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https://www.readbyqxmd.com/read/27906620/the-radiosensitizing-effect-of-fluorocyclopentenyl-cytosine-rx-3117-in-ovarian-and-lung-cancer-cell-lines
#1
Dzjemma Sarkisjan, Jaap van den Berg, Evelyn Smit, Young B Lee, Deog J Kim, Godefridus J Peters
RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.4-1.8), observed at pulse and fractionated irradiation...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#2
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#3
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903589/impact-of-left-atrial-appendage-closure-during-cardiac-surgery-on-the-occurrence-of-early-postoperative-atrial-fibrillation-stroke-and-mortality-a-propensity-score-matched-analysis-of-10-633-patients
#4
Rowlens M Melduni, Hartzell V Schaff, Hon-Chi Lee, Bernard J Gersh, Peter A Noseworthy, Kent R Bailey, Naser M Ammash, Stephen S Cha, Kaniz Fatema, Waldemar E Wysokinski, James B Seward, Douglas L Packer, Charanjit S Rihal, Samuel J Asirvatham
BACKGROUND: -Prophylactic exclusion of the left atrial appendage (LAA) is often performed during cardiac surgery ostensibly to reduce the risk of stroke. However, the clinical impact of LAA closure in humans remains inconclusive. METHODS: -Out of 10,633 adults who underwent CABG and/or valve surgery between January 2000 and December 2005, 9,792 patients with complete baseline characteristics, surgery procedure and follow-up data were included in this analysis. A propensity-score matching analysis based on 28 pretreatment covariates was performed and 461 matching pairs were derived and analyzed to estimate the association of LAA closure with early postoperative atrial fibrillation (POAF) (AF ≤30 days of surgery), ischemic stroke and mortality...
November 30, 2016: Circulation
https://www.readbyqxmd.com/read/27902784/dynamic-in-vivo-mutations-within-the-ica-operon-during-persistence-of-staphylococcus-aureus-in-the-airways-of-cystic-fibrosis-patients
#5
Bianca Schwartbeck, Johannes Birtel, Janina Treffon, Lars Langhanki, Alexander Mellmann, Devika Kale, Janina Kahl, Nina Hirschhausen, Claudia Neumann, Jean C Lee, Friedrich Götz, Holger Rohde, Hanae Henke, Peter Küster, Georg Peters, Barbara C Kahl
Cystic fibrosis (CF) is associated with chronic bacterial airway infections leading to lung insufficiency and decreased life expectancy. Staphylococcus aureus is one of the most prevalent pathogens isolated from the airways of CF patients. Mucoid colony morphology has been described for Pseudomonas aeruginosa, the most common pathogen in CF, but not for S. aureus. From the airways of 8 of 313 CF patients (2.5%) mucoid S. aureus isolates (n = 115) were cultured with a mean persistence of 29 months (range 1 month, 126 months)...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27898078/corrigendum-genetic-variants-associated-with-subjective-well-being-depressive-symptoms-and-neuroticism-identified-through-genome-wide-analyses
#6
Aysu Okbay, Bart M L Baselmans, Jan-Emmanuel De Neve, Patrick Turley, Michel G Nivard, Mark Alan Fontana, S Fleur W Meddens, Richard Karlsson Linnér, Cornelius A Rietveld, Jaime Derringer, Jacob Gratten, James J Lee, Jimmy Z Liu, Ronald de Vlaming, Tarunveer S Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-Wood, Nicholas A Furlotte, Victoria Garfield, Marie Henrike Geisel, Juan R Gonzalez, Saskia Haitjema, Robert Karlsson, Sander W van der Laan, Karl-Heinz Ladwig, Jari Lahti, Sven J van der Lee, Penelope A Lind, Tian Liu, Lindsay Matteson, Evelin Mihailov, Michael B Miller, Camelia C Minica, Ilja M Nolte, Dennis Mook-Kanamori, Peter J van der Most, Christopher Oldmeadow, Yong Qian, Olli Raitakari, Rajesh Rawal, Anu