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Cytokine release syndrome

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https://www.readbyqxmd.com/read/27908212/are-crh-ngf-as-psychoneuroimmune-regulators-in-women-with-polycystic-ovary-syndrome
#1
F Z Zangeneh, M M Naghizadeh, M Bagheri, M Jafarabadi
PURPOSE: Polycystic ovary syndrome (PCOS) affects quality of life and can worsen anxiety and depression either due to the features of PCOS or due to the diagnosis of a chronic disease. Corticotrophin-releasing hormone (CRH) and nerves growth factor (NGF) are the modulator for the actions of the sympathetic nervous and immune systems. METHODS: In total, 171 women divided into two groups: study and control groups. Serum CRH, NGF, and interleukins: IL-1α. IL-1β, 17A, and TNFα were determined by ELISA Kits in both groups...
December 2, 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#2
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#3
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27852964/spinal-astrocytic-activation-contributes-to-mechanical-allodynia-in-a-rat-model-of-cyclophosphamide-induced-cystitis
#4
Bolong Liu, Minzhi Su, ShaoJun Tang, Xiangfu Zhou, Hailun Zhan, Fei Yang, Wenbiao Li, Tengcheng Li, Juncong Xie
BACKGROUND: Previous studies have demonstrated that glial cells play an important role in the generation and maintenance of neuropathic pain. Activated glial cells produce numerous mediators such as proinflammatory cytokines that facilitate neuronal activity and synaptic plasticity. Similarly, bladder pain syndrome/interstitial cystitis shares many characteristics of neuropathic pain. However, related report on the involvement of spinal glia in bladder pain syndrome/interstitial cystitis-associated pathological pain and the underlying mechanisms are still lacking...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27849169/mechanisms-of-acute-toxicity-in-nkg2d-chimeric-antigen-receptor-t-cell-treated-mice
#5
Marie-Louise Sentman, Joana M Murad, W James Cook, Ming-Ru Wu, Jake Reder, Susanne H Baumeister, Glenn Dranoff, Michael W Fanger, Charles L Sentman
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed...
November 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27849166/first-in-human-study-in-healthy-subjects-with-fr104-a-pegylated-monoclonal-antibody-fragment-antagonist-of-cd28
#6
Nicolas Poirier, Gilles Blancho, Maryvonne Hiance, Caroline Mary, Tim Van Assche, Jos Lempoels, Steven Ramael, Weirong Wang, Virginie Thepenier, Cecile Braudeau, Nina Salabert, Regis Josien, Ian Anderson, Ian Gourley, Jean-Paul Soulillou, Didier Coquoz, Bernard Vanhove
FR104 is a monovalent pegylated Fab' Ab, antagonist of CD28, under development for treatment of transplant rejection and autoimmune diseases. In contrast to CD80/86 antagonists (CTLA4-Ig), FR104 selectively blunts CD28 costimulation while sparing CTLA-4 and PD-L1 coinhibitory signals. In the present work, FR104 has been evaluated in a first-in-human study to evaluate the safety, pharmacokinetics, pharmacodynamics, and potency of i.v. administrations in healthy subjects. Sixty-four subjects were randomly assigned to four single ascending dose groups, two double dose groups and four single ascending dose groups challenged with keyhole limpet hemocyanin...
November 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27846826/natural-product-htp-screening-for-antibacterial-e-coli-0157-h7-and-anti-inflammatory-agents-in-lps-from-e-coli-o111-b4-activated-macrophages-and-microglial-cells-focus-on-sepsis
#7
Elizabeth A Mazzio, Nan Li, David Bauer, Patricia Mendonca, Equar Taka, Mohammed Darb, Leeshawn Thomas, Henry Williams, Karam F A Soliman
BACKGROUND: Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means...
November 15, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27843478/serum-protein-kng1-apoc3-and-pon1-as-potential-biomarkers-for-yin-deficiency-heat-syndrome
#8
Changming Liu, Liangen Mao, Zepeng Ping, Tingting Jiang, Chong Wang, Zhongliang Chen, Zhongjie Li, Jicheng Li
Yin-deficiency-heat (YDH) syndrome is a concept in Traditional Chinese Medicine (TCM) for describing subhealth status. However, there are few efficient diagnostic methods available for confirming YDH syndrome. To explore the novel method for diagnosing YDH syndrome, we applied iTRAQ to observe the serum protein profiles in YDH syndrome rats and confirmed protein levels by ELISA. A total of 92 differentially expressed proteins (63 upregulated proteins and 29 downregulated proteins), which were mainly involved in complement and coagulation cascades and glucose metabolism pathway, were identified by the proteomic experiments...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27820973/emerging-biological-therapies-to-treat-acute-lymphoblastic-leukemia
#9
Françoise Huguet, Suzanne Tavitian
Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered. Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented...
