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Adverse outcome pathway

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https://www.readbyqxmd.com/read/29050311/tmem17-depresses-invasion-and-metastasis-in-lung-cancer-cells-via-erk-signaling-pathway
#1
Xiupeng Zhang, Yong Zhang, Yuan Miao, Haijing Zhou, Guiyang Jiang, Enhua Wang
Transmembrane protein 17(TMEM17) is a newly identified protein, its expression pattern and clinicopathological relevance is still unclear. In this study, western blot assay was performed in 20 paired lung cancer samples and found that TMEM17 protein levels were lower in lung cancer tissues than that in the corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143 cases lung cancer specimens also showed that TMEM17 expression in lung cancer tissues were significantly lower than adjacent normal lung tissues (35...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049352/exposure-to-intrauterine-inflammation-alters-metabolomic-profiles-in-the-amniotic-fluid-fetal-and-neonatal-brain-in-the-mouse
#2
Amy G Brown, Natalia M Tulina, Guillermo O Barila, Michael S Hester, Michal A Elovitz
INTRODUCTION: Exposure to prenatal inflammation is associated with diverse adverse neurobehavioral outcomes in exposed offspring. The mechanism by which inflammation negatively impacts the developing brain is poorly understood. Metabolomic profiling provides an opportunity to identify specific metabolites, and novel pathways, which may reveal mechanisms by which exposure to intrauterine inflammation promotes fetal and neonatal brain injury. Therefore, we investigated whether exposure to intrauterine inflammation altered the metabolome of the amniotic fluid, fetal and neonatal brain...
2017: PloS One
https://www.readbyqxmd.com/read/29045512/gemcitabine-plus-sirolimus-for-relapsed-and-progressing-osteosarcoma-patients-after-standard-chemotherapy-a-multicenter-single-arm-phase-ii-trial-of-spanish-group-for-research-on-sarcoma-geis
#3
J Martin-Broto, A Redondo, C Valverde, M A Vaz, J Mora, X Garcia Del Muro, A Gutierrez, C Tous, A Carnero, D Marcilla, A Carranza, P Sancho, J Martinez-Trufero, R Diaz-Beveridge, J Cruz, V Encinas, M Taron, D S Moura, P Luna, N Hindi, A Lopez-Pousa
Background: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. FAS and mTOR pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. Patients and Methods: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma (GEIS)...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045485/alterations-in-the-placental-methylome-with-maternal-obesity-and-evidence-for-metabolic-regulation
#4
Kohzoh Mitsuya, Ashley N Parker, Lu Liu, Jianhua Ruan, Margreet C M Vissers, Leslie Myatt
The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI<25) or obese (BMI>30) women...
2017: PloS One
https://www.readbyqxmd.com/read/29037750/environmental-toxicology-and-omics-a-question-of-sex
#5
Xuefang Liang, April Feswick, Denina Simmons, Christopher J Martyniuk
Molecular initiating events and downstream transcriptional/proteomic responses provide valuable information for adverse outcome pathways, which can be used predict the effects of chemicals on physiological systems. There has been a paucity of research that addresses sex-specific expression profiling in toxicology and due to cost, time, and logistical considerations, sex as a variable has not been widely considered. In response to this deficiency, federal agencies in the United States, Canada, and Europe have highlighted the importance of including sex as a variable in scientific investigations...
October 13, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29037211/pioglitazone-and-the-secondary-prevention-of-cardiovascular-disease-a-meta-analysis-of-randomized-controlled-trials
#6
REVIEW
Marit de Jong, H Bart van der Worp, Yolanda van der Graaf, Frank L J Visseren, Jan Westerink
BACKGROUND AND AIMS: Pioglitazone targets multiple pathogenic pathways involved in the development of cardiovascular diseases (CVD). The aim of this systematic review and meta-analysis is to assess the effects of pioglitazone treatment on the secondary prevention of CVD. METHODS: Randomized-controlled trials of pioglitazone in patients with CVD were identified through PubMed, Embase, Cochrane and CINAHL, in a search up to May 2016. Studies were included if pioglitazone was compared with any control (usual care, placebo or active comparator) and if patients were previously diagnosed with CVD...
