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Immunomodulatory drugs

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https://www.readbyqxmd.com/read/29334375/a-small-molecule-inhibitor-of-the-ubiquitin-activating-enzyme-for-cancer-treatment
#1
Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S Amidon, Neil F Bence
The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29333596/risk-of-adverse-events-associated-with-front-line-anti-myeloma-treatment-in-medicare-patients-with-multiple-myeloma
#2
Ying Chen, David R Lairson, Wenyaw Chan, Xianglin L Du
This study aims to examine the risks of adverse events associated with anti-multiple myeloma (MM) therapies in a large population-based cohort of elderly patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and receiving anti-MM therapy were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. We compared safety outcomes between novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and other therapies and between PI- or IMiD-based regimens and PI plus IMiD combination regimens...
January 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29332324/effects-of-macrolide-and-corticosteroid-in-neutrophilic-asthma-mouse-model
#3
Tai Joon An, Chin Kook Rhee, Ji Hye Kim, Young Rong Lee, Jin Young Chon, Chan Kwon Park, Hyoung Kyu Yoon
BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29331024/combination-therapy-of-lovastatin-and-ampk-activator-improves-mitochondrial-and-peroxisomal-functions-and-clinical-disease-in-eae-model
#4
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
https://www.readbyqxmd.com/read/29328883/a-systematic-review-of-interleukin-1%C3%AE-in-post-traumatic-stress-disorder-evidence-from-human-and-animal-studies
#5
Aysha Waheed, Bethan Dalton, Ulrich Wesemann, Mohammad A A Ibrahim, Hubertus Himmerich
Pro-inflammatory cytokines, such as interleukin (IL)-1β, have been implicated as underlying pathophysiological mechanisms and potential biomarkers of post-traumatic stress disorder (PTSD). This systematic review examines data regarding IL-1β production/concentration in human and animal studies of PTSD. In accordance with PRISMA guidelines, relevant articles from PubMed were reviewed from inception until July 10, 2017. Nineteen studies were eligible for inclusion. Animal studies demonstrated increased hippocampal IL-1β in rodent models of PTSD...
January 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29328364/genetically%C3%A2-modified-stem-cells-in-treatment-of-human-diseases-tissue-kallikrein-klk1-%C3%A2-based-targeted-therapy-review
#6
Marina Devetzi, Maria Goulielmaki, Nicolas Khoury, Demetrios A Spandidos, Georgia Sotiropoulou, Ioannis Christodoulou, Vassilis Zoumpourlis
The tissue kallikrein‑kinin system (KKS) is an endogenous multiprotein metabolic cascade which is implicated in the homeostasis of the cardiovascular, renal and central nervous system. Human tissue kallikrein (KLK1) is a serine protease, component of the KKS that has been demonstrated to exert pleiotropic beneficial effects in protection from tissue injury through its anti‑inflammatory, anti‑apoptotic, anti‑fibrotic and anti‑oxidative actions. Mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) constitute populations of well‑characterized, readily obtainable multipotent cells with special immunomodulatory, migratory and paracrine properties rendering them appealing potential therapeutics in experimental animal models of various diseases...
January 3, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29325915/in-vivo-nonspecific-immunomodulatory-and-antispasmodic-effects-of-common-purslane-portulaca-oleracea-linn-leaf-extracts-in-icr-mice
#7
Elena S Catap, Markyn Jared L Kho, Maria Rexie R Jimenez
ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea (common purslane) is used in traditional medicine to cure various illnesses. However, its immune-protective properties and antispasmodic effects still need more pharmacological data if the plant will be utilized in herbal and drug formulations. Therefore, the present study determined the capacity of this plant species to modulate nonspecific immune responses and to confirm its antispasmodic activity in vivo in ICR mice. MATERIALS AND METHODS: Phagocytic activity of peritoneal macrophage, splenic lymphocyte proliferation and plasma lysozyme levels were measured in mice that were immunosuppressed using cyclophosphamide and treated with the ethyl acetate extract of Portulaca oleracea...
