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Cytokine release syndrome

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https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#1
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28723682/release-of-danger-associated-molecular-patterns-following-chemotherapy-does-not-induce-immunoparalysis-in-leukemia-patients
#2
Kim Timmermans, Guus P Leijte, Matthijs Kox, Gert Jan Scheffer, Nicole M A Blijlevens, Peter P Pickkers
Chemotherapy may result in the release of danger-associated molecular patterns (DAMPs), which can cause immunoparalysis (deactivation of the immune system). We investigated DAMPs following chemotherapy and their relationship with markers of immunoparalysis in leukemia patients. In 6 patients with acute myeloid leukemia or myelodysplastic syndrome and 12 healthy subjects, DAMPs, cytokines, and markers of immunoparalysis were determined before and during the first week after chemotherapy initiation. In the patients, plasma levels of nuclear DNA (a marker of general DAMP release) were profoundly increased before chemotherapy and further increased 4-6 h afterwards, while the specific DAMP mitochondrial DNA showed only a trend towards increase...
July 20, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28717082/post-cytokine-release-salt-wasting-as-inverse-tumor-lysis-syndrome-in-a-non-cerebral-natural-killer-cell-neoplasm
#3
Hirotsugu Ariizumi, Yosuke Sasaki, Hiroshi Harada, Yui Uto, Remi Azuma, Tomohide Isobe, Koji Kishimoto, Eisuke Shiozawa, Masafumi Takimoto, Nobuyuki Ohike, Hiraku Mori
The pathogenesis of cerebral/renal salt-wasting syndrome remains unknown. We herein present a case of salt-wasting syndrome with a natural killer-cell neoplasm without cerebral invasion. A 78-year-old man with hemophagocytic syndrome received two cycles of chemotherapy that did not induce tumor lysis syndrome, but repeatedly caused polyuria and natriuresis. The expression of tumor necrosis factor-α in the neoplasm led us to hypothesize that an oncolysis-induced cytokine storm may have caused renal tubular damage and salt wasting...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#4
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
July 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28701474/detecting-human-coronary-inflammation-by-imaging-perivascular-fat
#5
Alexios S Antonopoulos, Fabio Sanna, Nikant Sabharwal, Sheena Thomas, Evangelos K Oikonomou, Laura Herdman, Marios Margaritis, Cheerag Shirodaria, Anna-Maria Kampoli, Ioannis Akoumianakis, Mario Petrou, Rana Sayeed, George Krasopoulos, Constantinos Psarros, Patricia Ciccone, Carl M Brophy, Janet Digby, Andrew Kelion, Raman Uberoi, Suzan Anthony, Nikolaos Alexopoulos, Dimitris Tousoulis, Stephan Achenbach, Stefan Neubauer, Keith M Channon, Charalambos Antoniades
Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701158/endotoxemia-is-associated-with-acute-coronary-syndrome-in-patients-with-end-stage-kidney-disease
#6
Chien-Chin Hsu, Tsui-Shan Wei, Chien-Cheng Huang, Yi-Ming Chen
BACKGROUND: Cardiovascular disease is the major cause of death in patients with end-staged kidney disease (ESRD). Most ESRD patients have systemic inflammation, and increasing the risk of cardiovascular event. Endotoxin derived from lipopolysaccharide of Gram negative bacteria accounts for 70% of intestinal bacteria, leading to release of proinflammatory cytokines and negative cardiovascular effect. Impaired intestinal barriers have been found in some ESRD patients, and may lead to bacteria translocation from gastrointestinal tract...
