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Immune programming

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https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#1
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#2
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27909947/vaccine-rejecting-parents-engagement-with-expert-systems-that-inform-vaccination-programs
#3
Katie Attwell, Julie Leask, Samantha B Meyer, Philippa Rokkas, Paul Ward
In attempting to provide protection to individuals and communities, childhood immunization has benefits that far outweigh disease risks. However, some parents decide not to immunize their children with some or all vaccines for reasons including lack of trust in governments, health professionals, and vaccine manufacturers. This article employs a theoretical analysis of trust and distrust to explore how twenty-seven parents with a history of vaccine rejection in two Australian cities view the expert systems central to vaccination policy and practice...
December 1, 2016: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/27909722/expression-of-soluble-programmed-death-1-protein-in-peripheral-blood-regulatory-t-cells-and-its-effects-on-rheumatoid-arthritis-progression
#4
Chun-Feng Ren, Ya-Xin Zhao, Chun-Feng Hou, Luan Luan, Guo-Qing Duan, Shu-Jie Li, Jian-Hong Zhao
The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry...
November 28, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#5
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27906022/risk-factors-for-unstructured-treatment-interruptions-and-association-with-survival-in-low-to-middle-income-countries
#6
James H McMahon, Tim Spelman, Nathan Ford, Jane Greig, Anita Mesic, Charles Ssonko, Esther C Casas, Daniel P O'Brien
BACKGROUND: Antiretroviral therapy (ART) treatment interruptions lead to poor clinical outcomes with unplanned or unstructured TIs (uTIs) likely to be underreported. This study describes; uTIs, their risk factors and association with survival. METHODS: Analysis of ART programmatic data from 11 countries across Asia and Africa between 2003 and 2013 where an uTI was defined as a ≥90-day patient initiated break from ART calculated from the last day the previous ART prescription would have run out until the date of the next ART prescription...
July 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905982/the-use-of-a-lot-quality-assurance-sampling-methodology-to-assess-and-manage-primary-health-interventions-in-conflict-affected-west-darfur-sudan
#7
Kiemanh Pham, Emily Chambers Sharpe, William M Weiss, Alexander Vu
BACKGROUND: Organizations working in conflict-affected areas have a need to monitor and evaluate their programs, however this is often difficult due to the logistical challenges of conflict areas. Lot quality assurance sampling may be a suitable method of assessing programs in these situations. METHODS: We conducted a secondary data analysis of information collected during Medair's routine program management functions. Medair's service area in West Darfur, Sudan was divided into seven supervisory areas...
October 6, 2016: Population Health Metrics
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#8
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903841/influence-of-a-moderate-intensity-exercise-program-on-early-nk-cell-immune-recovery-in-pediatric-patients-after-reduced-intensity-hematopoietic-stem-cell-transplantation
#9
Carolina Chamorro-Viña, Jaime Valentín, Lucía Fernández, Marta González-Vicent, Margarita Pérez-Ruiz, Alejandro Lucía, S Nicole Culos-Reed, Miguel Ángel Díaz, Antonio Pérez-Martínez
INTRODUCTION: After allogeneic hematopoietic stem cell transplantation (HSCT), NK cell reconstitution, which is crucial for positive outcomes, is dominated by the CD56(bright) subset with low NK cell cytotoxicity (NKCC) activity. Moderate exercise has been described as a potent NK cell stimulus in adults with cancer. PURPOSE: To determine the effects of a moderate-intensity exercise program on NK cell recovery early after HSCT and the feasibility of this intervention...
November 30, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27903604/what-does-pd-l1-positive-or-negative-mean
#10
Antoni Ribas, Siwen Hu-Lieskovan
Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response...
November 30, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27902946/social-regulation-of-the-lymph-node-transcriptome-in-rhesus-macaques-macaca-mulatta
#11
K Chun, J P Capitanio, D M Lamkin, E K Sloan, J M G Arevalo, S W Cole
Previous research has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type I interferon anti-viral genes in circulating blood cells. However, the impact of social conditions on lymphoid tissue gene regulation remains largely unexplored. This project assessed how social instability in adult male rhesus macaques (N=10, 5 in unstable, and 5 in stable social conditions) might regulate gene expression within secondary lymphoid tissue (lymph nodes; LN)...
