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https://www.readbyqxmd.com/read/28498946/overexpression-of-rev1-promotes-the-development-of-carcinogen-induced-intestinal-adenomas-via-accumulation-of-point-mutation-and-suppression-of-apoptosis-proportionally-to-the-rev1-expression-level
#1
Megumi Sasatani, Yang Xi, Junko Kajimura, Toshiyuki Kawamura, Jinlian Piao, Yuji Masuda, Hiroaki Honda, Kei Kubo, Takahiro Mikamoto, Hiromitsu Watanabe, Yanbin Xu, Hidehiko Kawai, Tsutomu Shimura, Asao Noda, Kanya Hamasaki, Yoichiro Kusunoki, Elena Karamfilova Zaharieva, Kenji Kamiya
Cancer development often involves mutagenic replication of damaged DNA by the error-prone translesion synthesis (TLS) pathway. Aberrant activation of this pathway plays a role in tumorigenesis by promoting genetic mutations. Rev1 controls the function of the TLS pathway, and Rev1 expression levels are associated with DNA damage induced cytotoxicity and mutagenicity. However, it remains unclear whether deregulated Rev1 expression triggers or promotes tumorigenesis in vivo. In this study, we generated a novel Rev1-overexpressing transgenic (Tg) mouse and characterized its susceptibility to tumorigenesis...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28498153/infliximab-trough-levels-at-induction-to-predict-treatment-failure-during-maintenance
#2
Claire Liefferinckx, Charlotte Minsart, Jean-François Toubeau, Anneline Cremer, Leila Amininejad, Eric Quertinmont, Jacques Devière, Ann Gils, André van Gossum, Denis Franchimont
BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data...
May 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28497687/eukaryotic-translesion-dna-synthesis-on-the-leading-and-lagging-strands-unique-detours-around-the-same-obstacle
#3
Mark Hedglin, Stephen J Benkovic
During S-phase, minor DNA damage may be overcome by DNA damage tolerance (DDT) pathways that bypass such obstacles, postponing repair of the offending damage to complete the cell cycle and maintain cell survival. In translesion DNA synthesis (TLS), specialized DNA polymerases replicate the damaged DNA, allowing stringent DNA synthesis by a replicative polymerase to resume beyond the offending damage. Dysregulation of this DDT pathway in human cells leads to increased mutation rates that may contribute to the onset of cancer...
May 12, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28490629/pharmacological-targeting-of-rad6-enzyme-mediated-translesion-synthesis-overcomes-resistance-to-platinum-based-drugs
#4
Matthew A Sanders, Brittany Haynes, Pratima Nangia-Makker, Lisa A Polin, Malathy P Shekhar
Platinum drug-induced crosslink repair requires the concerted activities of translesion synthesis (TLS), Fanconi anemia (FA) and homologous recombination repair pathways. The E2 ubiquitin-conjugating enzyme Rad6 is essential for TLS. Here, we show that Rad6 plays a universal role in platinum-based drug tolerance. Using a novel Rad6-selective small molecule inhibitor (SMI#9) targeting the Rad6 catalytic site, we demonstrate that SMI#9 potentiates the sensitivities of cancer cells with innate or acquired cisplatin or oxaliplatin resistance...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28480046/steroid-induced-tumour-lysis-syndrome-in-small-cell-lung-cancer
#5
Fasihul Khan, Shazeen Ayub, Qurrat Mehmood, Syed Fayyaz Hussain
A 64-year-old male presented to hospital with breathlessness and weight loss. Ultrasound-guided biopsy of supraclavicular lymph node confirmed a diagnosis of small-cell lung cancer. The patient was started on Dexamethasone 8 mg twice daily for symptom control while awaiting urgent oncology assessment. Three days later he was admitted with acute kidney injury and worsening breathlessness. Biochemical changes confirmed tumour lysis syndrome (TLS) that had occurred following steroid therapy. He was given allopurinol followed by rasburicase...
May 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28478879/tumor-lysis-syndrome-a-unique-solute-disturbance
#6
REVIEW
Penelope Z Strauss, Shannan K Hamlin, Johnny Dang
Tumor lysis syndrome (TLS) is a life-threatening disorder that is an oncologic emergency. Risk factors for TLS are well-known, but the current literature shows case descriptions of unexpected acute TLS. Solid tumors and untreated hematologic tumors can lyse under various circumstances in children and adults. International guidelines and recommendations, including the early involvement of the critical care team, have been put forward to help clinicians properly manage the syndrome. Advanced practice nurses may be in the position of triaging and initiating treatment of patients with TLS, and need a thorough understanding of the syndrome and its treatment...
