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https://www.readbyqxmd.com/read/28640935/additive-effect-of-radiosensitization-by-2-deoxy-d-glucose-delays-dna-repair-kinetics-and-suppresses-cell-proliferation-in-oral-squamous-cell-carcinoma
#1
Mayumi Kawata, Kazuhiro Ogi, Koyo Nishiyama, Sho Miyamoto, Takafumi Nakagaki, Makoto Shimanishi, Akihiro Miyazaki, Hiroyoshi Hiratsuka
BACKGROUND: It has well known that, compared to normal cells, tumor cells have a different manner of energy metabolism, which influences the sensitivity of radiotherapy (RT). However, whether inhibition of glycolysis enhances the efficacy of radiotherapy is a matter of debate in oral squamous cell carcinoma (OSCC). The aim of this study was to characterize whether the combination of radiotherapy with the glucose inhibitor 2-deoxy-D-glucose (2-DG) affected DNA repair kinetics. METHODS: To compare the synergistic effect of 2-DG, we examined the cell survival after treatment with radiation, 2-DG and a combination of the two in 5 OSCC cell lines and one lip fibroblast cell line, determined using clonogenic survival assay...
June 22, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28633670/preclinical-anti-myeloma-activity-of-edo-s101-a-new-bendamustine-derived-molecule-with-added-hdaci-activity-through-potent-dna-damage-induction-and-impairment-of-dna-repair
#2
Ana-Alicia López-Iglesias, Ana B Herrero, Marta Chesi, Laura San-Segundo, Lorena González-Méndez, Susana Hernández-García, Irena Misiewicz-Krzeminska, Dalia Quwaider, Montserrat Martín-Sánchez, Daniel Primo, Teresa Paíno, P Leif Bergsagel, Thomas Mehrling, Marcos González-Díaz, Jesús F San-Miguel, María-Victoria Mateos, Norma C Gutiérrez, Mercedes Garayoa, Enrique M Ocio
BACKGROUND: Despite recent advances in the treatment of multiple myeloma (MM), the prognosis of most patients remains poor, and resistance to traditional and new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as the fusion of a histone deacetylase inhibitor radical to bendamustine, with the aim of potentiating its alkylating activity. METHODS: The efficacy of EDO-S101 was evaluated in vitro, ex vivo and in vivo, alone, and in combination with standard anti-myeloma agents...
June 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#3
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28627709/the-homologous-recombination-protein-rad51-is-a-promising-therapeutic-target-for-cervical-carcinoma
#4
Qian Chen, Dongge Cai, Mu Li, Xiaoling Wu
RAD51 is one of the pivotal enzymes for DNA double-strand break (DSB) repair by the homologous recombination (HR) pathway, which implies it as a promising and novel target for cancer therapy. Recent findings have indicated RAD51 protein is overexpressed in a variety of tumors. The high-expression of RAD51 is related to poor prognosis. RAD51 is involved in the repair of DNA damage and the generation of genetic diversity by an evolutionarily conserved mechanism. However, the exact mechanism of Rad51 in the progression of cervical cancer remains unclear...
June 15, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627638/meiotic-defects-and-decreased-expression-of-genes-located-around-the-chromosomal-breakpoint-in-the-testis-of-a-patient-with-a-novel-46-x-t-y-1-p11-3-p31-translocation
#5
Guangyuan Li, Furhan Iqbal, Liu Wang, Zhipeng Xu, Xiaoyan Che, Wen Yu, Liang Shi, Tonghang Guo, Guixiang Zhou, Xiaohua Jiang, Huan Zhang, Yuanwei Zhang, Dexin Yu
Balanced translocations are known to be associated with infertility, spontaneous abortions and birth defects in mammals. Spermatocyte spreading and immunostaining were applied to detect meiotic prophase I progression, homologous chromosome pairing, synapsis and recombination in an azoospermic reciprocal translocation 46,X,t(Y;1)(p11.3;p31) carrier. Histological examination of testicular sections revealed a severely reduced number of germ cells with no spermatids or sperm in the carrier. A significant reduction in XY recombination was observed in the patient...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627616/distinct-cellular-phenotype-linked-to-defective-dna-interstrand-crosslink-repair-and-homologous-recombination
#6
Aleksandra M Gorniewska, Katarzyna Kluzek, Lidia Gackowska, Izabela Kubiszewska, Malgorzata Z Zdzienicka, Aneta Bialkowska
Repair of DNA interstrand crosslinks (ICLs) predominantly involves the Fanconi anemia (FA) pathway and homologous recombination (HR). The HR repair system eliminates DNA double strand breaks (DSBs) that emerge during ICLs removal. The current study presents a novel cell line, CL‑V8B, representing a new complementation group of Chinese hamster cell mutants hypersensitive to DNA crosslinking factors. CL‑V8B exhibits increased sensitivity to various DNA‑damaging agents, including compounds leading to DSBs formation (bleomycin and 6‑thioguanine), and is extremely sensitive to poly (ADP-ribose) polymerase inhibitor (>400‑fold), which is typical for HR‑defective cells...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28623401/biomarkers-in-the-assessment-of-oral-mucositis-in-head-and-neck-cancer-patients-a-systematic-review-and-meta-analysis
#7
REVIEW
Ana Gabriela Costa Normando, Camila Lopes Rocha, Isabela Porto de Toledo, Paulo Tadeu de Souza Figueiredo, Paula Elaine Diniz Dos Reis, Graziela De Luca Canto, Eliete Neves Silva Guerra
PURPOSE: The aim of this study was to evaluate the capability of biomarkers to predict the risk of oral mucositis in head and neck cancer patients, as well as to assess the correlation between these biomarkers and the severity of mucositis. METHODS: The search was performed at LILACS, PubMed, Science Direct, Scopus, and Web of Science. A search of the gray literature was performed on Google Scholar, OpenGrey, and ProQuest. The methodological quality of the included studies was assessed using the Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) tool, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system...
