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Anti- cytokine therapies

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https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#1
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#2
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633455/fetal-metabolic-stress-disrupts-immune-homeostasis-and-induces-pro-inflammatory-responses-in-hiv-1-and-cart-exposed-infants
#3
Johannes C Schoeman, Gontse P Moutloatse, Amy C Harms, Rob J Vreeken, Henriette J Scherpbier, Liesbeth Van Leeuwen, Taco W Kuijpers, Carools J Reinecke, Ruud Berger, Thomas Hankemeier, Madeleine J Bunders
Increased morbidity and fetal growth restriction are reported in uninfected children born to HIV-1-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART)-exposure on the infants' immune-metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning...
June 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28629242/differential-effect-of-p38-and-mk2-kinase-inhibitors-on-the-inflammatory-and-toxicity-biomarkers-in-vitro
#4
R K Singh, M Diwan, S G Dastidar, A K Najmi
BACKGROUND: Many inflammatory responses including chemotaxis, production of nitric oxide, and modulation of pro-inflammatory cytokines in immunological cells are mediated by p38MAPK. Due to its pivotal role, p38MAPK has been extensively explored as a molecular target for inhibition of chronic inflammation; however, it has not been successful so far due to serious toxicity issues. Among several downstream substrates of p38, mitogen-activated protein kinase-activated protein kinase 2 (MK2) has been reported to be a direct and essential downstream component in regulation of innate immune and inflammatory responses...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28628650/the-human-cytomegalovirus-glycoprotein-pul11-acts-via-cd45-to-induce-t-cell-il-10-secretion
#5
Jasmin Zischke, Panagiota Mamareli, Claudia Pokoyski, Ildar Gabaev, Sabine Buyny, Roland Jacobs, Christine S Falk, Matthias Lochner, Tim Sparwasser, Thomas F Schulz, Penelope C Kay-Fedorov
Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#6
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28627645/therapeutic-strategies-for-alcoholic-liver-disease-focusing-on-inflammation-and-fibrosis-review
#7
Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Masakazu Uejima, Mitsuteru Kitade, Kousuke Takeda, Yasushi Okura, Kousuke Kaji, Hiroaki Takaya, Norihisa Nishimura, Shinya Sato, Yasuhiko Sawada, Kenichiro Seki, Takuya Kubo, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Excessive alcohol consumption is the most common cause of liver disease in the world. Chronic alcohol abuse leads to liver damage, liver inflammation, fibrosis and hepatocellular carcinoma. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, induce liver injury, which leads to the develo-pment of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as interleukin (IL)-6 and IL-10, are also associated with ALD. IL-6 improves ALD via the activation of STAT3 and the subsequent induction of a variety of hepatoprotective genes in hepatocytes...
June 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627460/polysaccharides-from-epimedium-koreanum-nakai-with-immunomodulatory-activity-and-inhibitory-effect-on-tumor-growth-in-llc-bearing-mice
#8
Chengcheng Wang, Liang Feng, Jiayan Su, Li Cui, Dan Liu, Jun Yan, Chuanlin Ding, Xiaobin Tan, Xiaobin Jia
ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium koreanum Nakai is documented as tonic herbal in China for over a thousand years and has the potential to enhance the body's immunity according to the theory of traditional Chinese medicine. Polysaccharides are one of the most important effective compounds in Epimedium koreanum Nakai. Accumulating evidence indicated polysaccharides derived from traditional Chinese medicine have potent immune-enhancing properties and relatively nontoxic effects in cancer treatment...
June 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28627320/an-exploratory-study-on-the-anti-inflammatory-effects-of-fucoidan-in-relation-to-quality-of-life-in-advanced-cancer-patients
#9
Hidenori Takahashi, Mitsuhiko Kawaguchi, Kunihiro Kitamura, Seiji Narumiya, Munenori Kawamura, Isamu Tengan, Shinji Nishimoto, Yasuo Hanamure, Yasuo Majima, Shuichi Tsubura, Kiichiro Teruya, Sanetaka Shirahata
BACKGROUND: Conventional anticancer therapies still cause difficulties with selective eradication and accompanying side effects that reduce patients' quality of life (QOL). Fucoidan is extracted from seaweeds and has already exhibited broad bioactivities, including anticancer and anti-inflammatory properties, in basic studies. It is expected to enhance therapeutic efficacy and minimize side effects in cancer patients; however, despite its potential benefits, there are very few clinical trials using fucoidans...
