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https://www.readbyqxmd.com/read/28719798/chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#1
REVIEW
Eben I Lichtman, Gianpietro Dotti
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719602/prehospital-immune-responses-and-development-of-multiple-organ-dysfunction-syndrome-following-traumatic-injury-a-prospective-cohort-study
#2
Jon Hazeldine, David N Naumann, Emma Toman, David Davies, Jonathan R B Bishop, Zhangjie Su, Peter Hampson, Robert J Dinsdale, Nicholas Crombie, Niharika Arora Duggal, Paul Harrison, Antonio Belli, Janet M Lord
BACKGROUND: Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS)...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#3
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719462/spindle-cell-lipomas-in-women-a-report-of-53-cases
#4
Jennifer S Ko, Brianne Daniels, Patrick O Emanuel, Paul Elson, Vadim Khachaturov, Jesse K McKenney, John R Goldblum, Steven D Billings
Spindle cell lipomas (SCL) are typically tumors of the upper back/neck (shawl region) of men (80% to 90%). In general, there is a frequent tendency to restrict the diagnosis to this specific clinical scenario and a hesitancy to diagnose SCL in women. We hypothesized that SCL in women have a more varied presentation. A total of 395 SCL were diagnosed at our institution over the last 11 years. The diagnosis of SCL in women was confirmed by re-review. Immunohistochemical stains for CD34, desmin, estrogen receptor, and p16 were performed...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28719035/melatonin-inhibits-nucleus-pulposus-np-cell-proliferation-and-extracellular-matrix-ecm-remodeling-via-the-melatonin-membrane-receptors-mediated-pi3k-akt-pathway
#5
Zheng Li, Xingye Li, Chong Chen, Matthew T V Chan, William Ka Kei Wu, Jianxiong Shen
Pinealectomy in vertebrates accelerated intervertebral disc degeneration (IDD). However, the potential mechanisms, particularly, melatonin's role is still to be clarified. In this study, for first time, melatonin membrane receptors of MT1 and MT2 were found to be present in the human intervertebral disc tissues and nucleus pulposus (NP) cells, respectively. Melatonin treatment significantly inhibited NP cell proliferation in dose- dependent manner. Accordingly, melatonin down-regulated gene expression of cyclin D1, PCNA, matrix metallopeptidases-3 and -9 and upregulated gene expression of collagen type II alpha 1 chain and aggrecan in NP cells...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#6
REVIEW
Praveen Sridhar, Fabio Petrocca
Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28718768/selective-and-regulated-trapping-of-nicotinic-receptor-weak-base-ligands-and-relevance-to-smoking-cessation
#7
Anitha P Govind, Yolanda F Vallejo, Jacob R Stolz, Jing-Zhi Yan, Geoffrey T Swanson, William N Green
To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking (125)I-epibatidine binding and desensitizing α4β2Rs...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28717358/clinical-response-to-vedolizumab-in-ulcerative-colitis-patients-is-associated-with-changes-in-integrin-expression-profiles
#8
Friederike Fuchs, Daniela Schillinger, Raja Atreya, Simon Hirschmann, Sarah Fischer, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
BACKGROUND: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. METHODS: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28717244/trail-regulatory-receptors-constrain-human-hepatic-stellate-cell-apoptosis
#9
Harsimran D Singh, Itziar Otano, Krista Rombouts, Kasha P Singh, Dimitra Peppa, Upkar S Gill, Katrin Böttcher, Patrick T F Kennedy, Jude Oben, Massimo Pinzani, Henning Walczak, Giuseppe Fusai, William M C Rosenberg, Mala K Maini
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717031/phagocytic-receptors-activate-syk-and-src-signaling-during-borrelia-burgdorferi-phagocytosis
#10
Tess L Killpack, Maria Ballesteros, Stephen C Bunnell, Alice Bedugnis, Lester Kobzik, Linden T Hu, Tanja Petnicki-Ocwieja
Phagocytosis of the Lyme disease causing pathogen Borrelia burgdorferi has been shown to be important in generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in B. burgdorferi phagocytosis have been reported, including scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediated phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with B...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28717011/dysregulation-of-bcl-2-family-proteins-by-leukaemia-fusion-genes
#11
Lauren M Brown, Diane T Hanna, Seong L Khaw, Paul G Ekert
