162,217 results match your criteria dna damage


DNA damage response and PD-1/PD-L1 pathway in ovarian cancer.

DNA Repair (Amst) 2021 Apr 1;102:103112. Epub 2021 Apr 1.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin, 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, 300052, China. Electronic address:

Ovarian cancer has a poor prognosis due to drug resistance, relapse and metastasis. In recent years, immunotherapy has been applied in numerous cancers clinically. However, the effect of immunotherapy monotherapy in ovarian cancer is limited. Read More

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The responses of Salmonella enterica serovar Typhimurium to vanillin in apple juice through global transcriptomics.

Int J Food Microbiol 2021 Mar 31;347:109189. Epub 2021 Mar 31.

School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province 510640, China. Electronic address:

Salmonella enterica serovar Typhimurium can survive some extreme environment in food processing, and vanillin generally recognized as safe is bactericidal to pathogens. Thus, we need to explore the responses of S. Typhimurium to vanillin in order to apply this antimicrobial agent in food processing. Read More

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Pharmacological inhibition of HSP90 radiosensitizes HNSCC xenograft by inhibition of DNA damage repair, nucleotide metabolism, and radiation-induced tumor vasculogenesis.

Int J Radiat Oncol Biol Phys 2021 Apr 7. Epub 2021 Apr 7.

Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address:

Purpose: Recent pre-clinical studies suggest combining the HSP90 inhibitor AT13387 (Onalespib) with radiation (IR) against colon cancer and HNSCC. These studies emphasized that AT13387 down-regulates HSP90 client proteins involved in oncogenic signaling and DNA repair mechanisms as major drivers of enhanced radiosensitivity. Given the large array of client proteins HSP90 directs, we hypothesized that other key proteins or signaling pathways may be inhibited by AT13387 and contribute to enhanced radiosensitivity. Read More

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Copper chloride inhibits brush border membrane enzymes, alters antioxidant and metabolic status and damages DNA in rat intestine: a dose-dependent study.

Environ Sci Pollut Res Int 2021 Apr 10. Epub 2021 Apr 10.

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.

Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Read More

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Ruthenium (II)/allopurinol complex inhibits breast cancer progression via multiple targets.

J Biol Inorg Chem 2021 Apr 10. Epub 2021 Apr 10.

Laboratório de Genética Molecular E Citogenética Humana, sala 213, Departamento de Genética, Instituto de Ciências Biológicas I, Campus Samambaia, Universidade Federal de Goiás, Avenida Esperança, s/n, Cx Postal: 131, Goiânia, Goiás, CEP 74690-900, Brazil.

Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl(allo)(PPh)] (1) and [RuCl(allo)(dppb)] (2), where allo means allopurinol, PPh is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV-Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. Read More

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Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin.

Br J Cancer 2021 Apr 9. Epub 2021 Apr 9.

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.

Background: The prognosis for high-risk childhood acute leukaemias remains dismal and established treatment protocols often cause long-term side effects in survivors. This study aims to identify more effective and safer therapeutics for these patients.

Methods: A high-throughput phenotypic screen of a library of 3707 approved drugs and pharmacologically active compounds was performed to identify compounds with selective cytotoxicity against leukaemia cells followed by further preclinical evaluation in patient-derived xenograft models. Read More

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Multinucleation associated DNA damage blocks proliferation in p53-compromised cells.

Commun Biol 2021 Apr 9;4(1):451. Epub 2021 Apr 9.

School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.

Nuclear atypia is one of the hallmarks of cancers. Here, we perform single-cell tracking studies to determine the immediate and long-term impact of nuclear atypia. Tracking the fate of newborn cells exhibiting nuclear atypia shows that multinucleation, unlike other forms of nuclear atypia, blocks proliferation in p53-compromised cells. Read More

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Dosimetric evaluation of receptor-heterogeneity on the therapeutic efficacy of peptide receptor radionuclide therapy: correlation with DNA damage induction and survival.

J Nucl Med 2021 Apr 9. Epub 2021 Apr 9.

Erasmus MC, Netherlands.

To build a refined dosimetry model for [Lu]Lu-DOTA-[Tyr]octreotate (Lu-DOTATATE) experiments enabling the correlation of absorbed dose with double strand breaks (DSBs) induction and cell death. Somatostatin receptor type-2 (SSTR) expression of NCI-H69 xenografted mice, injected with Lu-DOTATATE, was imaged at 0, 2, 5, 11 days. This was used as input to reconstruct realistic 3 dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells. Read More

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Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors.

