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https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#1
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29150731/cellular-and-molecular-responses-of-adult-zebrafish-after-exposure-to-cuo-nanoparticles-or-ionic-copper
#2
Unai Vicario-Parés, Jose M Lacave, Paul Reip, Miren P Cajaraville, Amaia Orbea
Due to their antimicrobial, electrical and magnetic properties, copper nanoparticles (NPs) are suitable for a vast array of applications. Copper can be toxic to biota, making it necessary to assess the potential hazard of copper nanomaterials. Zebrafish (Danio rerio) were exposed to 10 µg Cu/L of CuO NPs of ≈100 nm (CuO-poly) or ionic copper to compare the effects provoked after 3 and 21 days of exposure and at 6 months post-exposure (mpe). At 21 days, significant copper accumulation was only detected in fish exposed to ionic copper...
November 17, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/29150442/functional-analyses-of-a-human-vascular-tumor-fos-variant-identify-a-novel-degradation-mechanism-and-a-link-to-tumorigenesis
#3
David G P van Ijzendoorn, Zary Forghany, Frauke Liebelt, Alfred C Vertegaal, Aart G Jochemsen, Judith V M G Bovée, Karoly Szuhai, David A Baker
Epithelioid hemangioma is a locally aggressive vascular neoplasm, found in bones and soft tissue, whose cause is currently unknown, but may involve oncogene activation. FOS was one of the earliest viral oncogenes to be characterized and normal cellular FOS forms part of the activator protein 1 (AP-1) transcription factor complex which plays a pivotal role in cell growth, differentiation and survival as well as the DNA damage response. Despite this, to date, a causal link between aberrant FOS function and naturally occurring tumors has not been established...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#4
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29149642/oxidative-stress-cell-cycle-arrest-dna-damage-and-apoptosis-in-adult-zebrafish-danio-rerio-induced-by-tris-1-3-dichloro-2-propyl-phosphate
#5
Hanyan Chen, Pingping Wang, Zhongkun Du, Guowei Wang, Shixiang Gao
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an additive flame retardant of high production volume, and frequently detected in biota and environment. However, knowledge on its potential risk and toxicological mechanism still remains limited. In this study, DNA damage, transcriptomic responses and biochemical changes in the liver of zebrafish (Danio rerio) induced by TDCPP were investigated. Zebrafish was exposed to 45.81μg/L (1/100 (96h-LC50)) and 229.05μg/L (1/20 (96h-LC50)) TDCPP for 7 d. The reactive oxygen species (ROS) and GSH contents, in addition to antioxidant enzyme activities in the liver changed significantly, and the mRNA levels of genes related to oxidative stress were alerted in a dose-dependent and/or sex-dependent manner after exposure to TDCPP...
November 10, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29149412/the-translationally-controlled-tumor-protein-and-the-cellular-response-to-ionizing-radiation-induced-dna-damage
#6
Jie Zhang, Grace Shim, Sonia M de Toledo, Edouard I Azzam
The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate (137)Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#7
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149203/alc1-chd1l-a-chromatin-remodeling-enzyme-is-required-for-efficient-base-excision-repair
#8
Masataka Tsuda, Kosai Cho, Masato Ooka, Naoto Shimizu, Reiko Watanabe, Akira Yasui, Yuka Nakazawa, Tomoo Ogi, Hiroshi Harada, Keli Agama, Jun Nakamura, Ryuta Asada, Haruna Fujiike, Tetsushi Sakuma, Takashi Yamamoto, Junko Murai, Masahiro Hiraoka, Kaoru Koike, Yves Pommier, Shunichi Takeda, Kouji Hirota
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2...
2017: PloS One
https://www.readbyqxmd.com/read/29149101/how-does-p53-induce-apoptosis-and-how-does-this-relate-to-p53-mediated-tumour-suppression
#9
REVIEW
Brandon J Aubrey, Gemma L Kelly, Ana Janic, Marco J Herold, Andreas Strasser
The tumour suppressor gene TP53 is mutated in ~50% of human cancers. In addition to its function in tumour suppression, p53 also plays a major role in the response of malignant as well as nontransformed cells to many anticancer therapeutics, particularly those that cause DNA damage. P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death...
