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https://www.readbyqxmd.com/read/29229854/interferon-beta-represses-cancer-stem-cell-properties-in-triple-negative-breast-cancer
#1
Mary R Doherty, HyeonJoo Cheon, Damian J Junk, Shaveta Vinayak, Vinay Varadan, Melinda L Telli, James M Ford, George R Stark, Mark W Jackson
Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29217470/safe-and-effective-interferon-beta-gene-therapy-for-the-treatment-of-multiple-sclerosis-by-regulating-biological-activity-through-the-design-of-interferon-beta-galectin-9-fusion-proteins
#2
Atsushi Hamana, Yuki Takahashi, Akane Tanioka, Makiya Nishikawa, Yoshinobu Takakura
Multiple sclerosis (MS) is the most common demyelinating disease. Despite the historical use of interferon-beta (IFN-β) for the treatment of patients with MS, concerns exist regarding the side effects of IFN-β. In this study, we designed a series of novel IFN-β fusion proteins containing galectin-9 (gal-9), which exerts immunosuppressive effects through the binding to its receptor on activated Th1 cells. We hypothesized that these fusion proteins would improve the therapeutic effects and reduce the side effects of IFN-β...
December 5, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29209636/neurofilament-light-chain-predicts-disease-activity-in-relapsing-remitting-ms
#3
Kristin N Varhaug, Christian Barro, Kjetil Bjørnevik, Kjell-Morten Myhr, Øivind Torkildsen, Stig Wergeland, Laurence A Bindoff, Jens Kuhle, Christian Vedeler
Objective: To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS). Methods: A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24...
January 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29206056/ease-of-use-of-two-autoinjectors-in-patients-with-multiple-sclerosis-treated-with-interferon-beta-1a-subcutaneously-three-times-weekly-results-of-the-randomized-crossover-redefine-study
#4
Sibyl Wray, Brooke Hayward, Fernando Dangond, Barry Singer
BACKGROUND: For interferon beta-1a subcutaneously three times weekly (IFN β-1a SC tiw), administration options include manually injected prefilled syringes; a preassembled, single-use autoinjector; and a reusable autoinjector. This study evaluated patient-perceived ease of use of two injection devices. RESEARCH DESIGN AND METHODS: REDEFINE, a Phase IV, multicenter crossover study, randomized patients with multiple sclerosis and ≥5 weeks' IFN β-1a 44 μg SC tiw use to 4 weeks using a single-use autoinjector, then 4 weeks using a reusable autoinjector, or vice versa...
December 5, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29205701/antibody-response-to-seasonal-influenza-vaccination-in-multiple-sclerosis-patients-receiving-immunomodulatory-therapy
#5
Henning K Olberg, Geir Egil Eide, Rebecca J Cox, Åsne Jul-Larsen, Sarah Larteley Lartey, Christian A Vedeler, Kjell-Morten Myhr
BACKGROUND: We have previously shown that multiple sclerosis patients receiving immunomodulatory treatment have reduced seroprotection rates after influenza immunization. OBJECTIVES: To further investigate the influence of immunomodulatory therapies on the antibody response and seroprotection rates in patients immunized with seasonal influenza vaccine in 2012/2013 compared to healthy controls. METHODS: Ninety patients receiving fingolimod, glatiramer acetate, interferon beta-1a/1b, natalizumab or no therapy were compared to 62 healthy controls...
December 4, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29205270/severe-multiple-sclerosis-reactivation-during-prolonged-lymphopenia-after-dimethyl-fumarate-discontinuation
#6
C Zecca, C G Antozzi, V Torri Clerici, M Ferrazzini, R E Mantegazza, S Rossi, C Gobbi
BACKGROUND: Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. CASE PRESENTATION: We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a...
December 3, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29203302/immunomodulatory-effects-of-a-rationally-designed-peptide-mimetic-of-human-ifn%C3%AE-in-eae-model-of-multiple-sclerosis
#7
Mansour Poorebrahim, Matin Asghari, Mohammad Foad Abazari, Hassan Askari, Solmaz Sadeghi, Asghar Taheri-Kafrani, Mohammad Hossein Nasr-Esfahani, Pegah Ghoraeian, Maryam Nouri Aleagha, Seyed Shahriar Arab, Derek Kennedy, Alireza Montaseri, Mahsa Mehranfar, Nima Sanadgol
The efficiency of interferon beta (IFNβ)-based drugs is considerably limited due to their undesirable properties, especially high immunogenicity. In this study, for the first time we investigated the impact of a computationally designed peptide mimetic of IFNβ, called MSPEP27, in the animal model of MS. A peptide library was constructed using the Rosetta program based on the predominant IFNAR1-binding site of IFNβ. Molecular docking studies were carried out using ClusPro and HADDOCK tools. The GROMACS package was subsequently used for molecular dynamics (MD) simulations...
