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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212535/integration-of-the-cancer-related-inflammatory-response-as-a-stratifying-biomarker-of-survival-in-hepatocellular-carcinoma-treated-with-sorafenib
#2
Jessica Howell, David J Pinato, Ramya Ramaswami, Tadaaki Arizumi, Carlotta Ferrari, Antonello Gibbin, Michela E Burlone, Giulia Guaschino, Pierluigi Toniutto, James Black, Laura Sellers, Masatoshi Kudo, Mario Pirisi, Rohini Sharma
BACKGROUND AND AIMS: Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy. RESULTS: 442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212529/expression-of-the-cancer-stem-cell-markers-abcg2-and-oct-4-in-right-sided-colon-cancer-predicts-recurrence-and-poor-outcomes
#3
Jun Hu, Jian Li, Xin Yue, Jiacang Wang, Jianzhong Liu, Lin Sun, Dalu Kong
Right-sided colon cancer (RCC) has a poorer prognosis and a higher relapse rate than left-sided colon cancer (LCC). Like cancer stem cells (CSCs), RCC cells cannot be fully eradicated and are often involved in relapse or metastasis. Because CSCs may be linked with poor outcomes, CSC markers may have prognostic value in RCC. ATP-binding cassette sub-family G member 2 (ABCG2) and OCT-4 (also known as POU5F1) are among the most useful markers for CSC identification. We therefore examined the malignant behavior of ABCG2 and OCT-4 in vitro and in vivo, and their expression was assessed in pathology tissues obtained from clinicopathologically recurrent and non-recurrent cases...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#4
William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, Ren Na, Qitao Ran
Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212470/-prediabetes-as-a-riskmarker-for-stress-induced-hyperglycemia-in-critically-ill-adults
#5
Diego Jesús García-Gallegos, Eliseo Luis-López
BACKGROUND: It is not known if patients with prediabetes, a subgroup of non-diabetic patients that usually present hyperinsulinemia, have higher risk to present stress-induced hyperglycemia. The objective was to determine if prediabetes is a risk marker to present stress-induced hyperglycemia. METHODS: Analytic, observational, prospective cohort study of non-diabetic critically ill patients of a third level hospital. We determined plasmatic glucose and glycated hemoglobin (HbA1c) at admission to diagnose stress-induced hyperglycemia (glucose ≥ 140 mg/dL) and prediabetes (HbA1c between 5...
2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#6
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28212453/bone-morphogenetic-protein-2-hybridized-with-nano-anchored-oligonucleotides-on-titanium-implants-enhances-osteogenic-differentiation-in-vivo
#7
Florian Böhrnsen, Jennifer Rublack, Nelia Aeckerle, Anne Foerster, Bernd Schwenzer, Judith Reichert, Dieter Scharnweber, Henning Schliephake
PURPOSE: Previous in vitro studies have shown that DNA oligonucleotides (ODN) can be successfully used as anchor strands for the binding and retarded release of biologically active recombinant human bone morphogenetic protein 2 (rhBMP-2). The aim of the present study was to test the hypothesis that rhBMP-2 bound to the surface of titanium implants through hybridization with nano-anchored ODN strands is biologically active and can enhance the induction of osteogenic markers in peri-implant bone in vivo...
February 17, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28212447/diffuse-large-b-cell-lymphoma-with-concurrent-high-myc-and-bcl2-expression-shows-evidence-of-active-b-cell-receptor-signaling-by-quantitative-immunofluorescence
#8
Agata M Bogusz, Alexandra E Kovach, Long P Le, Derek Feng, Richard H G Baxter, Aliyah R Sohani
B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28212413/scarless-deletion-of-up-to-seven-methyl-accepting-chemotaxis-genes-with-an-optimized-method-highlights-key-function-of-chem-in-salmonella-typhimurium
#9
Stefanie Hoffmann, Christiane Schmidt, Steffi Walter, Jennifer K Bender, Roman G Gerlach
Site-directed scarless mutagenesis is an essential tool of modern pathogenesis research. We describe an optimized two-step protocol for genome editing in Salmonella enterica serovar Typhimurium to enable multiple sequential mutagenesis steps in a single strain. The system is based on the λ Red recombinase-catalyzed integration of a selectable antibiotics resistance marker followed by replacement of this cassette. Markerless mutants are selected by expressing the meganuclease I-SceI which induces double-strand breaks in bacteria still harboring the resistance locus...
2017: PloS One
https://www.readbyqxmd.com/read/28212412/a-mathematical-model-of-aortic-aneurysm-formation
#10
Wenrui Hao, Shihua Gong, Shuonan Wu, Jinchao Xu, Michael R Go, Avner Friedman, Dai Zhu
Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient's aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#11
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28212394/de-novo-transcriptome-analysis-and-microsatellite-marker-development-for-population-genetic-study-of-a-serious-insect-pest-rhopalosiphum-padi-l-hemiptera-aphididae
#12
Xinle Duan, Kang Wang, Sha Su, Ruizheng Tian, Yuting Li, Maohua Chen
The bird cherry-oat aphid, Rhopalosiphum padi (L.), is one of the most abundant aphid pests of cereals and has a global distribution. Next-generation sequencing (NGS) is a rapid and efficient method for developing molecular markers. However, transcriptomic and genomic resources of R. padi have not been investigated. In this study, we used transcriptome information obtained by RNA-Seq to develop polymorphic microsatellites for investigating population genetics in this species. The transcriptome of R. padi was sequenced on an Illumina HiSeq 2000 platform...
