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https://www.readbyqxmd.com/read/28346439/hippo-signalling-governs-cytosolic-nucleic-acid-sensing-through-yap-taz-mediated-tbk1-blockade
#1
Qian Zhang, Fansen Meng, Shasha Chen, Steven W Plouffe, Shiying Wu, Shengduo Liu, Xinran Li, Ruyuan Zhou, Junxian Wang, Bin Zhao, Jianming Liu, Jun Qin, Jian Zou, Xin-Hua Feng, Kun-Liang Guan, Pinglong Xu
The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346272/influenza-in-children
#2
Janienne Kondrich, Michele Rosenthal
PURPOSE OF REVIEW: We review the current information and evidence available on the global burden of disease in the pediatric population, clinical presentation and complications, testing, treatment, and immunization. RECENT FINDINGS: In addition to multiple other risk factors for influenza complications, children with neurologic and neuromuscular disorders are significantly higher risk for serious complications. In practice, there is no lower age limit for children with influenza who can be treated with oseltamivir...
March 24, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28346031/chromogranin-a-cell-density-in-the-large-intestine-of-asian-and-european-patients-with-irritable-bowel-syndrome
#3
Magdy El-Salhy, Tanisa Patcharatrakul, Jan Gunnar Hatlebakk, Trygve Hausken, Odd Helge Gilja, Sutep Gonlachanvit
OBJECTIVE: Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients. METHODS: Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included...
March 27, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28345525/tolerance-of-monocytes-and-macrophages-in-response-to-bacterial-endotoxin
#4
Ewelina Wiśnik, Ewa Pikus, Piotr Duchnowicz, Maria Koter-Michalak
Monocytes belong to myeloid effector cells, which constitute the first line of defense against pathogens, also called the nonspecific immune system and play an important role in the maintenance of tissue homeostasis. In response to stimulation, monocytes differentiate into macrophages capable of microorganism phagocytosis and secrete factors that play a key role in the regulation of immune responses. However excessive exposure of monocytes/macrophages to the lipopolysaccharide (LPS) of Gram negative bacteria leads to the acquisition of immune tolerance by these cells...
March 7, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28344998/low-dose-liver-targeted-gene-therapy-for-pompe-disease-enhances-therapeutic-efficacy-of-ert-via-immune-tolerance-induction
#5
Sang-Oh Han, Giuseppe Ronzitti, Benjamin Arnson, Christian Leborgne, Songtao Li, Federico Mingozzi, Dwight Koeberl
Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10(11) vector genomes [vg]/kg)...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344992/mechanism-of-deletion-removing-all-dystrophin-exons-in-a-canine-model-for-dmd-implicates-concerted-evolution-of-x-chromosome-pseudogenes
#6
D Jake VanBelzen, Alock S Malik, Paula S Henthorn, Joe N Kornegay, Hansell H Stedman
Duchenne muscular dystrophy (DMD) is a lethal, X-linked, muscle-wasting disorder caused by mutations in the large, 2.4-Mb dystrophin gene. The majority of DMD-causing mutations are sporadic, multi-exon, frameshifting deletions, with the potential for variable immunological tolerance to the dystrophin protein from patient to patient. While systemic gene therapy holds promise in the treatment of DMD, immune responses to vectors and transgenes must first be rigorously evaluated in informative preclinical models to ensure patient safety...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#7
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344660/predictive-biomarkers-and-effectiveness-of-muc1-targeted-dendritic-cell-based-vaccine-in-patients-with-refractory-non-small-cell-lung-cancer
#8
Koji Teramoto, Yoshitomo Ozaki, Jun Hanaoka, Satoru Sawai, Noriaki Tezuka, Shozo Fujino, Yataro Daigo, Keiichi Kontani
BACKGROUND: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. METHODS: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344057/ruxolitinib-as-salvage-therapy-in-steroid-refractory-acute-graft-versus-host-disease-in-pediatric-hematopoietic-stem-cell-transplant-patients
#9
Pooja Khandelwal, Ashley Teusink-Cross, Adam S Nelson, Christopher E Dandoy, Javier El-Bietar, Rebecca A Marsh, Ashish R Kumar, Michael S Grimley, Stella M Davies, Sonata Jodele, Kasiani C Myers
We describe our retrospective clinical experience with ruxolitinib for steroid-refractory acute graft versus host disease (GVHD) in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients. Ruxolitinib was administered orally at 5 mg twice daily for children ≥ 25 kg or 2.5 mg twice daily if < 25 kg. We excluded patients who received new immune suppressive agents within two weeks before initiation of ruxolitinib from response analysis. Patients were called a treatment failure if ruxolitinib was stopped before completion of 4 weeks of therapy due to adverse effects and not because of progression of acute GVHD...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28343935/blood-derived-products-in-pediatrics-new-laboratory-tools-for-optimizing-potency-assignment-and-reducing-side-effects
#10
REVIEW
Jean Amiral, Jerard Seghatchian
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks...