June 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28616972/dss1-regulates-association-of-brh2-with-rad51
#8
Qingwen Zhou, William K Holloman
Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, mediates delivery of Rad51 to DNA during the course of homology-directed DNA repair. Rad51 interacts with Brh2 through the highly conserved BRC element and through a second region termed CRE located at the extreme carboxy-terminus. Dss1, a small intrinsically unstructured protein that interacts with Brh2 is crucial for its activity in DNA repair, but the mechanism of this regulation is uncertain. In previous studies we found that Brh2 interaction with DNA was strongly modulated by association with Dss1...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28615972/single-nucleotide-polymorphisms-and-unacceptable-late-toxicity-in-breast-cancer-adjuvant-radiotherapy-a-case-report
#9
Grazia Lazzari, Maria Iole Natalicchio, Angela Terlizzi, Francesco Perri, Giovanni Silvano
BACKGROUND: There has recently been a strong interest in the inter-individual variation in normal tissue and tumor response to radiotherapy (RT), because tissue radiosensitivity seems to be under genetic control. Evidence is accumulating on the role of polymorphic genetic variants, such as single nucleotide polymorphisms (SNPs) that could influence normal tissue response after radiation. The most studied SNPs include those in genes involved in DNA repair (single- and double-strand breaks, and base excision) and those active in the response to oxidative stress...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28612261/low-concentrations-of-antimony-impair-dna-damage-signaling-and-the-repair-of-radiation-induced-dsb-in-hela-s3-cells
#10
Barbara Koch, Elena Maser, Andrea Hartwig
Antimony is utilized in a large variety of industrial applications, leading to significant environmental and occupational exposure. Mainly based on animal experiments, the IARC and MAK Commission have classified antimony and its inorganic compounds as Group 2B or 2 carcinogens, respectively. However, the underlying mode(s) of action are still largely unknown. In the present study, we investigated the impact of non-cytotoxic up to cytotoxic concentrations of SbCl3 on DNA DSB repair and cell cycle control in HeLa S3 cells...
June 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28611105/the-dna-binding-polyamine-moiety-in-the-vectorized-dna-topoisomerase-ii-inhibitor-f14512-alters-reparability-of-the-consequent-enzyme-linked-dna-double-strand-breaks
#11
Oriane Bombarde, Florence Larminat, Dennis Gomez, Philippe Frit, Carine Racca, Bruno Gomes, Nicolas Guilbaud, Patrick Calsou
Poisons of Topoisomerase II (TOP2) kill cancer cells by preventing religation of intermediate DNA breaks during the enzymatic process and thus by accumulating enzyme-drug-DNA complexes called TOP2 cleavage-complex (TOP2cc). F14512 is a highly cytotoxic polyamine-vectorized TOP2 inhibitor derived from etoposide and currently in clinical trials. It was shown in vitro that F14512 has acquired DNA binding properties and that the stability of TOP2cc was strongly increased. Paradoxically, at equitoxic concentrations in cells, F14512 induced less DNA breaks than etoposide...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28610420/genetic-association-between-ercc2-nbn-rad51-gene-variants-and-osteosarcoma-risk-a-systematic-review-and-meta-analysis
#12
Masoud Mehdinejad, Mohammad Reza Sobhan, Mahta Mazaheri, Masoud Zare Shehneh, Hossein Neamatzadeh, Seyed Mahdi Kalantar
Background: To date, only a few studies have investigated associations between ERCC2, NBN, and RAD51 variants and risk of developing osteosarcoma. In this systematic review and meta-analysis, we focused on clarifying links. Materials and Methods: We systematically searched PubMed, Google Scholar, and ISI web of knowledge databases to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of associations with fixed effect models. Results: No statistical evidence of association was found between ERCC2 rs13181 (G vs...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28607006/nr4a2-promotes-dna-double-strand-break-repair-upon-exposure-to-uvr
#13
Kelvin Yin, Yash Chhabra, Romain Tropée, Yi Chieh Lim, Mitchell Fane, Eloise Dray, Richard Sturm, Aaron G Smith
Exposure of melanocytes to ultraviolet radiation (UVR) induces the formation of UV-lesions that can produce deleterious effects in genomic DNA. Encounters of replication forks with unrepaired UV-lesions can lead to several complex phenomena, such as the formation of DNA double strand breaks (DSBs). The NR4A family of nuclear receptors are transcription factors that have been associated with mediating DNA repair functions downstream of the MC1R signalling pathway in melanocytes. In particular, emerging evidence shows that upon DNA damage, the NR4A2 receptor can translocate to sites of UV-lesion by mechanisms requiring post-translational modifications within the N-terminal domain and at a serine residue in the DNA biding domain at position 337...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28602639/rad52-inverse-strand-exchange-drives-rna-templated-dna-double-strand-break-repair
#14
Olga M Mazina, Havva Keskin, Kritika Hanamshet, Francesca Storici, Alexander V Mazin
RNA can serve as a template for DNA double-strand break repair in yeast cells, and Rad52, a member of the homologous recombination pathway, emerged as an important player in this process. However, the exact mechanism of how Rad52 contributes to RNA-dependent DSB repair remained unknown. Here, we report an unanticipated activity of yeast and human Rad52: inverse strand exchange, in which Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA. We show that in eukaryotes, inverse strand exchange between homologous dsDNA and RNA is a distinctive activity of Rad52; neither Rad51 recombinase nor the yeast Rad52 paralog Rad59 has this activity...
