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Fingolimod

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https://www.readbyqxmd.com/read/29452218/tnf%C3%AE-disrupts-blood-brain-barrier-integrity-to-maintain-prolonged-depressive-like-behavior-in-mice
#1
Yuyan Cheng, Sachi Desse, Ana Martinez, Ryan J Worthen, Richard S Jope, Eleonore Beurel
Recovery from major depressive disorder is difficult, particularly in patients who are refractory to antidepressant treatments. To examine factors that regulate recovery, we developed a prolonged learned helplessness depression model in mice. After the induction of learned helplessness, mice were separated into groups that recovered or did not recover within 4 weeks. Comparisons were made between groups in hippocampal proteins, inflammatory cytokines, and blood brain barrier (BBB) permeability. Compared with mice that recovered and control mice, non-recovered mice displaying prolonged learned helplessness had greater hippocampal activation of glycogen synthase kinase-3 (GSK3), higher levels of tumor necrosis factor-α (TNFα), interleukin-17A, and interleukin-23, increased permeability of the blood brain barrier (BBB), and lower levels of the BBB tight junction proteins occludin, ZO1, and claudin-5...
February 13, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29435643/effectiveness-and-baseline-factors-associated-to-fingolimod-response-in-a-real-world-study-on-multiple-sclerosis-patients
#2
F Esposito, L Ferrè, F Clarelli, M A Rocca, G Sferruzza, L Storelli, M Radaelli, F Sangalli, L Moiola, B Colombo, F Martinelli Boneschi, G Comi, M Filippi, V Martinelli
BACKGROUND: Treatment choice in multiple sclerosis (MS) is crucial for optimizing risk-benefit profile. OBJECTIVE: To assess fingolimod (FTY) effectiveness and identify baseline features associated to disease activity in a large Italian cohort of Relapsing-Remitting (RR) MS patients. METHODS: Three-hundred sixty-seven RRMS patients starting FTY treatment at San Raffaele Hospital (Milan-Italy) underwent clinical and MRI evaluations for 2 years...
February 12, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29433094/fingolimod-reduces-the-clinical-expression-of-active-demyelinating-lesions-in-ms
#3
Signoriello Elisabetta, Landi Doriana, Monteleone Fabrizia, Saccà Francesco, Nicoletti Carolina Gabri, Buttari Fabio, Sica Francesco, Marfia Girolama Alessandra, Di Iorio Giuseppe, Lus Giacomo, Centonze Diego
BACKGROUND: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a...
February 5, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29431876/real-life-long-term-effectiveness-of-fingolimod-in-swiss-patients-with-relapsing-remitting-multiple-sclerosis-realite
#4
Chiara Zecca, Serge Roth, Oliver Findling, Guillaume Perriard, Valérie Bachmann, Misha L Pless, Andreas Baumann, Christian P Kamm, Patrice H Lalive, Adam Czaplinski
BACKGROUND AND PURPOSE: In 2011, fingolimod was approved in Switzerland for the treatment of relapsing remitting multiple sclerosis (RRMS). The aim of the present study was to assess the effectiveness and retention of fingolimod in a real life Swiss setting, in which patients can receive fingolimod both as first or second line treatment for RRMS. METHODS: This cross-sectional, observational study with retrospective data collection was performed at 19 sites that comprised both hospitals and office-based physicians across Switzerland...
February 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29431425/droplet-array-based-3d-coculture-system-for-high-throughput-tumor-angiogenesis-assay
#5
Xiaohui Du, Wanming Li, Guan-Sheng Du, Hansang Cho, Min Yu, Qun Fang, Luke P Lee, Jin Fang
Angiogenesis is critical for tumor progression and metastasis, and it progresses through orchestral multicellular interactions. Thus, there is urgent demand for high-throughput tumor angiogenesis assays for concurrent examination of multiple factors. For investigating tumor angiogenesis, we developed a microfluidic droplet array-based cell-coculture system comprising a two-layer polydimethylsiloxane chip featuring 6 × 9 paired-well arrays and an automated droplet-manipulation device. In each droplet-pair unit, tumor cells were cultured in 3D in one droplet by mixing cell suspensions with Matrigel, and in the other droplet, human umbilical vein endothelial cells (HUVECs) were cultured in 2D...