Genes Environ 2021 Apr 9;43(1):12. Epub 2021 Apr 9.

Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.

Background: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Read More

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Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Institute for Cardiovascular Physiology, Goethe University, 60590 Frankfurt am Main, Germany;

Reactive oxygen species (ROS) can cause cellular damage and promote cancer development. Besides such harmful consequences of overproduction of ROS, all cells utilize ROS for signaling purposes and stabilization of cell homeostasis. In particular, the latter is supported by the NADPH oxidase 4 (Nox4) that constitutively produces low amounts of HO By that mechanism, Nox4 forces differentiation of cells and prevents inflammation. Read More

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Enhanced cytarabine-induced killing in OGG1-deficient acute myeloid leukemia cells.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239;

Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents or tumor-specific genetic deficiencies. There is also evidence suggesting that inhibition of the BER enzyme 8-oxoguanine DNA glycosylase-1 (OGG1), which initiates repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-dG), could be useful in treating certain cancers. Specifically, in acute myeloid leukemia (AML), both the RUNX1-RUNX1T1 fusion and the CBFB-MYH11 subtypes have lower levels of expression, which correlate with increased therapeutic-induced cell cytotoxicity and good prognosis for improved, relapse-free survival compared with other AML patients. Read More

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DNA damage response and repair in osteosarcoma: Defects, regulation and therapeutic implications.

DNA Repair (Amst) 2021 Mar 24;102:103105. Epub 2021 Mar 24.

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents which has the survival rate of 20% in its advanced stages. Osteosarcomas are mostly resistance to our common treatments. DNA damage response (DDR) is a specialized multistep process containing abundant proteins which are necessary for the survival of any cell and organism. Read More

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DOES STORAGE CONDITIONS OF WHOLE BLOOD OR BLOOD CELLS EFFECT GENOTOXICITY ASSESSMENT BY COMET ASSAY?

Food Chem Toxicol 2021 Apr 6:112163. Epub 2021 Apr 6.

Hacettepe University Faculty of Pharmacy Department of Pharmaceutical Toxicology, Ankara, Turkey. Electronic address:

Comet assay, applied to in vitro, in vivo and ex vivo systems, is a quick, simple, and sensitive method for the detection of genotoxicity. In general, fresh whole blood or peripheral blood mononuclear cells (PBMCs) are used in the assay for the determination of DNA damage and repair. In this study, the effects of storage conditions on genotoxicity assessed by Comet assay in human whole blood and lymphocyte samples, were evaluated. Read More

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Application of portable real-time recombinase-aided amplification (rt-RAA) assay in the clinical diagnosis of ASFV and prospective DIVA diagnosis.

Appl Microbiol Biotechnol 2021 Apr 9. Epub 2021 Apr 9.

Beijing Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

African swine fever, a serious infectious disease, has been found in many countries around the world over the last nearly 100 years, and causes untold damage to the economy wherever it occurs. Diagnosis is currently performed by real-time PCR, which is highly sensitive but can only be carried out in a diagnostic laboratory environment with sophisticated equipment and expertise. A sensitive, rapid diagnostic method that can be implemented in agricultural settings is thus urgently needed for the detection and control of African swine fever virus (ASFV) infection. Read More

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Random sperm DNA fragmentation index is not associated with clinical outcomes in day-3 frozen embryo transfer.

Asian J Androl 2021 Apr 6. Epub 2021 Apr 6.

Center of Reproductive Medicine, the Affiliated Hospital of Nantong University, Nantong 226001, China.

Damage to sperm DNA was proposed to play an important role in embryonic development. Previous studies focused on outcomes after fresh embryo transfer, whereas this study investigated the influence of sperm DNA fragmentation index (DFI) on laboratory and clinical outcomes after frozen embryo transfer (FET). This retrospective study examined 381 couples using cleavage-stage FET. Read More

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Cell Metabolism and DNA Repair Pathways: Implications for Cancer Therapy.

Front Cell Dev Biol 2021 23;9:633305. Epub 2021 Mar 23.

Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, Australia.

DNA repair and metabolic pathways are vital to maintain cellular homeostasis in normal human cells. Both of these pathways, however, undergo extensive changes during tumorigenesis, including modifications that promote rapid growth, genetic heterogeneity, and survival. While these two areas of research have remained relatively distinct, there is growing evidence that the pathways are interdependent and intrinsically linked. Read More

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Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS-Induced Caspases Activation.