December 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29194430/human-cytomegalovirus-encoded-mir-us25-1-5p-attenuates-cd147-emmprin-mediated-early-antiviral-response
#8
Jun Chen, Sisi Xia, Xiangmin Yang, Huizi Chen, Fanni Li, Fenyong Liu, Zhinan Chen
Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses...
December 1, 2017: Viruses
https://www.readbyqxmd.com/read/29185487/cross-reactivity-of-antibodies-against-interferon-beta-in-multiple-sclerosis-patients-and-interference-of-the-jak-stat-signaling-pathway
#9
Isaac Hurtado-Guerrero, Maria Jesus Pinto-Medel, Patricia Urbaneja, Jose Luis Rodriguez-Bada, Jesús Ortega-Pinazo, Pedro Serrano, Óscar Fernández, Laura Leyva, Begoña Oliver-Martos
Interferon beta (IFNβ) therapy has immunogenic properties and induces the development of neutralizing antibodies (NAbs). From the extensive literature focused in the development of NAbs in multiple sclerosis (MS) patients, their ability to cross-react has been deficiently evaluated, despite having important consequences in the clinical practice. Here, the relation between the cross-reactivity and the NAbs titers has been evaluated in MS patients, by inhibition of the antiviral activity of IFNβ by bioassay and through the interference with the activation of the IFNß pathway (JAK-STAT), by phosphoflow...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29181127/oxidative-modification-of-blood-serum-proteins-in-multiple-sclerosis-after-interferon-beta-and-melatonin-treatment
#10
Monika Adamczyk-Sowa, Sabina Galiniak, Ewa Żyracka, Michalina Grzesik, Katarzyna Naparło, Paweł Sowa, Grzegorz Bartosz, Izabela Sadowska-Bartosz
Multiple sclerosis (MS) is a disease involving oxidative stress (OS). This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS), 36 patients with RRMS receiving interferon beta-1b (250 μg every other day), and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29178444/alemtuzumab-versus-interferon-beta-1a-for-relapsing-remitting-multiple-sclerosis
#11
REVIEW
Jian Zhang, Shengliang Shi, Yueling Zhang, Jiefeng Luo, Yousheng Xiao, Lian Meng, Xiaobo Yang
BACKGROUND: Alemtuzumab is a humanised monoclonal antibody that alters the circulating lymphocyte pool, causing prolonged lymphopenia, thus remoulding the immune repertoire that accompanies homeostatic lymphocyte reconstitution. It has been proved more effective than interferon (IFN) 1a for the treatment of relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To compare the efficacy, tolerability and safety of alemtuzumab versus interferon beta 1a in the treatment of people with RRMS to prevent disease activity...
November 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29171409/a-case-of-malignant-melanoma-that-developed-multiple-metastases-after-switching-from-interferon-beta-to-pegylated-interferon-alpha-2b-as-adjuvant-therapy
#12
Takeshi Fukumoto, Susumu Fujiwara, Masanobu Sakaguchi, Masahiro Oka, Chikako Nishigori
No abstract text is available yet for this article.
November 24, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29161701/yin-yang-1-dynamically-regulates-antiviral-innate-immune-responses-during-viral-infection
#13
Jie Zan, Hao Zhang, Ai-Ping Gu, Kai-Lun Zhong, Min-Yi Lu, Xiao-Xin Bai, Jin-Yang Zhang, Jun Cai
BACKGROUND/AIMS: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. METHODS: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells...
November 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29157944/down-regulation-of-tyk2-cblb-and-lmp7-genes-expression-in-relapsing-remitting-multiple-sclerosis-patients-treated-with-interferon-beta
#14
Mehrdokht Mazdeh, Najmeh Moradi, Elnaz Khoshroo, Zahra Shayesteh, Mohammad Taheri, Arezou Sayad, Mir Davood Omrani, Mehrdad Hajilooi, Ghodratollah Roshanaei, Ghasem Solgi
This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls. Seventy-eight RRMS patients treated with IFNβ-1a and 79 age- and ethnic-matched healthy subjects were studied. The mRNA expression levels of TYK2, CBLB and LMP7 in PBMCs were quantified by real-time PCR and plasma concentrations of three molecules were measured by ELISA. Results were compared between patients and controls, IFNβ-responders and non-responders...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29155646/combination-treatment-of-docosahexaenoic-acid-dha-and-all-trans-retinoic-acid-atra-inhibit-il-17-and-ror%C3%AE-t-gene-expression-in-pbmcs-of-patients-with-relapsing-remitting-multiple-sclerosis
#15
Ateke Mousavi Nasl-Khameneh, Abbas Mirshafiey, Abdorreza Naser Moghadasi, Reza Chahardoli, Maryam Mahmoudi, Karim Parastouei, Mir Saeed Yekaninejad, Ali Akbar Saboor-Yaraghi
OBJECTIVES: Multiple sclerosis (MS) is a demyelinating disorder with a complex autoimmune pathophysiology. Its initiation and progression correlate with IL-17 and the related transcription factor, RORγt. All-trans retinoic acid (ATRA) is a bioactive derivative of vitamin A, and docosahexaenoic acid (DHA) is an active metabolite of omega-3 fatty acid; both have immunomodulatory effects in many immune disorders. This study investigated the effects of DHA and ATRA individually and in combination on IL-17 and RORγt gene expression in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-β)...
