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Antibody-dependent cellular toxicity

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https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#1
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
#2
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
#3
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
#4
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
#5
Austin Duffy, Chi Ma, Susanna Ulahannan, Osama E Rahma, Oxana Makarova-Rusher, Liang Cao, Yunkai Yu, David Kleiner, Jane Trepel, Min-Jung Lee, Yusuke Tomita, Seth M Steinberg, Theo Heller, Baris Turkbey, Peter L Choyke, Cody J Peer, William D Figg, Bradford J Wood, Tim F Greten
Endoglin (CD105) is an endothelial membrane receptor expressed on tumor vasculature. Endoglin expression is induced by VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 monoclonal antibody that inhibits angiogenesis, causes antibody-dependent cellular cytotoxicity (ADCC) and apoptosis of proliferating endothelium. <br /><br />Experimental Design: Patients with HCC (Childs Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, 15mg/kg q 2wks given with sorafenib 400mg bid...
May 2, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27513568/stimulation-of-eryptosis-by-caspofungin
#13
Thomas Peter, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The echinocandin antifungal agent caspofungin has been shown to trigger apoptosis of fungal cells. Beyond that, caspofungin is toxic for host mitochondria. Even though lacking mitochondria, erythrocytes may enter apoptosis-like suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in triggering of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, caspase activation and/or activation of p38 kinase, protein kinase C, and casein kinase...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27507205/epsah-an-exopolysaccharide-from-aphanothece-halophytica-gr02-improves-both-cellular-and-humoral-immunity-as-a-novel-polysaccharide-adjuvant
#14
Lei Zhu, Fan Zhang, Li-Jun Yang, Yang Ge, Qing-Fang Wei, Yu Ou
EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH...
July 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27458141/a-phase-i-trial-to-evaluate-antibody-dependent-cellular-cytotoxicity-of-cetuximab-and-lenalidomide-in-advanced-colorectal-and-head-and-neck-cancer
#15
Erin M Bertino, Elizabeth L McMichael, Xiaokui Mo, Prashant Trikha, Melanie Davis, Bonnie Paul, Michael Grever, William E Carson, Gregory A Otterson
mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC...
September 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27435001/an-fc-optimized-cd133-antibody-for-induction-of-nk-cell-reactivity-against-myeloid-leukemia
#16
S P Koerner, M C André, J S Leibold, P C Kousis, A Kübler, M Pal, S P Haen, H-J Bühring, L Grosse-Hovest, G Jung, H R Salih
Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE)...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27291144/recent-advances-in-therapy-of-chronic-lymphocytic-leukaemia
#17
REVIEW
David J M Routledge, Adrian J C Bloor
The last 5 to 10 years have been marked by considerable advances in both our understanding of the biology and treatment of chronic lymphocytic leukaemia (CLL). Fludarabine-based immuno-chemotherapy is the current standard of care for first line therapy in younger fit patients and although this can be highly effective its use in older co-morbid patients is limited by toxicity, and the prognosis for patients with high risk or fludarabine-refractory disease is poor. The introduction of new antibodies has however, facilitated the use of immuno-chemotherapy in co-morbid patients...
August 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27067506/targeted-radionuclide-therapy-of-melanoma
#18
REVIEW
Abdullah Norain, Ekaterina Dadachova
An estimated 60,000 individuals in the United States and 132,000 worldwide are yearly diagnosed with melanoma. Until recently, treatment options for patients with stages III-IV metastatic disease were limited and offered marginal, if any, improvement in overall survival. The situation changed with the introduction of B-RAF inhibitors and anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1 immunotherapies into the clinical practice. With only some patients responding well to the immune therapies and with very serious side effects and high costs of immunotherapy, there is still room for other approaches for the treatment of metastatic melanoma...
May 2016: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/26994069/monophosphoryl-lipid-a-induced-pro-inflammatory-cytokine-expression-does-not-require-cd14-in-primary-human-dendritic-cells
#19
Sonja T H M Kolanowski, Suzanne N Lissenberg-Thunnissen, Diba Emal, S Marieke van Ham, Anja Ten Brinke
OBJECTIVE: To elucidate if TLR4-mediated MyD88 and TRIF signalling by the clinically applicable Lipopolysaccharide (LPS)-derivative monophosphoryl lipid A (MPLA) in primary human dendritic cells requires LPS cofactors LPS-binding protein (LBP) and CD14. METHODS: Cytokine production by monocyte-derived DCs stimulated with MPLA or LPS was determined using ELISA. To investigate involvement of CD14 for action of LPS or MPLA, CD14 was inhibited using blocking antibodies or down-modulated using specific siRNA...
June 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/26949913/a-phase-1-2a-study-to-test-the-safety-and-immunogenicity-of-a-p16-ink4a-peptide-vaccine-in-patients-with-advanced-human-papillomavirus-associated-cancers
#20
Miriam Reuschenbach, Claudia Pauligk, Julia Karbach, Mohammad-Reza Rafiyan, Matthias Kloor, Elena-Sophie Prigge, Madeleine Sauer, Salah-Eddin Al-Batran, Andreas M Kaufmann, Achim Schneider, Elke Jäger, Magnus von Knebel Doeberitz
BACKGROUND: The cyclin-dependent kinase inhibitor p16(INK4a) is strongly and consistently overexpressed in all human papillomavirus (HPV)-associated cancers. Therefore, the authors hypothesized that p16(INK4a) may be a vaccine target antigen for HPV-associated cancers. To test this hypothesis, the authors performed a phase 1/2a first-in-human trial to evaluate the safety and immunogenicity of a p16(INK4a) -based peptide vaccine. METHODS: A total of 26 patients with different, advanced, p16(INK4a) -overexpressing, HPV DNA-positive cancers were included after the completion of standard treatment...
May 1, 2016: Cancer
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