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Anti- cytokine therapies

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https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#1
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906698/ige-and-eosinophils-as-therapeutic-targets-in-asthma
#2
Tanvi R Patel, Sanjiv Sur
PURPOSE OF REVIEW: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#3
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#4
Adel Samson, Matthew J Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin
OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication...
November 15, 2016: Gut
https://www.readbyqxmd.com/read/27899899/cell-expansion-dependent-inflammatory-and-metabolic-profile-of-human-bone-marrow-mesenchymal-stem-cells
#5
Patricia Prieto, María Fernández-Velasco, María E Fernández-Santos, Pedro L Sánchez, Verónica Terrón, Paloma Martín-Sanz, Francisco Fernández-Avilés, Lisardo Boscá
Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in culture via plastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansion in vitro may be limited mainly due to "cell aging" related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27897220/impact-of-the-microbial-derived-short-chain-fatty-acid-propionate-on-host-susceptibility-to-bacterial-and-fungal-infections-in-vivo
#6
Eleonora Ciarlo, Tytti Heinonen, Jacobus Herderschee, Craig Fenwick, Matteo Mombelli, Didier Le Roy, Thierry Roger
Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896870/tetracyclines-and-or-nicotinamide-in-blistering-dermatoses
#7
Ayman Abdelmaksoud
I read with interest a report by von Köckritz et al(1) . Tetracycline therapy, particularly in autoimmune blistering conditions, has become an acceptable treatment modality among elderly individuals, particularly those with osteoporosis, DM, and hypertension. This drug has also been given in combination with immunosuppressive treatment for more rapid tapering of the latter(2) .Minocycline besides having antimicrobial activity, it possesses anti-inflammatory and anti-apoptotic properties and causes inhibition of proteolysis, angiogenesis, and collagenase, and ability to induce read-through of premature stop mutations(3) ...
November 29, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27895484/the-effect-of-dexamethasone-cell-penetrating-peptide-nanoparticles-on-gene-delivery-for-inner-ear-therapy
#8
Ji Young Yoon, Keum-Jin Yang, Shi-Nae Park, Dong-Kee Kim, Jong-Duk Kim
Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#9
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27894105/histone-deacetylase-inhibitors-provoke-a-tumor-supportive-phenotype-in-pancreatic-cancer-associated-fibroblasts
#10
Andrew H Nguyen, Irmina A Elliott, Nanping Wu, Cynthia Matsumura, Maria Vogelauer, Narsis Attar, Amanda Dann, Razmik Ghukasyan, Paul A Toste, Sanjeet G Patel, Jennifer L Williams, Luyi Li, David W Dawson, Caius Radu, Siavash K Kurdistani, Timothy R Donahue
Although histone deacetylase inhibitors (HDACi) are a promising class of anti-cancer drugs, thus far, they have been unsuccessful in early phase clinical trials for pancreatic ductal adenocarcinoma (PDAC). One potential reason for their poor efficacy is the tumor stroma, where cancer-associated fibroblasts (CAFs) are a prominent cell type and a source of resistance to cancer therapies. Here, we demonstrate that stromal fibroblasts contribute to the poor efficacy of HDACi's in PDAC. HDACi-treated fibroblasts show increased biological aggressiveness and are characterized by increased secretion of pro-inflammatory tumor-supportive cytokines and chemokines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893014/durability-of-the-rituximab-response-in-acetylcholine-receptor-autoantibody-positive-myasthenia-gravis
#11
Kimberly R Robeson, Aditya Kumar, Benison Keung, Daniel B DiCapua, Emily Grodinsky, Huned S Patwa, Panos A Stathopoulos, Jonathan M Goldstein, Kevin C O'Connor, Richard J Nowak
Importance: Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear. Objective: To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG...
