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https://www.readbyqxmd.com/read/28100346/-impact-of-cd137-cd137l-signaling-mediated-exocytosis-of-autophagosome-within-vascular-smooth-muscle-cells-on-the-formation-of-atherosclerotic-calcification
#1
B Li, X Y Li, W Zhong, C Shao, Z Q Wang, W Yuan, J C Yan
Objective: To explore whether CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells (VSMCs) could influence the formation of atherosclerotic calcification. Methods: Fifteen 8-week-old male ApoE(-/-)(C57BL/6J-KO) mice fed with high fat diet for 5 weeks were randomly divided into three groups by using stochastic indicator method as follows: control group, n=5; agonist-CD137 group: agonist-CD137 antibody 200 μg/2 weeks for 4 weeks, ip, n=5; anti-CD137 group: 200 μg anti-CD137 antibody+ 200 μg agonist-CD137 antibody/2 weeks for 4 weeks, ip, n=5...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28063668/activation-of-cd137-signaling-accelerates-vascular-calcification-in-vivo-and-vitro
#2
Yao Chen, Abdul Basit Bangash, Juan Song, Wei Zhong, Cuiping Wang, Chen Shao, Zhongqun Wang, Jinchuan Yan
OBJECTIVES: Vascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular risk. CD137 signaling has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In the present study, we investigated the effect of CD137 signaling on vascular calcification in ApoE(-/-) mice and in vascular smooth muscle cells (VSMCs) of mice...
December 30, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28056236/-cd137-cd137l-signaling-promotes-angiogenesis-in-atherosclerosis-plaque-of-mice-through-activating-nuclear-factor-of-activated-t-cells-c1
#3
J Y Weng, J C Yan, Y Chen, Z Q Wang, C P Wang, C Shao
Objective: To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1 (NFATc1). Methods: Apolipoprotein E knock out mice were divided into the following groups: control group (n=5), CD137 activated group(n=5)and CD137 inhibited group (n=5). Immunohistochemistry was performed to detect the expression of CD31 in aortic plaque. Endothelial cells (bEnd.3) were purchased from ATCC and divided into the following groups: control group, IgG isotype control group, CD137 activated group and CD137 inhibited group...
December 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28018351/allorecognition-of-hla-c-mismatches-by-cd8-t-cells-in-hematopoietic-stem-cell-transplantation-is-a-complex-interplay-between-mismatched-peptide-binding-region-residues-hla-c-expression-and-hla-dpb1-disparities
#4
Florence Bettens, Stéphane Buhler, Jean-Marie Tiercy
HLA-C locus mismatches (MMs) are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT) and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C MMs, we have developed a one-way in vitro mixed lymphocyte reaction (MLR) assay allowing to quantify activated CD56(-)CD137(+)CD8(+) lymphocytes in HLA-C incompatible combinations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011265/involvement-of-ly6c-4-1bb-and-klrg1-in-the-activation-of-lamina-propria-lymphocytes-in-the-small-intestine-of-sanroque-mice
#5
Dina Montufar-Solis, Alexander Williams, Nadarajah Vigneswaran, John R Klein
Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquin(san/san) or sanroque mice, develop broad-spectrum chronic inflammatory conditions and autoimmune pathologies. Our laboratory recently reported that sanroque mice also develop extensive inflammation that is localized in the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28000531/cytokines-and-metabolic-factors-regulate-tumoricidal-t-cell-function-during-cancer-immunotherapy
#6
Adam J Adler, Payal Mittal, Joseph M Ryan, Beiyan Zhou, Jeffrey S Wasser, Anthony T Vella
Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27979383/atezolizumab-versus-docetaxel-in-patients-with-previously-treated-non-small-cell-lung-cancer-oak-a-phase-3-open-label-multicentre-randomised-controlled-trial
#7
Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara
BACKGROUND: Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer. METHODS: We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1...
December 12, 2016: Lancet
https://www.readbyqxmd.com/read/27942918/immunological-low-dose-radiation-modulates-the-pediatric-medulloblastoma-antigens-and-enhances-antibody-dependent-cellular-cytotoxicity
#8
Arabinda Das, Daniel McDonald, Stephen Lowe, Amy-Lee Bredlau, Kenneth Vanek, Sunil J Patel, Samuel Cheshier, Ramin Eskandari
BACKGROUND: Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341)...
December 9, 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27903375/-in-vivo-and-in-vitro-effects-of-cd137-stimulation-on-vascular-calcification-in-high-fat-diet-fed-apoe-mice
#9
Y Chen, J C Yan, J Y Weng, Z Q Wang, C P Wang, C Shao
Objective: To investigate the effect and related mechanism of CD137 stimulation on aortic atherosclerotic plaque calcification in high fat diet fed ApoE(-/-) mice and on calcification of vascular smooth muscle cells (VSMCs). Methods: (1) ApoE(-/-) mice fed with high fat diet were randomly divided into 3 groups: CD137 activated group (treated by 200 μg CD137 agonist i. p. once per week for 6 weeks, n=5); CD137 inhibited group (anti-CD137 group: 200 μg anti-CD137 antibody + 200 μg CD137 agonist, i. p., once per week for 6 weeks, n=5) and control group (n=5)...
October 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27888029/drug-specific-upregulation-of-cd137-on-cd8-t-cells-aids-in-the-diagnosis-of-multiple-antibiotic-toxic-epidermal-necrolysis
#10
Jason A Trubiano, Alec Redwood, Kaija Strautins, Rebecca Pavlos, Emily Woolnough, Christina C Chang, Elizabeth Phillips
No abstract text is available yet for this article.