November 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29149093/evolutionarily-distant-streptophyta-respond-differently-to-genotoxic-stress
#10
Radka Vágnerová, Alena Lukešová, Martin Lukeš, Petra Rožnovská, Marcela Holá, Jana Fulnečková, Jiří Fajkus, Karel J Angelis
Research in algae usually focuses on the description and characterization of morpho-and phenotype as a result of adaptation to a particular habitat and its conditions. To better understand the evolution of lineages we characterized responses of filamentous streptophyte green algae of the genera Klebsormidium and Zygnema, and of a land plant-the moss Physcomitrellapatens-to genotoxic stress that might be relevant to their environment. We studied the induction and repair of DNA double strand breaks (DSBs) elicited by the radiomimetic drug bleomycin, DNA single strand breaks (SSB) as consequence of base modification by the alkylation agent methyl methanesulfonate (MMS) and of ultra violet (UV)-induced photo-dimers, because the mode of action of these three genotoxic agents is well understood...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29148554/modelling-direct-dna-damage-for-gold-nanoparticle-enhanced-proton-therapy
#11
Marios Sotiropoulos, Nicholas T Henthorn, John W Warmenhoven, Ranald I Mackay, Karen J Kirkby, Michael J Merchant
Gold nanoparticles have been proven as potential radiosensitizer when combined with protons. Initially the radiosensitization effect was attributed to the physical interactions of radiation with the gold and the production of secondary electrons that induce DNA damage. However, emerging data challenge this hypothesis, supporting the existence of alternative or supplementary radiosensitization mechanisms. In this work we incorporate a realistic cell model with detailed DNA geometry and a realistic gold nanoparticle biodistribution based on experimental data...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29146919/nucleosome-acidic-patch-targeting-binuclear-ruthenium-compounds-induce-aberrant-chromatin-condensation
#12
Gabriela E Davey, Zenita Adhireksan, Zhujun Ma, Tina Riedel, Deepti Sharma, Sivaraman Padavattan, Daniela Rhodes, Alexander Ludwig, Sara Sandin, Benjamin S Murray, Paul J Dyson, Curt A Davey
The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29145667/planarians-customize-their-stem-cell-responses-following-genotoxic-stress-as-a-function-of-exposure-time-and-regenerative-state
#13
An-Sofie Stevens, Annelies Wouters, Jan-Pieter Ploem, Nicky Pirotte, Andromeda Van Roten, Maxime Willems, Niels Hellings, Carmen Franken, Gudrun Koppen, Tom Artois, Michelle Plusquin, Karen Smeets
Aiming to in vivo characterise the responses of pluripotent stem cells and regenerative tissues to carcinogenic stress, we employed the highly regenerative organism Schmidtea mediterranea. Its broad regenerative capacities are attributable to a large pool of pluripotent stem cells, which are considered key players in the lower vulnerability towards chemically-induced carcinogenesis observed in regenerative organisms. S. mediterranea is, therefore, an ideal model to study pluripotent stem cell responses with stem cells residing in their natural environment...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29144457/a-ubiquitin-dependent-signalling-axis-specific-for-alkbh-mediated-dna-dealkylation-repair
#14
Joshua R Brickner, Jennifer M Soll, Patrick M Lombardi, Cathrine B Vågbø, Miranda C Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E Sullender, Elyse Blazosky, Andrea K Byrum, Yu Zhao, Mark A Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144413/epstein-barr-virus-hijacks-dna-damage-response-transducers-to-orchestrate-its-life-cycle
#15
REVIEW
Pok Man Hau, Sai Wah Tsao
The Epstein-Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has shown that EBV triggers a DNA damage response (DDR) during primary infection and lytic reactivation. The EBV-encoded viral proteins have been implicated in deregulating the DDR signaling pathways...
November 16, 2017: Viruses
https://www.readbyqxmd.com/read/29144403/the-non-homologous-end-joining-protein-paxx-acts-to-restrict-hsv-1-infection
#16
Ben J Trigg, Katharina B Lauer, Paula Fernandes Dos Santos, Heather Coleman, Gabriel Balmus, Daniel S Mansur, Brian J Ferguson
Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 infection...
November 16, 2017: Viruses
https://www.readbyqxmd.com/read/29143974/%C3%AE-h2ax-formation-in-the-urinary-bladder-of-rats-treated-with-two-norharman-derivatives-obtained-from-o-toluidine-and-aniline
#17
T Toyoda, Y Totsuka, K Matsushita, T Morikawa, N Miyoshi, K Wakabayashi, K Ogawa
Aminomethylphenylnorharman (AMPNH) and aminophenylnorharman (APNH) are mutagenic norharman derivatives obtained from o-toluidine and aniline, respectively. APNH is carcinogenic to the urinary bladder of rats and present in urine samples of healthy volunteers, indicating that norharman derivatives may be associated with cancer development in the urinary bladder of humans. To evaluate the possible role of AMPNH and APNH in bladder carcinogenesis, we examined the formation of γ-H2AX, a DNA damage response marker, in the urinary bladder of rats...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29142472/prostaglandin-e1-protects-hepatocytes-against-endoplasmic-reticulum-stress-induced-apoptosis-via-protein-kinase-a-dependent-induction-of-glucose-regulated-protein-78-expression
#18
Fang-Wan Yang, Yu Fu, Ying Li, Yi-Huai He, Mao-Yuan Mu, Qi-Chuan Liu, Jun Long, Shi-De Lin
AIM: To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS: Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29142297/5-aminolevulinic-acid-guided-sampling-of-glioblastoma-microenvironments-identifies-pro-survival-signaling-at-infiltrative-margins
#19
James L Ross, Lee A D Cooper, Jun Kong, David Gutman, Merete Williams, Carol Tucker-Burden, Myles R McCrary, Alexandros Bouras, Milota Kaluzova, William D Dunn, Duc Duong, Constantinos G Hadjipanayis, Daniel J Brat
Glioblastoma (GBM) contains diverse microenvironments with uneven distributions of oncogenic alterations and signaling networks. The diffusely infiltrative properties of GBM result in residual tumor at neurosurgical resection margins, representing the source of relapse in nearly all cases and suggesting that therapeutic efforts should be focused there. To identify signaling networks and potential druggable targets across tumor microenvironments (TMEs), we utilized 5-ALA fluorescence-guided neurosurgical resection and sampling, followed by proteomic analysis of specific TMEs...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142107/is-inflammatory-micronucleation-the-key-to-a-successful-anti-mitotic-cancer-drug
#20
REVIEW
T J Mitchison, J Pineda, J Shi, S Florian
Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours...
November 2017: Open Biology
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