Realo, Rico Rueedi, Börge Schmidt, Albert V Smith, Evie Stergiakouli, Toshiko Tanaka, Kent Taylor, Gudmar Thorleifsson, Juho Wedenoja, Juergen Wellmann, Harm-Jan Westra, Sara M Willems, Wei Zhao, Najaf Amin, Andrew Bakshi, Sven Bergmann, Gyda Bjornsdottir, Patricia A Boyle, Samantha Cherney, Simon R Cox, Gail Davies, Oliver S P Davis, Jun Ding, Nese Direk, Peter Eibich, Rebecca T Emeny, Ghazaleh Fatemifar, Jessica D Faul, Luigi Ferrucci, Andreas J Forstner, Christian Gieger, Richa Gupta, Tamara B Harris, Juliette M Harris, Elizabeth G Holliday, Jouke-Jan Hottenga, Philip L De Jager, Marika A Kaakinen, Eero Kajantie, Ville Karhunen, Ivana Kolcic, Meena Kumari, Lenore J Launer, Lude Franke, Ruifang Li-Gao, David C Liewald, Marisa Koini, Anu Loukola, Pedro Marques-Vidal, Grant W Montgomery, Miriam A Mosing, Lavinia Paternoster, Alison Pattie, Katja E Petrovic, Laura Pulkki-Råback, Lydia Quaye, Katri Räikkönen, Igor Rudan, Rodney J Scott, Jennifer A Smith, Angelina R Sutin, Maciej Trzaskowski, Anna E Vinkhuyzen, Lei Yu, Delilah Zabaneh, John R Attia, David A Bennett, Klaus Berger, Lars Bertram, Dorret I Boomsma, Harold Snieder, Shun-Chiao Chang, Francesco Cucca, Ian J Deary, Cornelia M van Duijn, Johan G Eriksson, Ute Bültmann, Eco J C de Geus, Patrick J F Groenen, Vilmundur Gudnason, Torben Hansen, Catharine A Hartman, Claire M A Haworth, Caroline Hayward, Andrew C Heath, David A Hinds, Elina Hyppönen, William G William, Marjo-Riitta Järvelin, Karl-Heinz Jöckel, Jaakko Kaprio, Sharon L R Kardia, Liisa Keltikangas-Järvinen, Peter Kraft, Laura D Kubzansky, Terho Lehtimäki, Patrik K E Magnusson, Nicholas G Martin, Matt McGue, Andres Metspalu, Melinda Mills, Renée de Mutsert, Albertine J Oldehinkel, Gerard Pasterkamp, Nancy L Pedersen, Robert Plomin, Ozren Polasek, Christine Power, Stephen S Rich, Frits R Rosendaal, Hester M den Ruijter, David Schlessinger, Helena Schmidt, Rauli Svento, Reinhold Schmidt, Behrooz Z Alizadeh, Thorkild I A Sørensen, Tim D Spector, John M Starr, Kari Stefansson, Andrew Steptoe, Antonio Terracciano, Unnur Thorsteinsdottir, A Roy Thurik, Nicholas J Timpson, Henning Tiemeier, André G Uitterlinden, Peter Vollenweider, Gert G Wagner, David R Weir, Jian Yang, Dalton C Conley, George Davey Smith, Albert Hofman, Magnus Johannesson, David I Laibson, Sarah E Medland, Michelle N Meyer, Joseph K Pickrell, Tõnu Esko, Robert F Krueger, Jonathan P Beauchamp, Philipp D Koellinger, Daniel J Benjamin, Meike Bartels, David Cesarini
No abstract text is available yet for this article.
November 29, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27897242/cortical-synaptic-and-dendritic-spine-abnormalities-in-a-presymptomatic-tdp-43-model-of-amyotrophic-lateral-sclerosis
#7
Matthew J Fogarty, Paul M Klenowski, John D Lee, Joy R Drieberg-Thompson, Selena E Bartlett, Shyuan T Ngo, Massimo A Hilliard, Mark C Bellingham, Peter G Noakes
Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43(Q331K) mutation...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896895/five-year-efficacy-and-safety-of-tenofovir-based-salvage-therapy-for-patients-with-chronic-hepatitis-b-who-previously-failed-lam-adv-therapy
#8
Lucy Lim, Alexander Thompson, Scott Patterson, Jacob George, Simone Strasser, Alice Lee, William Sievert, Amanda Nicoll, Paul Desmond, Stuart Roberts, Kaye Marion, Scott Bowden, Stephen Locarnini, Peter Angus
BACKGROUND: Multidrug resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is effective salvage therapy through 96 weeks for LAM resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5 year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study. METHODS: 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300mg daily...