November 22, 2016: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/27887866/continuously-expanding-car-nk-92-cells-display-selective-cytotoxicity-against-b-cell-leukemia-and-lymphoma
#11
Sarah Oelsner, Miriam E Friede, Congcong Zhang, Juliane Wagner, Susanne Badura, Peter Bader, Evelyn Ullrich, Oliver G Ottmann, Hans Klingemann, Torsten Tonn, Winfried S Wels
BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. METHODS: To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63...
February 2017: Cytotherapy
https://www.readbyqxmd.com/read/27855539/mouse-p2y4-nucleotide-receptor-is-a-negative-regulator-of-cardiac-adipose-derived-stem-cell-differentiation-and-cardiac-fat-formation
#12
Anne Lemaire, Marion Vanorlé, Michael Horckmans, Larissa di Pietrantonio, Sophie Clouet, Bernard Robaye, Jean-Marie Boeynaems, Didier Communi
Cardiac adipose tissue-derived stem cells (cASCs) have the ability to differentiate into multiple cell lineages giving them a high potential for use in regenerative medicine. Cardiac fat tissue still raises many unsolved questions related to its formation and features. P2Y nucleotide receptors have already been described as regulators of differentiation of bone-marrow derived stem cells, but remain poorly investigated in cASCs. We defined, in this study, the P2Y4 nucleotide receptor as a negative regulator of cardiac fat formation and cASC adipogenic differentiation...
December 23, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#13
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27831501/characterizing-cd137-upregulation-on-nk-cells-in-patients-receiving-monoclonal-antibody-therapy
#14
A Makkouk, V Sundaram, C Chester, S Chang, A D Colevas, J B Sunwoo, H Maecker, M Desai, H E Kohrt
BACKGROUND: In the era of personalized cancer medicine, identifying techniques for effectively matching patients to efficacious treatments is a critical step in the treatment process. The advent of anti-cancer immunotherapies necessitates novel approaches to biomarker identification beyond traditional genomic profiling. One promising approach is incorporation of nomograms into treatment decisions. Nomograms are prediction tools, based on statistical modeling, designed to predict treatment outcomes...
November 9, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27827318/isolation-of-t-cell-receptors-specifically-reactive-with-mutated-tumor-associated-antigens-from-tumor-infiltrating-lymphocytes-based-on-cd137-expression
#15
Maria R Parkhurst, Alena Gros, Anna Pasetto, Todd D Prickett, Jessica S Crystal, Paul F Robbins, Steven A Rosenberg
PURPOSE: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T cell receptors (TCRs) can mediate tumor regression. Some tumor infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TIL target tumor specific neoantigens. Here we attempted to isolate neoantigen reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27826331/the-roles-of-cd137-signaling-in-atherosclerosis
#16
REVIEW
In-Hyuk Jung, Goo Taeg Oh
The tumor necrosis factor receptor superfamily (TNFRSF), which includes CD40, LIGHT, and OX40, plays important roles in the initiation and progression of cardiovascular diseases, involving atherosclerosis. CD137, a member of TNFRSF, is a well-known activation-induced T cell co-stimulatory molecule and has been reported to be expressed in human atherosclerotic plaque lesions, and plays pivotal roles in mediating disease processes. In this review, we focus on and summarize recent advances in mouse studies on the involvement of CD137 signaling in the pathogenesis and plaque stability of atherosclerosis, thereby highlighting a valuable therapeutic target in atherosclerosis...
November 2016: Korean Circulation Journal
https://www.readbyqxmd.com/read/27760761/mva-vaccine-encoding-cmv-antigens-safely-induces-durable-expansion-of-cmv-specific-t-cells-in-healthy-adults
#17
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
https://www.readbyqxmd.com/read/27756788/results-from-an-integrated-safety-analysis-of-urelumab-an-agonist-anti-cd137-monoclonal-antibody
#18
Neil H Segal, Theodore F Logan, F Stephen Hodi, David F McDermott, Ignacio Melero, Omid Hamid, Henrik Schmidt, Caroline Robert, Vanna Chiarion-Sileni, Paolo A Ascierto, Michele Maio, Walter J Urba, Tara C Gangadhar, Satyendra Suryawanshi, Jaclyn Neely, Maria Jure-Kunkel, Suba Krishnan, Holbrook E Kohrt, Mario Sznol, Ronald Levy
PURPOSE: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma. PATIENTS AND METHODS: Three hundred and forty-six patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27697858/il-2-variant-circumvents-icos-regulatory-t-cell-expansion-and-promotes-nk-cell-activation
#19
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27637001/eicosapentaenoic-acid-promotes-mitochondrial-biogenesis-and-beige-like-features-in-subcutaneous-adipocytes-from-overweight-subjects
#20
L M Laiglesia, S Lorente-Cebrián, P L Prieto-Hontoria, M Fernández-Galilea, S M R Ribeiro, N Sáinz, J A Martínez, M J Moreno-Aliaga
Eicosapentaenoic acid (EPA), a n-3 long-chain polyunsaturated fatty acid, has been reported to have beneficial effects in obesity-associated metabolic disorders. The objective of the present study was to determine the effects of EPA on the regulation of genes involved in lipid metabolism, and the ability of EPA to induce mitochondrial biogenesis and beiging in subcutaneous adipocytes from overweight subjects. Fully differentiated human subcutaneous adipocytes from overweight females (BMI: 28.1-29.8kg/m(2)) were treated with EPA (100-200 μM) for 24 h...
August 26, 2016: Journal of Nutritional Biochemistry
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