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TNF alpha antagonists

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https://www.readbyqxmd.com/read/28095262/biosimilars-in-inflammatory-bowel-disease-accumulating-clinical-evidence
#1
Sean McConachie, Sheila M Wilhelm, Pramodini B Kale-Pradhan
Biologic antagonists to tumor necrosis factor alpha (TNF- α) are effective medications and have become well established in the treatment of both Crohn's disease and ulcerative colitis. Biosimilar medications, which are medications deemed to be equivalent to reference biologic products in terms of clinical effectiveness, safety, pharmacokinetic analysis, and immunogenicity, have now been approved in inflammatory bowel diseases (IBD) based on indication exploration from clinical data in alternate disease states...
January 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28065908/ticagrelor-but-not-clopidogrel-active-metabolite-displays-antithrombotic-properties-in-the-left-atrial-endocardium
#2
Martin F Reiner, Alexander Breitenstein, Erik W Holy, Martina Glanzmann, Heidi Amstalden, Simon F Stämpfli, Nicole R Bonetti, Volkmar Falk, Stephan Keller, Gianluigi Savarese, Stefano Benussi, Francesco Maisano, Thomas F Lüscher, Jürg H Beer, Jan Steffel, Giovanni G Camici
AIMS: Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown...
January 8, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#3
Constantin Aschauer, Paul Perco, Andreas Heinzel, Judith Sunzenauer, Rainer Oberbauer
OBJECTIVE: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. MATERIALS AND METHODS: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology...
2017: PloS One
https://www.readbyqxmd.com/read/28054230/tumor-necrosis-factor-alpha-and-pregnancy-focus-on-biologics-an-updated-and-comprehensive-review
#4
REVIEW
Jaume Alijotas-Reig, Enrique Esteve-Valverde, Raquel Ferrer-Oliveras, Elisa Llurba, Josep Maria Gris
Tumor necrosis factor-α (TNF-α) is a central regulator of inflammation, and TNF-α antagonists may be effective in treating inflammatory disorders in which TNF-α plays a major pathogenic role. TNF-α has also been associated with inflammatory mechanisms related to implantation, placentation, and pregnancy outcome. TNF-α is secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. TNF-α is also related to JAK/STAT pathways, which opens up hypothetical new targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-α, Th17, and Th2, particularly IL-10 is essential to achieve good obstetric outcomes...
January 4, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28028070/ticagrelor-but-not-clopidogrel-reduces-arterial-thrombosis-via-endothelial-tissue-factor-suppression
#5
Martin F Reiner, Alexander Akhmedov, Simona Stivala, Stephan Keller, Daniel S Gaul, Nicole R Bonetti, Gianluigi Savarese, Martina Glanzmann, Cuicui Zhu, Wolfram Ruf, Zhihong Yang, Christian M Matter, Thomas F Lüscher, Giovanni G Camici, Juerg H Beer
AIMS: The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated. METHODS AND RESULTS: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibitor (TFPI) and the underlying mechanisms were determined...
November 15, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/28007956/upregulation-of-rpa2-promotes-nf-%C3%AE%C2%BAb-activation-in-breast-cancer-by-relieving-the-antagonistic-function-of-menin-on-nf-%C3%AE%C2%BAb-regulated-transcription
#6
Chao-Chung Chen, Chi-Wen Juan, Kuan-Yu Chen, Yi-Chien Chang, Janq-Chang Lee, Ming-Chung Chang
RPA2, a subunit of the heterotrimeric replication protein A (RPA) complex, is overexpressed in various cancers. In this study, we showed a significant RPA2 upregulation in breast cancer tissues and cell lines. Ectopic expression of RPA2 in MCF7 and MDA-MB-231 cells promoted cell proliferation, adhesion, migration and invasion, and induced epithelial-mesenchymal transition (EMT) of MCF7 cells. Ablation of RPA2 in MDA-MB-231 cells induced apoptosis and suppressed colony formation, EMT and invasion. Binding assays indicated that menin, the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene product, interacted with RPA2...
