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Gene expression in lymphocytes

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https://www.readbyqxmd.com/read/29792201/cerium-dioxide-nanoparticles-exacerbate-house-dust-mite-induced-type-ii-airway-inflammation
#1
Kirsty Meldrum, Sarah B Robertson, Isabella Römer, Tim Marczylo, Lareb S N Dean, Andrew Rogers, Timothy W Gant, Rachel Smith, Terry D Tetley, Martin O Leonard
BACKGROUND: Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2 NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2 NPs in a house dust mite (HDM) induced murine model of asthma. RESULTS: Repeated intranasal instillation of CeO2 NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia...
May 23, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29791856/activation-of-the-arterial-program-drives-development-of-definitive-hemogenic-endothelium-with-lymphoid-potential
#2
Mi Ae Park, Akhilesh Kumar, Ho Sun Jung, Gene Uenishi, Oleg V Moskvin, James A Thomson, Igor I Slukvin
Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29789608/downregulation-of-endothelin-receptor-b-contributes-to-defective-b-cell-lymphopoiesis-in-trisomy-21-pluripotent-stem-cells
#3
Glenn A MacLean, Jennifer McEldoon, Jialiang Huang, Jeremy Allred, Matthew C Canver, Stuart H Orkin
Individuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (EDNRB), and its ligand Endothelin1 (EDN1)...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789399/ebf1-gene-polymorphism-and-its-interaction-with-smoking-and-drinking-on-the-risk-of-coronary-artery-disease-for-chinese-patients
#4
Yongjun Ying, Yuxuan Luo, Hui Peng
Objective : Early B cell factor 1 (EBF1) is a transcription factor that is expressed in early B cells, adipocytes, and olfactory neurons, and is essential for the maturation of early B lymphocytes. This study analyzes the influence of EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease (CAD). Methods: In this study, 243 CAD cases were enrolled as the CAD group and 215 non-CAD patients as the control group by case-control study. We analyzed their genotypes of the rs987401919, rs36071027, and rs1056065671 loci of the EBF1 gene by Sanger sequencing, and detected their content of HDL-C, LDL-C, and TG...
May 22, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29789121/aire-is-not-essential-for-regulating-neuroinflammatory-disease-in-mice-transgenic-for-human-autoimmune-diseases-associated-mhc-class-ii-genes-hla-dr2b-and-hla-dr4
#5
Saisha A Nalawade, Niannian Ji, Itay Raphael, Andrew Pratt, Ellen Kraig, Thomas G Forsthuber
The human autoimmune disease-associated HLA alleles HLA-DR2b (DRB1*1501) and HLA-DR4 (DRB1*0401) are strongly linked to increased susceptibility for multiple sclerosis (MS) and rheumatoid arthritis (RA), respectively. The underlying mechanisms are not fully understood, but these MHC alleles may shape the repertoire of pathogenic T cells via central tolerance. The transcription factor autoimmune regulator (AIRE) promotes central T cell tolerance via ectopic expression of tissue-specific antigens (TSAs). Aire deficiency in humans causes autoimmune polyendocrinopathy syndrome type 1 (APS1), and Aire knockout mice (Aire-/- ) develop spontaneous autoimmune pathology characterized by multi-organ lymphocytic infiltrates...
May 14, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29788230/tumor-infiltrating-lymphocytes-in-patients-receiving-trastuzumab-pertuzumab-based-chemotherapy-a-tryphaena-substudy
#6
Michail Ignatiadis, Gert Van den Eynden, Salgado Roberto, Marco Fornili, Yacine Bareche, Christine Desmedt, Françoise Rothé, Marion Maetens, David Venet, Esther Holgado, Virginia McNally, Astrid Kiermaier, Heidi M Savage, Timothy R Wilson, Javier Cortes, Andreas Schneeweiss, Karen Willard-Gallo, Elia Biganzoli, Christos Sotiriou
Background: There is an urgent requirement to identify biomarkers to tailor treatment in human epidermal growth factor receptor 2 (HER2)-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Methods: Among the 225 patients randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 patients, of which 126 demonstrated a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) events...
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29788141/a-single-nucleotide-polymorphism-in-the-vitamin-d-receptor-gene-is-associated-with-decreased-levels-of-the-protein-and-a-penetrating-pattern-in-crohn-s-disease
#7
Laura Gisbert-Ferrándiz, Pedro Salvador, Dolores Ortiz-Masiá, Dulce Carolina Macías-Ceja, Samuel Orden, Juan Vicente Esplugues, Sara Calatayud, Joaquín Hinojosa, Maria Dolores Barrachina, Carlos Hernández
Background: Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR). The synonymous single nucleotide polymorphism (SNP) rs731236, located in the VDR gene, has been associated with a higher risk of Crohn's disease (CD). We analyzed differences in VDR expression levels among CD patients who were homozygous for allelic variants in this SNP and their relevance for disease course. Methods: DNA was extracted from blood samples of CD patients, and SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism...