November 21, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27892456/il-12-protects-from-psoriasiform-skin-inflammation
#12
Paulina Kulig, Stephanie Musiol, Sandra Nicole Freiberger, Bettina Schreiner, Gabor Gyülveszi, Giancarlo Russo, Stanislav Pantelyushin, Kenji Kishihara, Francesca Alessandrini, Thomas Kündig, Federica Sallusto, Günther F L Hofbauer, Stefan Haak, Burkhard Becher
Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#13
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#14
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the anti-tumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing Phase I clinical testing, in multiple myeloma (MM)...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890816/pathophysiology-of-hemophilic-arthropathy-and-potential-targets-for-therapy
#15
REVIEW
Astrid E Pulles, Simon C Mastbergen, Roger E G Schutgens, Floris P J G Lafeber, Lize F D van Vulpen
Hemophilia is a congenital clotting factor deficiency characterized by spontaneous and trauma-related bleeding. Spontaneous bleeding shows a predilection for joints, and repeated hemarthroses lead to a disabling condition called hemophilic arthropathy. Treatment of this condition consists of preventing joint bleeding on the one hand and orthopedic surgery as a last resort on the other. Up till now, there is no disease modifying therapy available to fill the gap between these extremes. This review provides an overview of the pathogenesis of hemophilic arthropathy in order to identify potential targets for therapy...
November 24, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27889959/fumaric-acid-esters-attenuate-secondary-degeneration-following-spinal-cord-injury
#16
Marika Cordaro, Giovanna Casili, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Spinal cord injury (SCI) causes permanent changes in motor, sensory and autonomic functions. Unfortunately, there are not a stable cures and current treatments include surgical decompression, methylprednisolone and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. Because of their potent anti-inflammatory effects, they have been introduced in multiple sclerosis. Investigation shown not only anti-inflammatory, but also supposed neuroprotective mechanism of action...
November 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27888159/transmembrane-tnf-alpha-reverse-signaling-leading-to-tgf-beta-production-is-selectively-activated-by-tnf-targeting-molecules-therapeutic-implications
#17
REVIEW
Zsuzsa Szondy, Anna Pallai
Tumor necrosis factor (TNF)-α is a potent pro-inflammatory cytokine exerting pleiotropic effects on various cell types. It is synthesized in a precursor form called transmembrane TNF-α (mTNF-α) which, after being processed by metalloproteinases, is released in a soluble form to mediate its biological activities through Type 1 and 2 TNF receptors in TNF receptor expressing cells. In addition to acting in soluble form, TNF-α also acts in the transmembrane form both as a ligand by activating TNF receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into mTNF-α bearing cells...
November 22, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27886802/advancements-in-the-management-of-uveitis
#18
REVIEW
Sergio Schwartzman
Uveitis may exist as a clinical manifestation of an underlying systemic disease or may represent an idiopathic entity, sometimes with a very characteristic pattern. Different forms of uveitis have been defined on the basis of three important variables: chronicity, anatomic location, and underlying etiology. The evolving understanding of the immune system has resulted in a more targeted approach to manage patients with different forms of uveitis, although clearly this approach is at a very early stage. Altered patterns of cellular processing and different cytokine expression, including TNF, IL-1, IL-2, IL-6, and IL17, have been defined in uveitis, and this has laid the pathway for targeted therapy...
April 2016: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/27886796/adult-onset-still-s-disease-advances-in-the-treatment
#19
REVIEW
Santos Castañeda, Ricardo Blanco, Miguel A González-Gay
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder mainly characterized by persistent high spiking fevers, evanescent rash, and joint involvement. The pathogenesis of AOSD is only partially known, but pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-18, and IFN-γ seem to play a major role in this disorder. AOSD is at the crossroad of auto-inflammatory syndromes and autoimmune diseases. It is diagnosed by exclusion to determine the presence of high serum ferritin levels, which is usually >1000 μg/L...
April 2016: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/27886433/the-burkholderia-cenocepacia-peptidoglycan-associated-lipoprotein-is-involved-in-epithelial-cell-attachment-and-elicitation-of-inflammation
#20
Ruth Dennehy, Maria Romano, Alessia Ruggiero, Yasmine F Mohamed, Simon L Dignam, Cristóbal Mujica Troncoso, Máire Callaghan, Miguel A Valvano, Rita Berisio, Siobhán McClean
The Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. The identification of novel targets for anti-virulence therapies should improve therapeutic options for infected CF patients. We previously identified that the peptidoglycan-associated lipoprotein (Pal) was immunogenic in Bcc infected CF patients; however, its role in Bcc pathogenesis is unknown...
November 7, 2016: Cellular Microbiology
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