December 22, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27997433/tuberculosis-screening-and-reactivation-among-a-national-cohort-of-patients-with-inflammatory-bowel-disease-treated-with-tumor-necrosis-factor-alpha-antagonists
#7
Jason K Hou, Jennifer R Kramer, Peter Richardson, Shubhada Sansgiry, Hashem B El-Serag
BACKGROUND: Tumor necrosis factor antagonists (anti-TNFs) are effective in treating inflammatory bowel disease (IBD) but may cause reactivation of tuberculosis (TB). TB screening rates and related outcomes are not well described among patients with IBD. This study aims to evaluate the prevalence and determinants of TB screening before anti-TNF initiation and related outcomes among patients with IBD. METHODS: We identified patients with IBD with filled prescriptions for anti-TNFs using the National Veterans Affairs administrative data sets...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27982551/use-of-biological-treatments-in-patients-with-hidradenitis-suppurativa
#8
Gemma Martin-Ezquerra, Emili Masferrer, Ramon M Pujol
Pilosebaceous unit occlusion and secondary inflammatory perifollicular lympho-histiocytic infiltration seem to be the underlying etiopathogenic mechanisms giving rise to hidradenitis suppurativa (HS). Increased levels of tumor necrosis factor (TNF)-alpha and other cytokines such as interleukins 12 and 23 (IL12/23) and interleukins 10 and 17 have been observed in HS lesional skin. Biological drugs have been reported to be effective for HS, but the level and duration of the response are quite variable. Among anti-TNF drugs, adalimumab and infliximab are the drugs that seem to obtain better results in HS...
December 16, 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27931132/guillain-barr%C3%A3-syndrome-during-adalimumab-therapy-for-crohn%C3%A2-s-disease-coincidence-or-consequence
#9
Guilherme Grossi Lopes Cançado, Eduardo Garcia Vilela
We report the case of a 64-year-old patient diagnosed with extensive ileal Crohn´s disease who developed Guillain-Barré syndrome after starting biological therapy with adalimumab. Neurologic involvement associated with inflammatory bowel diseases is recognized as an extra-intestinal manifestation. After the breakthrough of antitumor necrosis factor alpha (anti-TNF-α) agents, an increasing number of cases of acute inflammatory demyelinating polyneuropathies have been reported; however, only one case has been described in a patient with Crohn´s disease...
December 8, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27930739/heterogeneity-in-comparisons-of-discontinuation-of-tumor-necrosis-factor-antagonists-in-rheumatoid-arthritis-a-meta-analysis
#10
Anat Fisher, Ken Bassett, Gautam Goel, Dana Stanely, M Alan Brookhart, Hugh R Freeman, James M Wright, Colin R Dormuth
OBJECTIVE: We did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity. METHODS: We searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained...
2016: PloS One
https://www.readbyqxmd.com/read/27930408/vedolizumab-as-induction-and-maintenance-therapy-for-crohn-s-disease-in-patients-na%C3%A3-ve-to-or-who-have-failed-tumor-necrosis-factor-antagonist-therapy
#11
Bruce E Sands, William J Sandborn, Gert Van Assche, Milan Lukas, Jing Xu, Alexandra James, Brihad Abhyankar, Karen Lasch
BACKGROUND: Vedolizumab is a gut-selective α4β7 integrin antagonist for the treatment of moderately to severely active Crohn's disease (CD). Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha (TNF-α) antagonist therapy (TNF-naïve) or who had discontinued TNF-α antagonist therapy because of inadequate response (i.e., primary nonresponse), loss of response, or intolerance (collectively classified as the TNF-failure population)...
January 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27924646/influence-of-anti-tnf-immunogenicity-on-safety-in-rheumatic-disease-a-narrative-review
#12
Andrea Matucci, Daniele Cammelli, Fabrizio Cantini, Delia Goletti, Valentina Marino, Giuseppe Maria Milano, Raffaele Scarpa, Giuliano Tocci, Enrico Maggi, Alessandra Vultaggio
Tumor necrosis factor-alpha (TNF-α) antagonists have been shown to be effective in the treatment of chronic inflammatory rheumatic conditions. The use of anti-TNF agents, combined with improved diagnosis, aggressive regimens and regular monitoring, have substantially improved patient outcomes. However, all biological agents are immunogenic, resulting in the formation of anti-drug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27924645/cardiovascular-outcomes-and-tumour-necrosis-factor-antagonists-in-chronic-inflammatory-rheumatic-disease-a-focus-on-rheumatoid-arthritis
#13
Giuliano Tocci, Delia Goletti, Valentina Marino, Andrea Matucci, Giuseppe Maria Milano, Fabrizio Cantini, Raffaele Scarpa
Many chronic rheumatic diseases have an inflammatory etiology, leading to accelerated atherosclerosis and increased occurrence of vascular diseases. In rheumatoid arthritis (RA), a reduction in cardiovascular (CV) events has been reported under treatments reducing systemic inflammation. Areas covered: Given the central role of tumour necrosis factor alpha (TNFα) in chronic inflammatory conditions and in atherosclerosis, it has been suggested that TNFα-antagonists may reduce CV risk and mortality. Although there are no randomized controlled or head-to-head trials investigating the effect of specific anti-TNF-agents on CV outcomes, observational cohort studies, national registry data, and meta-analyses in RA have reported improved CV outcomes with anti-TNF therapy...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27909742/the-anti-inflammatory-effect-of-montelukast-a-cysteinyl-leukotriene-receptor-1-antagonist-against-estradiol-induced-nonbacterial-inflammation-in-the-rat-prostate
#14
Mahmoud M Said, Maarten C Bosland
There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0...
