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https://www.readbyqxmd.com/read/29141790/cerebral-toxoplasmosis-in-an-ms-patient-receiving-fingolimod
#1
Alejandro Enriquez-Marulanda, Jaime Valderrama-Chaparro, Laura Parrado, Juan Diego Vélez, Ana Maria Granados, Jorge Luis Orozco, Jairo Quiñones
Multiple Sclerosis (MS) is an autoimmune disease in which lymphocytes target putative myelin antigens in the CNS, causing inflammation and neurodegeneration. Fingolimod (FTY720) is an immunosuppressive drug used as a second line therapy for relapsing forms of MS due to its safety profile and good response to treatment. Despite its safety, there are still concerns about the possibility of Fingolimod being linked to the development of opportunistic infections like disseminated varicella zoster infections and herpes simplex encephalitis...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29140922/fingolimod-reduces-neuropathic-pain-behaviors-in-a-mouse-model-of-multiple-sclerosis-by-a-sphingosine-1-phosphate-receptor-1-dependent-inhibition-of-central-sensitization-in-the-dorsal-horn
#2
Suzanne Doolen, Tommaso Iannitti, Benjamin C Shaw, Carolyn M Grachen, Renee R Donahue, Bradley K Taylor
Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow the progression of MS and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist/functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. We used a myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) mouse model of experimental autoimmune encephalomyelitis (EAE), modified to avoid frank paralysis and thus allow for assessment of withdrawal behaviors to somatosensory stimuli...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29137549/the-impact-of-a-long-acting-oral-sphingosine-1-phosphate-analogue-on-ovarian-aging-in-a-rat-model
#3
Sezcan Mumusoglu, Volkan Turan, Hasan Uckan, Aysegul Suzer, Lale Karakoc Sokmensuer, Gurkan Bozdag
In animal studies, intravenous continuous infusion or peritoneal injection of sphingosine-1-phosphate (S1P) has been shown to decrease chemotherapy- and radiotherapy-induced apoptosis on primordial follicles. Although a long-acting oral form of an S1P analogue (FTY720, fingolimod) has been recently developed and utilized in women with multiple sclerosis, there are no data exploring its ability to avoid spontaneous follicle apoptosis. Thirty 10-month-old female rats were randomly assigned to 3 groups to investigate whether fingolimod would be able to decrease the spontaneous ovarian follicle apoptosis ratio...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29128799/fty720-inhibits-the-nrf2-are-pathway-in-human-glioblastoma-cell-lines-and-sensitizes-glioblastoma-cells-to-temozolomide
#4
Li Zhang, Handong Wang
BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor regulating the expression of various cytoprotective genes. Constitutive Nrf2 activation in many cancers enhances cell survival and resistance to anti-cancer drugs. Our previous studies have shown that FTY720 induced autophagy-related apoptosis and necroptosis and inhibited invasion and migration in human glioblastoma cells. However, whether FTY720 regulated Nrf2 in glioblastoma cells remained unclear...
July 4, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127024/the-sphingosine-1-phosphate-receptor-modulator-fingolimod-as-a-therapeutic-agent-recent-findings-and-new-perspectives
#5
REVIEW
Andrea Huwiler, Uwe Zangemeister-Wittke
The immunomodulatory drug fingolimod (FTY720, Gilenya(R)) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P1 subtype by induction of receptor downregulation. Since S1P1 is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression...
November 7, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29114096/fingolimod-protects-against-ischemic-white-matter-damage-by-modulating-microglia-toward-m2-polarization-via-stat3-pathway
#6
Chuan Qin, Wen-Hui Fan, Qian Liu, Ke Shang, Madhuvika Murugan, Long-Jun Wu, Wei Wang, Dai-Shi Tian
BACKGROUND AND PURPOSE: White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination after WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model...
