The Role of Immunogenic Cell Death
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
LRRK2 Knockout Mice Have an Intact
Hinkle et al. Molecular Neurodegeneration 2012, 7:25 http://www.molecularneurodegeneration.com/content/7/1/25 RESEARCH ARTICLE Open Access LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors Kelly M Hinkle1†, Mei Yue1†, Bahareh Behrouz1, Justus C Dächsel1, Sarah J Lincoln1, Erin E Bowles1, Joel E Beevers1, Brittany Dugger1, Beate Winner2, Iryna Prots2, Caroline B Kent1, Kenya Nishioka1, Wen-Lang Lin1, Dennis W Dickson1, Christopher J Janus3, Matthew J Farrer1,4 and Heather L Melrose1* Abstract Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes. -
Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells Through Intracellular Oxidative Stress
International Journal of Molecular Sciences Article Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress Abraham Lin 1, Billy Truong 1, Sohil Patel 1, Nagendra Kaushik 2, Eun Ha Choi 2, Gregory Fridman 1, Alexander Fridman 1 and Vandana Miller 1,* 1 C. & J. Nyheim Plasma Institute, Drexel University, Philadelphia, PA 19104, USA; [email protected] (A.L.); [email protected] (B.T.); [email protected] (S.P.); [email protected] (G.F.); [email protected] (A.F.) 2 Plasma Bioscience Research Center, Kwangwoon University, Seoul 139791, Korea; [email protected] (N.K.); [email protected] (E.H.C.) * Correspondence: [email protected]; Tel.: +1-215-571-4074 Academic Editor: Hsueh-Wei Chang Received: 1 March 2017; Accepted: 28 April 2017; Published: 3 May 2017 Abstract: A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. -
Killing Cancer Cells, Twice with One Shot
Cell Death and Differentiation (2014) 21, 1–2 & 2014 Macmillan Publishers Limited All rights reserved 1350-9047/14 www.nature.com/cdd Editorial Killing cancer cells, twice with one shot ME Bianchi*,1 Cell Death and Differentiation (2014) 21, 1–2; doi:10.1038/cdd.2013.147 I can still remember lecturing that chemotherapy and radio- shows that transglutaminase (TG) 2, a protein with several therapy are effective because they kill cancer cells. That was complex activities, can prevent calreticulin exposure on the simple enough, and when I wanted to make it a bit more cell surface, and therefore TG2-overexpressing cancer cells complex, I ventured into explaining how they mainly killed can escape activation of the immune system.9 cancer cells because they divided much more than other cells, Curiously, calreticulin is also surface exposed by spermato- and how the killing involved apoptosis. Things have moved on zoa, both in mammals and nematodes, to facilitate fertiliza- quite a bit since then. Evidence accumulated in the past few tion. Following the phylogenetic trail to its widest extent, years indicates that some anti-cancer drugs do not kill cancer Sukkurwala et al.10 show that yeast calreticulin, CNE1 protein, cells, but merely push them into senescence, some do kill is surface exposed following ER stress, and facilitates yeast cells but not via apoptosis, and some do kill cells via apoptosis mating too.10 The binding of yeast pheromone a-factor to its G but that is not the main ingredient in their efficacy. protein-coupled receptor (GPCR) induces CNE1 surface The main theme of this issue is that dying cancer cells presentation. -
Stress-Induced Inflammation Evoked by Immunogenic Cell Death Is
www.nature.com/cdd ARTICLE OPEN Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting Nicole Rufo1,2, Dimitris Korovesis3,Sofie Van Eygen1,2, Rita Derua4, Abhishek D. Garg 1, Francesca Finotello5, Monica Vara-Perez1,2, ž 6,7 2,8 9 7,10 11 6 Jan Ro anc , Michael Dewaele , Peter A. de Witte , Leonidas G. Alexopoulos✉ , Sophie Janssens , Lasse Sinkkonen , Thomas Sauter6, Steven H. L. Verhelst 3,12 and Patrizia Agostinis 1,2 © The Author(s) 2021 Mounting evidence indicates that immunogenic therapies engaging the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress favor proficient cancer cell-immune interactions, by stimulating the release of immunomodulatory/ proinflammatory factors by stressed or dying cancer cells. UPR-driven transcription of proinflammatory cytokines/chemokines exert beneficial or detrimental effects on tumor growth and antitumor immunity, but the cell-autonomous machinery governing the cancer cell inflammatory output in response to immunogenic therapies remains poorly defined. Here, we profiled the transcriptome of cancer cells responding to immunogenic or weakly immunogenic treatments. Bioinformatics-driven pathway analysis indicated that immunogenic treatments instigated a NF-κB/AP-1-inflammatory stress response, which dissociated from both cell death and UPR. This stress-induced inflammation was specifically abolished by the IRE1α-kinase inhibitor KIRA6. Supernatants from immunogenic chemotherapy and KIRA6 co-treated cancer cells were deprived of proinflammatory/chemoattractant factors and failed to mobilize neutrophils and induce dendritic cell maturation. Furthermore, KIRA6 significantly reduced the in vivo vaccination potential of dying cancer cells responding to immunogenic chemotherapy. Mechanistically, we found that the anti-inflammatory effect of KIRA6 was still effective in IRE1α-deficient cells, indicating a hitherto unknown off-target effector of this IRE1α-kinase inhibitor. -
