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Antibody dependent cellular toxicity

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https://www.readbyqxmd.com/read/29176838/inhibition-of-group-i-metabotropic-glutamate-receptors-protects-against-prion-toxicity
#1
Despoina Goniotaki, Asvin K K Lakkaraju, Amulya N Shrivastava, Pamela Bakirci, Silvia Sorce, Assunta Senatore, Rajlakshmi Marpakwar, Simone Hornemann, Fabrizio Gasparini, Antoine Triller, Adriano Aguzzi
Prion infections cause inexorable, progressive neurological dysfunction and neurodegeneration. Expression of the cellular prion protein PrPC is required for toxicity, suggesting the existence of deleterious PrPC-dependent signaling cascades. Because group-I metabotropic glutamate receptors (mGluR1 and mGluR5) can form complexes with the cellular prion protein (PrPC), we investigated the impact of mGluR1 and mGluR5 inhibition on prion toxicity ex vivo and in vivo. We found that pharmacological inhibition of mGluR1 and mGluR5 antagonized dose-dependently the neurotoxicity triggered by prion infection and by prion-mimetic anti-PrPC antibodies in organotypic brain slices...
November 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29141474/assessment-of-immunotoxicity-in-female-fischer-344-n-and-sprague-dawley-rats-and-female-b6c3f1-mice-exposed-to-hexavalent-chromium-via-the-drinking-water
#2
Kelly A Shipkowski, Christopher M Sheth, Matthew J Smith, Michelle J Hooth, Kimber L White, Dori R Germolec
Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#3
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#4
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29074301/identification-of-immune-biomarkers-related-to-disease-progression-and-treatment-efficacy-in-human-visceral-leishmaniasis
#5
Áquila S B Portela, Lourena E Costa, Beatriz C S Salles, Mariana P Lima, Thaís T O Santos, Fernanda F Ramos, Daniela P Lage, Vívian T Martins, Rachel B Caligiorne, Daniela R Lessa, Fabiana R Silva, Amanda S Machado, Guilherme F Nascimento, Isabela S Gama, Miguel A Chávez-Fumagalli, Antonio L Teixeira, Manoel O C Rocha, Regina L Rocha, Eduardo A F Coelho
Visceral leishmaniasis (VL) is a potentially fatal disease, in which the treatment based on chemotherapy is considered toxic. The cure of disease is associated with the life-long Th1-type immunity against the infection. The Th1-related cytokines production by peripheral blood mononuclear cells (PBMCs) seems to be crucial for host control of parasite load and clinical cure. In the current study, we used five proteins (IgE-dependent histamine-releasing factor [HRF], LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic in the canine VL, aiming to evaluate the antigen-specific antibody levels and cytokine production in PBMCs culture supernatants collected from VL patients before and after anti-VL treatment...
October 20, 2017: Immunobiology
https://www.readbyqxmd.com/read/28992681/ofatumumab-monoclonal-antibody-affinity-maturation-through-in-silico-modeling
#6
Zahra Payandeh, Masoumeh Rajabibazl, Yousef Mortazavi, Azam Rahimpour, Amir Hossein Taromchi
Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28987943/a-standardized-extract-of-butea-monosperma-lam-flowers-suppresses-the-il-1%C3%AE-induced-expression-of-il-6-and-matrix-metalloproteases-by-activating-autophagy-in-human-osteoarthritis-chondrocytes
#7
Mohammad Y Ansari, Nazir M Khan, Tariq M Haqqi
BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions...
October 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28874561/localized-cd47-blockade-enhances-immunotherapy-for-murine-melanoma
#8
Jessica R Ingram, Olga S Blomberg, Jonathan T Sockolosky, Lestat Ali, Florian I Schmidt, Novalia Pishesha, Camilo Espinosa, Stephanie K Dougan, K Christopher Garcia, Hidde L Ploegh, Michael Dougan
CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#9
Theodoros Eleftheriadis, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Triggered by the successful administration of the proteasome inhibitor bortezomib in kidney transplant recipients with acute or chronic antibody-mediated rejection, we evaluated the effect of the proteasome inhibitor CEP-18770 and of the selective immunoproteasome inhibitor ONX-0914 on cellular and humoral alloimmunity. Cellular alloimmunity was assessed by cell proliferation in a two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method, where humoral alloimmunity was induced in one-way MLR...