2017: PloS One
https://www.readbyqxmd.com/read/28212313/chemoprevention-of-rat-mammary-carcinogenesis-by-apiaceae-spices
#13
Farrukh Aqil, Jeyaprakash Jeyabalan, Radha Munagala, Srivani Ravoori, Manicka V Vadhanam, David J Schultz, Ramesh C Gupta
Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212293/targeting-angiogenesis-in-biliary-tract-cancers-an-open-option
#14
REVIEW
Valeria Simone, Oronzo Brunetti, Luigi Lupo, Mario Testini, Eugenio Maiorano, Michele Simone, Vito Longo, Christian Rolfo, Marc Peeters, Aldo Scarpa, Amalia Azzariti, Antonio Russo, Domenico Ribatti, Nicola Silvestris
Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212289/the-effects-of-myo-inositol-and-b-and-d-vitamin-supplementation-in-the-db-mouse-model-of-gestational-diabetes-mellitus
#15
Jasmine F Plows, Florence Budin, Rebecka A M Andersson, Valerie J Mills, Katherine Mace, Sandra T Davidge, Mark H Vickers, Philip N Baker, Irma Silva-Zolezzi, Joanna L Stanley
Gestational diabetes mellitus (GDM) is a growing concern, affecting an increasing number of pregnant women worldwide. By predisposing both the affected mothers and children to future disease, GDM contributes to an intergenerational cycle of obesity and diabetes. In order to stop this cycle, safe and effective treatments for GDM are required. This study sought to determine the treatment effects of dietary supplementation with myo-inositol (MI) and vitamins B2, B6, B12, and D in a mouse model of GDM (pregnant db/+ dams)...
February 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28212276/preventive-effects-of-pentoxifylline-on-the-development-of-colonic-premalignant-lesions-in-obese-and-diabetic-mice
#16
Kazufumi Fukuta, Yohei Shirakami, Akinori Maruta, Koki Obara, Soichi Iritani, Nobuhiko Nakamura, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212273/oxidative-stress-in-copd-sources-markers-and-potential-mechanisms
#17
REVIEW
Adam John Anthony McGuinness, Elizabeth Sapey
Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. However, the involvement of ROS in the development and progression of COPD is not proven. Here, we discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. We address the role that ROS may have in the development and progression of COPD, as well as current therapeutic attempts at limiting the damage they cause...
February 15, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28212266/individual-patterns-in-blood-borne-indicators-of-fatigue-trait-or-chance
#18
Ross Julian, Tim Meyer, Hugh H K Fullagar, Sabrina Skorski, Mark Pfeiffer, Michael Kellmann, Alexander Ferrauti, Anne Hecksteden
Julian, R, Meyer, T, Fullagar, HHK, Skorski, S, Pfeiffer, M, Kellmann, M, Ferrauti, A, and Hecksteden, A. Individual patterns in blood-borne indicators of fatigue-trait or chance. J Strength Cond Res 31(3): 608-619, 2017-Blood-borne markers of fatigue such as creatine kinase (CK) and urea (U) are widely used to fine-tune training recommendations. However, predictive accuracy is low. A possible explanation for this dissatisfactory characteristic is the propensity of athletes to react to different patterns of fatigue indicators (e...
March 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28212265/variations-in-oxidative-stress-levels-in-3-days-follow-up-in-ultramarathon-mountain-race-athletes
#19
Ypatios Spanidis, Dimitrios Stagos, Marina Orfanou, Nikolaos Goutzourelas, David Bar-Or, Demetrios Spandidos, Demetrios Kouretas
Spanidis, Y, Stagos, D, Orfanou, M, Goutzourelas, N, Bar-or, D, Spandidos, D, and Kouretas, D. Variations in oxidative stress levels in 3 days follow-up in ultramarathon mountain race athletes. J Strength Cond Res 31(3): 582-594, 2017-The aim of the present study was the monitoring of the redox status of runners participating in a mountain ultramarathon race of 103 km. Blood samples from 12 runners were collected prerace and 24, 48, and 72 hours postrace. The samples were analyzed by using conventional oxidative stress markers, such as protein carbonyls (CARB), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC) in plasma, as well as glutathione (GSH) levels and catalase (CAT) activity in erythrocytes...
March 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28212251/serum-mast-cell-tryptase-as-a-marker-of-posttraumatic-joint-contracture-in-a-rabbit-model
#20
Michaela Kopka, Michael J Monument, A Dean Befus, Mei Zhang, David A Hart, Paul T Salo, Prism S Schneider, Cun-Yi Fan, Xiangdang Liang, Alexandra Garven, Kevin A Hildebrand
OBJECTIVES: Mast cells have been identified as key mediators of posttraumatic joint contracture, and stabilizing medications (ketotifen) have been shown to decrease contracture severity. Serum mast cell tryptase (SMCT) levels are used clinically to monitor mast cell-mediated conditions. The goals of this study were to determine if SMCT levels are elevated in the setting of joint contracture, if they can be decreased in association with ketotifen therapy, and if they correlate with contracture severity...
March 2017: Journal of Orthopaedic Trauma
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