November 29, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27895165/rats-with-a-missense-mutation-in-atm-display-neuroinflammation-and-neurodegeneration-subsequent-to-accumulation-of-cytosolic-dna-following-unrepaired-dna-damage
#9
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27893897/imaging-of-glial-cell-activation-and-white-matter-integrity-in-brains-of-active-and-recently-retired-national-football-league-players
#10
Jennifer M Coughlin, Yuchuan Wang, Il Minn, Nicholas Bienko, Emily B Ambinder, Xin Xu, Matthew E Peters, John W Dougherty, Melin Vranesic, Soo Min Koo, Hye-Hyun Ahn, Merton Lee, Chris Cottrell, Haris I Sair, Akira Sawa, Cynthia A Munro, Christopher J Nowinski, Robert F Dannals, Constantine G Lyketsos, Michael Kassiou, Gwenn Smith, Brian Caffo, Susumu Mori, Tomas R Guilarte, Martin G Pomper
Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury...
November 28, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27887854/significant-regional-variation-exists-in-morbidity-and-mortality-after-repair-of-abdominal-aortic-aneurysm
#11
Sara L Zettervall, Peter A Soden, Dominique B Buck, Jack L Cronenwett, Phillip P Goodney, Mohammad H Eslami, Jason T Lee, Marc L Schermerhorn
OBJECTIVE: Limited data exist comparing perioperative morbidity and mortality after open and endovascular abdominal aortic aneurysm (AAA) repair (EVAR) among regions of the United States. This study evaluated the regional variation in mortality and perioperative outcomes after repair of AAAs. METHODS: The Vascular Quality Initiative (VQI) was used to identify patients undergoing open AAA repair and EVAR between 2009 and 2014. Ruptured and intact aneurysms were evaluated separately, and the analysis of intact aneurysms was limited to infrarenal AAAs...
November 22, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27887805/patterns-of-care-of-imrt-usage-in-postoperative-management-of-uterine-cancer
#12
Virginia Osborn, David Schwartz, Yi-Chun Lee, Anna Lee, Elizabeth Garay, Kwang Choi, Peter Han, David Schreiber
OBJECTIVE: To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. METHODS: The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004-2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy...
November 22, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27886551/reconsidering-azobenzene-as-a-component-of-small-molecule-hypoxia-mediated-cancer-drugs-a-theranostic-case-study
#13
Peter Verwilst, Jiyou Han, Jiyeong Lee, Sora Mun, Hee-Gyoo Kang, Jong Seung Kim
An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation...
November 16, 2016: Biomaterials
https://www.readbyqxmd.com/read/27885818/the-impact-of-bevacizumab-in-metastatic-colorectal-cancer-with-an-intact-primary-tumor-results-from-a-large-prospective-cohort-study
#14
Belinda Lee, Hui-Li Wong, Mark Tacey, Jeanne Tie, Rachel Wong, Margaret Lee, Louise Nott, Jeremy Shapiro, Ross Jennens, Natalie Turner, Ben Tran, Sumitra Ananda, Desmond Yip, Gary Richardson, Phillip Parente, Lionel Lim, Greg Stefanou, Matthew Burge, Mahesh Iddawela, Jeremy Power, Peter Gibbs
BACKGROUND: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT...
November 25, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27885390/ct-angiography-in-the-setting-of-suspected-acute-mesenteric-ischemia-prevalence-of-ischemic-and-alternative-diagnoses
#15
Frank Oliver Henes, Perry J Pickhardt, Andrzej Herzyk, Scott J Lee, Utaroh Motosugi, Thorsten Derlin, Meghan G Lubner, Gerhard Adam, Gerhard Schön, Peter Bannas
PURPOSE: The purpose of the study was to determine the prevalence of ischemic and alternative diagnoses and the diagnostic accuracy of CT angiography (CTA) in the setting of suspected acute mesenteric ischemia (AMI). MATERIAL AND METHODS: We included 959 patients undergoing CTA for the evaluation of suspected AMI. The final clinical diagnosis was used to determine the prevalence of ischemic and alternative diagnoses and to calculate the diagnostic accuracy of CTA...
