (basic pH) form of TPT were studied by means of molecular dynamic simulations, QM/MM calculations, and topological analysis...
February 7, 2018: Biochemistry
https://www.readbyqxmd.com/read/29412642/sn-38-conjugated-gold-nanoparticles-activated-by-ewing-sarcoma-specific-mrnas-exhibit-in-vitro-and-in-vivo-efficacy
#19
Jordan A Naumann, John C Widen, Leslie A Jonart, Maryam Ebadi, Jian Tang, David J Gordon, Daniel A Harki, Peter M Gordon
The limited delivery of chemotherapy agents to cancer cells and the non-specific action of these agents are significant challenges in oncology. We have previously developed a customizable drug delivery and activation system in which a nucleic acid functionalized gold nanoparticle (Au-NP) delivers a drug that is selectively activated within a cancer cell by the presence of an mRNA unique to the cancer cell. The amount of drug released from sequestration to the Au-NP is determined by both the presence and abundance of the cancer cell specific mRNA in a cell...
February 7, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29412515/l-methionine-anti-biofilm-activity-against-pseudomonas-aeruginosa-is-enhanced-by-the-cystic-fibrosis-transmembrane-conductance-regulator-potentiator-ivacaftor
#20
Do-Yeon Cho, Dong-Jin Lim, Calvin Mackey, Christopher G Weeks, Jaime A Peña Garcia, Daniel Skinner, Jessica W Grayson, Harrison S Hill, David K Alexander, Shaoyan Zhang, Bradford A Woodworth
BACKGROUND: Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms...
February 7, 2018: International Forum of Allergy & Rhinology
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