November 7, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29100396/combination-therapy-of-human-umbilical-cord-mesenchymal-stem-cells-and-fty720-attenuates-acute-lung-injury-induced-by-lipopolysaccharide-in-a-murine-model
#7
Zili Zhang, Wenfei Li, Zhizhi Heng, Jing Zheng, Puyuan Li, Xin Yuan, Wenkai Niu, Changqing Bai, Huiying Liu
ALI/ARDS remain the main reason of morbidity and mortality in the critically ill. Studies have indicated that human umbilical cord mesenchymal stem cells (hUC-MSCs) can be useful in the treatment of ALI/ARDS. Sphingosine-1-phosphate (S1P) and its analog FTY720 significantly reduce lipopolysaccharide (LPS)-induced lung edema and inflammatory lung injury. This study aimed to assess the therapeutic effects of hUC-MSCs combined with FTY720 in an LPS-induced murine model of ALI. Eight-week-old female C57BL/6 mice were divided into a normal control group, an LPS group, an hUC-MSC group, an FTY720 group, and an hUC-MSCs+FTY720 group randomly...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093655/plasmacytoid-dendritic-cells-contribute-to-the-protective-immunity-induced-by-intranasal-treatment-with-fc-fused-interleukin-7-against-lethal-influenza-virus-infection
#8
Moon Cheol Kang, Han Wook Park, Dong-Hoon Choi, Young Woo Choi, Yunji Park, Young Chul Sung, Seung-Woo Lee
Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called TRM-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs...
October 2017: Immune Network
https://www.readbyqxmd.com/read/29078883/doxorubicin-effect-is-enhanced-by-sphingosine-1-phosphate-signaling-antagonist-in-breast-cancer
#9
Eriko Katsuta, Li Yan, Masayuki Nagahashi, Ali Raza, Jamie L Sturgill, Debra E Lyon, Omar M Rashid, Nitai C Hait, Kazuaki Takabe
BACKGROUND: Doxorubicin is one of the most commonly used chemotherapeutic drugs for breast cancer; however, its use is limited by drug resistance and side effects. We hypothesized that adding FTY720, a sphingosine-1-phosphate (S1P) receptor functional antagonist, to doxorubicin would potentiate its effects by suppression of drug-induced inflammation. MATERIALS AND METHODS: The Cancer Genome Atlas, Gene Expression Omnibus data sets, and National Cancer Institute-60 panel were used for gene expressions and gene set enrichment analysis...
November 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29062000/fty720-induced-endocytosis-of-yeast-and-human-amino-acid-transporters-is-preceded-by-reduction-of-their-inherent-activity-and-torc1-inhibition
#10
Céline Barthelemy, Abdoulaye Oury Barry, Laure Twyffels, Bruno André
FTY720 is a sphingoid base analog that acts as an anticancer agent in animal models. Its effect on tumor cells stems largely from its ability to trigger endocytosis of several nutrient transporters. The observation that FTY720 similarly stimulates downregulation of amino acid permeases in yeast suggests that the cellular mechanisms it targets, which are still poorly characterized, are evolutionarily conserved. We here report that adding FTY720 to yeast cells results in rapid inhibition of the intrinsic activity of multiple permeases...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#11
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28966593/sphingosine-1-phosphate-receptor-modulator-fingolimod-fty720-attenuates-myocardial-fibrosis-in-post-heterotopic-heart-transplantation
#12
Naseer Ahmed, Daniele Linardi, Nazeer Muhammad, Cristiano Chiamulera, Guido Fumagalli, Livio San Biagio, Mebratu A Gebrie, Muhammad Aslam, Giovanni Battista Luciani, Giuseppe Faggian, Alessio Rungatscher
Background and Objective: Sphingosine 1-phosphate (S1P), and S1P receptor modulator fingolimod have been suggested to play important cardioprotective role in animal models of myocardial ischemia/reperfusion injuries. To understand the cardioprotective function of S1P and its mechanism in vivo, we analyzed apoptotic, inflammatory biomarkers, and myocardial fibrosis in an in vivo heterotopic rat heart transplantation model. Methods: Heterotopic heart transplantation is performed in 60 Sprague-Dawley (SD) rats (350-400 g)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28956455/a-novel-intracellular-ph-responsive-formulation-for-fty720-based-on-pegylated-graphene-oxide-nano-sheets
#13
Elham Masoudipour, Soheila Kashanian, Nasim Maleki, Ali Karamyan, Kobra Omidfar
OBJECTIVE: This study was performed to investigate a novel pH-responsive nanocarrier based on modified nano graphene oxide (nGO) to promote the acid-triggered intracellular release of a poorly soluble drug, FTY720. METHODS: To synthesize a drug conjugated to modified nGO, first the polyethylene glycol (PEG) was conjugated to nGO, then the produced PEG-nGO was functionalized with the anticancer drug, FTY720, through amide bonding. It was characterized by the scanning electron microscopy (SEM), the atomic force microscopy (AFM), the Fourier transform infrared (FTIR) spectroscopy and the UV-vis spectroscopy...