November 24, 2016: Abdominal Radiology
https://www.readbyqxmd.com/read/27882742/esophageal-adenocarcinoma-and-barrett-esophagus-in-a-neurologically-impaired-teenager
#16
Jae-Yeon Hwang, Yeoun Joo Lee, Peter Chun, Dong Hoon Shin, Jae Hong Park
Esophageal adenocarcinoma (EAC) accompanied by Barrett esophagus (BE) is rare in patients younger than 20 years old. EAC in the upper esophagus is also rare. We report a rare case of EAC with BE that developed in the upper esophagus after chronic, untreated gastroesophageal reflux disease in a neurologically impaired teenager. A 19-year-old neurologically impaired man underwent endoscopy for evaluation of dysphagia and vomiting, and was diagnosed with EAC with BE. He underwent transthoracic esophagectomy, extensive lymph node dissection, and cervical esophagogastric anastomosis, but the prognosis was poor...
November 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27881263/utilities-for-type-2-diabetes-treatment-related-attributes-in-a-south-korean-and-taiwanese-population
#17
Narayan Rajan, Kristina S Boye, Meaghan Gibbs, Yoon Ji Lee, Peter Davey, Mark Ball, Steve M Babineaux
OBJECTIVES: To elicit utilities associated with type 2 diabetes medication-related attributes from South Korean and Taiwanese populations and to identify key drivers of preferences. METHODS: Data from 59 respondents from the general population in South Korea and Taiwan were analyzed. Respondents' preferences were elicited using a paper-based standard gamble questionnaire. Health states were designed to identify the utility or disutility of type 2 diabetes medication-related attributes, including dose frequency, nausea/vomiting (hereafter referred to as nausea), and weight change...
May 2016: Value in Health Regional Issues
https://www.readbyqxmd.com/read/27880901/stress-kinase-gcn2-controls-the-proliferative-fitness-and-trafficking-of-cytotoxic-t-cells-independent-of-environmental-amino-acid-sensing
#18
Lee-Ann Van de Velde, Xi-Zhi J Guo, Lidija Barbaric, Amber M Smith, Thomas H Oguin, Paul G Thomas, Peter J Murray
GCN2 is one of four "stress kinases" that block translation by phosphorylating eIF2α. GCN2 is thought to bind uncharged tRNAs to "sense" amino acid availability. In mammals, myeloid cells expressing indoleamine dioxygenases locally deplete tryptophan, which is detected by GCN2 in T cells to cause proliferative arrest. GCN2-deficient T cells were reported to ectopically enter the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed to T cell receptor (TCR) transgenic backgrounds, we found GCN2 is essential for induction of stress target genes such as CHOP...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879602/health-related-quality-of-life-following-reconstruction-for-common-head-and-neck-surgical-defects
#19
Wess A Cohen, Claudia R Albornoz, Peter G Cordeiro, Jennifer Cracchiolo, Elizabeth Encarnacion, Meghan Lee, Michele Cavalli, Snehal Patel, Andrea L Pusic, Evan Matros
BACKGROUND: Improved understanding and management of health-related quality of life represents one of the greatest unmet needs for patients with head and neck malignancies. The purpose of this study was to prospectively measure health-related quality of life associated with different anatomical (head and neck) surgical resections. METHODS: A prospective analysis of health-related quality of life was performed in patients undergoing surgical resection with flap reconstruction for stage II or III head and neck malignancies...
December 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27879265/il-6-signaling-in-peripheral-blood-t-cells-predicts-clinical-outcome-in-breast-cancer
#20
Lei Wang, Andrea K Miyahira, Diana Simons, Xuyang Lu, Andrew Chang, Carrie Wang, Maria Suni, Vernon C Maino, Frederick M Dirbas, John H Yim, James Waisman, Peter P Lee
Interleukin-6 (IL-6) is a pleiotropic cytokine with both pro- and anti-inflammatory properties which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL-6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL-6 on cancer cells. How IL-6 modulates the host immune response in cancer patients is unclear. Here we show the IL-6 signaling response in peripheral blood T cells is impaired in breast cancer (BC) patients and is associated with blunted Th17 differentiation...
November 22, 2016: Cancer Research
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