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https://www.readbyqxmd.com/read/28629912/calprotectin-and-the-magnitude-of-antibodies-to-infliximab-in-clinically-stable-ulcerative-colitis-patients-are-more-relevant-than-infliximab-trough-levels-and-pharmacokinetics-for-therapeutic-escalation
#1
Fernando Magro, Joana Afonso, Susana Lopes, Rosa Coelho, Raquel Gonçalves, Paulo Caldeira, Paula Lago, Helena Tavares de Sousa, Jaime Ramos, Ana Rita Gonçalves, Paula Ministro, Isadora Rosa, Ana Isabel Vieira, Patrícia Andrade, João-Bruno Soares, Diana Carvalho, Paula Sousa, Tânia Meira, Joanne Lopes, Joana Moleiro, Cláudia Camila Dias, Amílcar Falcão, Karel Geboes, Fatima Carneiro
Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs...
June 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28619756/alpha-particle-enhanced-blood-brain-tumor-barrier-permeabilization-in-glioblastomas-using-integrin-alpha-v-beta-3-targeted-liposomes
#2
Anirudh Sattiraju, Xiaobing Xiong, Darpan N Pandya, Thaddeus J Wadas, Ang Xuan, Yao Sun, Youngkyoo Jung, Kiran Kumar Solingapuram Sai, Jay F Dorsey, King C Li, Akiva Mintz
<span style="font-size: 11.0pt; line-height: 200%; color: windowtext;">Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of anti-tumor therapeutics has been a major challenge due to the complications caused by the blood brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB)...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28618390/thirty-day-non-seizure-outcomes-following-temporal-lobectomy-for-adult-epilepsy
#3
Brandon A Sherrod, Matthew C Davis, Kristen O Riley
OBJECTIVE: Multi-institutional rates of acute adverse outcomes other than seizures after temporal lobectomy (TL) are not well understood. Here we analyzed short-term morbidity and mortality following TL using a validated national database. PATIENTS AND METHODS: The multi-institutional American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried by Current Procedural Terminology (CPT) code for TL procedures performed for adult patients with diagnoses related to epilepsy from 2008 to 2014...
June 8, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28607059/human-genome-wide-repair-map-of-dna-damage-caused-by-the-cigarette-smoke-carcinogen-benzo-a-pyrene
#4
Wentao Li, Jinchuan Hu, Ogun Adebali, Sheera Adar, Yanyan Yang, Yi-Ying Chiou, Aziz Sancar
Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. BaP forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method for capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors, and after damage-specific immunoprecipitation, the adaptor-ligated oligonucleotides are converted to dsDNA with an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28601494/a-comparative-analysis-of-translesion-dna-synthesis-catalyzed-by-a-high-fidelity-dna-polymerase
#5
Anvesh Dasari, Tejal Deodhar, Anthony J Berdis
Translesion DNA synthesis (TLS) is the ability of DNA polymerases to incorporate nucleotides opposite and beyond damaged DNA. TLS activity is an important risk factor for the initiation and progression of genetic diseases such as cancer. In this study, we evaluate the ability of a high-fidelity DNA polymerase to perform TLS with 8-oxo-guanine, a highly pro-mutagenic DNA lesion formed by reactive oxygen species. Results of kinetic studies monitoring the incorporation of modified nucleotide analogs demonstrate that the binding affinity of the incoming dNTP is controlled by the overall hydrophobicity of the nucleobase...
June 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28588796/analysis-of-the-incidence-of-tumor-lysis-syndrome-in-patients-with-hematological-malignancies-treated-with-rasburicase
#6
Eiseki Usami, Michio Kimura, Mina Iwai, Hitomi Teramachi, Tomoaki Yoshimura
The purpose of this study was to assess the incidence of tumor lysis syndrome (TLS) in patients with hematological malignancies treated with rasburicase, and to evaluate the dose and duration of rasburicase administration. A total of 52 patients were enrolled. The background of the patients, incidence of TLS and laboratory data were retrospectively examined; in addition, the dose and duration of rasburicase administration and the factors affecting the onset of TLS were evaluated and compared among TLS risk categories...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28587951/treatment-na%C3%A3-ve-spontaneous-tumor-lysis-syndrome-in-metastatic-prostate-adenocarcinoma-an-unusual-suspect
#7
Maya Ignaszewski, Patrick Kohlitz
Tumor lysis syndrome (TLS) is a potentially fatal condition defined both by laboratory and clinical criteria. It is caused by the catabolism of tumor cells which leads to considerable release and elevated levels of phosphate, potassium and uric acid in the bloodstream. These electrolyte derangements predispose patients to renal tubule uric acid precipitation, acute kidney injury, arrhythmias, neuromuscular irritability and even seizures. Although this phenomenon is well described with hematological malignancies, it is also known to occur among solid tumors...
May 26, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28573173/ex-vivo-experimental-study-on-the-thulium-laser-system-new-horizons-for-interventional-endoscopy-with-videos
#8
Gian Eugenio Tontini, Helmut Neumann, Alessandro Rimondi, Sara Vavassori, Barbara Bruni, Gregorio Cattignoli, Ping-Hong Zhou, Luca Pastorelli, Maurizio Vecchi
BACKGROUND AND STUDY AIMS:  The Thulium laser system (TLS) is an emerging interventional tool adopted in many surgical specialties. Its 2.0-μm wavelength allows precise coagulation (0.2 - 0.4 mm in depth) and cutting, limiting the possibilities of collateral injuries. We tested the impact of the TLS for gastric endoscopic submucosal dissection (ESD) and per oral endoscopic myotomy (POEM) ex vivo in pigs. MATERIALS AND METHODS:   Ex vivo porcine stomach and esophagus models underwent 2 POEMs, and 3 ESDs (mean diameter 3...
June 2017: Endoscopy International Open
https://www.readbyqxmd.com/read/28566194/non-invasive-vagus-nerve-stimulation-acutely-improves-spontaneous-cardiac-baroreflex-sensitivity-in-healthy-young-men-a-randomized-placebo-controlled-trial
#9
Diego Antonino, André L Teixeira, Paulo M Maia-Lopes, Mayara C Souza, Jeann L Sabino-Carvalho, Aaron R Murray, Jim Deuchars, Lauro C Vianna
BACKGROUND: Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. OBJECTIVE: To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN...
May 19, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28546148/translation-initiation-factor-eif4g1-preferentially-binds-yeast-transcript-leaders-containing-conserved-oligo-uridine-motifs
#10
Boris Zinshteyn, Maria F Rojas Duran, Wendy V Gilbert
Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here we comprehensively determined the RNA-binding preferences of the initiation factor eIF4G to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs...
May 25, 2017: RNA
https://www.readbyqxmd.com/read/28541665/identification-of-small-molecule-translesion-synthesis-inhibitors-that-target-the-rev1-ct-rir-protein-protein-interaction
#11
Vibhavari Sail, Alessandro A Rizzo, Nimrat Chatterjee, Radha C Dash, Zuleyha Ozen, Graham C Walker, Dmitry M Korzhnev, M Kyle Hadden
Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate...
June 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28534480/molecular-basis-for-primpol-recruitment-to-replication-forks-by-rpa
#12
Thomas A Guilliam, Nigel C Brissett, Aaron Ehlinger, Benjamin A Keen, Peter Kolesar, Elaine M Taylor, Laura J Bailey, Howard D Lindsay, Walter J Chazin, Aidan J Doherty
DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA...
May 23, 2017: Nature Communications
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
June 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28472716/combined-loss-of-three-dna-damage-response-pathways-renders-c-elegans-intolerant-to-light
#20
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
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