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Dimethylfumarate

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https://www.readbyqxmd.com/read/27743338/erratum-to-dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#1
Guocan Han, Qiang Zhou
No abstract text is available yet for this article.
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27496192/dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#2
Guocan Han, Qiang Zhou
Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 μM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting...
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27468725/dimethylfumarate-inhibits-melanoma-cell-proliferation-via-p21-and-p53-induction-and-bcl-2-and-cyclin-b1-downregulation
#3
Irina Kaluzki, Igor Hrgovic, Tsige Hailemariam-Jahn, Monika Doll, Johannes Kleemann, Eva Maria Valesky, Stefan Kippenberger, Roland Kaufmann, Nadja Zoeller, Markus Meissner
Recent evidence suggests that dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties in melanoma. It has recently been demonstrated that DMF inhibits melanoma proliferation by apoptosis and cell cycle inhibition and therefore inhibits melanoma metastasis. Nonetheless, the underlying mechanisms remain to be evaluated. To elucidate the effects of DMF on melanoma cell lines (A375, SK-Mel), we first performed cytotoxicity assays. No significant lactatedehydogenase (LDH) release could be found...
July 29, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27376248/dimethyl-and-monomethylfumarate-regulate-indolamine-2-3-dioxygenase-ido-activity-in-human-immune-cells
#4
Sevgi Eminel, Na Jin, Martin Rostami, Stefan Dibbert, Ulrich Mrowietz, Ina Suhrkamp
Fumaric acid esters (FAEs) are used as an oral treatment for psoriasis. Dimethylfumarate (DMF) and its metabolite monomethylfumarate (MMF) are regarded as the pharmacologically active moieties. Indoleamine 2,3-dioxygenase (IDO) is the key enzyme for the metabolism of tryptophan. The kynurenine pathway is established as a major regulator of innate and adaptive immunity. Here we investigated the effect of DMF and MMF on IDO activity and expression in human peripheral blood mononuclear cells (PBMCs). IDO activity was determined by measuring the concentration of kynurenine in the culture medium using a HPLC technique...
July 4, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27312167/immunological-treatment-of-multiple-sclerosis
#5
Martin Diebold, Tobias Derfuss
Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27277809/distinct-nrf2-signaling-mechanisms-of-fumaric-acid-esters-and-their-role-in-neuroprotection-against-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-experimental-parkinson-s-like-disease
#6
Manuj Ahuja, Navneet Ammal Kaidery, Lichuan Yang, Noel Calingasan, Natalya Smirnova, Arsen Gaisin, Irina N Gaisina, Irina Gazaryan, Dmitry M Hushpulian, Ismail Kaddour-Djebbar, Wendy B Bollag, John C Morgan, Rajiv R Ratan, Anatoly A Starkov, M Flint Beal, Bobby Thomas
UNLABELLED: A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27192495/the-keap1-nrf2-are-pathway-as-a-potential-preventive-and-therapeutic-target-an-update
#7
REVIEW
Meng-Chen Lu, Jian-Ai Ji, Zheng-Yu Jiang, Qi-Dong You
The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2-ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO-Me, was terminated for safety reasons...
September 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27105770/severe-recalcitrant-cutaneous-manifestations-in-systemic-lupus-erythematosus-successfully-treated-with-fumaric-acid-esters
#8
A M Saracino, C H Orteu
Fumaric acid esters (FAE) have proven efficacy in the treatment of psoriasis and have been in use for decades. More recently, as their mechanism of action and abundant immunomodulatory effects become clearer, potential benefits in other inflammatory skin conditions are becoming increasingly recognized. The use of FAE as combination systemic therapy has not been well studied, and data on safety and efficacy in this scenario is lacking. Three patients with severe, extensive and recalcitrant cutaneous manifestations of systemic lupus erythematosus; one case of disseminated discoid lesions and two with severe chilblain lesions, were treated with Fumaderm(®) (containing the FAE dimethylfumarate and monoethylhydrogen fumarate salts), after failing to respond to a multitude of other mono and combination therapies...
