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https://www.readbyqxmd.com/read/29351057/global-gene-expression-response-in-mouse-models-of-dna-repair-deficiency-after-gamma-irradiation
#1
Nils Rudqvist, Evagelia C Laiakis, Shanaz A Ghandhi, Suresh Kumar, Jeffrey D Knotts, Mashkura Chowdhury, Albert J Fornace, Sally A Amundson
In the event of an improvised nuclear device or "dirty bomb" in a highly populated area, potentially hundreds of thousands of people will require screening to ensure that exposed individuals receive appropriate treatment. For this reason, there is a need to develop tools for high-throughput radiation biodosimetry. Gene expression represents an emerging approach to biodosimetry and could potentially provide an estimate of both absorbed dose and individual radiation-induced injury. Since approximately 2-4% of humans are thought to be radiosensitive, and would suffer greater radiological injury at a given dose than members of the general population, it is of interest to explore the potential impact of such sensitivity on the biodosimetric gene expression signatures being developed...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29349619/1h-15n-and-13c-chemical-shift-assignments-of-the-micelle-immersed-fat-c-terminal-fatc-domains-of-the-human-protein-kinases-ataxia-telangiectasia-mutated-atm-and-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs-fused-to-the-b1-domain-of-streptococcal
#2
Munirah S Abd Rahim, Lisa A M Sommer, Anja Wacker, Martin Schaad, Sonja A Dames
FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent NMR- and CD-monitored interaction studies indicated that the FATC domains of all PIKKs can interact with membrane mimetics albeit with different preferences for membrane properties such as surface charge and curvature. Thus they may generally act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical shift assignments of the DPC micelle immersed FATC domains of the human PIKKs ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue long B1 domain of Streptococcal protein G (GB1)...
January 18, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29348882/microrna203a-suppresses-glioma-tumorigenesis-through-an-atm-dependent-interferon-response-pathway
#3
Chuan He Yang, Yinan Wang, Michelle Sims, Chun Cai, Ping He, Hans Häcker, Junming Yue, Jinjun Cheng, Frederick A Boop, Lawrence M Pfeffer
Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348875/radiosensitization-of-the-pi3k-inhibitor-hs-173-through-reduction-of-dna-damage-repair-in-pancreatic-cancer
#4
Jung Hee Park, Kyung Hee Jung, Soo Jung Kim, Zhenghuan Fang, Hong Hua Yan, Mi Kwon Son, Juyoung Kim, Yeo Wool Kang, Ji Eun Lee, Boreum Han, Joo Han Lim, Soon-Sun Hong
Activation of PI3K/AKT pathway occurs frequently in tumors and is correlated with radioresistance. The PI3K/AKT pathway can be an important target for improvement of radiotherapy. Although adding of chemotherapy to radiation therapy regimen enhances survival in patients with locally advanced pancreatic cancer, more effective therapies for increasing radiosensitivity are urgently needed. In this study, we investigated whether the novel PI3K inhibitor HS-173 could attenuate radiation-induced up-regulation of DNA damage repair processes and assessed its efficacy as a radio- and chemo-sensitizer...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348823/prevalence-of-pathogenic-germline-variants-detected-by-multigene-sequencing-in-unselected-japanese-patients-with-ovarian-cancer
#5
Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Hiroyuki Nomura, Kiyoshi Masuda, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki
Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348487/h1-phgfk1-nanoparticles-exert-anti-tumoural-and-radiosensitising-effects-by-inhibition-of-met-in-glioblastoma
#6
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#7
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29344228/expression-and-clinical-significance-of-atm-and-puma-gene-in-patients-with-colorectal-cancer
#8
Hui Xiong, Jiangnan Zhang
The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343641/degradation-of-fbxo31-by-apc-c-is-regulated-by-akt-and-atm-mediated-phosphorylation
#9
Srinadh Choppara, Sunil K Malonia, Ganga Sankaran, Michael R Green, Manas Kumar Santra
The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29340025/the-novel-atm-inhibitor-az31-enhances-antitumor-activity-in-patient-derived-xenografts-that-are-resistant-to-irinotecan-monotherapy
#10
Justin Greene, Anna Nguyen, Stacey M Bagby, Gemma N Jones, W M Tai, Kevin S Quackenbush, Anna Schreiber, Wells A Messersmith, Kalpana M Devaraj, Patrick Blatchford, S Gail Eckhardt, Elaine B Cadogan, Gareth D Hughes, Aaron Smith, Todd M Pitts, John J Arcaroli
Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by generating double strand breaks resulting in DNA damage. The activation of the ATM pathway plays a fundamental role in regulating the cellular response and repair to DNA damage. The objective of this preclinical study was to determine whether ATM inhibition would enhance sensitivity to irinotecan treatment. Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in CRC cell lines and CRC patient derived xenografts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339439/idh1-2-mutations-sensitize-acute-myeloid-leukemia-to-parp-inhibition-and-this-is-reversed-by-idh1-2-mutant-inhibitors
#11
Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartlomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E Bleeker, Johanna W Wilmink, Hetty Carraway, Sudipto Mukherjee, Mikkael A Sekeres, Cornelis J F Van Noorden, Jaroslaw P Maciejewski
PURPOSE: Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increases in DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. EXPERIMENTAL DESIGN: Well-characterized primary IDH1MUT, IDH2MUT and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation and PARP inhibitors...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#12
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29337323/conversion-of-co2-into-cyclic-carbonates-by-a-co-ii-metal-organic-framework-and-the-improvement-of-catalytic-activity-via-nanocrystallization
#13
Xiao-He Ji, Ning-Ning Zhu, Jian-Gong Ma, Peng Cheng
The Co(ii) metal-organic framework (MOF) {[Co(μ3-L)(H2O)]·0.5H2O}n (1, H2L = thiazolidine 2,4-dicarboxylic acid) with rich Lewis acid sites was used as a catalyst for the conversion of CO2 and propylene oxide into propylene carbonate with a yield of up to 98% under 50 °C and 1 atm. 1 exhibited excellent reusability, which could be regenerated easily for at least five runs without a decrease in the yield. Importantly, we synthesized two types of nano-crystals (N1 and N2) of 1 with polyvinylpyrrolidone (PVP) and hexadecyltrimethylammonium bromide (CTAB) as surfactants, respectively, and investigated their catalytic properties in comparison with that of 1 in the powder phase...