January 8, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29325864/infections-genetic-and-environmental-factors-in-pathogenesis-of-autoimmune-thyroid-diseases
#8
REVIEW
Sanjeev Kumar Shukla, Govind Singh, Shahzad Ahmad, Prabhat Pant
In Autoimmune disease a combination of infection, genetic and environmental factors causes an autoimmune response to the thyroid gland (characterized by lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and different thyroid antigens. Graves' and Hashimoto disease are autoimmune disorders with genetic predisposition. CD40 that stimulates the proliferation and differentiation of lymphocytes is an essential immunomodulatory component for follicular cells in the thyroid and the cell that present the antigen...
January 8, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29322348/optimisation-of-a-potency-assay-for-the-assessment-of-immunomodulative-potential-of-clinical-grade-multipotent-mesenchymal-stromal-cells
#9
Irene Oliver-Vila, Carmen Ramírez-Moncayo, Marta Grau-Vorster, Sílvia Marín-Gallén, Marta Caminal, Joaquim Vives
Clinical use of multipotent Mesenchymal Stromal Cell (MSC)-based medicinal products requires their production in compliance with Good Manufacturing Practices, thus ensuring that the final drug product meets specifications consistently from batch to batch in terms of cell viability, identity, purity and potency. Potency relates to the efficacy of the medicine in its target clinical indication, so adequate release tests need to be defined and validated as quality controls. Herein we report the design and optimisation of parameters affecting the performance of an in vitro cell-based assay for assessing immunomodulatory potential of clinical grade MSC for human use, based on their capacity to inhibit proliferation of T lymphocytes under strong polyclonal stimuli...
January 10, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29322016/evaluation-of-in%C3%A2-vitro-and-in%C3%A2-vivo-antileishmanial-potential-of-bergenin-rich-bergenia-ligulata-wall-engl-root-extract-against-visceral-leishmaniasis-in-inbred-balb-c-mice-through-immunomodulation
#10
Rupinder Kaur, Sukhbir Kaur
Background: Medicinal plants with immunomodulatory properties can provide good alternative therapeutics for curing visceral leishmaniasis. Bergenia ligulata (Wall.) Engl. is an interesting plant with strong antioxidant, antimicrobial, immunomodulatory and hepatoprotective properties. Aim: The present study was planned to determine the antileishmanial activity of plant extract by modulating the immune responses of inbred BALB/c mice. Methodology: Bergenin, the principle active component of B...
January 2018: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29320554/a-census-of-p-longum-s-phytochemicals-and-their-network-pharmacological-evaluation-for-identifying-novel-drug-like-molecules-against-various-diseases-with-a-special-focus-on-neurological-disorders
#11
Neha Choudhary, Vikram Singh
Piper longum (P. longum, also called as long pepper) is one of the common culinary herbs that has been extensively used as a crucial constituent in various indigenous medicines, specifically in traditional Indian medicinal system known as Ayurveda. For exploring the comprehensive effect of its constituents in humans at proteomic and metabolic levels, we have reviewed all of its known phytochemicals and enquired about their regulatory potential against various protein targets by developing high-confidence tripartite networks consisting of phytochemical-protein target-disease association...
2018: PloS One
https://www.readbyqxmd.com/read/29317734/combined-sep-and-anti-pd-l1-antibody-produces-a-synergistic-antitumor-effect-in-b16-f10-melanoma-bearing-mice
#12
Zhengping Hu, Liang Ye, Yingying Xing, Jinhang Hu, Tao Xi
The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and αPD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8+ and CD4+ T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316271/fingolimod-improved-axonal-and-myelin-integrity-of-white-matter-tracts-associated-with-multiple-sclerosis-related-functional-impairments
#13
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/29314819/modulating-phagocytic-cell-sequestration-by-tailoring-nanoconstruct-softness
#14
Roberto Palomba, Anna Lisa Palange, Ilaria Francesca Rizzuti, Miguel Ferreira, Antonio Cervadoro, Maria Grazia Barbato, Claudio Canale, Paolo Decuzzi
The effect of nanoparticle size, shape and surface properties on cellular uptake has been extensively investigated for its basic science and translational implications. Recently, softness is emerging as a design parameter for modulating the interaction of nanoparticles with cells and the biological microenvironment. Here, circular, quadrangular and elliptical polymeric nanoconstructs of different sizes are realized with a Young's modulus ranging from ∽ 100 kPa (soft) to 10 MPa (rigid). The interaction of these nanoconstructs with professional phagocytic cells is assessed via confocal microscopy and flow cytometry analyses...