April 23, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/26946710/-pharmacovigilance-update
#9
Kim Dao, Haithem Chtioui, Laura E Rothuizen, Léonore Diezi, Sylvain Prod'hom, Ursula Winterfeld, Thierry Buclin, Françoise Livio
The main pharmacovigilance updates in 2015are reviewed. Sofosbuvir amiodarone interaction: risk of severe bradycardia. Dasabuvir clopidogrel interaction: increased dasabuvir concentrations and potential risk of QTprolongation. SGLT2 inhibitors: risks of diabetic acidocetosis and bone fracture. Dabigatran: therapeutic drug monitoring may improve benefit-risk ratio. Ibuprofen: at higher dosage, vascular risks are comparable to coxibs. Pregabaline, gabapentine: potential for abuse and addiction. Varenicline: potentiates alcohol's effects...
January 13, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/26921765/attenuation-of-7-ketocholesterol-induced-overproduction-of-reactive-oxygen-species-apoptosis-and-autophagy-by-dimethyl-fumarate-on-158n-murine-oligodendrocytes
#10
Amira Zarrouk, Thomas Nury, El-Mostafa Karym, Anne Vejux, Randa Sghaier, Catherine Gondcaille, Pierre Andreoletti, Doriane Trompier, Stéphane Savary, Mustapha Cherkaoui-Malki, Meryam Debbabi, Agnès Fromont, Jean-Marc Riedinger, Thibault Moreau, Gérard Lizard
Mitochondrial dysfunctions and oxidative stress are involved in several non demyelinating or demyelinating neurodegenerative diseases. Some of them, including multiple sclerosis (MS), are associated with lipid peroxidation processes leading to increased levels of 7-ketocholesterol (7KC). So, the eventual protective effect of dimethylfumarate (DMF), which is used for the treatment of MS, was evaluated on 7KC-treated oligodendrocytes, which are myelin synthesizing cells. To this end, murine oligodendrocytes 158N were exposed to 7KC (25, 50μM) for 24h without or with DMF (1, 25, 50μM)...
February 24, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/26903865/different-contribution-of-redox-sensitive-transient-receptor-potential-channels-to-acetaminophen-induced-death-of-human-hepatoma-cell-line
#11
Heba Badr, Daisuke Kozai, Reiko Sakaguchi, Tomohiro Numata, Yasuo Mori
Acetaminophen (APAP) is a safe analgesic antipyretic drug at prescribed doses. Its overdose, however, can cause life-threatening liver damage. Though, involvement of oxidative stress is widely acknowledged in APAP-induced hepatocellular death, the mechanism of this increased oxidative stress and the associated alterations in Ca(2+) homeostasis are still unclear. Among members of transient receptor potential (TRP) channels activated in response to oxidative stress, we here identify that redox-sensitive TRPV1, TRPC1, TRPM2, and TRPM7 channels underlie Ca(2+) entry and downstream cellular damages induced by APAP in human hepatoma (HepG2) cells...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/26831413/multiple-sclerosis-new-treatment-modalities
#12
Rocco Totaro, Caterina Di Carmine, Carmine Marini, Antonio Carolei
Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability...
December 2015: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/26763431/dimethylfumarate-impairs-neutrophil-functions
#13
COMPARATIVE STUDY
Susen Müller, Martina Behnen, Katja Bieber, Sonja Möller, Lars Hellberg, Mareike Witte, Martin Hänsel, Detlef Zillikens, Werner Solbach, Tamás Laskay, Ralf J Ludwig
Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration...
January 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/26690241/dimethyl-fumarate-reduces-inflammatory-responses-in-experimental-colitis
#14
Giovanna Casili, Marika Cordaro, Daniela Impellizzeri, Giuseppe Bruschetta, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
BACKGROUND AND AIMS: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. METHODS: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks' treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8-10 weeks of age...