June 2017: Nursing Clinics of North America
https://www.readbyqxmd.com/read/28474855/chromatin-regulates-genome-targeting-with-cisplatin
#7
Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, Valérie Bergoglio, Blerta Xhemalce, Kyle M Miller, Raphaël Rodriguez
Cisplatin derivatives can form various types of DNA lesions (DNA-Pt) and trigger pleiotropic DNA damage responses. Here, we report a strategy to visualize DNA-Pt with high resolution, taking advantage of a novel azide-containing derivative of cisplatin we named APPA, a cellular pre-extraction protocol and the labeling of DNA-Pt by means of click chemistry in cells. Our investigation revealed that pretreating cells with the histone deacetylase (HDAC) inhibitor SAHA led to detectable clusters of DNA-Pt that colocalized with the ubiquitin ligase RAD18 and the replication protein PCNA...
May 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28472716/combined-loss-of-three-dna-damage-response-pathways-renders-c-elegans-intolerant-to-light
#8
Ivo van Bostelen, Marcel Tijsterman
Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not...
April 14, 2017: DNA Repair
https://www.readbyqxmd.com/read/28471523/laparoscopic-surgery-for-elective-abdominal-aortic-aneurysm-repair
#9
REVIEW
Lindsay Robertson, Sandip Nandhra
BACKGROUND: Abdominal aortic aneurysm (AAA) is an abnormal dilatation of the infradiaphragmatic aorta that is equal to or greater than 30 mm or a local dilatation of equal to or greater than 50% compared to the expected normal diameter of the artery. AAAs rarely occur in individuals under 50 years of age, but thereafter the prevalence dramatically increases with age, with men at a six-fold greater risk of developing an AAA than women. Prevalence of AAA has been reported to range from 1...
May 4, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28461998/detection-of-early-dj-stent-encrustation-by-sonographic-twinkling-artifacts-a-pilot-study
#10
Roman A Blaheta, Anton Oertl, Hans-Joachim Freisleben, Karen Nelson, Hanns Ackermann, Axel Haferkamp, Tobias Engl
INTRODUCTION: Ureter obstruction caused by a retro-peritoneal tumor is treated by inserting an indwelling ureter splint (DJ-stent). Indwelling duration is limited by cumulative crystalline deposits into the splint, eventually causing the repeated impairment of urine flow. Deciding when a DJ-stent must be replaced is important since belated removal can be accompanied by severe complications. X-ray or conventional sonography do not allow satisfactory evaluation of early incrustation, therefore, the use of sonographic twinkling artifacts (TA) to provide accurate stent surveillance was investigated...
2017: Central European Journal of Urology
https://www.readbyqxmd.com/read/28454137/dynamic-stark-shift-induced-by-a-single-photon-packet
#11
D Valente, F Brito, T Werlang
The dynamic Stark shift results from the interaction of an atom with the electromagnetic field. We show how a propagating single-photon wave packet can induce a time-dependent dynamical Stark shift on a two-level system (TLS). A non-perturbative fully quantum treatment is employed, where the quantum dynamics of both the field and the TLS are analyzed. We also provide the means to experimentally access such time-dependent frequency by measuring the interference pattern in the electromagnetic field inside a 1D waveguide...
May 1, 2017: Optics Letters
https://www.readbyqxmd.com/read/28445232/organised-chaos-in-late-specialisation-team-sports-weekly-training-loads-of-elite-adolescent-rugby-union-players
#12
Padraic J Phibbs, Ben Jones, Gregory Roe, Dale Read, Joshua Darrall-Jones, Jonathon Weakley, Andrew Rock, Kevin Till
The aim of this study was to quantify the mean weekly training load (TL) of elite adolescent rugby union players participating in multiple teams, and examine the differences between playing positions. Twenty elite male adolescent rugby union players (17.4 ± 0.7 years) were recruited from a regional academy and categorised by playing position; forwards (n=10) and backs (n=10). Global positioning system and accelerometer microtechnology was used to quantify external TL, and session-rating of perceived exertion (sRPE) was used to quantify internal TL during all sessions throughout a 10-week in-season period...