November 8, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27819271/water-soluble-acacetin-prodrug-confers-significant-cardioprotection-against-ischemia-reperfusion-injury
#10
Hui Liu, Lei Yang, Hui-Jun Wu, Kui-Hao Chen, Feng Lin, Gang Li, Hai-Ying Sun, Guo-Sheng Xiao, Yan Wang, Gui-Rong Li
The morbidity and mortality of patients with ischemic cardiomyopathy resulted from ischemia/reperfusion injury are very high. The present study investigates whether our previously synthesized water-soluble phosphate prodrug of acacetin was cardioprotective against ischemia/reperfusion injury in an in vivo rat model. We found that intravenous administration of acacetin prodrug (10 mg/kg) decreased the ventricular arrhythmia score and duration, reduced ventricular fibrillation and infarct size, and improved the impaired heart function induced by myocardial ischemia/reperfusion injury in anesthetized rats...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816725/blinatumomab-provoked-fatal-heart-failure
#11
REVIEW
Behrad Darvishi, Leila Farahmand, Neda Jalili, Keivan Majidzadeh-A
Mentioned in Blinatumomab (Blincyto®) clinical safety report, a 5 year old boy with acute lymphoblastic leukemia (ALL) receiving Blincyto® with the concentration of 30μg/m(2)/day on the fourth day of therapy developed both Cytokine Release Syndrome (CRS) and Tumor Lysis Syndrome (TLS). Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Bilirubin peaks were 18, 7 and 8 folds more than upper normal limit (UNL) respectively. However, albumin was reduced to approximately half of the lower Normal limit (LNL)...
October 28, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27816481/nk-cell-effector-functions-in-a-ch%C3%A3-diak-higashi-patient-undergoing-cord-blood-transplantation-effects-of-in-vitro-treatment-with-il-2
#12
Loredana Cifaldi, Rita Maria Pinto, Ippolita Rana, Maurizio Caniglia, Adriano Angioni, Stefano Petrocchi, Caterina Cancrini, Laura Cursi, Giuseppe Palumbo, Alessandra Zingoni, Angela Gismondi, Paolo Rossi, Angela Santoni, Cristina Cerboni
NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment...
November 2, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27799606/successful-reintroduction-of-blinatumomab-in-a-patient-with-relapsed-refractory-acute-lymphoblastic-leukemia-following-grade-4-cytokine-release-syndrome
#13
Bernard L Marini, Yihan Sun, Patrick W Burke, Anthony J Perissinotti
Relapsed/refractory acute lymphoblastic leukemia poses a clinical challenge due to its poor prognosis and lack of effective treatment. Blinatumomab, a novel immunotherapy, has demonstrated excellent efficacy in relapsed/refractory acute lymphoblastic leukemia; however, life-threatening toxicities such as cytokine release syndrome have been reported in pivotal clinical trials. In this report, we describe the safe reintroduction of blinatumomab in an adult patient with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia after experiencing grade 4 blinatumomab-induced cytokine release syndrome using a unique dosing strategy and a very diligent monitoring approach...
October 31, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27783864/modulation-of-systemic-metabolism-by-mmp-2-from-mmp-2-deficiency-in-mice-to-mmp-2-deficiency-in-patients
#14
Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27783862/adipose-tissue-derived-plasminogen-activator-inhibitor-1-function-and-regulation
#15
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27777379/impaired-autophagy-activity-is-linked-to-elevated-er-stress-and-inflammation-in-aging-adipose-tissue
#16
Amiya Kumar Ghosh, Theresa Mau, Martin O'Brien, Sanjay Garg, Raymond Yung
Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort...
October 24, 2016: Aging
https://www.readbyqxmd.com/read/27766632/natural-killer-cell-activity-and-dysfunction-in-hermansky-pudlak-syndrome
#17
Aleksandra Gil-Krzewska, Yousuke Murakami, Giovanna Peruzzi, Kevin J O'Brien, Melissa A Merideth, Andrew R Cullinane, William A Gahl, John E Coligan, Bernadette R Gochuico, Konrad Krzewski
Hermansky-Pudlak syndrome (HPS) encompasses disorders with abnormal function of lysosomes and lysosome-related organelles, and some patients who develop immunodeficiency. The basic mechanisms contributing to immune dysfunction in HPS are ill-defined. We analysed natural killer (NK) cells from patients diagnosed with HPS-1, HPS-2, HPS-4, and an unreported HPS subtype. NK cells from an HPS-2 and an unreported HPS subtype share a similar cellular phenotype with defective granule release and cytotoxicity, but differ in cytokine exocytosis...
October 21, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27766364/applicability-of-predictive-toxicology-methods-for-monoclonal-antibody-therapeutics-status-quo-and-scope
#18
Arathi Kizhedath, Simon Wilkinson, Jarka Glassey
Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few...
October 20, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27757303/efficient-tumor-regression-by-adoptively-transferred-cea-specific-car-t-cells-associated-with-symptoms-of-mild-cytokine-release-syndrome
#19
Linan Wang, Ning Ma, Sachiko Okamoto, Yasunori Amaishi, Eiichi Sato, Naohiro Seo, Junichi Mineno, Kazutoh Takesako, Takuma Kato, Hiroshi Shiku
Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27753812/ssa-04-3-leptin-adiponectin-in-cardiometabolic-disease
#20
Patricio Lopez-Jaramillo
Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2)...
September 2016: Journal of Hypertension
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