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Petra Cerkovnik, Barbara Jezeršek Novaković, Vida Stegel, Srdjan Novaković
In our previous studies, it has been demonstrated that in more than 80% of mice long-lasting antitumor immunity has been established following intraperitoneal (i.p.) vaccination with tumor vaccine composed of irradiated syngeneic tumor cells and CpG ODNs class C. The aim of this study was, therefore, to investigate molecular mechanisms through which this vaccine triggers the immunity and to define genes particularly involved in this process. Changes in gene expression were followed in mononuclear cells isolated from peritoneal lavages, spleens and bone marrow samples...
September 24, 2016: Molecular Immunology
Tobias M Gorges, Andra Kuske, Katharina Röck, Oliver Mauermann, Volkmar Müller, Sven Peine, Karl Verpoort, Vendula Novosadova, Mikael Kubista, Sabine Riethdorf, Klaus Pantel
BACKGROUND: Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS: CTCs were enriched based on their EpCAM expression (CellSearch®) or by size and deformability (Parsortix™), identified by EpCAM and/or pan-keratin-specific antibodies, and isolated for single cell multiplex RNA profiling. RESULTS: Distinct breast and prostate CTC expression signatures could be discriminated from RNA profiles of leukocytes...
September 14, 2016: Clinical Chemistry
Shanieek Lawrence, Samuel T Pellom, Anil Shanker, Margaret M Whalen
Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo...
September 7, 2016: Journal of Immunotoxicology
Ana Montalban-Arques, Philipp Wurm, Slave Trajanoski, Silvia Schauer, Sabine Kienesberger, Bettina Halwachs, Christoph Högenauer, Cord Langner, Gregor Gorkiewicz
Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8(+) T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnes as a possible disease trigger...
August 19, 2016: Journal of Pathology
Rashmi Supriya, Bjorn T Tam, Xiao M Pei, Christopher W Lai, Lawrence W Chan, Benjamin Y Yung, Parco M Siu
Anti-cancer agent doxorubicin (DOX) has been demonstrated to worsen insulin signaling, engender muscle atrophy, trigger pro-inflammation, and induce a shift to anaerobic glycolytic metabolism in skeletal muscle. The myotoxicity of DOX in diabetic skeletal muscle remains largely unclear. This study examined the effects of DOX on insulin signaling, muscle atrophy, pro-/anti-inflammatory microenvironment, and glycolysis metabolic regulation in skeletal muscle of db/db diabetic and db/+ non-diabetic mice. Non-diabetic db/+ mice and diabetic db/db mice were randomly assigned to the following groups: db/+CON, db/+DOX, db/dbCON, and db/dbDOX...
2016: Frontiers in Physiology
Yufei Wang, Durdana Rahman, Mukesh Mistry, Thomas Lehner
Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K(+) efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant...
September 23, 2016: Journal of Biological Chemistry
Andrew L Doedens, Mark P Rubinstein, Emilie T Gross, J Adam Best, David H Craig, Megan K Baker, David J Cole, Jack D Bui, Ananda W Goldrath
Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration...
September 2, 2016: Cancer Immunology Research
J Teler, M Tarnowski, K Safranow, A Maciejewska, M Sawczuk, V Dziedziejko, S Sluczanowska-Glabowska, A Pawlik
Gestational diabetes mellitus (GDM) is a glucose intolerance that occurs during pregnancy. Several studies suggest that inflammation contributes to pregnancy-induced insulin resistance and the development of glucose intolerance. The aim of this study is to examine the association between the CCL2, CCL5, IL4 and IL15 gene polymorphisms and the development of GDM. This study included 411 pregnant women who underwent a 75 g oral glucose tolerance test at 24-28 weeks of gestation. Participants were categorised into 2 groups according to results of the oral glucose tolerance test (OGTT)...
July 29, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Theodore P Ciaraldi, Alexander J Ryan, Sunder R Mudaliar, Robert R Henry
Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes...
2016: PloS One
Michael Camilleri, Paula Carlson, Nelson Valentin, Andres Acosta, Jessica O'Neill, Deborah Eckert, Roy Dyer, Jie Na, Eric W Klee, Joseph A Murray
Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2((-ΔΔCT)) formula...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Xiao Liang, Min Luo, Xia-Wei Wei, Cui-Cui Ma, Yu-Han Yang, Bin Shao, Yan-Tong Liu, Ting Liu, Jun Ren, Li Liu, Zhi-Yao He, Yu-Quan Wei
Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0...
July 11, 2016: Oncotarget
Małgorzata Dawidowska, Maria Kosmalska, Łukasz Sędek, Aleksandra Szczepankiewicz, Magdalena Twardoch, Alicja Sonsala, Bronisława Szarzyńska-Zawadzka, Katarzyna Derwich, Monika Lejman, Katarzyna Pawelec, Agnieszka Obitko-Płudowska, Katarzyna Pawińska-Wąsikowska, Kinga Kwiecińska, Andrzej Kołtan, Agnieszka Dyla, Władysław Grzeszczak, Jerzy R Kowalczyk, Tomasz Szczepański, Ewa Ziętkiewicz, Michał Witt
Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33)...