February 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28625245/-effects-of-different-sedation-regimens-on-sedation-and-inflammatory-response-in-critically-ill-children-with-multiple-trauma
#10
Wenjia Tong, Conglei Song, Danqun Jin, Jingmin Sun, Yating Wang, Daliang Xu
OBJECTIVE: To compare the sedation and anti-inflammatory effects of dexmedetomidine and midazolam on critical ill children with multiple trauma. METHODS: A prospective randomized controlled trial was conducted. Sixty-five critical ill children with multiple trauma admitted to pediatric intensive care unit (PICU) of Anhui Province Children's Hospital from January 2014 to September 2016 were enrolled, who were randomly divided into dexmedetomidine group (33 cases) and midazolam group (32 cases)...
June 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28624362/pulvis-fellis-suis-extract-attenuates-ovalbumin-induced-airway-inflammation-in-murine-model-of-asthma
#11
Jiao He, Le Lv, Ziye Wang, Chuanchuan Huo, Zongwei Zheng, Bing Yin, Peizhi Jiang, Yang Yang, Jing Li, Yuan Gao, Jing Xue
ETHNOPHARMACOLOGICAL RELEVANCE: Pulvis Fellis Suis (PFS), named with "Zhu Danfen" in China, has been extensively used for the therapy of enteritis, acute pharyngitis, whooping cough and asthma in folk medicine. Although PFS shows anti-inflammatory activities, its effect on airway inflammation in asthma has not been studied. AIM OF THE STUDY: To explore the protective effect of PFS ethanol extract against airway inflammation in asthmatic mice. MATERIALS AND METHODS: Allergic asthma in mice was sensitized and challenged by OVA...
June 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28623000/medical-ozone-promotes-nrf2-phosphorylation-reducing-oxidative-stress-and-pro-inflammatory-cytokines-in-multiple-sclerosis-patients
#12
Livan Delgado-Roche, Mario Riera-Romo, Fernando Mesta, Yanet Hernández-Matos, Juan M Barrios, Gregorio Martínez-Sánchez, Said M Al-Dalaien
Oxidative stress and inflammation play key roles in the pathogenesis of Multiple sclerosis (MS). Different drugs have been used in the clinical practice, however, there is not a completely effective treatment. Due to its potential therapeutic action, medical ozone represents a promising approach for neurodegenerative disorders. The aim of the present study was to address the role of ozone therapy on the cellular redox state in MS patients. Ozone (20μg/ml) was administered three times per week during a month by rectal insufflation...
June 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28622097/evolution-of-cytokines-and-inflammatory-biomarkers-during-infliximab-induction-therapy-and-the-impact-of-inflammatory-burden-on-primary-response-in-patients-with-crohn-s-disease
#13
Thomas Billiet, Isabelle Cleynen, Vera Ballet, Karolien Claes, Fred Princen, Sharat Singh, Marc Ferrante, Gert Van Assche, Ann Gils, Severine Vermeire
OBJECTIVE: Primary non-response to infliximab in Crohn's disease is still incompletely understood. Our aim was to further characterize the role of inflammatory burden during infliximab induction therapy. MATERIALS AND METHODS: We studied a well-characterized cohort of 201 anti-TNF naive Crohn's disease patients treated with infliximab 5mg/kg at week 0, 2, 6 and 14 who had serum samples drawn just before every infusion. All serum samples were analyzed for CRP, albumin, TNF, IFN-γ, IL-6, IL-8, IL-10, infliximab trough concentrations (in-house-developed ELISA) and antibodies to infliximab (HMSA, Prometheus Laboratories Inc...