The genomic lesions that characterise acute lymphoblastic leukaemia in childhood include recurrent translocations that result in the expression of fusion proteins. These translocations typically involve the rearrangement of genes encoding tyrosine kinases, including receptor tyrosine kinase, cytokine receptors and transcription factors. These confer phenotypic changes that are the hallmarks of malignant transformation, including unrestricted proliferation and a relative resistance to apoptosis. In this review, we explore the molecular mechanisms that link these fusions to the control of cell death...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716937/altered-metabotropic-glutamate-receptor-5-markers-in-ptsd-in-vivo-and-postmortem-evidence
#12
Sophie E Holmes, Matthew J Girgenti, Margaret T Davis, Robert H Pietrzak, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Steven Southwick, Ronald S Duman, Richard E Carson, John H Krystal, Irina Esterlis
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [(18)F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#13
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716901/structural-determination-of-lipid-antigens-captured-at-the-cd1d-t-cell-receptor-interface
#14
Patrick J Brennan, Tan-Yun Cheng, Daniel G Pellicci, Gerald F M Watts, Natacha Veerapen, David C Young, Jamie Rossjohn, Gurdyal S Besra, Dale I Godfrey, Michael B Brenner, D Branch Moody
Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a "foreign" lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716895/ctla4-promotes%C3%A2-tyk2-stat3-dependent-b-cell-oncogenecity
#15
Andreas Herrmann, Christoph Lahtz, Toshikage Nagao, Joo Y Song, Wing C Chan, Heehyoung Lee, Chanyu Yue, Thomas Look, Ronja Muelfarth, Wenzhao Li, Kurt Jenkins, John Williams, Lihua E Budde, Stephen J Forman, Larry W Kwak, Thomas Blankenstein, Hua Yu
Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. The pro-tumorigenic function of CTLA4 is believed to be limited to T cell inhibition by countering the activity of the T cell co-stimulating receptor CD28. However, as we demonstrate here, there are two additional roles for CTLA4 in cancer, including via CTLA4 overexpression in diverse B cell lymphomas and in melanoma-associated B cells. CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and survival...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716889/cytokines-transcription-factors-and-the-initiation-of-t-cell-development
#16
Hiroyuki Hosokawa, Ellen V Rothenberg
Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716883/role-of-the-%C3%AE-common-%C3%AE-c-family-of-cytokines-in-health-and-disease
#17
Timothy R Hercus, Winnie L T Kan, Sophie E Broughton, Denis Tvorogov, Hayley S Ramshaw, Jarrod J Sandow, Tracy L Nero, Urmi Dhagat, Emma J Thompson, Karen S Cheung Tung Shing, Duncan R McKenzie, Nicholas J Wilson, Catherine M Owczarek, Gino Vairo, Andrew D Nash, Vinay Tergaonkar, Timothy Hughes, Paul G Ekert, Michael S Samuel, Claudine S Bonder, Michele A Grimbaldeston, Michael W Parker, Angel F Lopez
The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#18
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28716437/tumor-programmed-cell-death-ligand-1-expression-correlates-with-nodal-metastasis-in-patients-with-cutaneous-squamous-cell-carcinoma-of-the-head-and-neck
#19
Juana María García-Pedrero, Pablo Martínez-Camblor, Susana Diaz-Coto, Pablo Munguia-Calzada, Aitana Vallina-Alvarez, Francisco Vazquez-Lopez, Juan Pablo Rodrigo, Jorge Santos-Juanes
BACKGROUND: Binding of tumor-expressed programmed cell death ligand 1 (PD-L1) to the programmed cell death 1 (PD-1) surface receptor blocks T-cell activation thereby leading to immune evasion. Tumor PD-L1 expression has been associated with poor outcome in a wide variety of cancers; however, data in cutaneous squamous cell carcinoma (cSCC) are scarce and conflicting. OBJECTIVE: To investigate the relationship of tumor PD-L1 expression with the clinicopathologic features and prognosis of cSCC...
July 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28716390/impact-of-cytokine-genetic-polymorphisms-on-the-risk-of-renal-parenchymal-infection-in-children
#20
Almontaser Hussein, Eman Askar, Ahlam Badawy, Khaled Saad, Asmaa Zahran, Ahmad A Elderwy
BACKGROUND: Acute pyelonephritis is associated with renal scarring in up to 30% of patients. Renal scarring may cause significant long-term morbidity. The pathogenesis of acute pyelonephritis remains unclear, although it involves interaction among uroepithelium, the immune system cells, and the locally produced cytokines. That some UTI-prone children develop acute pyelonephritis, and eventually renal parenchymal scarring, suggests a genetic role. Interleukin-6, interleukin-8, chemokine receptor-1 (CXCR1), and tumor necrosis factor-alpha (TNFα), the key regulators of the host immune responses, are proteins whose secretion is controlled by genes...
July 3, 2017: Journal of Pediatric Urology
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