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https://www.readbyqxmd.com/read/29156836/the-role-of-rak-in-the-regulation-of-stability-and-function-of-brca1
#1
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Mitchell F Denning, Tarun B Patel, Clodia Osipo, Shiaw-Yih Lin, Eun-Kyoung Breuer
BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#2
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156764/the-neil1-g83d-germline-dna-glycosylase-variant-induces-genomic-instability-and-cellular-transformation
#3
Heather A Galick, Carolyn G Marsden, Scott Kathe, Julie A Dragon, Lindsay Volk, Antonia A Nemec, Susan S Wallace, Aishwarya Prakash, Sylvie Doublié, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156754/functional-characterization-of-a-novel-transcript-of-ercc1-in-chemotherapy-resistance-of-ovarian-cancer
#4
Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu, Weiling Li
Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156695/mir-2964a-5p-binding-site-snp-regulates-atm-expression-contributing-to-age-related-cataract-risk
#5
Han Rong, Shanshan Gu, Guowei Zhang, Lihua Kang, Mei Yang, Junfang Zhang, Xinyue Shen, Huaijin Guan
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156686/crosstalk-between-mismatch-repair-and-base-excision-repair-in-human-gastric-cancer
#6
Valeria Simonelli, Giuseppe Leuzzi, Giorgia Basile, Mariarosaria D'Errico, Paola Fortini, Annapaola Franchitto, Valentina Viti, Ashley R Brown, Eleonora Parlanti, Barbara Pascucci, Domenico Palli, Alessandro Giuliani, Fabio Palombo, Robert W Sobol, Eugenia Dogliotti
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#7
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156675/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#8
Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156531/heated-naringin-mitigate-the-genotoxicity-effect-of-mitomycin-c-in-balb-c-mice-through-enhancing-the-antioxidant-status
#9
Mouna Maatouk, Nadia Mustapha, Imen Mokdad-Bzeouich, Hind Chaaban, Irina Ioannou, Kamel Ghedira, Mohamed Ghoul, Leila Chekir-Ghedira
A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#10
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29156408/label-free-electrochemical-dna-biosensor-for-guanine-and-adenine-by-ds-dna-poly-l-cysteine-fe3o4-nanoparticles-graphene-oxide-nanocomposite-modified-electrode
#11
Majid Arvand, Mona Sanayeei, Shiva Hemmati
In this study, we aim to design a simple and effective electrochemical DNA biosensor based on a carbon paste electrode modified with ds-DNA/poly(L-cysteine)/Fe3O4 nanoparticles-graphene oxide (ds-DNA/p(L-Cys)/Fe3O4 NPs-GO/CPE) for sensitive detection of adenine (A) and guanine (G). The electrocatalytic oxidation of A and G on the electrode was explored by differential pulse voltammetry (DPV) and cyclic voltammetry (CV). This sensor shows separated and well-defined peaks for A and G, by which one can determine these biological bases individually or simultaneously...
November 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29156348/development-of-photoprotective-antiphototoxic-and-antiphotogenotoxic-formulations-of-ocular-drugs-with-fluoroquinolones
#12
Anna Zgadzaj, Joanna Kornacka, Anita Jastrzębska, Andrzej Parzonko, Sylwester Sommer, Grzegorz Nałęcz-Jawecki
The development of innovative solutions in photosafety of photolabile pharmaceutical products may help to reduce the adverse effects of these products, caused by light exposure. Providing new data in this area of study is particularly important in case of drugs applied topically on sensitive organs such as eyes. The main goal of this research is to investigate whether two potential excipients, namely: p-coumaric acid and benzophenone-4, affect the photodegradation, phototoxicity and photogenotoxicity of water solutions of four fluoroquinolones: ciprofloxacin, lomefloxacin, fleroxacin and clinafloxacin...
November 9, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29156305/effect-of-dietary-supplementation-with-spirulina-platensis-on-atrazine-induced-oxidative-stress-mediated-hepatic-damage-and-inflammation-in-the-common-carp-cyprinus-carpio-l
#13
Hosam Toughan, Samah R Khalil, Ashraf Ahmed El-Ghoneimy, Ashraf Awad, A Sh Seddek
The present study evaluated the potential modulatory effect(s) of dietary supplementation with Spirulina platensis (SP) on Atrazine (ATZ)-induced oxidative stress and inflammation in common carp (Cyprinus carpio L.). Common carp was exposed to ATZ (428μg/L) and SP (1%), either alone or in combination, for 40 days. Subsequently, the treatment groups were evaluated for ATZ-induced oxidative stress-mediated hepatic damage and the potential antioxidant effect(s) of SP supplementation. The results indicated that ATZ exposure led to a significant increase in the oxidative stress as suggested by the increased levels of lipid and DNA oxidative damage markers and the significant decline of antioxidant status biomarkers...