February 12, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29429970/relapse-occurrence-in-women-with-multiple-sclerosis-during-pregnancy-in-the-new-treatment-era
#6
Raed Alroughani, Maryam S Alowayesh, Samar F Ahmed, Raed Behbehani, Jasem Al-Hashel
OBJECTIVE: To determine the rate of relapse occurrence during pregnancy and postpartum. METHODS: In a cross-sectional study using the national multiple sclerosis (MS) registry, pregnant women with relapsing MS were identified. Data on demographics, clinical characteristics, and disease-modifying therapies (DMTs), including washout periods, were collected. Timings and durations of relapses were extracted. A multivariate logistic regression was used to assess the relationship between relapses and prior use of different DMTs...
February 2, 2018: Neurology
https://www.readbyqxmd.com/read/29429031/the-changing-multiple-sclerosis-treatment-landscape-impact-of-new-drugs-and-treatment-recommendations
#7
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29427804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-immune-checkpoint-inhibitors-cell-adhesion-inhibitors-sphingosine-1-phosphate-receptor-modulators
#8
REVIEW
Gil Redelman-Sidi, Olivier Michielin, Carlos Cervera, Camillo Ribi, José María Aguado, Mario Fernández-Ruiz, Oriol Manuel
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29417951/erratum-characterization-of-lymphopenia-in-patients-with-ms-treated-with-dimethyl-fumarate-and-fingolimod
#9
(no author information available yet)
[This corrects the article on p. e432 in vol. 5, PMID: 29296636.].
March 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29397790/potential-neuroprotective-effect-of-fingolimod-in-multiple-sclerosis-and-its-association-with-clinical-variables
#10
Marco Pitteri, Roberta Magliozzi, Albulena Bajrami, Valentina Camera, Massimiliano Calabrese
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system affecting both white matter and grey matter in the earliest phases of its course. The crucial role of neurodegeneration in disability progression in MS, regardless of white matter damage, has been confirmed by several imaging and neuropathological studies. Fingolimod is an effective immunomodulator of the sphingosine 1-phosphate receptor, approved in relapsing remitting MS and able to cross the blood-brain barrier and to slow disability progression and brain volume loss...
February 3, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29377379/sphk1-s1pr1-rankl-axis-regulates-the-interactions-between-macrophages-and-bmscs-in-inflammatory-bone-loss
#11
Lan Xiao, Yinghong Zhou, Lingxin Zhu, Shasha Yang, Rong Huang, Wei Shi, Bin Peng, Yin Xiao
Accumulating evidence indicates that the immune and skeletal systems interact with each other through various regulators during the osteoclastogenic process. Among these regulators, the bioactive lipid sphingosine-1-phosphate (S1P), which is synthesized by sphingosine kinase 1/2 (SPHK1/2), has recently been recognized to play a role in immunity and bone remodeling through its receptor sphingosine-1-phosphate receptor 1 (S1PR1). However, little is known regarding the potential role of S1PR1 signaling in inflammatory bone loss...
January 26, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29377126/sphingosine-1-phosphate-receptors-regulate-tlr4-induced-cxcl5-release-from-astrocytes-and-microglia
#12
Sinead A O'Sullivan, Catherine O'Sullivan, Luke M Healy, Kumlesh K Dev, Graham K Sheridan
Sphingosine 1-phosphate receptors (S1PR) are G protein-coupled and compose a family with five subtypes, S1P1R - S1P5R. The drug Gilenya® (Fingolimod; FTY720) targets S1PRs and was the first oral therapy for patients with relapsing-remitting multiple sclerosis (MS). The phosphorylated form of FTY720 (pFTY720) binds S1PRs causing initial agonism, then subsequent receptor internalisation and functional antagonism. Internalisation of S1P1R attenuates sphingosine 1-phosphate (S1P)-mediated egress of lymphocytes from lymph nodes, limiting aberrant immune function in MS...