October 17, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28940479/activation-of-the-nlrp3-inflammasome-in-microglia-the-role-of-ceramide
#14
Hannah Scheiblich, Anna Schlütter, Douglas T Golenbock, Eicke Latz, Pilar Martinez-Martinez, Michael T Heneka
Inflammation within the CNS is a major component of many neurodegenerative diseases. A characteristic feature is the generation of microglia-derived factors that play an essential role in the immune response. IL-1β is a pro-inflammatory cytokine released by activated microglia, able to exacerbate injury at elevated levels. In the presence of caspase-1, pro-IL-1β is cleaved to the mature cytokine following NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. Growing evidence suggests that ceramide plays a critical role in NLRP3 inflammasome assembly, however, the relationship between ceramide and inflammasome activation in microglia remains unknown...
September 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28926402/reversing-hiv-latency-via-sphingosine-1-phosphate-receptor-1-signaling
#15
Charline Duquenne, Sandrine Gimenez, Adeline Guigues, Benjamin Viala, Caroline Boulouis, Clément Mettling, Damien Maurel, Noëlie Campos, Etienne Doumazane, Laetitia Comps-Agrar, Jamal Tazi, Laurent Prézeau, Christina Psomas, Pierre Corbeau, Vincent François
OBJECTIVE: In this study, we looked for a new family of latency reversing agents. DESIGN: We searched for G-protein-coupled receptors (GPCR) coexpressed with the C-C chemokine receptor type 5 (CCR5) in primary CD4 T cells that activate infected cells and boost HIV production. METHODS: GPCR coexpression was unveiled by reverse transcriptase-PCR. We used fluorescence resonance energy transfer to analyze the dimerization with CCR5 of the expressed GPCR...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#16
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28887841/evidence-for-a-contributory-role-of-a-xenogeneic-immune-response-in-experimental-epidermolysis-bullosa-acquisita
#17
Markus Niebuhr, Michael Kasperkiewicz, Sebastian Maass, Eva Hauenschild, Katja Bieber, Ralf J Ludwig, Jürgen Westermann, Kathrin Kalies
Autoimmune diseases affect a large fraction of the population in Western countries. To elucidate the underlying causes, autoantibody transfer-induced mouse models have been established that greatly contributed to the understanding of the pathophysiology of these diseases. However, the role of a potentially co-occurring murine xenogeneic immune response to commonly utilized rabbit anti-mouse IgG remains poorly understood. Using the established rabbit anti-mouse type VII collagen (COL7) IgG-induced mouse model of the mucocutaneous blistering disorder epidermolysis bullosa acquisita (EBA), we found in this study a profound T and B cell response along with an altered cytokine expression profile in draining lymph nodes of mice injected with the xenogeneic IgG...
September 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28823092/inhibition-of-p2x7-receptors-improves-outcomes-after-traumatic-brain-injury-in-rats
#18
Xiaofeng Liu, Zhengqing Zhao, Ruihua Ji, Jiao Zhu, Qian-Qian Sui, Gillian E Knight, Geoffrey Burnstock, Cheng He, Hongbin Yuan, Zhenghua Xiang
Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI...
August 19, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28822836/fty720-fingolimod-an-oral-s1pr-modulator-mitigates-radiation-induced-cognitive-deficits
#19
Alexander M Stessin, Matei A Banu, Mariano Guardia Clausi, Nicholas Berry, John A Boockvar, Samuel Ryu
PURPOSE: This study evaluates FTY720/Fingolimod, modulator of sphingosine-1-phosphate (S1P) receptor, as a potential mitigator of radiation-induced neurocognitive dysfunction. METHODS AND MATERIALS: To study radiation-induced neurocognitive deficits, 6 week-old C57/Bl/6J mice received 0 or 7Gy cranial irradiation and were treated with FTY720 or vehicle for seven weeks. Fear conditioning and Morris water maze were then employed to test learning and memory. Immunohistochemical staining for neural progenitor cells (NPCs) and mature neurons was used to assess changes in hippocampal neurogenesis...
September 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28815584/maintenance-of-cd8-memory-t-lymphocytes-in-the-spleen-but-not-in-the-bone-marrow-is-dependent-on-proliferation
#20
Francesco Siracusa, Özen Sercan Alp, Patrick Maschmeyer, Mairi McGrath, Mir-Farzin Mashreghi, Shintaro Hojyo, Hyun-Dong Chang, Koji Tokoyoda, Andreas Radbruch
It is current belief that numbers of CD8(+) memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here, we compare the proliferation of CD8(+) memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and bone marrow (BM). Fifty percent of CD8(+) memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8(+) memory T lymphocytes are maintained by proliferation...
November 2017: European Journal of Immunology
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