July 12, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28694757/neuroprotective-effect-of-azadirachta-indica-standardized-extract-in-partial-sciatic-nerve-injury-in-rats-evidence-from-anti-inflammatory-antioxidant-and-anti-apoptotic-studies
#7
Amit D Kandhare, Anwesha A Mukherjee, Subhash L Bodhankar
Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28694325/tcr-cxcr4-signaling-stabilizes-cytokine-mrna-transcripts-via-a-prex1-rac1-pathway-implications-for-ctcl
#8
Kimberly N Kremer, Brittney A Dinkel, Rosalie M Sterner, Douglas G Osborne, Dragan Jevremovic, Karen E Hedin
As with many immunopathologically-driven diseases, the malignant T cells of cutaneous T cell lymphomas (CTCL), such as Sezary Syndrome, display aberrant cytokine secretion patterns that contribute to pathology and disease progression. Targeting this disordered release of cytokines is complicated by the changing cytokine milieu that drives the phenotypic changes of CTCL. Here, we characterize a novel signaling pathway that can be targeted to inhibit the secretion of cytokines by modulating either CXCR4 or CXCR4-mediated signaling...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28681506/safety-and-pharmacodynamics-of-intranasal-gsk2245035-a-tlr7-agonist-for-allergic-rhinitis-a-randomized-trial
#9
Anne K Ellis, Daphne C Tsitoura, Diana Quint, William Powley, Laurie A Lee
BACKGROUND: Toll-like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development. OBJECTIVE: Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035. METHODS: This randomized, double-blind, placebo-controlled study (TL7116958) was conducted over two pollen seasons (2013-2014) and follow-up study (204509) conducted one year later...
July 5, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28667503/antipyretic-effects-of-citral-and-possible-mechanisms-of-action
#10
Maycon T Emílio-Silva, Clarissa M D Mota, Clélia A Hiruma-Lima, José Antunes-Rodrigues, Evelin C Cárnio, Luiz G S Branco
Citral is a mixture of the two monoterpenoid isomers (neral and geranial) widely used as a health-promoting food additive safe for human and animal (approved by the US Food and Drug Administration). In vitro studies have reported on the capability of citral to reduce inflammation. Here, we report antipyretic effects of citral in vivo using the most well-accepted model of sickness syndrome, i.e., systemic administration of lipopolysaccharide ( LPS ) to rats. Citral given by gavage caused no change in control euthermic rats (treated with saline) but blunted most of the assessed parameters related to the sickness syndrome [fever (hallmark of infection), plasma cytokines (IL-1β, IL-6, and TNF-α) release, and prostaglandin E2 (PGE2) synthesis (both peripherally and hypothalamic)]...
June 30, 2017: Inflammation
https://www.readbyqxmd.com/read/28661853/chimeric-antigen-receptor-t-cell-therapy-the-next-big-thing-faces-challenges
#11
Jack McCain
Some are using the word "cure" for chimeric antigen receptor T cells. The modular nature of CAR T cells could provide novel strategies to combat resistance and convert more initial complete responses into lasting complete responses. Problems include: cytokine release syndrome, resistance, and finding ways to produce them more efficiently.
May 2017: Managed Care
https://www.readbyqxmd.com/read/28656487/chimeric-antigen-receptor-therapy-in-acute-lymphoblastic-leukemia-clinical-practice
#12
REVIEW
Marlise R Luskin, Daniel J DeAngelo
Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance...
June 27, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28640452/role-of-epicardial-adipose-tissue-in-health-and-disease-a-matter-of-fat
#13
Bénédicte Gaborit, Coralie Sengenes, Patricia Ancel, Alexis Jacquier, Anne Dutour
Epicardial adipose tissue (EAT) is a small but very biologically active ectopic fat depot that surrounds the heart. Given its rapid metabolism, thermogenic capacity, unique transcriptome, secretory profile, and simply measurability, epicardial fat has drawn increasing attention among researchers attempting to elucidate its putative role in health and cardiovascular diseases. The cellular crosstalk between epicardial adipocytes and cells of the vascular wall or myocytes is high and suggests a local role for this tissue...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28617889/erdheim-chester-disease-presenting-with-histiocytic-colitis-and-cytokine-storm
#14
George P Christophi, Yeshika Sharma, Quader Farhan, Umang Jain, Ted Walker, Gregory S Sayuc, Deborah C Rubin
BACKGROUND: Non-Langerhans histiocytosis is a group of inflammatory lymphoproliferative disorders originating from non-clonal expansion of hematopoietic stem cells into cytokine-secreting dendritic cells or macrophages. Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans cell histiocytosis characterized by tissue inflammation and injury caused by macrophage infiltration and histologic findings of foamy histiocytes. Often ECD involves the skeleton, retroperitoneum and the orbits...