June 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28583171/comparison-of-neurons-derived-from-mouse-p19-rat-pc12-and-human-sh-sy5y-cells-in-the-assessment-of-chemical-and-toxin-induced-neurotoxicity
#10
Dina Popova, Jessica Karlsson, Stig O P Jacobsson
BACKGROUND: Exposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide...
June 5, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28527237/the-n-terminus-of-the-prion-protein-is-a-toxic-effector-regulated-by-the-c-terminus
#11
Bei Wu, Alex J McDonald, Kathleen Markham, Celeste B Rich, Kyle P McHugh, Jörg Tatzelt, David W Colby, Glenn L Millhauser, David A Harris
PrP(C), the cellular isoform of the prion protein, serves to transduce the neurotoxic effects of PrP(Sc), the infectious isoform, but how this occurs is mysterious. Here, using a combination of electrophysiological, cellular, and biophysical techniques, we show that the flexible, N-terminal domain of PrP(C) functions as a powerful toxicity-transducing effector whose activity is tightly regulated in cis by the globular C-terminal domain. Ligands binding to the N-terminal domain abolish the spontaneous ionic currents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents when expressed in the absence of the C-terminal domain...
May 20, 2017: ELife
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#12
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28465443/phase-i-and-preliminary-phase-ii-study-of-trc105-in-combination-with-sorafenib-in-hepatocellular-carcinoma
#13
Austin G Duffy, Chi Ma, Susanna V Ulahannan, Osama E Rahma, Oxana Makarova-Rusher, Liang Cao, Yunkai Yu, David E Kleiner, Jane Trepel, Min-Jung Lee, Yusuke Tomita, Seth M Steinberg, Theo Heller, Baris Turkbey, Peter L Choyke, Cody J Peer, William D Figg, Brad J Wood, Tim F Greten
Purpose: Endoglin (CD105) is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including that of hepatocellular carcinoma (HCC), and is associated with poor prognosis. Endoglin is essential for angiogenesis, and its expression is induced by hypoxia and VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 mAb that inhibits angiogenesis and causes antibody-dependent cellular cytotoxicity and apoptosis of proliferating endothelium.Experimental Design: Patients with HCC (Child-Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, and 15 mg/kg every 2 weeks given with sorafenib 400 mg twice daily...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28463630/safety-and-activity-of-varlilumab-a-novel-and-first-in-class-agonist-anti-cd27-antibody-in-patients-with-advanced-solid-tumors
#14
Howard A Burris, Jeffrey R Infante, Stephen M Ansell, John J Nemunaitis, Geoffrey R Weiss, Victor M Villalobos, Branimir I Sikic, Matthew H Taylor, Donald W Northfelt, William E Carson, Thomas R Hawthorne, Thomas A Davis, Michael J Yellin, Tibor Keler, Timothy Bullock
Purpose CD27, a costimulatory molecule on T cells, induces intracellular signals that mediate cellular activation, proliferation, effector function, and cell survival upon binding to its ligand, CD70. Varlilumab is a novel, first-in-class, agonist CD27 antibody that stimulates the CD27 pathway, which results in T-cell activation and antitumor activity in tumor models. This first-in-human, dose-escalation and expansion study evaluated the safety, pharmacology, and activity of varlilumab in patients with advanced solid tumors...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28445969/glypican-1-targeted-antibody-based-therapy-induces-preclinical-antitumor-activity-against-esophageal-squamous-cell-carcinoma
#15
