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G Lohmann, E Vasyutina, J Bloehdorn, N Reinart, J I Schneider, V Babu, G Knittel, G Crispatzu, P Mayer, C Prinz, J K Muenzner, B Biersack, D G Efremov, L Chessa, C D Herling, S Stilgenbauer, M Hallek, R Schobert, H C Reinhardt, B Schumacher, M Herling
Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, but is also an increasing concern in the era of more targeted therapies. As cells with low replicative activity rely on repair that triggers checkpoint-independent non-canonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Maxine Revoltar, Joo-Shik Shin, Stephanie Lim, Thein-Ga Tut, Irani Dissanayake, Joseph Descallar, Vincent Ho, Wei Chua, Weng Ng, Mark Lee, Christopher Henderson, Paul De Souza, Matthew Morgan, C Soon Lee
No abstract text is available yet for this article.
February 2016: Pathology
Bryan A Johnson, Heather L Aloor, Cary A Moody
Human papillomaviruses (HPV) exhibit constitutive activation of ATM and ATR DNA damage response (DDR) pathways, which are required for productive viral replication. Expression of HPV31 E7 alone is sufficient to activate the DDR through an unknown mechanism. Here, we demonstrate that the E7 Rb binding domain is required to increase levels of many DDR proteins, including ATM, Chk2, Chk1, the MRN components MRE11, Rad50, and NBS1, as well as the homologous recombination repair proteins BRCA1 and Rad51. Interestingly, we have found that the increase in these DNA repair proteins does not occur solely at the level of transcription, but that E7 broadly increases the half-life of these DDR factors, a phenotype that is lost in the E7 Rb binding mutant...
October 19, 2016: Virology
Katarzyna Jonak, Monika Kurpas, Katarzyna Szoltysek, Patryk Janus, Agata Abramowicz, Krzysztof Puszynski
No abstract text is available yet for this article.
October 21, 2016: BMC Systems Biology
Sanja Dacic, Liza C Villaruz, Shira Abberbock, Alyssa Mahaffey, Pimpin Incharoen, Marina N Nikiforova
Break-apart ALK FISH probe is the FDA approved approach for detection of ALK rearrangements in lung carcinoma patients who may benefit from ALK kinase inhibitors. The FISH assay can be technically challenging and difficult to interpret. ALK immunohistochemistry and next generation sequencing have been proposed as alternative approaches. In this study, we compared various ALK -FISH patterns to next -generation sequencing (NGS) for gene fusion detection, ALK immunohistochemistry (IHC) and tumor responses to crizotinib...
October 17, 2016: Oncotarget
Damoon Sohrabi Baba Heidary, Clive A Randall
Both Li2CO3-coated nickel particles and fast firing technique were utilized in the manufacturing of MLCCs. They preserved the conductivity of Ni electrodes and provided the possibility of sintering the devices in oxidizing atmospheres. By using our method, the partial pressure of oxygen increase from 10-10 atm in conventional methods to 10-4 atm. The oxidizing atmosphere reduced the oxygen vacancy concentration as illustrated by the color change of the samples, and the results of EELS (electron energy loss spectroscopy)...
October 21, 2016: ACS Applied Materials & Interfaces
Katayoun Mahdavi Ara, Farhad Raofie
Essential oils and volatile components of pomegranate (Punica granatum L.) peel of the Malas variety from Meybod, Iran, were extracted using supercritical fluid extraction (SFE) and hydro-distillation methods. The experimental parameters of SFE that is pressure, temperature, extraction time, and modifier (methanol) volume were optimized using a central composite design after a (2(4-1)) fractional factorial design. Detailed chemical composition of the essential oils and volatile components obtained by hydro-distillation and optimum condition of the supercritical CO2 extraction were analyzed by GC-MS, and seventy-three and forty-six compounds were identified according to their retention indices and mass spectra, respectively...
July 2016: Journal of Food Science and Technology
Gamze Cebi, Şenol Yildiz, Gunalp Uzun, Yeşim Oztas, Suna Sabuncuoglu, Ayhan Kutlu, Yasin Ilgaz, Iclal Karatop-Cesur, Eyup Dogan, Emin Oztas
Myoglobinuric acute renal failure (MARF) may develop after severe muscle injury. Heme oxygenase-1 (HO-1), a stress-response protein, has been implicated as a protective agent against MARF. We hypothesized that hyperbaric oxygen therapy (HBOT) may alleviate MARF by inducing renal HO-1 expression. Wistar-Albino rats were randomly assigned into three groups: Control (n = 4), MARF (n = 8), MARF + HBO (n = 8). MARF was induced by intramuscular glycerol (50%, 8 mL/kg) injection. Saline (8 mL/kg) was injected into the hind limb of the animals in the control group...