November 17, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29155820/mass-spectrometry-based-quantification-of-the-cellular-response-to-ultraviolet-radiation-in-hela-cells
#14
Hong Xu, Xuanyi Chen, Nanjiao Ying, Meixia Wang, Xiaoli Xu, Rongyi Shi, Yuejin Hua
Ultraviolet (UV) irradiation is a common form of DNA damage that can cause pyrimidine dimers between DNA, which can cause gene mutations, even double-strand breaks and threaten genome stability. If DNA repair systems default their roles at this stage, the organism can be damaged and result in disease, especially cancer. To better understand the cellular response to this form of damage, we applied highly sensitive mass spectrometry to perform comparative proteomics of phosphorylation in HeLa cells. A total of 4367 phosphorylation sites in 2100 proteins were identified, many of which had not been reported previously...
2017: PloS One
https://www.readbyqxmd.com/read/29155785/modeling-neuronal-death-and-degeneration-in-mouse-primary-cerebellar-granule-neurons
#15
Matthew Laaper, Takrima Haque, Ruth S Slack, Arezu Jahani-Asl
Cerebellar granule neurons (CGNs) are a commonly used neuronal model, forming an abundant homogeneous population in the cerebellum. In light of their post-natal development, abundance, and accessibility, CGNs are an ideal model to study neuronal processes, including neuronal development, neuronal migration, and physiological neuronal activity stimulation. In addition, CGN cultures provide an excellent model for studying different modes of cell death including excitotoxicity and apoptosis. Within a week in culture, CGNs express N-methyl-D-aspartate (NMDA) receptors, a specific ionotropic glutamate receptor with many critical functions in neuronal health and disease...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155761/advanced-confocal-microscopy-techniques-to-study-protein-protein-interactions-and-kinetics-at-dna-lesions
#16
Soňa Legartová, Jana Suchánková, Jana Krejčí, Alena Kovaříková, Eva Bártová
Local microirradiation with lasers represents a useful tool for studies of DNA-repair-related processes in live cells. Here, we describe a methodological approach to analyzing protein kinetics at DNA lesions over time or protein-protein interactions on locally microirradiated chromatin. We also show how to recognize individual phases of the cell cycle using the Fucci cellular system to study cell-cycle-dependent protein kinetics at DNA lesions. A methodological description of the use of two UV lasers (355 nm and 405 nm) to induce different types of DNA damage is also presented...
November 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155394/label-free-and-dynamic-monitoring-of-cytotoxicity-to-the-blood-brain-barrier-cells-treated-with-nanometre-copper-oxide
#17
Duan Lian, Zhang Chonghua, Gu Wen, Zhang Hongwei, Bai Xuetao
A cytotoxicity study was conducted with a primary culture of the nervous system cells, including brain microvascular endothelial cells (BMECs) and astrocytes, which are important components of the blood-brain barrier. The real-time cell analysis (RTCA) was used to determine the cytotoxicity of copper-oxide nanoparticles (CuO NPs). The IC50 values of CuO NPs in astrocytes and BMECs were determined by the RTCA at different exposure times and were used as base values for further research. DNA damage after exposure to CuO NPs for 3 and 24 h was assessed using comet assay at the IC50 obtained from RTCA...
December 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29155363/homocysteine-inhibits-endothelial-progenitor-cell-proliferation-via-dnmt1-mediated-hypomethylation-of-cyclin-a
#18
Hui-Ping Zhang, Yan-Hua Wang, Sheng-Chao Ma, Hui Zhang, An-Ning Yang, Xiao-Ling Yang, Ming-Hao Zhang, Jian-Min Sun, Yin-Ju Hao, Yi-Deng Jiang
Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner...
November 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29155258/insights-into-the-multifunctional-role-of-natural-killer-enhancing-factor-a-nkef-a-prx1-in-big-belly-seahorse-hippocampus-abdominalis-dna-protection-insulin-reduction-h2o2-scavenging-and-immune-modulation-activity
#19
G I Godahewa, N C N Perera, Jehee Lee
Natural killer enhancing factor A (NKEF-A), also known as peroxiredoxin 1 (Prx1), is a well-known antioxidant involved in innate immunity. Although NKEF-A/Prx1 has been studied in different fish species, the present study broadens the knowledge of NKEF-A gene in terms of molecular structure, function, and immune responses in fish species. Hippocampus abdominalis NKEF-A (HaNKEF-A) cDNA encoded a putative protein of 198 amino acids containing a thioredoxin_2 domain, VCP motifs, and three conserved cysteine residues including peroxidatic and resolving cysteines...
November 16, 2017: Gene
https://www.readbyqxmd.com/read/29155239/mechanisms-controlling-the-anti-neoplastic-functions-of-foxo-proteins
#20
REVIEW
Tianyun Hou, Zhiming Li, Ying Zhao, Wei-Guo Zhu
The Forkhead box O (FoxO) proteins comprise a family of evolutionarily conserved transcription factors that predominantly function as tumor suppressors. These proteins assume diverse roles in the cellular anti-neoplastic response, including regulation of apoptosis and autophagy, cancer metabolism, cell-cycle arrest, oxidative stress and the DNA damage response. More recently, FoxO proteins have been implicated in cancer immunity and cancer stem-cell (CSC) homeostasis. Interestingly, in some sporadic sub-populations, FoxO protein function may also be manipulated by factors such as β-catenin whereby they instead can facilitate cancer progression via maintenance of CSC properties or promoting drug resistance or metastasis and invasion...
November 16, 2017: Seminars in Cancer Biology
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