November 14, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27902905/pathogenicity-of-genome-reassortant-infectious-bursal-disease-viruses-in-chickens-and-turkeys
#12
Daral J Jackwood, Simone T Stoute, Beate M Crossley
Infectious bursal disease virus (IBDV) contains two genome segments (segment A/segment B) that can reassort among the viruses. Reassortant IBDVs have been identified in several countries including the United States. These reassortant viruses usually include at least one genome segment from a very virulent (vv)IBDV strain. In vivo virulence of six reassortant IBDV from the United States was assessed relative to the virulence of three frequently described IBDV pathotypes: vvIBDV (rB strain), classic virulent (cv)IBDV (STC strain), and subclinical (sc)IBDV (Del-E strain)...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902900/sensitivity-and-specificity-estimation-for-the-clinical-diagnosis-of-highly-pathogenic-avian-influenza-in-the-egyptian-participatory-disease-surveillance-program
#13
C Verdugo, I El Masry, Y Makonnen, H Hannah, F Unger, M Soliman, S Galal, J Lubroth, D Grace
Many developing countries lack sufficient resources to conduct animal disease surveillance. In recent years, participatory epidemiology has been used to increase the cover and decrease the costs of surveillance. However, few diagnostic performance assessments have been carried out on participatory methods. The objective of the present study was to estimate the diagnostic performance of practitioners working for the Community-Based Animal Health and Outreach (CAHO) program, which is a participatory disease surveillance system for the detection of highly pathogenic avian influenza outbreaks in Egypt...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902649/increasing-incidence-of-life-threatening-pertussis-a-retrospective-cohort-study-in-new-zealand
#14
Emma Macdonald-Laurs, Anusha Ganeshalingham, Jonathan Lillie, Brent McSharry, Elizabeth R Segedin, Emma Best, Avinesh Pillai, Anthony Harnden, Catherine A Gilchrist, Cameron C Grant
BACKGROUND: Pertussis immunization programs aim to prevent severe infant disease. We investigated temporal trends in infant pertussis deaths and pediatric intensive care unit (PICU) admissions and associations of changes in disease detection and vaccines used with death and PICU admission rates. METHODS: Using national data from New Zealand (NZ) we described infant pertussis deaths and PICU admissions from 1991-2013, over which time national immunization coverage at age 2 years increased from <80% to 92%...
November 28, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27900506/arabidopsis-thaliana-methionine-sulfoxide-reductase-b8-influences-stress-induced-cell-death-and-effector-triggered-immunity
#15
Shweta Roy, Ashis Kumar Nandi
Reactive oxygen species (ROS) oxidize methionine to methionine sulfoxide (MetSO) and thereby inactivate proteins. Methionine sulfoxide reductase (MSR) enzyme converts MetSO back to the reduced form and thereby detoxifies the effect of ROS. Our results show that Arabidopsis thaliana MSR enzyme coding gene MSRB8 is required for effector-triggered immunity and containment of stress-induced cell death in Arabidopsis. Plants activate pattern-triggered immunity (PTI), a basal defense, upon recognition of evolutionary conserved molecular patterns present in the pathogens...
November 29, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#16
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899571/engineering-robust-and-tunable-spatial-structures-with-synthetic-gene-circuits
#17
Wentao Kong, Andrew E Blanchard, Chen Liao, Ting Lu
Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899535/a-tomato-universal-stress-protein-involved-in-oxidative-stress-is-a-cipk6-phosphorylation-target
#18
Emilio Gutierrez-Beltran, José María Personat, Fernando N de la Torre, Olga Del Pozo
Calcineurin B-like interacting protein kinases (CIPKs) decode calcium signals upon interaction with the calcium sensors calcineurin B like proteins (CBLs) into phosphorylation events that result into adaptation to environmental stresses. Few phosphorylation targets of CIPKs are known and therefore the molecular mechanisms underlying their downstream output responses are not fully understood. Tomato (Solanum lycopersicum) Cipk6 regulates immune and susceptible Programmed cell death (PCD) in immunity transforming Ca2+ signals into Reactive Oxygen Species (ROS) signaling...
November 29, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#19
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27899114/developing-translational-medicine-professionals-the-marie-sk%C3%A5-odowska-curie-action-model
#20
Alessandra Petrelli, Berent J Prakken, Norman D Rosenblum
End goal of translational medicine is to combine disciplines and expertise to eventually promote improvement of the global healthcare system by delivering effective therapies to individuals and society. Well-trained experts of the translational medicine process endowed with profound knowledge of biomedical technology, ethical and clinical issues, as well as leadership and teamwork abilities are essential for the effective development of tangible therapeutic products for patients. In this article we focus on education and, in particular, we discuss how programs providing training on the broad spectrum of the translational medicine continuum have still a limited degree of diffusion and do not provide professional support and mentorship in the long-term, resulting in the lack of well established professionals of translational medicine (TMPs) in the scientific community...
November 29, 2016: Journal of Translational Medicine
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