March 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28343820/commensal-microbes-and-hair-follicle-morphogenesis-coordinately-drive-treg-migration-into-neonatal-skin
#11
Tiffany C Scharschmidt, Kimberly S Vasquez, Mariela L Pauli, Elizabeth G Leitner, Kevin Chu, Hong-An Truong, Margaret M Lowe, Robert Sanchez Rodriguez, Niwa Ali, Zoltan G Laszik, Justin L Sonnenburg, Sarah E Millar, Michael D Rosenblum
Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation...
March 18, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28343398/an-anti-programmed-death-1-antibody-a%C3%AF-pd-1-fusion-protein-that-self-assembles-into-a-multivalent-and-functional-apd-1-nanoparticle
#12
Peng Zhao, Djordje Atanackovic, Shuyun Dong, Hideo Yagita, Xiao He, Mingnan Chen
Cancer immune checkpoint therapy has achieved remarkable clinical successes in various cancers. However, current immune checkpoint inhibitors block the checkpoint of not only the immune cells that are important to cancer therapy but also the immune cells that are irrelevant to the therapy. Such an indiscriminate blockade limits the efficacy and causes the autoimmune toxicity of the therapy. It might be beneficial to use a carrier to target immune checkpoint inhibitors to cancer-reactive immune cells. Here, we explore a method to load the inhibitors into carriers...
March 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28343198/-why-ovarian-cancer-cells-escape-from-immune-surveillance
#13
Iwona Wertel, Karolina Okła, Justyna Surówka, Monika Bilska, Grzegorz Polak, Wiesława Bednarek, Jan Kotarski
Ovarian cancer is a malignancy of high mortality rates. In respect of the number of deaths caused by cancers it occupies the fourth place among women in Poland. Recent studies are focusing on the role of immune system in ovarian cancer pathogenesis. It has been reported that immune response against ovarian cancer cells may be inhibited by a number of immunosuppressive mechanisms active in cancer microenvironment. It causes difficulties in recognizing and destroying cancer cells by immune system which leads to the development of immune tolerance and is associated with a low efficacy of standard therapeutic strategies...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#14
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28340570/the-therapeutic-hiv-env-c5-gp41-vaccine-candidate-vacc-c5-induces-specific-t-cell-regulation-in-a-phase-i-ii-clinical-study
#15
Kristin Brekke, Maja Sommerfelt, Mats Ökvist, Anne Margarita Dyrhol-Riise, Dag Kvale
BACKGROUND: Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41(732-744) as well as the effects on pre-existing AB levels to C5/gp41(732-744), immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation...
March 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28340094/nlrp2-is-a-suppressor-of-nf-%C3%A6-b-signaling-and-hla-c-expression-in-human-trophoblasts
#16
Tamara Tilburgs, Torsten B Meissner, Leonardo M R Ferreira, Arend Mulder, Kiran Musunuru, Junqiang Ye, Jack L Strominger
During human pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of Human Leukocyte Antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated. The MHC class I and class II transcriptional activators NLRC5 and CIITA are expressed neither by EVT nor by the EVT model cell line JEG3, which has an MHC expression pattern identical to that of EVT...
March 7, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339029/hydroxychloroquine-sensitizes-chronic-myeloid-leukemia-cells-to-v%C3%AE-9v%C3%AE-2-t-cell-mediated-lysis-independent-of-autophagy
#17
Biqing Han, Yanmin Zhao, Yu Lin, Shan Fu, Limengmeng Wang, Mingming Zhang, Ruxiu Tie, Binsheng Wang, Yi Luo, Lizhen Liu, Jian Yu, He Huang
Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7...
March 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338920/dendritic-cell-expression-of-the-signaling-molecule-traf6-is-required-for-immune-tolerance-in-the-lung
#18
Daehee Han, Matthew C Walsh, Kwang Soon Kim, Sung-Wook Hong, Junyoung Lee, Jaeu Yi, Gloriany Rivas, Yongwon Choi, Charles D Surh
Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung...
March 11, 2017: International Immunology
https://www.readbyqxmd.com/read/28337764/a-national-french-noninterventional-study-to-assess-the-long-term-safety-and-efficacy-of-reformulated-nonacog-alfa
#19
Thierry Lambert, Chantal Rothschild, Fabienne Volot, Annie Borel-Derlon, Marc Trossaërt, Ségolène Claeyssens-Donadel, Sepideh Attal
BACKGROUND: Nonacog alfa, the recombinant Factor IX (F IX) used for the treatment of hemophilia B, was approved in Europe in 1998. A reformulated version was approved for European use in 2007. STUDY DESIGN AND METHODS: This postmarketing study, as recommended by the risk management plan, was conducted to confirm the safety of reformulated nonacog alfa in a usual care setting in France. This open-label, noninterventional, prospective, longitudinal postmarketing study comprised 19 French hemophilia centers...
March 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#20
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
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