2016: Scientific Reports
Héctor Cordero, Manuela Mauro, Alberto Cuesta, Matteo Cammarata, María Ángeles Esteban
Skin is the first barrier of defense on fish, which is crucial to protection against different stressors, including pathogens. Skin samples obtained from dorsal and ventral part of Sparus aurata specimens were incubated with Photobacterium damselae subsp. piscicida (a pathogen for this fish species), with Shewanella putrefaciens Pdp11 (a probiotic bacteria isolated from healthy gilthead seabream skin) or with both bacteria. The gene expression profile of nine cytokines (il1b, tnfa, il6, il7, il8, il15, il18, il10 and tgfb) was studied by qPCR in all the skin samples...
September 2016: Fish & Shellfish Immunology
Jun-Feng Ye, Yuan-Qiang Lin, Xiu-Hua Yu, Ming-Yuan Liu, Yang Li
The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones...
September 2016: International Immunopharmacology
Jérôme Nicod, Robert W Davies, Na Cai, Carl Hassett, Leo Goodstadt, Cormac Cosgrove, Benjamin K Yee, Vikte Lionikaite, Rebecca E McIntyre, Carol Ann Remme, Elisabeth M Lodder, Jennifer S Gregory, Tertius Hough, Russell Joynson, Hayley Phelps, Barbara Nell, Clare Rowe, Joe Wood, Alison Walling, Nasrin Bopp, Amarjit Bhomra, Polinka Hernandez-Pliego, Jacques Callebert, Richard M Aspden, Nick P Talbot, Peter A Robbins, Mark Harrison, Martin Fray, Jean-Marie Launay, Yigal M Pinto, David A Blizard, Connie R Bezzina, David J Adams, Paul Franken, Tom Weaver, Sara Wells, Steve D M Brown, Paul K Potter, Paul Klenerman, Arimantas Lionikas, Richard Mott, Jonathan Flint
Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content...
August 2016: Nature Genetics
O S Nepsha, I V Nikitina, A E Donnikov, A A Bystritsky, S M Mullabaeva, S V Pavlovich, N V Aleksandrova
The expression of immune response gene mRNA in the umbilical and venous blood were compared in newborns of the first day of life with and without signs of infection. The expression of il1b, il6, il8, il10, il12a, il15, il18, tnfa, tgfb1, tbx21, gata3, foxp3, rorc2, cd45, cd68, cd69, tlr2, tlr4, tlr9, and mmp8 mRNA was evaluated in umbilical and venous blood cells of newborns by reverse transcription real time PCR. In full-term newborns without signs of infection, the expression of il8, tlr2, tlr4, and mmp8 in venous blood was higher than in umbilical blood, while in preterm newborns, the levels of mmp8 transcript were elevated while the levels of tlr9, cd45, and gata3 were reduced...
April 2016: Bulletin of Experimental Biology and Medicine
Nahid Khaziri, Momeneh Mohammadi, Zeinab Aliyari, Jafar Soleimani Rad, Hamid Tayefi Nasrabadi, Hojjatollah Nozad Charoudeh
PURPOSE: Although bone marrow represents the main site for NK cell development and also distinct thymic-dependentNK cell pathway was identified, the cytokines effect on the NK cell generation from cord blood is unclear. Studies were identified the role of cytokines in the regulation of bone marrow and thymic NK cells. Previous studies reported that IL15 are critical for bone marrow dependent and IL7 is important for thymic NK cells. It is remain unclear the cytokines influence on the expantion of NK cells in cord blood mononuclear cells...
March 2016: Advanced Pharmaceutical Bulletin
Christian S Hinrichs
Adoptive transfer of T cells genetically engineered to express a tumor-targeting chimeric antigen receptor (CAR) or T-cell receptor (TCR) can mediate cancer regression in some patients. CARs are synthetic single-chain proteins that use antibody domains to target cell surface antigens. TCRs are natural heterodimeric proteins that can target intracellular antigens through recognition of peptides bound to human leukocyte antigens. CARs have shown promise in B-cell malignancies and TCRs in melanoma, but neither approach has achieved clear success in an epithelial cancer...
April 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alessandra Micera, Antonio Di Zazzo, Graziana Esposito, Roberto Sgrulletta, Virginia L Calder, Stefano Bonini
OBJECTIVE: Vernal keratoconjunctivitis (VKC) is a chronic recurrent bilateral inflammation of the conjunctiva associated with atopy. Several inflammatory and tissue remodeling factors contribute to VKC disease. The aim is to provide a chip-based protein analysis in tears from patients suffering from quiescent or active VKC. METHODS: This study cohort included 16 consecutive patients with VKC and 10 controls. Participants were subjected to clinical assessment of ocular surface and tear sampling...
2016: BioMed Research International
Hatem Zayed
Type 1 diabetes (T1D) is a complex autoimmune disorder that results from the T cell-mediated destruction of the pancreatic β cells and is due to interactions between environmental and genetic factors. Although Arabs have one of the highest global incidence and prevalence rates of T1D, unfortunately, there is a dearth of information regarding the genetic epidemiology of T1D in the Arab world. Arabs share several HLA haplotypes with other ethnic groups, which confer either susceptibility or protection to T1D, but they have specific haplotypes that are distinctive from other ethnicities...
May 2016: Current Diabetes Reports
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