Oxid Med Cell Longev 2021 25;2021:8840692. Epub 2021 Mar 25.

Institute of Advanced Diagnostic and Clinical Medicine, Zhongshan People's Hospital, Guangzhou University & Zhongshan People's Hospital Joint Biomedical Institute, 2 Sun Wen East Road, Zhongshan, Guangdong 528400, China.

Numerous studies have shown that resveratrol can induce apoptosis in cancer cells. Trans-3, 5, 4'-trimethoxystilbene (TMS), a novel derivative of resveratrol, is a more potent anticancer compound than resveratrol and can induce apoptosis in cancer cells. Herein, we examined the mechanisms involved in TMS-mediated sensitization of human osteosarcoma (143B) cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis. Read More

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Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence.

Front Physiol 2021 23;12:649547. Epub 2021 Mar 23.

Key Laboratory of Renal Disease, Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Ministry of Health of China, Beijing, China.

Acute kidney injury (AKI) is a worldwide health problem currently lacking therapeutics that directly promote renal repair or prevent the occurrence of chronic fibrosis. DNA damage is a feature of many forms of kidney injury, and targeting DNA damage and repair might be effective strategies for kidney protection in AKI. Boosting nicotinamide adenine dinucleotide (NAD) levels is thought to have beneficial effects on DNA damage repair and fibrosis in other organs. Read More

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Zinc Nanoparticles Ameliorate the Reproductive Toxicity Induced by Silver Nanoparticles in Male Rats.

Int J Nanomedicine 2021 31;16:2555-2568. Epub 2021 Mar 31.

Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Introduction: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects. Read More

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Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia.

Nat Genet 2021 Apr 8. Epub 2021 Apr 8.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Transposable elements or transposons are major players in genetic variability and genome evolution. Aberrant activation of long interspersed element-1 (LINE-1 or L1) retrotransposons is common in human cancers, yet their tumor-type-specific functions are poorly characterized. We identified MPHOSPH8/MPP8, a component of the human silencing hub (HUSH) complex, as an acute myeloid leukemia (AML)-selective dependency by epigenetic regulator-focused CRISPR screening. Read More

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lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury.

Aging (Albany NY) 2021 Apr 4;13. Epub 2021 Apr 4.

Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal University, Nanyang 473000, China.

Cerebral ischemia-reperfusion injury (CIRI) is an important pathophysiological process of ischemic stroke associated with various physiological and pathological processes, including autophagy and apoptosis. In this study, we examined the role and mechanism of long noncoding RNA CAMK2D-associated transcript 2 (C2dat2) in regulating CIRI in vivo and in vitro. C2dat2 up-regulation facilitated neuronal autophagy and apoptosis induced by CIRI. Read More

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Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer.

J Exp Clin Cancer Res 2021 Apr 8;40(1):122. Epub 2021 Apr 8.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients with BRCA mutations, and their efficacy is even more limited in triple-negative breast cancer (TNBC) due to clinical primary and acquired resistance. Here, we found that the efficacy of the PARPi olaparib in TNBC can be improved by combination with the CDK4/6 inhibitor (CDK4/6i) palbociclib.

Methods: We screened primary olaparib-sensitive and olaparib-resistant cell lines from existing BRCA/TNBC cell lines and generated cells with acquired olaparib resistance by gradually increasing the concentration. Read More

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Protective effects of resveratrol and avocado oil against paracetamol-induced hepatotoxicity in rats.

Drug Chem Toxicol 2021 Apr 8:1-9. Epub 2021 Apr 8.

Bucak School of Health, Department of Nursing, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.

This study sought to assess the protective effects of resveratrol and avocado oil in relation to paracetamol-induced hepatotoxicity in rats. The rats were divided into five groups, namely the control, paracetamol (600 mg/kg), resveratrol (RES; 10 mg/kg) + paracetamol, avocado oil (AVO; 200 mg/kg) + paracetamol, and RES + AVO + paracetamol groups. The hepatoprotective activity was evaluated by measuring biochemical parameters such as the total antioxidant status (TAS) and the total oxidant status (TOS) in each rat's liver homogenates. Read More

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Assessment of reproductive toxicity and genotoxicity of Aconiti Lateralis Radix Praeparata and its processed products in male mice.