October 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29035972/hyperammonemia-and-proteostasis-in-cirrhosis
#7
Srinivasan Dasarathy, Maria Hatzoglou
PURPOSE OF REVIEW: Skeletal muscle loss or sarcopenia is a frequent complication of cirrhosis that adversely affects clinical outcomes. As skeletal muscle is the largest store of proteins in the body, proteostasis or protein homeostasis is required for maintenance of muscle mass. This review will focus on disordered skeletal muscle proteostasis in liver disease. RECENT FINDINGS: Increased skeletal muscle uptake of ammonia initiates responses that result in disordered proteostasis including impaired protein synthesis and increased autophagy...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29035711/childhood-adversity-social-support-and-telomere-length-among-perinatal-women
#8
Amanda M Mitchell, Jennifer M Kowalsky, Elissa S Epel, Jue Lin, Lisa M Christian
Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum...
October 5, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29027395/prognostic-value-of-programmed-death-ligand-1-pd-l1-expression-in-ovarian-clear-cell-carcinoma
#9
Jun Zhu, Hao Wen, Rui Bi, Yong Wu, Xiaohua Wu
OBJECTIVE: Programmed death-ligand 1 (PD-L1) was expressed in various tumors and antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and its correlation with clinicopathologic features and clinical outcomes in ovarian clear cell carcinoma (OCCC). METHODS: The PD-L1 expression was measured by tissue-microarray-based immunohistochemistry from 122 eligible patients diagnosed with OCCC...
November 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29021553/development-of-a-cell-based-assay-for-measuring-base-excision-repair-responses
#10
Tyler Golato, Boris Brenerman, Daniel R McNeill, Jianfeng Li, Robert W Sobol, David M Wilson
Base excision repair (BER) is the predominant pathway for coping with most forms of hydrolytic, oxidative or alkylative DNA damage. Measuring BER capacity in living cells is valuable for both basic science applications and epidemiological studies, since deficiencies in this pathway have been associated with cancer susceptibility and other adverse health outcomes. At present, there is an ongoing effort to develop methods to effectively quantify the rate of BER as a whole. We present a variation of a previously described "Oligonucleotide Retrieval Assay" designed to measure DNA excision repair that is capable of quantifying the rate of repair of thymine glycol in a variety of human cells with a high degree of sensitivity...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#11
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29020312/explaining-the-impact-of-poverty-on-old-age-frailty-in-europe-material-psychosocial-and-behavioural-factors
#12
Erwin Stolz, Hannes Mayerl, Anja Waxenegger, Wolfgang Freidl
Previous research found poverty to be associated with adverse health outcomes among older adults but the factors that translate low economic resources into poor physical health are not well understood. The goal of this analysis was to assess the impact of material, psychosocial, and behavioural factors as well as education in explaining the poverty-health link. In total, 28 360 observations from 11 390 community-dwelling respondents (65+) in the Survey of Health, Ageing and Retirement in Europe (2004-13, 10 countries) were analysed...
May 31, 2017: European Journal of Public Health
https://www.readbyqxmd.com/read/29020216/outpatient-management-of-children-with-world-health-organization-chest-indrawing-pneumonia-implementation-risks-and-proposed-solutions
#13
Eric D McCollum, Amy Sarah Ginsburg
This Viewpoints article details our recommendation for the World Health Organization Integrated Management of Childhood Illness guidelines to consider additional referral or daily monitoring criteria for children with chest indrawing pneumonia in low-resource settings. We review chest indrawing physiology in children and relate this to the risk of adverse pneumonia outcomes. We believe there is sufficient evidence to support referring or daily monitoring of children with chest indrawing pneumonia and signs of severe respiratory distress, oxygen saturation <93% (when not at high altitude), moderate malnutrition, or an unknown human immunodeficiency virus (HIV) status in an HIV-endemic setting...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29018118/transgenerational-diapause-as-an-avoidance-strategy-against-bacterial-pathogens-in-caenorhabditis%C3%A2-elegans
#14
M Fernanda Palominos, Lidia Verdugo, Carolaing Gabaldon, Bernardo Pollak, Javiera Ortíz-Severín, Macarena A Varas, Francisco P Chávez, Andrea Calixto
The dynamic response of organisms exposed to environmental pathogens determines their survival or demise, and the outcome of this interaction depends on the host's susceptibility and pathogen-dependent virulence factors. The transmission of acquired information about the nature of a pathogen to progeny may ensure effective defensive strategies for the progeny's survival in adverse environments. Environmental RNA interference (RNAi) is a systemic and heritable mechanism and has recently been linked to antibacterial and antifungal defenses in both plants and animals...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/28994813/a-primary-human-trophoblast-model-to-study-the-effect-of-inflammation-associated-with-maternal-obesity-on-regulation-of-autophagy-in-the-placenta
#15
Bailey Simon, Matthew Bucher, Alina Maloyan
Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture...