January 16, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29337287/revealing-determinants-of-two-phase-dynamics-of-p53-network-under-gamma-irradiation-based-on-a-reduced-2d-relaxation-oscillator-model
#14
Gökhan Demirkıran, Güleser Kalaycı Demir, Cüneyt Güzeliş
This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator...
February 2018: IET Systems Biology
https://www.readbyqxmd.com/read/29335925/germline-deleterious-mutations-in-genes-other-than-brca2-are-infrequent-in-male-breast-cancer
#15
Florentia Fostira, Emmanouil Saloustros, Paraskevi Apostolou, Andromahi Vagena, Despoina Kalfakakou, Davide Mauri, Dimitrios Tryfonopoulos, Vassileios Georgoulias, Drakoulis Yannoukakos, Georgios Fountzilas, Irene Konstantopoulou
PURPOSE: Male breast cancer (MBC) is a rare cancer entity, with mutations in BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing has already entered clinical practice for female breast cancer, whereas the performance of panel testing in MBC has not been studied extensively. Therefore, the aim of this study was to evaluate the clinical utility of panel testing for MBC, by the largest gene panel used so far, through investigation of patients deriving from a population with known founder effects...
January 15, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29335219/thermal-removal-of-arsenic-from-copper-concentrates-three-dimensional-isothermal-predominance-diagrams-for-the-cu-as-s-o-system
#16
M Sadegh Safarzadeh, Stanley M Howard
The three-dimensional predominance volume diagrams (PVDs) for the system Cu-As-S-O were constructed at 900 K using [Formula: see text] as independent coordinates. The constant total pressure surface was used to identify the equilibrium phases that are stable at 0.25 atm total pressure. The isobaric surface superimposed on the predominance diagram provides useful insights into the roasting of complex copper sulfosalts such as enargite (Cu3AsS4) and tennantite (Cu12As4S13). There are nine interior invariant points each with four associated condensed phases at 900 K...
January 5, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#17
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333574/unique-metabolic-activation-of-adipose-tissue-macrophages-in-obesity-promotes-inflammatory-responses
#18
Lily Boutens, Guido J Hooiveld, Sourabh Dhingra, Robert A Cramer, Mihai G Netea, Rinke Stienstra
AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29331863/airborne-volatile-aromatic-hydrocarbons-at-an-urban-monitoring-station-in-korea-from-2013-to-2015
#19
Azmatullah Khan, Jan E Szulejko, Ki-Hyun Kim, Richard J C Brown
The concentrations of C6-C10 volatile aromatic hydrocarbons (AHCs) in air were measured at an urban air quality monitoring station in Jong-Ro, Seoul, Korea, between 2013 and 2015. Their temporal patterns (e.g., diurnal, intraweek, daily) were assessed individually and collectively as groups of benzene, toluene, ethylbenzene, styrene, and xylene (BTESX); total aliphatic hydrocarbon (TALHC: C2-C12); total aromatic hydrocarbon (TARHC: C6-C10); and total hydrocarbon (THC: C2-C12). The highest mean AHC concentrations over the 3-year study (in ppb (v/v)) were observed for toluene (6...
January 11, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29330575/a-new-technique-for-minimal-invasive-complete-spinal-cord-injury-in-minipigs
#20
Elena E Foditsch, Gratian Miclaus, Irina Patras, Ioan Hutu, Karin Roider, Sophina Bauer, Günter Janetschek, Ludwig Aigner, Reinhold Zimmermann
BACKGROUND: The aim of this study was to develop a minimal invasive complete spinal cord injury (SCI) minipig model for future research applications. The minipig is considered a translationally relevant model for SCI research. However, a standardized minimal invasive complete SCI model for pigs has not yet been established. METHODS: Adult Göttingen minipigs were anesthetized and placed in extended prone position. After initial computed tomography (CT) scan, the skin was incised, a needle placed in the epidural fatty tissue...
January 12, 2018: Acta Neurochirurgica
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