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https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#1
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#2
REVIEW
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Hamid Fiuji, Saman Soleimanpour, Gordon A Ferns, Amir Avan, Majid Khazaei
Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150846/cancer-stem-cells-as-targets-for-immunotherapy
#3
REVIEW
Amy S Codd, Takayuki Kanaseki, Toshihiko Torigo, Zsuzsanna Tabi
Current cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasise to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypic and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarise some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression...
November 18, 2017: Immunology
https://www.readbyqxmd.com/read/29150718/re-educating-immunity-in-respiratory-allergies-the-potential-for-hematopoietic-stem-cell-mediated-gene-therapy
#4
REVIEW
Jeremy F Brooks, Janet M Davies, James W Wells, Raymond J Steptoe
Respiratory allergies represent a significant disease burden worldwide affecting up to 300 million people globally. Medication and avoidance of known triggers do not address the underlying pathology. Traditional immunotherapies for allergy aim to reinstate immune homeostasis but require years of treatment and have poor long-term efficacy. Novel approaches, such as gene-engineered hematopoietic stem cell transplantation, induce profound antigen-specific tolerance in autoimmunity. Recent evidence shows this approach may also have therapeutic utility for allergy...
November 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#5
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#6
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150377/urgent-versus-post-stabilisation-antiretroviral-treatment-in-hospitalised-hiv-infected-children-in-kenya-push-a-randomised-controlled-trial
#7
Irene N Njuguna, Lisa M Cranmer, Vincent O Otieno, Cyrus Mugo, Hellen M Okinyi, Sarah Benki-Nugent, Barbra Richardson, Joshua Stern, Elizabeth Maleche-Obimbo, Dalton C Wamalwa, Grace C John-Stewart
BACKGROUND: Urgent antiretroviral therapy (ART) among hospitalised HIV-infected children might accelerate recovery or worsen outcomes associated with immune reconstitution. We aimed to compare urgent versus post-stabilisation ART among hospitalised HIV-infected children in Kenya. METHODS: In this unmasked randomised controlled trial, we randomly assigned (1:1) HIV-infected, ART-naive children aged 0-12 years who were eligible for treatment to receive ART within 48 h (urgent group) or in 7-14 days (post-stabilisation group) at four hospitals in Kenya (two in Nairobi and two in western Kenya)...
November 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29150293/a-unique-and-promising-combination-of-medications-for-the-treatment-of-alzheimer-s-disease
#8
James D Weinstein
At present there is no therapy for Alzheimer's Disease which completely stops the progressive dementia effecting late onset Alzheimer's Disease (AD) patients. It is felt that the main reason for this failure is that AD appears to be a disease caused by four major pathological processes. To date, efforts to develop treatments have addressed only one or another of these four etiologies. However, even a partially effective therapy against one cause allows the others, untreated, to continue their inexorable destruction of the neurons of the brain...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150266/interleukin-35-and-hepatocyte-growth-factor-as-a-novel-combined-immune-gene-therapy-for-multiple-sclerosis-disease
#9
Samira Moghadam, Maryam Erfanmanesh, Abdolreza Esmaeilzadeh
An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150002/gene-editing-and-crispr-therapeutics-strategies-taught-by-cell-and-gene-therapy
#10
Juan C Ramirez
A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29149982/marrow-mesenchymal-stem-cells-effectively-reduce-histologic-changes-in-a-rat-model-of-chronic-renal-allograft-rejection
#11
P Yu, Z Wang, Y Liu, Z Xiao, Y Guo, M Li, M Zhao
BACKGROUND: Chronic allograft rejection remains as the leading cause of the chronic renal grafts loss post-transplantation. No therapy has been found really effective to prevent and treat chronic allograft rejection. Mesenchymal stem cells (MSCs) have characteristics of immunomodulation and are expected to be used for inducing graft immune tolerance in organ transplantation. We investigated the efficacy and safety of early infusion of donor-derived marrow MSCs in a rat model of chronic renal allograft rejection...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149942/mechanisms-of-organ-dysfunction-in-sepsis
#12
REVIEW
Rachel Pool, Hernando Gomez, John A Kellum
Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149938/novel-interventions-what-s-new-and-the-future
#13
REVIEW
Jean-Louis Vincent, David Grimaldi
Despite decades of sepsis research, no specific therapies for sepsis have emerged and current management still relies on source control, antibiotics, and organ support. With improved understanding of sepsis pathophysiology and the development of new techniques to enable better characterization of patients with sepsis, clinical trials are beginning to better target new interventions at those patients most likely to respond. This article discusses advances in sepsis therapeutics designed to improve endothelial cell function, purify the blood to help restore immune homeostasis, and provide immunostimulation for patients with immune exhaustion...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149832/optimizing-metal-based-chemotherapeutics-targeting-chemoresistance-related-patterns-in-molecular-tumor-immunology-and-immunosuppressive-tumor-networks
#14
Athanasios Salifoglou, Savvas Petanidis, Efrosini Kioseoglou
Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer agents yet they exhibit undesirable side-effects and are effective against only a few types of cancers. A need, therefore, arises for new metallodrugs with an improved spectrum of efficacy and lower toxicity. Development of anticancer drugs based on antitumor metals is currently a very active field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate structural modification...
November 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29149824/gene-therapy-and-retinal-diseases
#15
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29149821/statins-therapy-for-connective-tissue-diseases-new-therapeutic-opportunities
#16
Przemyslaw J Kotyla, Eugene J Kucharz
Background and Objective Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149077/rna-virus-evolution-via-a-quasispecies-based-model-reveals-a-drug-target-with-a-high-barrier-to-resistance
#17
Richard J Bingham, Eric C Dykeman, Reidun Twarock
The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29148731/conjugation-of-transforming-growth-factor-beta-to-antigen-loaded-poly-lactide-co-glycolide-nanoparticles-enhances-efficiency-of-antigen-specific-tolerance
#18
Liam M Casey, Ryan M Pearson, Kevin Hughes, Jeffrey Liu, Justin Rose, Madeleine G North, Leon Wang, Lei Mei, Stephen D Miller, Lonnie D Shea
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen(Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that co-delivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#19
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29147991/the-role-of-the-gut-microbiome-in-multiple-sclerosis-risk-and-progression-towards-characterization-of-the-ms-microbiome
#20
REVIEW
Anne-Katrin Pröbstel, Sergio E Baranzini
Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i...
November 16, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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