December 1, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27888159/transmembrane-tnf-alpha-reverse-signaling-leading-to-tgf-beta-production-is-selectively-activated-by-tnf-targeting-molecules-therapeutic-implications
#15
REVIEW
Zsuzsa Szondy, Anna Pallai
Tumor necrosis factor (TNF)-α is a potent pro-inflammatory cytokine exerting pleiotropic effects on various cell types. It is synthesized in a precursor form called transmembrane TNF-α (mTNF-α) which, after being processed by metalloproteinases, is released in a soluble form to mediate its biological activities through Type 1 and 2 TNF receptors in TNF receptor expressing cells. In addition to acting in soluble form, TNF-α also acts in the transmembrane form both as a ligand by activating TNF receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into mTNF-α bearing cells...
January 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27886444/incidence-and-classification-of-cutaneous-manifestations-in-rheumatoid-arthritis
#16
Mirjana Ziemer, Anne-Katrin Müller, Gert Hein, Peter Oelzner, Peter Elsner
BACKGROUND AND OBJECTIVE: There have only been few studies examining rheumatoid arthritis (RA)-related skin manifestations in larger patient populations. Herein, we present current data on the prevalence and spectrum of cutaneous lesions in RA, addressing disease activity scores, anti-CCP antibodies as well as novel pharmacological approaches. PATIENTS AND METHODS: Between November 2006 and July 2007, 214 patients with RA treated at the Division of Rheumatology, University Hospital Jena, Germany, were prospectively examined...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27858860/antagonistic-effects-of-endostatin-vascular-endothelial-growth-inhibitor-chimeric-recombinant-adenovirus-on-homocysteine-induced-vascular-endothelial-cells-injury-in-vitro-and-in-vivo
#17
Zhen-Tian Cui, Jian-Ping Liu, Jian-Min Yao
BACKGROUND: The study is inclined to investigate the antagonistic effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenovirus (Ad-hENDO-VEGI) on homocysteine (Hcy)-induced vascular endothelial cells (VECs) injury in vitro and in vivo. METHODS: Human VECs cell line ECV304 was selected and infected with Ad-hENDO-VEGI. The LDH leakage, SOD activity, and MDA levels were measured by the automatic biochemical analyzer. Cell survival rate was counted by Trypanblau dying...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27833035/tumor-necrosis-factor-%C3%AE-in-the-onset-and-progression-of-leukemia
#18
REVIEW
Xiaoxi Zhou, Zhuoya Li, Jianfeng Zhou
Tumor necrosis factor alpha (TNF-α), originally described as an anti-neoplastic cytokine, has been found, in apparent contradiction to its name, to play an important role in promoting the development and progression of malignant disease. Targeting TNF-α with TNF antagonists has elicited an objective response in certain solid tumors in phase I and II clinical trials. This review focuses on the relationship of TNF-α expressed by leukemia cells and adverse clinical features of leukemia. TNF-α is involved in all steps of leukemogenesis, including cellular transformation, proliferation, angiogenesis, and extramedullary infiltration...
January 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27805476/the-acute-exercise-induced-inflammatory-response-a-comparison-of-young-adult-smokers-and-nonsmokers
#19
Tegan E Kastelein, Cheyne E Donges, Amy E Mendham, Rob Duffield
PURPOSE: This study examined postexercise inflammatory and leukocyte responses in smokers and nonsmokers, as well as the effects of cigarette smoking on the acute postexercise inflammatory and leukocyte response in habitual smokers. METHOD: Eleven recreationally active male smokers and 11 nonsmokers matched for age and aerobic fitness were familiarized and underwent baseline fitness testing. Participants then completed 40 min of cycling at 50% peak aerobic workload...
November 2, 2016: Research Quarterly for Exercise and Sport
https://www.readbyqxmd.com/read/27766695/invasive-fungal-infections-in-pediatric-patients-treated-with-tumor-necrosis-alpha-tnf-%C3%AE-inhibitors
#20
Athanasios Tragiannidis, Ioannis Kyriakidis, Ilse Zündorf, Andreas H Groll
Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid-refractory graft-vs-host disease and other immune-mediated conditions...
October 21, 2016: Mycoses
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