November 18, 2017: Neurological Research
https://www.readbyqxmd.com/read/29153606/pegylated-interferon-beta-in-the-treatment-of-the-theiler-s-murine-encephalomyelitis-virus-mouse-model-of-multiple-sclerosis
#16
Francesca Gilli, Darlene B Royce, Krista D DiSano, Andrew R Pachner
We evaluated the effects of pegylated-interferonβ-1a (pegIFNβ) therapy on intrathecal antibody responses, disability progression, and viral load in the CNS in mice infected with the Theiler's virus (TMEV), an animal model of progressive disability in Multiple Sclerosis (MS). The lack of a direct antiviral activity in the CNS, the absence of any effect upon the intrathecal immune response, and the failure to treat disease progression, indicate that the immunomodulatory effects of pegIFNβ-1a likely occur in the systemic circulation rather than within the CNS...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29150375/type-i-interferon-and-proinflammatory-cytokine-levels-in-cerebrospinal-fluid-of-newborns-with-rotavirus-associated-leukoencephalopathy
#17
Kyung Yeon Lee, Chang Hoon Moon, Seong Hoon Choi
OBJECTIVE: The purpose of this study was to identify whether there is an increase in type I interferon and proinflammatory cytokine levels in the cerebrospinal fluid of newborns with rotavirus-associated leukoencephalopathy. METHODS: Levels of type I interferons (interferon-alpha and interferon-beta) and proinflammatory cytokines (interleukin-6 and interferon-gamma) were measured in the cerebrospinal fluid of 23 newborns with rotavirus-associated leukoencephalopathy (patient group) and 39 infants under 90 days-of-age (control group)...
November 14, 2017: Brain & Development
https://www.readbyqxmd.com/read/29141831/long-term-follow-up-of-a-randomized-study-of-combination-interferon-and-glatiramer-acetate-in-multiple-sclerosis-efficacy-and-safety-results-up-to-7-years
#18
Fred D Lublin, Stacey S Cofield, Gary R Cutter, Tarah Gustafson, Stephen Krieger, Ponnada A Narayana, Flavia Nelson, Amber R Salter, Jerry S Wolinsky
BACKGROUND: To report the long-term results of the blinded extension phase of the randomized, controlled study of the combined use of interferon beta-1a (IFN) 30μg IM weekly and glatiramer acetate (GA) 20mg daily compared to each agent alone in relapsing-remitting multiple sclerosis (RRMS). METHODS: 1008 RRMS patients were followed on protocol until the last participant enrolled completed 3 years, allowing some subjects to be followed for up to 7 years. The primary endpoint was reduction in annualized relapse rate...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141817/lymphocytes-in-the-treatment-with-interferon-beta-1-b
#19
Zbyšek Pavelek, Oldřich Vyšata, Blanka Klímová, Ctirad Andrýs, Doris Vokurková, Martin Vališ
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease affecting the central nervous system. One of the basic medications for the treatment of a clinically isolated syndrome (CIS) or relapsing-remitting MS is interferon beta (INFβ). Although the exact mechanism of its effects is unknown, the medication has an anti-inflammatory and immunomodulatory effect. The goal of this study was to determine the characters which are affected in patients treated with INFβ...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141809/treatment-satisfaction-across-injectable-infusion-and-oral-disease-modifying-therapies-for-multiple-sclerosis
#20
Tessa Eagle, Fiona Stuart, Alicia S Chua, Allison LaRussa, Kaitlynne Leclaire, Sandra L Cook, Tanuja Chitnis, Howard L Weiner, Bonnie I Glanz, Brian C Healy
BACKGROUND: The recent approval of oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) has provided patients with a new route of therapy administration. Little research has compared patients' experiences with and perceptions of injectable, infusion and oral MS therapies. METHODS: Three hundred fifty-seven treated MS patients enrolled in the CLIMB study completed the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM provides information regarding perceived effectiveness, side effects, convenience and overall satisfaction...
November 2017: Multiple Sclerosis and related Disorders
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