June 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#15
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28599495/investigation-of-the-relative-biological-effectiveness-and-uniform-isobiological-killing-effects-of-irradiation-with-a-clinical-carbon-sobp-beam-on-dna-repair-deficient-cho-cells
#16
Shigeaki Sunada, Ian M Cartwright, Hirokazu Hirakawa, Akira Fujimori, Mitsuru Uesaka, Takamitsu A Kato
Spread-out Bragg peak (SOBP) C ions have been used clinically in charged particle radiation therapy for years. An SOBP beam consists of various monoenergetic Bragg peaks; however, the biological effect of irradiation with an SOBP beam track has not been well-studied. In order to determine the clinically prospective molecular targets, radiosensitivity to the beam track in DNA repair deficient cell lines was investigated. A total of four distinct Chinese hamster ovary (CHO) cell lines, including CHO10B2 (wild-type), V3 (protein kinase DNA-activated catalytic polypeptide deficient), 51D1 (RAD51 paralog D deficient) and PADR9 [poly(ADP-ribose) polymerase (PARP) deficient], were irradiated with gamma-rays, C ions (290 MeV/n) and Fe ions (500 MeV/n), in order to compare cellular lethality...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28591950/-functional-analysis-of-dna-damage-repair-factor-wdr70-and-its-mutation-in-ovarian-cancer
#17
Lian-di Guo, Dan Wang, Fan Yang, Yu-Jia Liang, Xue-Qin Yang, Yi-Yang Qin, Lai-Feng Ren, Ming Zeng, Zi-Zhi Tang, Xiao-Jun Wang, Si Wang, Cong Liu, Jiang-Yan Lou, Jie Chen
OBJECTIVES: To analyze the cellular function of the newly discovered DNA damage repair factor WDR70, and investigate the mutation in ovarian cancer to verify if function loss of the WDR70gene was associated with ovarian cancer. METHODS: The WDR70 gene was silenced by using siRNA technique or overexpressed its wild and mutation type by with lentivirus and plasmid in hunman cells. The subcellular localization and biochemical function of WDR70 was analyzes by indirect immunofluorescence and immunoblotting...
July 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28591715/brca2-egfr-and-ntrk-mutations-in-mismatch-repair-deficient-colorectal-cancers-with-msh2-or-mlh1-mutations
#18
Safoora Deihimi, Avital Lev, Michael Slifker, Elena Shagisultanova, Qifang Xu, Kyungsuk Jung, Namrata Vijayvergia, Eric A Ross, Joanne Xiu, Jeffrey Swensen, Zoran Gatalica, Mark Andrake, Roland L Dunbrack, Wafik S El-Deiry
Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580318/targeting-ongoing-dna-damage-in-multiple-myeloma-effects-of-dna-damage-response-inhibitors-on-plasma-cell-survival
#19
Ana Belén Herrero, Norma Carmen Gutiérrez
Human myeloma cell lines (HMCLs) and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS), leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs) in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR), the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28579617/hdac1-2-inhibition-and-doxorubicin-impair-mre11-dependent-dna-repair-and-disc-to-override-bcr-abl1-driven-dsb-repair-in-philadelphia-chromosome-positive-b-cell-precursor-acute-lymphoblastic-leukemia
#20
S T Promod, D P Johnson, S E Bennett, E M Dennis, B G Banowsky, S S Jones, J R Shearstone, S N Quayle, C Min, M Jarpe, T Mosbruger, A D Pomicter, R R Miles, W Y Chen, K N Bhalla, P A Zweidler-McKay, D C Shrieve, M W Deininger, M B Chandrasekharan, S Bhaskara
Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here, we report that a first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB repair networks in Ph+ B-cell precursor ALL cells using common as well as distinct mechanisms...
June 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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