Emi Harada, Satoshi Serada, Minoru Fujimoto, Yusuke Takahashi, Tsuyoshi Takahashi, Hisashi Hara, Rie Nakatsuka, Takahito Sugase, Takahiko Nishigaki, Yurina Saito, Kosuke Hiramatsu, Satoshi Nojima, Risa Mitsuo, Tomoharu Ohkawara, Eiichi Morii, Masaki Mori, Yuichiro Doki, Yasufumi Kaneda, Tetsuji Naka
Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite the development of multimodal therapy. Expression of glypican-1 (GPC1) has been reported to be elevated in a subset of patients with ESCC and associated with chemoresistance. This study aimed to determine the association of GPC1 with ESCC growth and potential usefulness of the GPC1 targeted therapy by monoclonal antibody (mAb) in ESCC. Expression of GPC1 was higher in ESCC tumor tissues than in adjacent non-tumoral tissues and normal tissues...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28214842/inhibition-of-methylglyoxal-induced-ages-rage-expression-contributes-to-dermal-protection-by-n-acetyl-l-cysteine
#16
Chun-Tao Yang, Fu-Hui Meng, Li Chen, Xiang Li, Lai-Jian Cen, Yu-Hua Wen, Hui Zhang, Cai-Chen Li
BACKGROUND/AIM: Accumulation of advanced glycation end products (AGEs) is a major cause of diabetes mellitus (DM) skin complications. Methylglyoxal (MGO), a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC), an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27967303/immune-responses-induced-by-diclofenac-or-carbamazepine-in-an-oral-exposure-model-using-tnp-ficoll-as-reporter-antigen
#17
Lydia Kwast, Tetsuo Aida, Daniëlle Fiechter, Laura Kruijssen, Rob Bleumink, Louis Boon, Irene Ludwig, Raymond Pieters
Immune-mediated drug hypersensitivity reactions (IDHR) may result from immuno-sensitization to a drug-induced neo-antigen. They rarely occur in patients and are usually not predicted preclinically using standard toxicity studies. To assess the potential of a drug to induce T-cell sensitization, trinitrophenyl (TNP)-Ficoll was used here as a bystander antigen in animal experiments. TNP-Ficoll will only elicit TNP-specific IgG antibodies in the presence of non-cognate T-cell help. Therefore, the presence of TNP-specific IgG antibodies after co-injection of drug and TNP-Ficoll was indicative of T-cell sensitization potential...
November 2016: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#18
REVIEW
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27901071/staphylococcus-aureus-dependent-septic-arthritis-in-murine-knee-joints-local-immune-response-and-beneficial-effects-of-vaccination
#19
Alessia Corrado, Paolo Donato, Silvia Maccari, Raffaella Cecchi, Tiziana Spadafina, Letizia Arcidiacono, Simona Tavarini, Chiara Sammicheli, Donatello Laera, Andrea Guido Oreste Manetti, Paolo Ruggiero, Bruno Galletti, Sandra Nuti, Ennio De Gregorio, Sylvie Bertholet, Anja Seubert, Fabio Bagnoli, Giuliano Bensi, Emiliano Chiarot
Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27697031/reactivation-of-latent-hiv-1-in-latently-infected-cells-by-coumarin-compounds-hymecromone-and-scoparonereactivation-of-latent-hiv-1-in-latently-infected-cells-by-coumarin-compounds-hymecromone-and-scoparone
#20
Xian Li, Hanxian Zeng, Pengfei Wang, Lu Lin, Lin Liu, Pinyi Zhen, Yuanzhe Fu, Panpan Lu, Huanzhang Zhu
BACKGROUND: Current antiretroviral therapy (ART) cannot cure HIV-1 infection due to the presence of latent viral reservoirs. The "shock and kill" strategy is a promising approach to eliminate the viral reservoir. However, there are various limits existing in current latency-reversing agents, searching for new activators are urgently needed. OBJECTIVE: The present study aimed at investigating the ability of hymecromone and scoparone for activating HIV-1 from latent reservoirs...
2016: Current HIV Research
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