J Ethnopharmacol 2021 Apr 5:114102. Epub 2021 Apr 5.

Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China. Electronic address:

Ethnopharmacological Relevance: Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi), the root of Aconitum carmichaelii Debx., is a representative medicine for restoring yang and rescuing patient from collapse. However, less studies had been reported on the reproductive toxicity and genotoxicity of Fuzi. Read More

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The uncharacterized SANT and BTB domain-containing protein SANBR inhibits class switch recombination.

J Biol Chem 2021 Apr 5:100625. Epub 2021 Apr 5.

Department of Biology, The Graduate Center and The City College of New York, New York, NY, 10031, USA. Electronic address:

Class switch recombination (CSR) is the process by which B cells switch production from IgM/IgD to other immunoglobulin isotypes, enabling them to mount an effective immune response against pathogens. Timely resolution of CSR prevents damage due to an uncontrolled and prolonged immune response. While many positive regulators of CSR have been described, negative regulators of CSR are relatively unknown. Read More

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A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden.

Eur J Endocrinol 2021 Apr 1. Epub 2021 Apr 1.

I Weigand, Department of Medicine IV, University Hospital Munich, München, Germany.

Background The response of advanced adrenocortical carcinoma (ACC) to current chemotherapies is unsatisfactory and a limited rate of response to immunotherapy was observed in clinical trials. High tumour mutational burden (TMB) and the presence of a specific DNA signature are characteristic features of tumours with mutations in the gene MUTYH encoding the mutY DNA glycosylase. Both have been shown to potentially predict the response to immunotherapy. Read More

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Integrated Analysis of mRNA-mA-protein Profiles Reveals Novel Insights into the Mechanisms for Cadmium-induced Urothelial Transformation.

Biomarkers 2021 Apr 8:1-23. Epub 2021 Apr 8.

Department of Geratology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 510080.

This study aimed to investigate the mechanisms underlying Cd-induced urothelial transformation, using multi-omics analyses (transcriptome, epitranscriptome, and proteome). Transcriptomics analysis was performed to estimate the expression of genes, methylated RNA immunoprecipitation sequencing analysis was used to detect mA modification, while proteomics analysis was used to identify differentially expressed proteins. Differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Read More

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Simultaneous detection of sperm membrane integrity and DNA fragmentation by flow cytometry: a novel and rapid tool for sperm analysis.

Andrology 2021 Apr 8. Epub 2021 Apr 8.

Centre for Reproductive Medicine and Andrology, University of Münster, Münster, Germany.

Background: Sperm DNA integrity has become one of the most discussed and promising biomarkers for the assessment of male fertility. However, an easy-to-apply method capable of estimating DNA fragmentation in the live fraction of spermatozoa has remained elusive, preventing this parameter from being fully applied in clinical settings.

Objectives: To validate a novel co-staining for the analysis of DNA fragmentation in membrane-intact spermatozoa. Read More

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DNA breaks-mediated fitness cost reveals RNase HI as a new target for selectively eliminating antibiotic resistant bacteria.

Mol Biol Evol 2021 Apr 8. Epub 2021 Apr 8.

Instituto Gulbenkian de Ciência, Oeiras, 2780-156, Portugal.

Antibiotic resistance often generates defects in bacterial growth called fitness cost. Understanding the causes of this cost is of paramount importance, as it is one of the main determinants of the prevalence of resistances upon reducing antibiotics use. Here we show that the fitness costs of antibiotic resistance mutations that affect transcription and translation in Escherichia coli strongly correlate with DNA breaks, which are generated via transcription-translation uncoupling, increased formation of RNA-DNA hybrids (R-loops) and elevated replication-transcription conflicts. Read More

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DNA and chromosomal damage in peripheral blood lymphocytes in patients with acute coronary syndrome undergoing a coronary angiography.

Anatol J Cardiol 2021 Apr;25(4):243-249

Department of Genetics, Faculty of Medical Sciences, University of Kragujevac; Kragujevac-Serbia.

Objective: The aim of the study was to evaluate the DNA and chromosomal damage in peripheral blood lymphocytes (PBLs) of patients with acute coronary syndrome (ACS) and to explore the effect of coronary angiographies in these patients.

Methods: The study included ACS patients who underwent a coronary angiography (CAG) and healthy controls. The ACS sample was divided into two groups: patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). Read More

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