The Cerebrospinal Fluid Homovanillic Acid Concentration in Patients with Parkinsonism Treated with L-Dopa
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.33.1.1 on 1 February 1970. Downloaded from J. NeuroL Neurosurg. Psychiat., 1970, 33, 1-6 The cerebrospinal fluid homovanillic acid concentration in patients with Parkinsonism treated with L-dopa G. CURZON, R. B. GODWIN-AUSTEN, E. B. TOMLINSON, AND B. D. KANTAMANENI From the Institute ofNeurology, The National Hospital, Queen Square, London Almost all the dopamine in normal human brain is standing of the mechanism of action of L-dopa in contained in the basal ganglia and related structures Parkinsonism. (Bertler, 1961). Very low dopamine concentrations are present in the caudate nucleus, putamen, and METHODS substantia nigra of subjects with Parkinson's disease (Ehringer and Hornykiewicz, 1960; Hornykiewicz, Nine patients were studied. They all had been resident 1963; Bernheimer and Hornykiewicz, 1965). Lesions in a long-stay hospital for between three months and guest. Protected by copyright. seven years. They were selected from a population of in the substantia nigra have been considered chara- 24 patients suffering from Parkinsonism and were teristic of Parkinsonism (Hassler, 1938; Greenfield accepted for treatment only if their agreement were given and Bosanquet, 1953) and, therefore, the clinical after details of the treatment and investigation had been significance of these biochemical observations is explained. Patients were excluded from this trial if they increased by the finding that stereotactic lesions in the showed significant physical disability unrelated to substantia nigra of the rat or monkey cause depletion Parkinsonism. of dopamine in the caudate nucleus (Anden, Clinical assessment was carried out using a standard Carlsson, Dahlstrom, Fuxe, Hillarp, and Larsson, proforma of 57 items (Godwin-Austen et al., 1969). -
Biogenic Amine Reference Materials
Biogenic Amine reference materials Epinephrine (adrenaline), Vanillylmandelic acid (VMA) and homovanillic norepinephrine (noradrenaline) and acid (HVA) are end products of catecholamine metabolism. Increased urinary excretion of VMA dopamine are a group of biogenic and HVA is a diagnostic marker for neuroblastoma, amines known as catecholamines. one of the most common solid cancers in early childhood. They are produced mainly by the chromaffin cells in the medulla of the adrenal gland. Under The biogenic amine, serotonin, is a neurotransmitter normal circumstances catecholamines cause in the central nervous system. A number of disorders general physiological changes that prepare the are associated with pathological changes in body for fight-or-flight. However, significantly serotonin concentrations. Serotonin deficiency is raised levels of catecholamines and their primary related to depression, schizophrenia and Parkinson’s metabolites ‘metanephrines’ (metanephrine, disease. Serotonin excess on the other hand is normetanephrine, and 3-methoxytyramine) are attributed to carcinoid tumours. The determination used diagnostically as markers for the presence of of serotonin or its metabolite 5-hydroxyindoleacetic a pheochromocytoma, a neuroendocrine tumor of acid (5-HIAA) is a standard diagnostic test when the adrenal medulla. carcinoid syndrome is suspected. LGC Quality - ISO Guide 34 • GMP/GLP • ISO 9001 • ISO/IEC 17025 • ISO/IEC 17043 Reference materials Product code Description Pack size Epinephrines and metabolites TRC-E588585 (±)-Epinephrine -
Pathogen Response-Like Recruitment and Activation of Neutrophils by Sterile Immunogenic Dying Cells Drives Neutrophil-Mediated Residual Cell Killing