October 20, 2016: Renal Failure
Yuguang Zhao, Lei Yang, Di Wu, Hua He, Mengmeng Wang, Tingwen Ge, Yudi Liu, Huimin Tian, Jiuwei Cui, Lin Jia, Ziqiang Wan, Fujun Han
PURPOSE: We conducted two meta-analyses of ATM genetic polymorphisms and cancer risk in individuals with or without radiation exposure to determine whether there was a joint effect between the ATM gene and radiation exposure in carcinogenesis. RESULTS: rs1801516, which was the only ATM polymorphism investigated by more than 3 studies of radiation exposure, was eligible for the present study. The meta-analysis of 23333 individuals without radiation exposure from 24 studies showed no association between the rs1801516 polymorphism and cancer risk, without heterogeneity across studies...
October 18, 2016: Oncotarget
Isaac Choi, Hyunho Chung, Jang Won Park, Young Keun Chung
A cobalt-rhodium heterobimetallic nanoparticle-catalyzed reductive cyclization of 2-(2-nitroaryl)acetonitriles to indoles has been achieved. The tandem reaction proceeds without any additives under the mild conditions (1 atm H2 and 25 °C). This procedure could be scaled up to the gram scale. The catalytic system is significantly stable under these reaction conditions and could be reused more than ten times without loss of catalytic activity.
October 20, 2016: Organic Letters
(no author information available yet)
[This corrects the article DOI: 10.21037/atm.2016.08.28.].
September 2016: Annals of Translational Medicine
Robert L Dilley, Priyanka Verma, Nam Woo Cho, Harrison D Winters, Anne R Wondisford, Roger A Greenberg
Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance...
October 19, 2016: Nature
Igor Koturbash, Matt Merrifield, Olga Kovalchuk
PURPOSE: While the effects of high doses of ionizing radiation (IR) are relatively well characterized, the molecular mechanisms underlying cellular responses to prolonged exposure to low doses of radiation remain largely under-investigated. MATERIALS AND METHODS: Here, we addressed the DNA damage and apoptotic response in the spleen tissue of C57BL/6 male mice after fractionated exposure to X-rays within the 0.1-0.5 Gy dose range. RESULTS: The response to initial exposure to 0...
October 19, 2016: International Journal of Radiation Biology
Qiang Xiao, Hongxia Guo
In this paper, we construct an efficient and simple coarse grained (CG) model for atactic polystyrene (PS) by using a 1 : 1 mapping scheme at 463 K and 1 atm pressure and derive the corresponding bonded and non-bonded potentials in the CG force field (FF) via a direct Boltzmann inversion approach and a combined structure-based and thermodynamic quantities-based CG method, respectively. For computational considerations, the non-bonded interaction between CG particles is described by Lennard-Jones (LJ) type potentials, and both the radial distribution function (RDF) and the bulk density of the atomistic simulations are taken as target properties in the parameterization of the two LJ parameters...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
Minglun Cheng, Mei Wang, Dehua Zheng, Licheng Sun
Three biomimetic models of the [FeFe]-hydrogenase active site, namely diiron dithiolates of [(μ-edt){Fe(CO)3}{Fe(CO)(κ(2)-PNP)}] (1, edt = ethane-1,2-dithiolate, PNP = Ph2PCH2N(nPr)CH2PPh2), [(μ-bdtMe){Fe(CO)3}{Fe(CO)(κ(2)-PNP)}] (2, bdtMe = 4-methylbenzene-1,2-dithiolate), and [(μ-adtBn){Fe(CO)3}{Fe(CO)(κ(2)-PNP)}] (3, adtBn = N-benzyl-2-azapropane-1,3-dithiolate), were prepared and structurally characterized. These complexes feature the same PNP ligand but different S-to-S bridges. Influence of the S-to-S bridge on the electrochemical properties and chemical oxidation reactivity of 1-3 was studied by cyclic voltammetry and by in situ IR spectroscopy...
October 18, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Zhoushuai Qin, Zhiqiang Bai, Ying Sun, Xiaohong Niu, Wei Xiao
In response to replication-blocking lesions, proliferating cell nuclear antigen (PCNA) can be sequentially ubiquitinated at the K164 residue leading to two modes of DNA-damage tolerance, namely translesion DNA synthesis (TLS) and error-free lesion bypass. Ectopic expression of PCNA fused with ubiquitin (Ub) lacking the two C-terminal Gly residues resembles PCNA monoubiquitination-mediated TLS. However, if the fused Ub contains C-terminal Gly residues, it is further polyubiquitinated and inhibits cell proliferation...
October 18, 2016: Cell Cycle
Juan A Montero, Cristina Sanchez-Fernandez, Carlos I Lorda-Diez, Juan A Garcia-Porrero, Juan M Hurle
DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage...
October 18, 2016: Scientific Reports
Elena Castro, Joaquin Mateo, David Olmos, Johann S de Bono
Several genomic studies have identified DNA repair gene defects in prostate cancer in the last 5 years. The mechanisms by which these DNA repair defects promote carcinogenesis and tumor progression in the prostate have not been fully elucidated, but their presence in at least 20-25% of metastatic castration-resistant prostate cancers (CRPCs) provides an opportunity for a therapeutic strategy that turns a tumor strength into its weakness and may lead to arguably the first molecularly stratified treatment for this disease...
September 2016: Cancer Journal
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
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