April 18, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28440919/rev7-the-regulatory-subunit-of-pol%C3%AE-undergoes-uv-induced-and-cul4-dependent-degradation
#13
Audesh Bhat, Zhoushuai Qin, Guifen Wang, Wangyang Chen, Wei Xiao
In eukaryotic cells, Rev7 interacts with Rev3 and functions as a regulatory subunit of Polζ, a translesion DNA synthesis (TLS) polymerase. In addition to its role in TLS, mammalian Rev7, also known as Mad2B/Mad2L2, participates in multiple cellular activities including cell cycle progression and double-strand break repair through its interaction with several proteins. Here we show that in mammalian cells Rev7 undergoes ubiquitin/proteasome-mediated degradation upon UV irradiation in a time-dependent manner...
April 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#14
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28430587/parkin-regulates-translesion-dna-synthesis-in-response-to-uv-radiation
#15
Xuefei Zhu, Xiaolu Ma, Yingfeng Tu, Min Huang, Hongmei Liu, Fengli Wang, Juanjuan Gong, Jiuqiang Wang, Xiaoling Li, Qian Chen, Hongyan Shen, Shu Zhu, Yun Wang, Yang Liu, Caixia Guo, Tie-Shan Tang
Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416251/initial-asthma-severity-assessment-tools-as-predictors-of-hospitalization
#16
Natalia Paniagua, Amaia Elosegi, Isabel Duo, Ana Fernandez, Elisa Mojica, Lorea Martinez-Indart, Santiago Mintegi, Javier Benito
BACKGROUND: Assessment tools to classify and prioritize patients, such as systems of triage, and indicators of severity, such as clinical respiratory scores, are helpful in guiding the flow of asthmatic patients in the emergency department. OBJECTIVE: Our aim was to assess the performance of the Pediatric Assessment Triangle (PAT), triage level (TL), Pulmonary Score (PS), and initial O2 saturation (O2 sat), in predicting hospitalization in pediatric acute asthma exacerbations...
April 14, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28413674/spontaneous-tumor-lysis-syndrome-in-a-patient-with-metastatic-prostate-cancer
#17
Naomi Serling-Boyd, Zoe Quandt, Nazima Allaudeen
Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, with most cases occurring in hematological malignancies following the initiation of treatment. However, on rare occasions, TLS may occur in solid tumors as well. In the present case study, the case is reported of a 56-year-old African-American man who presented with a recent diagnosis of prostate cancer, abdominal pain, elevated transaminases, renal insufficiency, hyperkalemia, and hyperuricemia, consistent with spontaneous TLS in the setting of metastatic prostate cancer...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28413217/lymphotoxin-signalling-in-tertiary-lymphoid-structures-and-immunotherapy
#18
REVIEW
Haidong Tang, Mingzhao Zhu, Jian Qiao, Yang-Xin Fu
Tertiary lymphoid structures (TLS) often develop at sites of persistent inflammation, including cancers and autoimmune diseases. In most cases, the presence of TLS correlates with active immune responses. Because of their proximity to pathological loci, TLS are an intriguing target for the manipulation of immune responses. For several years, it has become clear that lymphotoxin (LT) signalling plays critical roles in lymphoid tissue organogenesis and maintenance. In the current review, we will discuss the role of LT signalling in the development of TLS...
April 17, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28402640/mutagenic-replication-of-n-2-deoxyguanosine-benzo-a-pyrene-adducts-by-escherichia-coli-dna-polymerase-i-and-sulfolobus-solfataricus-dna-polymerase-iv
#19
A S Prakasha Gowda, Jacek Krzeminski, Shantu Amin, Zucai Suo, Thomas E Spratt
Benzo[a]pyrene, a potent human carcinogen, is metabolized in vivo to a diol epoxide that reacts with the N(2)-position of guanine to produce N(2)-BP-dG adducts. These adducts are mutagenic causing G to T transversions. These adducts block replicative polymerases but can be bypassed by the Y-family translesion synthesis polymerases. The mechanisms by which mutagenic bypass occurs is not well-known. We have evaluated base pairing structures using atomic substitution of the dNTP with two stereoisomers, 2'-deoxy-N-[(7R,8S,9R,10S)-7,8,9,10-tetrahydro-7,8,9-trihydroxybenzo[a]pyren-10-yl]guanosine and 2'-deoxy-N-[(7S,8R,9S,10R)-7,8,9,10-tetrahydro-7,8,9-trihydroxybenzo[a]pyren-10-yl]guanosine...
April 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28396594/human-primpol-activity-is-enhanced-by-rpa
#20
María I Martínez-Jiménez, Antonio Lahera, Luis Blanco
Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates...
April 10, 2017: Scientific Reports
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