Cell Death and Differentiation (2017) 24, 832–843 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1350-9047/17 www.nature.com/cdd Pathogen response-like recruitment and activation of neutrophils by sterile immunogenic dying cells drives neutrophil-mediated residual cell killing Abhishek D Garg*,1,2, Lien Vandenberk3, Shentong Fang4, Tekele Fasche4, Sofie Van Eygen1, Jan Maes5, Matthias Van Woensel6,7, Carolien Koks3, Niels Vanthillo5, Norbert Graf8, Peter de Witte5, Stefaan Van Gool9, Petri Salven4 and Patrizia Agostinis*,1 Innate immune sensing of dying cells is modulated by several signals. Inflammatory chemokines-guided early recruitment, and pathogen-associated molecular patterns-triggered activation, of major anti-pathogenic innate immune cells like neutrophils distinguishes pathogen-infected stressed/dying cells from sterile dying cells. However, whether certain sterile dying cells stimulate innate immunity by partially mimicking pathogen response-like recruitment/activation of neutrophils remains poorly understood. We reveal that sterile immunogenic dying cancer cells trigger (a cell autonomous) pathogen response-like chemokine (PARC) signature, hallmarked by co-release of CXCL1, CCL2 and CXCL10 (similar to cells infected with bacteria or viruses). This PARC signature recruits preferentially neutrophils as first innate immune responders in vivo (in a cross-species, evolutionarily conserved manner; in mice and zebrafish). Furthermore, key danger signals emanating from these dying cells, that is, surface calreticulin, ATP and nucleic acids stimulate phagocytosis, purinergic receptors and toll-like receptors (TLR) i.e. TLR7/8/9-MyD88 signaling on neutrophil level, respectively. Engagement of purinergic receptors and TLR7/8/9-MyD88 signaling evokes neutrophil activation, which culminates into H2O2 and NO-driven respiratory burst-mediated killing of viable residual cancer cells. -
Α-TEA's Tumor Toxicity May Be Attributed to Its Capability of Inducing Oxidative Damage in the Endoplasmic Reticulum
Portland State University PDXScholar University Honors Theses University Honors College 2015 α-TEA's Tumor Toxicity may be Attributed to its Capability of Inducing Oxidative Damage in the Endoplasmic Reticulum Diego Mathias Barragan Echenique Portland State University Follow this and additional works at: https://pdxscholar.library.pdx.edu/honorstheses Let us know how access to this document benefits ou.y Recommended Citation Barragan Echenique, Diego Mathias, "α-TEA's Tumor Toxicity may be Attributed to its Capability of Inducing Oxidative Damage in the Endoplasmic Reticulum" (2015). University Honors Theses. Paper 124. https://doi.org/10.15760/honors.172 This Thesis is brought to you for free and open access. It has been accepted for inclusion in University Honors Theses by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. α-TEA’s Tumor Toxicity may be Attributed to its Capability of Inducing Oxidative Damage in the Endoplasmic Reticulum by Diego Mathias Barragan Echenique An undergraduate honors thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in University Honors and Biology Thesis Adviser William L. Redmond, PhD Portland State University 2015 Abstract α-tocopherol ether linked acetic acid (α-TEA) is a Vitamin E derivative with antineoplastic and anti-metastatic properties, tumor specificity, and immunogenic characteristics. The compound is structurally similar to vitamin E, however a key difference is that it doesn’t retain any antioxidant properties. Interestingly, orally administered α-TEA appears to stimulate anti-tumor immunity, which, along with its anti-metastatic and antineoplastic properties, makes the molecule’s mechanism of action worth investigating. -
Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion
cancers Review Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion Andromachi Kotsafti 1 , Marco Scarpa 2 , Ignazio Castagliuolo 3 and Melania Scarpa 1,* 1 Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy; [email protected] 2 General Surgery Unit, Azienda Ospedaliera di Padova, 35128 Padua, Italy; [email protected] 3 Department of Molecular Medicine DMM, University of Padua, 35121 Padua, Italy; [email protected] * Correspondence: [email protected] Received: 8 June 2020; Accepted: 28 June 2020; Published: 1 July 2020 Abstract: The immune system is a crucial regulator of tumor biology with the capacity to support or inhibit cancer development, growth, invasion and metastasis. Emerging evidence show that reactive oxygen species (ROS) are not only mediators of oxidative stress but also players of immune regulation in tumor development. This review intends to discuss the mechanism by which ROS can affect the anti-tumor immune response, with particular emphasis on their role on cancer antigenicity, immunogenicity and shaping of the tumor immune microenvironment. Given the complex role that ROS play in the dynamics of cancer-immune cell interaction, further investigation is needed for the development of effective strategies combining ROS manipulation and immunotherapies for cancer treatment. Keywords: reactive oxygen species; oxidative stress; immunity; inflammation; cancer 1. Introduction Reactive oxygen species (ROS) are defined as chemically reactive derivatives of oxygen that elicits both harmful and beneficial effects in cells depending on their concentration. Oxidative stress occurs when ROS production overcomes the scavenging potential of cells or when the antioxidant response is severely impaired; as a consequence nonradical and free radical ROS such as hydrogen peroxide (H2O2), the superoxide radical (O2•) or the hydroxyl radical (OH•) accumulate [1]. -