April 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/26663097/dimethylfumarate-effectively-inhibits-lymphangiogenesis-via-p21-induction-and-g1-cell-cycle-arrest
#15
Eva Maria Valesky, Igor Hrgovic, Monika Doll, Xiao-Fan Wang, Andreas Pinter, Johannes Kleemann, Roland Kaufmann, Stefan Kippenberger, Markus Meissner
Different pathologies, such as lymphoedema, cancer or psoriasis, are associated with abnormal lymphatic vessel formation. Therefore, influencing lymphangiogenesis is an interesting target. Recent evidence suggests that dimethylfumarate (DMF), an antipsoriatic agent, might have antitumorigenic and antilymphangiogenic properties. To prove this assumption, we performed proliferation and functional assays with primary human dermal lymphendothelial cells (DLEC). We could demonstrated that DMF suppresses DLEC proliferation and formation of capillary-like structures...
March 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/26533924/budget-impact-analysis-of-delayed-release-dimethylfumarate-in-the-treatment-of-relapsing-remitting-multiple-sclerosis-in-italy
#16
G Furneri, C Marchesi, L Santoni
No abstract text is available yet for this article.
November 2015: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/26436330/dimethylfumarate-impairs-neutrophil-functions
#17
Susen Müller, Martina Behnen, Katja Bieber, Sonja Möller, Lars Hellberg, Mareike Witte, Martin Hänsel, Detlef Zillikens, Werner Solbach, Tamás Laskay, Ralf J Ludwig
Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases; eg psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to effects on lymphocytes and dendritic cells. Here, we focused on effects of dimethyl fumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps and migration...
October 5, 2015: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/26246800/dimethylfumarate-protects-against-tnf-%C3%AE-induced-secretion-of-inflammatory-cytokines-in-human-endothelial-cells
#18
Simon Gerhardt, Veronika König, Monika Doll, Tsige Hailemariam-Jahn, Igor Hrgovic, Nadja Zöller, Roland Kaufmann, Stefan Kippenberger, Markus Meissner
BACKGROUND: Inflammation, angiogenesis and oxidative stress have been implicated in the pathogenesis of various vascular diseases. Recent evidence suggests that dimethylfumarate (DMF), an antiposriatic and anti-multiple sclerosis agent, possesses anti-inflammatory, anti-oxidative and anti-angiogenic properties. Here, we analyze the influence of DMF on TNF-α-induced expression of the important pro-inflammatory and pro-atherogenic chemokine MCP-1 and investigate the underlying mechanisms of this expression...
2015: Journal of Inflammation
https://www.readbyqxmd.com/read/26198914/low-dose-fumaric-acid-esters-are-effective-in-a-mouse-model-of-spontaneous-chronic-encephalomyelitis
#19
Seray Demir, Sandra Heckers, Xiomara Pedreiturria, Daniela Hess, Anne-Kathrin Trampe, Andrew Chan, Ralf Gold
In this study we examined the role of fumaric acid esters (FAE) in a spontaneous and chronic animal model, the opticospinal EAE (OSE). Preventive treatment of dimethylfumarate (DMF) promotes onset of disease in animals treated with high dose DMF. This group also exhibited a significantly exacerbated disease course in a therapeutic treatment as compared to the low dose DMF approach, where less demyelination, macrophage infiltration, and increased Nrf2 expression in the spinal cord were observed. We conclude that low dose DMF treatment is effective in the therapy of the spontaneous opticospinal EAE model and mediates neuroprotective effects via the oxidative stress response pathway...
August 15, 2015: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/26188148/nrf2-activators-modulate-oxidative-stress-responses-and-bioenergetic-profiles-of-human-retinal-epithelial-cells-cultured-in-normal-or-high-glucose-conditions
#20
Roberta Foresti, Claudio Bucolo, Chiara Maria Bianca Platania, Filippo Drago, Jean-Luc Dubois-Randé, Roberto Motterlini
Retinal pigment epithelial cells exert an important supporting role in the eye and develop adaptive responses to oxidative stress or high glucose levels, as observed during diabetes. Endogenous antioxidant defences are mainly regulated by Nrf2, a transcription factor that is activated by naturally-derived and electrophilic compounds. Here we investigated the effect of the Nrf2 activators dimethylfumarate (DMF) and carnosol on antioxidant pathways, oxygen consumption rate and wound healing in human retinal pigment epithelial cells (ARPE-19) cultured in medium containing normal (NG, 5mM) or high (HG, 25 mM) glucose levels...
September 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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