January 9, 2018: ACS Nano
https://www.readbyqxmd.com/read/29312812/characterization-and-toxicity-of-citral-incorporated-with-nanostructured-lipid-carrier
#15
Noraini Nordin, Swee Keong Yeap, Nur Rizi Zamberi, Nadiah Abu, Nurul Elyani Mohamad, Heshu Sulaiman Rahman, Chee Wun How, Mas Jaffri Masarudin, Rasedee Abdullah, Noorjahan Banu Alitheen
The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54...
2018: PeerJ
https://www.readbyqxmd.com/read/29304807/laquinimod-ameliorates-excitotoxic-damage-by-regulating-glutamate-re-uptake
#16
Antonietta Gentile, Alessandra Musella, Francesca De Vito, Diego Fresegna, Silvia Bullitta, Francesca Romana Rizzo, Diego Centonze, Georgia Mandolesi
BACKGROUND: Laquinimod is an immunomodulatory drug under clinical investigation for the treatment of the progressive form of multiple sclerosis (MS) with both anti-inflammatory and neuroprotective effects. Excitotoxicity, a prominent pathophysiological feature of MS and of its animal model, experimental autoimmune encephalomyelitis (EAE), involves glutamate transporter (GluT) dysfunction in glial cells. The aim of this study was to assess whether laquinimod might exert direct neuroprotective effects by interfering with the mechanisms of excitotoxicity linked to GluT function impairments in EAE...
January 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29303710/vaccinations-in-adults-with-rheumatoid-arthritis-in-an-era-of-new-disease-modifying-anti-rheumatic-drugs
#17
REVIEW
Pier Luigi Meroni, Daniela Zavaglia, Corrado Girmenia
Patients with rheumatoid arthritis are at greater risk of infectious morbidity and mortality due to disease-related abnormalities and use of immunosuppressive medications. Vaccinations are recommended by international guidelines among infection control strategies, but vaccination rates are reported to be still suboptimal in both America and Europe. Furthermore, with the increasing number of immunomodulatory medications used in RA patients, safety and efficacy of vaccinations in RA patients on such therapies have been questioned...
December 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29296968/a-fully-recombinant-human-igg1-fc-multimer-gl-2045-inhibits-complement-mediated-cytotoxicity-and-induces-ic3b
#18
Hua Zhou, Henrik Olsen, Edward So, Emmanuel Mérigeon, Denis Rybin, Jane Owens, Gregory LaRosa, David S Block, Scott E Strome, Xiaoyu Zhang
GL-2045 is a recombinant human immunoglobulin G1 (IgG1)-based Fc multimer designed to recapitulate the anti-inflammatory activities of intravenous immunoglobulin (IVIG) on the innate and adaptive immune responses. We used functional in vitro studies to determine if GL-2045 could mimic the modulatory activity of IVIG on complement activation. GL-2045, at log-order lower concentrations than heat-aggregated IgG (HAGG) and IVIG, protected antibody-opsonized cells from complement-dependent cytotoxicity. These protective effects were completely mediated by the higher order multimer fractions of GL-2045 and were partially dependent upon sequestration of C1q...
March 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296961/network-meta-analysis-of-randomized-trials-in-multiple-myeloma-efficacy-and-safety-in-relapsed-refractory-patients
#19
Cirino Botta, Domenico Ciliberto, Marco Rossi, Nicoletta Staropoli, Maria Cucè, Teresa Galeano, Pierosandro Tagliaferri, Pierfrancesco Tassone
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296798/a-phase-2-study-of-panobinostat-with-lenalidomide-and-weekly-dexamethasone-in-myeloma
#20
Ajai Chari, Hearn J Cho, Amishi Dhadwal, Gillian Morgan, Lisa La, Katarzyna Zarychta, Donna Catamero, Erika Florendo, Nadege Stevens, Daniel Verina, Elaine Chan, Violetta Leshchenko, Alessandro Laganà, Deepak Perumal, Anna Huo-Chang Mei, Kaity Tung, Jami Fukui, Sundar Jagannath, Samir Parekh
Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively...
August 22, 2017: Blood Advances
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