2018-PED Oncology
Medical Guidelines Institute Pediatric Oncology Imaging Guidelines Version 10.1.2018 Medical Guidelines Institute Clinical Decision Support Tool Diagnostic Strategies: This tool addresses common symptoms and symptom complexes. Imaging requests for individuals with atypical symptoms or clinical presentations that are not specifically addressed will require consultation with the referring physician, specialist and/or individual’s Primary Care Physician (PCP) who may be able to provide additional insight. CPT® (Current Procedural Terminology) is a registered trademark of the American Medical Association (AMA). CPT ® five digit codes, nomenclature and other data are copyright 2016 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in the CPT® book. AMA does not directly or indirectly practice medicine or dispense medical services. AMA assumes no liability for the data contained herein or not contained herein. © 2018-2019 Medical Guidelines Institute. All rights reserved. Pediatric Oncology Imaging Guidelines Abbreviations For Pediatric Oncology Imaging Guidelines........................ 3 PEDONC-1: General Guidelines.................................................................... 9 PEDONC-2: Screening Imaging in Cancer Predisposition Syndromes .... 22 PEDONC-3: Pediatric Leukemias ................................................................ 39 PEDONC-4: Pediatric CNS Tumors ............................................................ 45 PEDONC-5: Pediatric -
Biochemical Procedures As Aids in Diagnosis of Different Forms of Cancer
A n n a l s o f C l i n i c a l An d L a b o r a t o r y S c i e n c e , Vol. 4, No. 2 Copyright © 1974, Institute for Clinical Science Biochemical Procedures as Aids in Diagnosis of Different Forms of Cancer MORTON K. SCHWARTZ, Ph.D. Memorial Sloan-Kettering Cancer Center, New York, NY 10021 ABSTRACT The application of biochemical analyses as aids in the diagnosis of cancer is discussed with emphasis on the fact that biochemical testing is more useful in following the regression and progression of disease than in early initial diagnosis. The uses of biochemical analyses of metabolic degradation products, lipids, hormones and their receptors, enzymes, including isoenzymes, and trace metals are included. Introduction indicated in table I these include neuro Diagnostic procedures in cancer must be blastoma, pheochromocytoma, carcinoid, designed to achieve several purposes. They hepatocellular carcinoma, multiple mye must define the disease, describe its extent loma, osteogenic sarcoma and other osteo and be useful in following its progression blastic bone tumors. In these diseases, the or regression. For more than 75 years, in assay of the listed components is essential vestigators have searched for biochemical for confirmation of the diagnosis and in defects in cancer cells that could be ex following the response to therapy. ploited in diagnosis. Despite these long and continuing studies, few biochemical proce Serum Enzymes dures have been developed for early diag Historically, the biochemical procedure nosis of specific forms of cancer. The most used for the longest time as a diagnostic useful application of biochemical assays aid in cancer is acid phosphatase. -
Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy
cancers Article Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy Kevin Chih-Yang Huang 1,2 , Shu-Fen Chiang 3,4, Pei-Chen Yang 4, Tao-Wei Ke 5,6, Tsung-Wei Chen 7,8, Ching-Han Hu 4, Yi-Wen Huang 4, Hsin-Yu Chang 4, William Tzu-Liang Chen 5,9,10,* and K. S. Clifford Chao 4,8,11,* 1 Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan; [email protected] 2 Translation Research Core, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan 3 Lab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung 42055, Taiwan; [email protected] 4 Cancer Center, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; [email protected] (P.-C.Y.); [email protected] (C.-H.H.); [email protected] (Y.-W.H.); [email protected] (H.-Y.C.) 5 Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; [email protected] 6 School of Chinese Medicine & Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan Citation: Huang, K.C.-Y.; 7 Department of Pathology, Asia University Hospital, Asia University, Taichung 41354, Taiwan; Chiang, S.-F.; Yang, P.-C.; Ke, T.-W.; [email protected] Chen, T.-W.; Hu, C.-H.; Huang, Y.-W.; 8 Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan Chang, H.-Y.; Chen, W.T.-L.; 9 Department of Surgery, School of Medicine, China Medical University, Taichung 40402, Taiwan Chao, K.S.C.