May 18, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29787419/a-locus-at-7p14-3-predisposes-to-refractory-celiac-disease-progression-from-celiac-disease
#8
Barbara Hrdlickova, Chris J Mulder, Georgia Malamut, Bertrand Meresse, Mathieu Platteel, Yoichiro Kamatani, Isis Ricaño-Ponce, Roy L J van Wanrooij, Maria M Zorro, Marc Jan Bonder, Javier Gutierrez-Achury, Christophe Cellier, Alexandra Zhernakova, Petula Nijeboer, Pilar Galan, Sebo Withoff, Mark Lathrop, Gerd Bouma, Ramnik J Xavier, Bana Jabri, Nadine C Bensussan, Cisca Wijmenga, Vinod Kumar
BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII...
May 21, 2018: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29784906/the-anti-cancer-activity-of-an-andrographolide-analogue-functions-through-a-gsk-3%C3%AE-independent-wnt-%C3%AE-catenin-signaling-pathway-in-colorectal-cancer-cells
#9
Somrudee Reabroi, Rungnapha Saeeng, Nittaya Boonmuen, Teerapich Kasemsuk, Witchuda Saengsawang, Kanoknetr Suksen, Weiming Zhu, Pawinee Piyachaturawat, Arthit Chairoungdua
The Wnt/β-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP-050), an andrographolide analogue and determine its activity in the Wnt/β-catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#10
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29779068/new-insights-into-the-inflamed-tumor-immune-microenvironment-of-gastric-cancer-with-lymphoid-stroma-from-morphology-and-digital-analysis-to-gene-expression
#11
Irene Gullo, Patrícia Oliveira, Maria Athelogou, Gilza Gonçalves, Marta L Pinto, Joana Carvalho, Ana Valente, Hugo Pinheiro, Sara Andrade, Gabriela M Almeida, Ralf Huss, Kakoli Das, Patrick Tan, José C Machado, Carla Oliveira, Fátima Carneiro
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations...
May 19, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29776374/the-toxoplasma-gondii-me-49-strain-upregulates-levels-of-a20-that-inhibit-nf-%C3%AE%C2%BAb-activation-and-promotes-apoptosis-in-human-leukaemia-t-cell-lines
#12
Qian Chen, Min-Hui Pang, Xiao-Hong Ye, Guang Yang, Chen Lin
BACKGROUND: Acute T-lymphocyte leukaemia is a form of haematological malignancy with abnormal activation of NF-κB pathway, which results in high expression of A20 and ABIN1, which constitute a negative feedback mechanism for the regulation of NF-κB activation. Clinical studies have found that acute T-lymphocyte leukaemia patients are susceptible to Toxoplasma gondii infection; however, the effect of T. gondii on the proliferation and apoptosis of human leukaemia T-cells remains unclear...
May 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#13
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29774490/higher-activation-of-the-interferon-gamma-signaling-pathway-in-systemic-lupus-erythematosus-patients-with-a-high-type-i-ifn-score-relation-to-disease-activity
#14
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29774240/mannan-induced-nos2-in-macrophages-enhances-il-17-driven-psoriatic-arthritis-by-innate-lymphocytes
#15
Jianghong Zhong, Tatjana Scholz, Anthony C Y Yau, Simon Guerard, Ulrike Hüffmeier, Harald Burkhardt, Rikard Holmdahl
Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-l-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#16
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#17
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29770136/cd3%C3%AE%C2%B5-expression-defines-functionally-distinct-subsets-of-v%C3%AE-1-t-cells-in-patients-with-human-immunodeficiency-virus-infection
#18
Pádraic J Dunne, Christina O Maher, Michael Freeley, Katie Dunne, Andreea Petrasca, Judy Orikiiriza, Margaret R Dunne, Derval Reidy, Siobhan O'Dea, Aisling Loy, Jim Woo, Aideen Long, Thomas R Rogers, Fiona Mulcahy, Derek G Doherty
Human γδ T cells expressing the Vδ1 T cell receptor (TCR) recognize self and microbial antigens and stress-inducible molecules in a major histocompatibility complex-unrestricted manner and are an important source of innate interleukin (IL)-17. Vδ1 T cells are expanded in the circulation and intestines of patients with human immunodeficiency virus (HIV) infection. In this study, we show that patients with HIV have elevated frequencies, but not absolute numbers, of circulating Vδ1 T cells compared to control subjects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29765537/stat3-activated-cd36-facilitates-fatty-acid-uptake-in-chronic-lymphocytic-leukemia-cells
#19
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755109/regulated-intratumoral-expression-of-il-12-using-a-rheoswitch-therapeutic-system-%C3%A2-rts-%C3%A2-gene-switch-as-gene-therapy-for-the-treatment-of-glioma
#20
John A Barrett, Hongliang Cai, John Miao, Pranay D Khare, Paul Gonzalez, Jessica Dalsing-Hernandez, Geeta Sharma, Tim Chan, Laurence J N Cooper, Francois Lebel
The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System® (RTS® ) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex...
May 14, 2018: Cancer Gene Therapy
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