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https://www.readbyqxmd.com/read/29374146/neutralization-of-cd95-ligand-protects-the-liver-against-ischemia-reperfusion-injury-and-prevents-acute-liver-failure
#1
Mohammed Al-Saeedi, Niels Steinebrunner, Hassan Kudsi, Niels Halama, Carolin Mogler, Markus W Büchler, Peter H Krammer, Peter Schemmer, Martina Müller
Ischemia-reperfusion injury is a common pathological process in liver surgery and transplantation, and has considerable impact on the patient outcome and survival. Death receptors are important mediators of ischemia-reperfusion injury, notably the signaling pathways of the death receptor CD95 (Apo-1/Fas) and its corresponding ligand CD95L. This study investigates, for the first time, whether the inhibition of CD95L protects the liver against ischemia-reperfusion injury. Warm ischemia was induced in the median and left liver lobes of C57BL/6 mice for 45 min...
January 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29156673/induction-of-dise-in-ovarian-cancer-cells-in-vivo
#2
Andrea E Murmann, Kaylin M McMahon, Ashley Haluck-Kangas, Nandini Ravindran, Monal Patel, Calvin Y Law, Sonia Brockway, Jian-Jun Wei, C Shad Thaxton, Marcus E Peter
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3'UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150026/regulatory-t-cells-friends-or-foe-in-human-mycobacterium-leprae-infection
#3
Ana T Chaves, Atvaldo F Ribeiro-Junior, Sandra Lyon, Nayara I Medeiros, Fábio Cassirer-Costa, Karina S Paula, Edilamar S Alecrim, Cristiane A S Menezes, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes
Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients...
November 13, 2017: Immunobiology
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#4
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29092660/identification-of-dise-inducing-shrnas-by-monitoring-cellular-responses
#5
Monal Patel, Marcus E Peter
Off-target effects (OTE) are an undesired side effect of RNA interference (RNAi) caused by partial complementarity between the targeting siRNA and mRNAs other than the gene to be silenced. The death receptor CD95 and its ligand CD95L contain multiple sequences that when expressed as either si- or shRNAs kill cancer cells through a defined OTE that targets critical survival genes. Death induced by survival gene elimination (DISE) is characterized by specific morphological changes such as elongated cell shapes, senescence-like enlarged cells, appearance of large intracellular vesicles, release of mitochondrial ROS followed by activation of caspase-2, and induction of a necrotic form of mitotic catastrophe...
November 1, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29063830/many-si-shrnas-can-kill-cancer-cells-by-targeting-multiple-survival-genes-through-an-off-target-mechanism
#6
William Putzbach, Quan Q Gao, Monal Patel, Stijn van Dongen, Ashley Haluck-Kangas, Aishe A Sarshad, Elizabeth T Bartom, Kwang-Youn A Kim, Denise M Scholtens, Markus Hafner, Jonathan C Zhao, Andrea E Murmann, Marcus E Peter
Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29032605/non-apoptotic-functions-of-fas-cd95-in-the-immune-response
#7
REVIEW
Jean-Philippe Guégan, Patrick Legembre
CD95 (also known as Fas) is a member of the tumor necrosis factor receptor (TNFR) superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Mutations in this receptor are associated with a loss of apoptotic signaling and have been detected in an autoimmune disorder called autoimmune lymphoproliferative syndrome (ALPS) type Ia, which shares some clinical features with systemic lupus erythematosus (SLE). In addition, deletions and mutations of CD95 have been described in many cancers, which led researchers to initially classify this receptor as a tumor suppressor...
