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CD40 Ligand

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https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#1
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29751949/platelet-storage-lesions-what-more-do-we-know-now
#2
REVIEW
Monica Suet Ying Ng, John-Paul Tung, John Francis Fraser
Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage...
April 17, 2018: Transfusion Medicine Reviews
https://www.readbyqxmd.com/read/29740798/new-insight-on-a-combination-of-policosanol-and-10-dehydrogingerdione-phytochemicals-as-inhibitors-for-platelet-activation-biomarkers-and-atherogenicity-risk-in-dyslipidemic-rabbits-role-of-cetp-and-pcsk9-inhibition
#3
Mohamed Mahmoud Elseweidy, Rawia Sarhan Amin, Hebatallah Husseini Atteia, Reham Raafat El-Zeiky, Naif A Al-Gabri
Platelet markers [soluble p selectin (sP-selectin) and soluble CD40 ligand (sCD40L)] are associated with platelet activation and cardiovascular risk. Both policosanol and 10-dehydrogingerdione are natural products with proven CETP inhibitory and antiatherogenic effects. Present work aimed mainly to investigate the levels of platelet activation biomarkers in the serum of dyslipidemic rabbits and the potential of these phytochemicals either alone or in a combination form to protect against atherogenicity. Additionally, this work clarified their effect on PCSK9, a key player in atherosclerosis progression...
May 9, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29739685/b-cell-subsets-imbalance-and-reduced-expression-of-cd40-in-ataxia-telangiectasia-patients
#4
C T M Pereira, D C Bichuetti-Silva, N V F da Mota, R Salomão, M K C Brunialti, B T Costa-Carvalho
BACKGROUND: Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production...
May 5, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29730558/increased-expression-of-il-1r8-and-a-possible-immunomodulatory-role-of-its-ligand-il-37-in-allergic-rhinitis-patients
#5
Cong Li, Yang Shen, Jue Wang, Zu-Xia Ma, Xia Ke, Zhi-Hai Wang, Su-Ling Hong, Guo-Hua Hu
Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4+ T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response...
May 3, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29725338/cd22-binding-synthetic-sialosides-regulate-b-lymphocyte-proliferation-through-cd22-ligand-dependent-and-independent-pathways-and-enhance-antibody-production-in-mice
#6
Naoko Matsubara, Akihiro Imamura, Tatsuya Yonemizu, Chizuru Akatsu, Hongrui Yang, Akiharu Ueki, Natsuki Watanabe, Hajjaj Abdu-Allah, Nobutaka Numoto, Hiromu Takematsu, Shinobu Kitazume, Thomas F Tedder, Jamey D Marth, Nobutoshi Ito, Hiromune Ando, Hideharu Ishida, Makoto Kiso, Takeshi Tsubata
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29715163/the-role-of-soluble-cd40l-ligand-in-human-carcinogenesis
#7
Anastasios Angelou, Efstathios Antoniou, Nikolaos Garmpis, Christos Damaskos, Stamatios Theocharis, Georgios-Antonios Margonis
BACKGROUND: The role of CD40/CD40L in carcinogenesis is widely examined. The mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with neoplasia are nowadays a topic of intensive research. CD40L and sCD40L belong to the TNF superfamily and are molecules with a proinflammatory role. A variety of cells express CD40L such as the immune system cells, the endothelial cells and activated platelets. Although many medications such as statins have been shown to reduce sCD40L, it is still debated whether specific treatments targeting the CD40/CD40L system will prove to be effective against carcinogenesis in the near future...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29670037/expression-and-regulation-of-thymic-stromal-lymphopoietin-and-thymic-stromal-lymphopoietin-receptor-heterocomplex-in-the-innate-adaptive-immunity-of-pediatric-asthma
#8
REVIEW
Sheng-Chieh Lin, Fang-Yi Cheng, Jun-Jen Liu, Yi-Ling Ye
Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29658605/aerobic-exercise-regulates-blood-lipid-and-insulin-resistance-via-the-toll%C3%A2-like-receptor-4%C3%A2-mediated-extracellular-signal%C3%A2-regulated-kinases-amp%C3%A2-activated-protein-kinases-signaling-pathway
#9
Mei Wang, Sen Li, Fubaihui Wang, Jinhui Zou, Yanfeng Zhang
Diabetes mellitus is a complicated metabolic disease with symptoms of hyperglycemia, insulin resistance, chronic damage and dysfunction of tissues, and metabolic syndrome for insufficient insulin production. Evidence has indicated that exercise treatments are essential in the progression of type‑ІІ diabetes mellitus, and affect insulin resistance and activity of islet β‑cells. In the present study, the efficacy and signaling mechanism of aerobic exercise on blood lipids and insulin resistance were investigated in the progression of type‑ІІ diabetes mellitus...
April 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29652910/elderly-dendritic-cells-respond-to-lps-ifn-%C3%AE-and-cd40l-stimulation-despite-incomplete-maturation
#10
Joanne K Gardner, Scott M J Cornwall, Arthur W Musk, John Alvarez, Cyril D S Mamotte, Connie Jackaman, Anna K Nowak, Delia J Nelson
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation...
2018: PloS One
https://www.readbyqxmd.com/read/29627569/ticam-1-is-dispensable-in-sting-mediated-innate-immune-responses-in-myeloid-immune-cells
#11
Ken Takashima, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Stimulator of interferon genes (STING) is an essential molecule for the production of type I interferon (IFN), and other inflammatory cytokines, in response to cytosolic DNA. STING contributes to host defense against infection and anti-tumor responses. Previous reports have demonstrated that STING signaling is required by the adaptor Toll-IL-1 receptor-containing adaptor molecule-1 (TICAM-1), which has been identified as a TLR3-adaptor molecule using mouse embryonic fibroblasts. Here, we demonstrate that TICAM-1 does not affect STING-mediated innate immune responses, as increases in the mRNA expression levels of IFN-β, IL-6, and CCL5 were observed in bone marrow-derived or splenic myeloid cells...