June 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28621675/the-regulation-of-immune-cells-by-lactobacilli-a-potential-therapeutic-target-for-anti-atherosclerosis-therapy
#14
REVIEW
Ya-Hui Ding, Lin-Yan Qian, Jie Pang, Jing-Yang Lin, Qiang Xu, Li-Hong Wang, Dong-Sheng Huang, Hai Zou
Atherosclerosis is an inflammatory disease regulated by several immune cells including lymphocytes, macrophages and dendritic cells. Gut probiotic bacteria like Lactobacilli have been shown immunomodificatory effects in the progression of atherogenesis. Some Lactobacillus stains can upregulate the activity of regulatory T-lymphocytes, suppress T-lymphocyte helper (Th) cells Th1, Th17, alter the Th1/Th2 ratio, influence the subsets ratio of M1/M2 macrophages, inhibit foam cell formation by suppressing macrophage phagocytosis of oxidized low-density lipoprotein, block the activation of the immune system with dendritic cells, which are expected to suppress the atherosclerosis-related inflammation...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620220/coupling-killing-to-neutralization-combined-therapy-with-ceftriaxone-pep19-2-5-counteracts-sepsis-in-rabbits
#15
Sergio Bárcena-Varela, Guillermo Martínez-de-Tejada, Lukas Martin, Tobias Schuerholz, Ana Gloria Gil-Royo, Satoshi Fukuoka, Torsten Goldmann, Daniel Droemann, Wilmar Correa, Thomas Gutsmann, Klaus Brandenburg, Lena Heinbockel
Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28619088/chemokine-signals-are-crucial-for-enhanced-homing-and-differentiation-of-circulating-osteoclast-progenitor-cells
#16
Alan Sucur, Zrinka Jajic, Marinko Artukovic, Marina Ikic Matijasevic, Branimir Anic, Darja Flegar, Antonio Markotic, Tomislav Kelava, Sanja Ivcevic, Natasa Kovacic, Vedran Katavic, Danka Grcevic
BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28618326/inflammation-as-target-in-cancer-therapy
#17
REVIEW
Giulia Marelli, Antonio Sica, Luca Vannucci, Paola Allavena
Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies...
June 12, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28618186/therapeutic-efficacy-of-fresh-allogeneic-mesenchymal-stem-cells-for-severe-refractory-feline-chronic-gingivostomatitis
#18
Boaz Arzi, Kaitlin C Clark, Ayswarya Sundaram, Mathieu Spriet, Frank J M Verstraete, Naomi J Walker, Megan R Loscar, Nasim Fazel, William J Murphy, Natalia Vapniarsky, Dori L Borjesson
Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28615225/enhanced-therapeutic-efficacy-and-memory-of-tumor-specific-cd8-t-cells-by-ex-vivo-pi3k-%C3%AE-inhibition
#19
Rasha Abu-Eid, Shamim Ahmad, Yuan Lin, Mason Webb, Zuzana Berrong, Rajeev K Shrimali, Takumi Kumai, Sudha Ananth, Paulo C Rodriguez, Esteban Celis, John E Janik, Mikayel Mkrtichyan, Samir N Khleif
Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating anti-tumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T cell differentiation and assessed the potential use of PI3K isoform-specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors...
June 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28611778/peg-interferon-lambda-treatment-induces-robust-innate-and-adaptive-immunity-in-chronic-hepatitis-b-patients
#20
Sandra Phillips, Sameer Mistry, Antonio Riva, Helen Cooksley, Tanya Hadzhiolova-Lebeau, Slava Plavova, Krum Katzarov, Marieta Simonova, Stephan Zeuzem, Clive Woffendin, Pei-Jer Chen, Cheng-Yuan Peng, Ting-Tsung Chang, Stefan Lueth, Robert De Knegt, Moon-Seok Choi, Heiner Wedemeyer, Michael Dao, Chang-Wook Kim, Heng-Chen Chu, Megan Wind-Rotolo, Roger Williams, Elizabeth Cooney, Shilpa Chokshi
IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks...
2017: Frontiers in Immunology
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