October 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29021794/cd95-fas-non-apoptotic-signaling-pathways-and-kinases
#8
REVIEW
Matthieu Le Gallo, Amanda Poissonnier, Patrick Blanco, Patrick Legembre
Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28766682/fasr-and-fasl-in-colorectal-cancer
#9
Magdalena Szarynska, Agata Olejniczak, Piotr Wierzbicki, Jaroslaw Kobiela, Dariusz Laski, Zbigniew Sledzinski, Krystian Adrych, Marek Guzek, Zbigniew Kmiec
Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#10
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28560426/dcr3-promotes-hepatoma-cell-migration-by-downregulating-e-cadherin-expression
#11
Hongling Zhang, Xuhong Chen, Dongming Li, Lulu Cui, Xin Li, Xiufeng Ye, Xiaochun Wan
Decoy receptor 3 (DcR3), a decoy molecule belonging to the tumor necrosis factor receptor superfamily (TNFRSF), is a soluble receptor that can neutralize the biological effects of three other TNFSF members, namely, Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). DcR3 expression is increased in tumor cells. As such, DcR3 has been considered a potential biomarker to predict cancer invasion and progression of inflammation. However, the molecular mechanisms of DcR3 in tumor progression and metastasis remain poorly described...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28514658/cns-macrophages-control-neurovascular-development-via-cd95l
#12
Si Chen, Nathalie Tisch, Marcel Kegel, Rosario Yerbes, Robert Hermann, Hannes Hudalla, Cecilia Zuliani, Gülce Sila Gülcüler, Klara Zwadlo, Jakob von Engelhardt, Carmen Ruiz de Almodóvar, Ana Martin-Villalba
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445729/caspase-10-negatively-regulates-caspase-8-mediated-cell-death-switching-the-response-to-cd95l-in-favor-of-nf-%C3%AE%C2%BAb-activation-and-cell-survival
#13
Sebastian Horn, Michelle A Hughes, Ramon Schilling, Carsten Sticht, Tencho Tenev, Michaela Ploesser, Pascal Meier, Martin R Sprick, Marion MacFarlane, Martin Leverkus
Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#14
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28273453/cd95-fas-increases-stemness-in-cancer-cells-by-inducing-a-stat1-dependent-type-i-interferon-response
#15
Abdul S Qadir, Paolo Ceppi, Sonia Brockway, Calvin Law, Liang Mu, Nikolai N Khodarev, Jung Kim, Jonathan C Zhao, William Putzbach, Andrea E Murmann, Zhuo Chen, Wenjing Chen, Xia Liu, Arthur R Salomon, Huiping Liu, Ralph R Weichselbaum, Jindan Yu, Marcus E Peter
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95(high)-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#16
Mario Stephan, Bärbel Edelmann, Supandi Winoto-Morbach, Ottmar Janssen, Uwe Bertsch, Cristiana Perrotta, Stefan Schütze, Jürgen Fritsch
Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28149915/myeloid-derived-suppressor-cell-arginase-1-il-17-and-cl-cd95l-an-explosive-cocktail-in-lupus
#17
COMMENT
Robin J Flynn, Patrick Legembre
No abstract text is available yet for this article.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28078597/cd95-and-the-mrl-lpr-mouse-model
#18
Robin J Flynn
CD95 (Fas-ligand) is a key mediator of cell death in multiple setting, thus its loss within the MRL-lpr (Fas(lpr)) homozygote mice results in spontaneous autoimmunity. This is characterized by the development of arthritis and immune complex glomerulonephrosis making this strain a useful model for studying systemic lupus erythematosus. Herein we describe a method to exploit the heterozygote offspring of this strain in a model to study the effects of a CD95L blocking peptide on lupus-like disease in vivo.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078596/liquid-chromatography-high-resolution-mass-spectrometry-method-to-study-sphingolipid-metabolism-changes-in-response-to-cd95l
#19
Fatima Bilal, Michaël Pérès, Pauline Le Faouder, Aude Dupuy, Justine Bertrand-Michel, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingolipids are sphingoid base-containing lipids, among which some metabolites behave as bioactive molecules in various biological processes, including cell death. Whereas ceramide is now viewed as an anti-oncometabolite, leading to cancer cell death, CD95L-induced apoptosis is associated with sphingolipid changes, which likely contribute to caspase-dependent signaling pathway activation. Here, we describe Liquid Chromatography-high resolution mass spectrometry method (LC-HRMS) to analyze sphingolipid metabolism changes triggered by CD95L...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#20
Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingomyelin synthases 1 and 2 convert the anti-oncometabolite ceramide to sphingomyelin, the most abundant sphingolipid in plasma membrane. CD95L-induced ceramide increase is associated with the caspase-dependent inhibition of sphingomyelin synthesis, which enhances the mitochondrial route to apoptosis. Knocking down sphingomyelin synthase 1 or inhibiting sphingomyelin synthesis facilitates ceramide accumulation, cytochrome c release from mitochondria, and caspase-9 activation in cancer cell upon CD95L treatment...
2017: Methods in Molecular Biology
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