April 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#12
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
March 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29593736/type-i-interferon-independent-dendritic-cell-priming-and-antitumor-t-cell-activation-induced-by-a-mycoplasma-fermentans-lipopeptide
#13
Yohei Takeda, Masahiro Azuma, Kenji Funami, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Mycoplasma fermentans -derived diacylated lipoprotein M161Ag (MALP404) is recognized by human/mouse toll-like receptor (TLR) 2/TLR6. Short proteolytic products including macrophage-activating lipopeptide 2 (MALP2) have been utilized as antitumor immune-enhancing adjuvants. We have chemically synthesized a short form of MALP2 named MALP2s ( S -[2,3-bis(palmitoyloxy)propyl]-CGNNDE). MALP2 and MALP2s provoke natural killer (NK) cell activation in vitro but only poorly induce tumor regression using in vivo mouse models loading NK-sensitive tumors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29576376/complex-interplay-between-epitope-specificity-and-isotype-dictates-the-biological-activity-of-anti-human-cd40-antibodies
#14
Xiaojie Yu, H T Claude Chan, Christian M Orr, Osman Dadas, Steven G Booth, Lekh N Dahal, Christine A Penfold, Lyn O'Brien, C Ian Mockridge, Ruth R French, Patrick Duriez, Leon R Douglas, Arwen R Pearson, Mark S Cragg, Ivo Tews, Martin J Glennie, Ann L White
Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane...
March 3, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29569917/terminal-sugar-moiety-determines-immunomodulatory-properties-of-poly-propyleneimine-glycodendrimers
#15
Micha Gorzkiewicz, Krzysztof Sztandera, Izabela Jatczak-Pawlik, Robin Zinke, Dietmar Appelhans, Barbara Klajnert-Maculewicz, Łukasz Pułaski
Poly(propyleneimine) (PPI) dendrimers fully surface-modified with disaccharide moieties (maltose, cellobiose and lactose) designed to mimic natural lectin receptor ligands, were tested for their bioactivity in two myeloid cell lines: THP-1 and HL-60. Depending on the sugar modification, we observed variable activation of NF-κB, AP-1 and NF-AT signaling pathways: lactose-coated dendrimers had the strongest impact on marker gene expression and most signaling events, with a notable exception of NF-κB activation in THP-1 cells...
March 23, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29569129/cytokine-responses-in-severe-traumatic-brain-injury-where-there-is-smoke-is-there-fire
#16
Colin Casault, Abdulaziz S Al Sultan, Mohammad Banoei, Philippe Couillard, Andreas Kramer, Brent W Winston
This scoping review will discuss the basic functions and prognostic significance of the commonly researched cytokines implicated in severe traumatic brain injury (sTBI), including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), transforming growth factor-β (TGF-β), substance P, and soluble CD40 ligand (sCD40L). A scoping review was undertaken with an electronic search for articles from the Ovid MEDLINE, PUBMED and EMBASE databases from 1995 to 2017...
March 22, 2018: Neurocritical Care
https://www.readbyqxmd.com/read/29568866/incorporation-of-cd40-ligand-enhances-the-immunogenicity-of-tumor%C3%A2-associated-calcium-signal-transducer-2-virus%C3%A2-like-particles-against-lung-cancer
#17
Wang Xi, Dong Ke, Long Min, Wang Lin, Zuo Jiahui, Lin Fang, Gao Zhaowei, Zhang Zhe, Chen Xi, Zhang Huizhong
The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lung cancer, and has recently been used as an effective immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor superfamily member, is a promising immune adjuvant. Human immunodeficiency virus (HIV) gag‑based virus‑like particles (VLPs) are highly immunogenic, and foreign antigens can be incorporated onto their membrane envelope for cancer vaccine development. In the present study, a HIV gag‑based VLP strategy and Bac‑to‑Bac system were utilized to construct Trop‑2, CD40L and gag recombinant baculoviruses, which were then used to infect TN5 cells in order to form Trop‑2 VLPs or Trop‑2‑CD40L VLPs...
March 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29565449/dna-damage-induced-by-human-cd40-ligand-mutant-promotes-senescence-and-induces-demethylation-of-gata4-in-lung-cancer
#18
Yue Li, Yunyan Wei, Weiwei Yuan, Qiqing Huang, Yaya Zhao, Weihong Zhao, Wei Xu, Jianqing Wu
The ligand of CD40, known as CD154 or CD40L, is the key to immunostimulatory and anticancer activity, but how CD40L affects cellular senescence is unclear. Thus, we studied a membrane‑stable mutant form CD40L (CD40L‑M) to explore tumor growth and cellular senescence in CD40‑positive NSCLC cells. We found that CD40L‑M‑expressing cells had senescent characteristics, including reduced cell proliferation and enlargement, increased SA‑β‑gal staining activity, and overexpression of several cell cycle regulators p53 and p21...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29558818/biomarkers-of-inflammation-thrombogenesis-and-collagen-turnover-in-patients-with-atrial-fibrillation
#19
Sallu Jabati, Jawed Fareed, Jeffrey Liles, Abigail Otto, Debra Hoppensteadt, Jack Bontekoe, Trung Phan, Amanda Walborn, Mushabbar Syed
The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#20
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
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