September 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28993808/micrornas-new-players-in-the-pathobiology-of-preeclampsia
#16
REVIEW
Kelsey R Bounds, Valorie L Chiasson, Lu J Pan, Sudhiranjan Gupta, Piyali Chatterjee
Our understanding of how microRNAs (miRNAs) regulate gene networks and affect different molecular pathways leading to various human pathologies has significantly improved over the years. In contrary, the role of miRNAs in pregnancy-related hypertensive disorders such as preeclampsia (PE) is only beginning to emerge. Recent papers highlight that adverse pregnancy outcomes are associated with aberrant expression of several miRNAs. Presently, efforts are underway to determine the biologic function of these placental miRNAs which can shed light on their contribution to these pregnancy-related disease conditions...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28993730/molecular-guided-therapy-provides-sustained-clinical-response-in-refractory-choroid-plexus-carcinoma
#17
Albert Cornelius, Jessica Foley, Jeffrey Bond, Abhinav B Nagulapally, Julie Steinbrecher, William P D Hendricks, Maria Rich, Sangeeta Yendrembam, Genevieve Bergendahl, Jeffrey M Trent, Giselle S Sholler
Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. TP53 Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28993607/liver-transplantation-for-high-risk-hepatocellular-carcinoma-after-liver-resection-a-sequential-or-salvage-approach
#18
Chih-Che Lin, Ahmed M Elsarawy, Wei-Feng Li, Ting-Lung Lin, Chee-Chien Yong, Shih-Ho Wang, Chih-Chi Wang, Fang-Ying Kuo, Yu-Fan Cheng, Chao-Long Chen
BACKGROUND Liver transplantation (LT) is the best radical treatment of hepatocellular carcinoma (HCC). Salvage liver transplantation (SalvLT) provides good outcomes for recurrent HCC cases after initial curative liver resection (LR). However, the salvage strategy is not feasible in all situations due to aggressive recurrences. Recently, sequential liver transplantation (SeqLT) was proposed for cases that show adverse pathological features after LR, thus LT is performed pre-emptively before recurrence. In this report, we compared the outcomes of SalvLT and SeqLT for surgical treatment of HCC...
October 10, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28993098/acute-oncology-care-a-narrative-review-of-the-acute-management-of-neutropenic-sepsis-and-immune-related-toxicities-of-checkpoint-inhibitors
#19
Thomas Knight, Shin Ahn, Terry W Rice, Tim Cooksley
Cancer care has become increasingly specialized and advances in therapy have resulted in a larger number of patients receiving care. There has been a significant increase in the number of patients presenting with cancer related emergencies including treatment toxicities and those directly related to the malignancy. Suspected neutropenic sepsis is an acute medical emergency and empirical antibiotic therapy should be administered immediately. The goal of empirical therapy is to cover the most likely pathogens that will cause life-threatening infections in neutropenic patients...
October 6, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28992598/global-transcriptomic-analysis-of-zebrafish-in-response-to-embryonic-exposure-to-three-antidepressants-amitriptyline-fluoxetine-and-mianserin
#20
Minghong Wu, Shuai Liu, Lei Hu, Haidong Qu, Chenyuan Pan, Penghui Lei, Yingjia Shen, Ming Yang
Antidepressants are among the most commonly detected pharmaceuticals in aqueous systems, and, as emerging organic pollutants, may exert negative effects on non-target aquatic organisms. Previously, it has been revealed that antidepressant exposure significantly inhibits the growth and development of fish during their early developmental stages. Thus, in the present study, we aimed to identify and compare the underlying mechanisms of action of different antidepressants at the transcriptional level using zebrafish (Danio rerio) embryos...
September 28, 2017: Aquatic Toxicology
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