January 27, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#13
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29345065/fingolimod-targets-cerebral-endothelial-activation-to-block-leukocyte-recruitment-in-the-central-nervous-system
#14
Yawei Zhao, Dongyan Shi, Kelei Cao, Fengjiao Wu, Xingxing Zhu, Shuang Wen, Qiang You, Keqi Zhang, Lixin Liu, Hong Zhou
Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection. We found that FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in the CNS by inhibiting leukocyte recruitment in cerebral microvessels...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344580/successful-treatment-with-fingolimod-of-graft-versus-host-disease-of-the-central-nervous-system
#15
Jordan Gauthier, Patrick Vermersch, Paul Chauvet, Pauline Varlet, Valérie Coiteux, Leonardo Magro, Ibrahim Yakoub-Agha
Fingolimod could be efficient to treat GVHD of the central nervous system.Further research should explore the use of fingolimod and other sphingosine-1-phosphate receptor agonists to prevent or treat GVHD.
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29337457/-pharmacovigilance-update
#16
Françoise Livio
The main pharmacovigilance updates in 2017 are reviewed. Denosumab : rebound-associated multiple vertebral fractures after discontinuation. Canagliflozine: increased risk of foot/leg amputations. Biologic and targeted cancer therapies, direct-acting antivirals for chronic hepatitis C: risk of hepatitis B reactivation. Checkpoint inhibitors : immune-related adverse events and graft rejection. Fingolimod : rebound-associated reactivation of MS following withdrawal. Daclizumab: risk of severe liver injury leading to restricted use in MS patients...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29317954/a-multiple-treatment-comparison-of-eleven-disease-modifying-drugs-used-for-multiple-sclerosis
#17
Vida Hamidi, Elisabeth Couto, Tove Ringerike, Marianne Klemp
Background: Several disease-modifying drug therapies are available for the treatment of multiple sclerosis (MS). To ensure the most appropriate MS management, we assessed the effectiveness and cost-effectiveness of the disease-modifying medicines used for MS. Methods: We conducted a systematic review including 11 disease-modifying drugs used for treatment of adult patients diagnosed with relapsing-remitting MS. We performed a network meta-analysis using both direct and indirect evidence...
February 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29317850/long-term-safety-and-real-world-effectiveness-of-fingolimod-in-relapsing-multiple-sclerosis
#18
REVIEW
Charlotte Druart, Souraya El Sankari, Vincent van Pesch
With a growing number of disease-modifying therapies becoming available for relapsing multiple sclerosis, there is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in unselected patient populations. Although not providing as high a level of evidence as randomized controlled trials, and prone to bias, real-world studies from observational studies or registries nevertheless provide crucial information on real-world outcomes of a given therapy. In addition, evaluation of treatment satisfaction and impact on quality of life are increasingly regarded as complementary outcome measures...
2018: Patient related Outcome Measures
https://www.readbyqxmd.com/read/29316271/fingolimod-improved-axonal-and-myelin-integrity-of-white-matter-tracts-associated-with-multiple-sclerosis-related-functional-impairments
#19
Michael Gurevich, Roy Waknin, Evan Stone, Anat Achiron
AIMS: Fingolimod hydrochloride is an effective immunomodulatory drug in improving relapsing-remitting multiple sclerosis (RRMS). However, data on the neuroradiologic effects on white matter (WM) have not been demonstrated. In this study, we aimed elucidating the impact of 1-year fingolimod treatment on WM integrity in patients with RRMS. METHODS: Diffusion tensor imaging (DTI) was applied to assess axonal and myelin integrity in specific WM tracts of patients with RRMS prior to and 1 year postfingolimod treatment (n = 30)...
January 5, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29314605/transcriptome-profiling-of-peripheral-blood-immune-cell-populations-in-multiple-sclerosis-patients-before-and-during-treatment-with-a-sphingosine-1-phosphate-receptor-modulator
#20
Ines C Angerer, Michael Hecker, Dirk Koczan, Luisa Roch, Jörg Friess, Annelen Rüge, Brit Fitzner, Nina Boxberger, Ina Schröder, Kristin Flechtner, Hans-Jürgen Thiesen, Alexander Winkelmann, Stefanie Meister, Uwe K Zettl
AIMS: Fingolimod is a sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of the relapsing form of multiple sclerosis (MS). It prevents the egress of lymphocyte subpopulations from lymphoid tissues into the circulation. Here, we explored the broad effects of fingolimod on gene expression in different immune cell subsets. METHODS: Utilizing 150 high-resolution microarrays from Affymetrix, we obtained the transcriptome profiles of 5 cell populations, which were separated from the peripheral blood of MS patients prior to and following oral administration of fingolimod...
January 3, 2018: CNS Neuroscience & Therapeutics
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