June 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28615539/necroptosis-as-a-potential-therapeutic-target-in-multiple-organ-dysfunction-syndrome
#15
Yao-Li Cui, Li-Hua Qiu, Shi-Yong Zhou, Lan-Fang Li, Zheng-Zi Qian, Xian-Ming Liu, Hui-Lai Zhang, Xiu-Bao Ren, Yong-Qiang Wang
PURPOSE: To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS. EXPERIMENTAL DESIGN: A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615125/effect-of-mycoplasma-bovis-on-bovine-neutrophils
#16
Steve Jimbo, Muhammad Suleman, Teresia Maina, Tracy Prysliak, Musa Mulongo, Jose Perez-Casal
Mycoplasma bovis (M. bovis) is a small bacterium that lacks a cell wall. M. bovis infection results in chronic pneumonia and polyarthritis syndrome (CPPS), otitis media, conjunctivitis, and meningitis in feedlot cattle and mastitis in dairy cattle. Numerous studies of peripheral mononuclear cells (PBMC) indicate that M. bovis evades host immunity through targeted effects on immune cell activity, including inhibition of effector function and simultaneous aberrant activation of immune cell activity that has no effect on protection against the bacterium...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28588486/potential-of-il-1-il-18-and-inflammasome-inhibition-for-the-treatment-of-inflammatory-skin-diseases
#17
REVIEW
Gabriele Fenini, Emmanuel Contassot, Lars E French
In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28583018/a-review-of-cd19-targeted-immunotherapies-for-relapsed-or-refractory-acute-lymphoblastic-leukemia
#18
Ryan K DasGupta, Bernard L Marini, Joslyn Rudoni, Anthony J Perissinotti
Aim Novel immunotherapies have generated high response rates and unique adverse effects among patients with relapsed or refractory acute lymphoblastic leukemia. Therapies engaging endogenous T-cells against acute lymphoblastic leukemia are emerging for children and adults with various poor prognostic factors, thus accurate knowledge of immunotherapies is necessary for their effective implementation in the future. In this review, we evaluate clinical trial data regarding chimeric antigen receptor T-cells and blinatumomab, for the treatment of relapsed or refractory acute lymphoblastic leukemia...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28582466/aberrant-plasma-il-7-and-soluble-il-7-receptor-levels-indicate-impaired-t-cell-response-to-il-7-in-human-tuberculosis
#19
Christian Lundtoft, Anthony Afum-Adjei Awuah, Jens Rimpler, Kirstin Harling, Norman Nausch, Malte Kohns, Ernest Adankwah, Franziska Lang, Laura Olbrich, Ertan Mayatepek, Ellis Owusu-Dabo, Marc Jacobsen
T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28567535/immune-mediated-syndromes-following-intravenous-bisphosphonate-therapy
#20
Noa Markovits, Ronen Loebstein, Ilan Bank
OBJECTIVES: Intravenous (IV) infusion of aminobisphosphonates (ABP) induces cytokine release by peripheral blood Vγ9δ2 T cells, resulting in an immediate short-term inflammatory response in up to 50% of patients. We evaluated possible long-term pro-inflammatory effects of IV ABP. METHODS: Retrospective case-series study from one rheumatology specialist's clinic. 2261 electronic charts were reviewed for administration of 'zoledronate' or different brand names of zoledronic acid, and relevant clinical data was retrieved for patients who had received the infusion...
May 31, 2017: Inflammopharmacology
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