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https://www.readbyqxmd.com/read/28314753/transethnic-meta-analysis-identifies-gsdma-and-prdm1-as-susceptibility-genes-to-systemic-sclerosis
#1
Chikashi Terao, Takahisa Kawaguchi, Philippe Dieude, John Varga, Masataka Kuwana, Marie Hudson, Yasushi Kawaguchi, Marco Matucci-Cerinic, Koichiro Ohmura, Gabriela Riemekasten, Aya Kawasaki, Paolo Airo, Tetsuya Horita, Akira Oka, Eric Hachulla, Hajime Yoshifuji, Paola Caramaschi, Nicolas Hunzelmann, Murray Baron, Tatsuya Atsumi, Paul Hassoun, Takeshi Torii, Meiko Takahashi, Yasuharu Tabara, Masakazu Shimizu, Akiko Tochimoto, Naho Ayuzawa, Hidetoshi Yanagida, Hiroshi Furukawa, Shigeto Tohma, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Toshiyuki Yamamoto, Daisuke Goto, Yoshihide Asano, Masatoshi Jinnin, Hirahito Endo, Hiroki Takahashi, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn, Soumya Raychaudhuri, Katherine Liao, Peter Gregersen, Naoyuki Tsuchiya, Valeria Riccieri, Inga Melchers, Gabriele Valentini, Anne Cauvet, Maria Martinez, Tsuneyo Mimori, Fumihiko Matsuda, Yannick Allanore
OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28296250/different-genetic-alteration-of-a20-in-a-s%C3%A3-zary-syndrome-case-with-v%C3%AE-2-j%C3%AE-22-t-cell-clone
#2
Lingling Zhou, Haitao Zheng, Xin Huang, Lihua Zhu, Suijing Wu, Chengwu Zeng, Lijian Yang, Shaohua Chen, Gengxin Luo, Xin Du, Yangqiu Li
BACKGROUND: The comprehensive genetic alterations underlying the pathogenesis of Sézary syndrome (SS) remains largely unknown. Previous studies showed that alterations of tumor necrosis factor-α-induced protein 3 gene (TNFAIP3; A20) are frequent in SS. In this study, we characterized the mutation and polymorphisms of A20 in a case with SS and compared with the genetic feature of A20 in T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Using a novel approach based on the combination of fine-tiling array comparative genomic hybridization ( and ligation-mediated polymerase chain reaction (LM-PCR) to identify SS clone, the polymorphisms in the A20 gene (promoter, exons 2-9 [coding region] and 3'UTR) were detected by PCR and sequencing...
March 14, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28288707/malt-lymphoma-genetic-abnormalities-immunological-stimulation-and-molecular-mechanism
#3
REVIEW
Ming-Qing Du
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurs at diverse anatomic sites and is closely associated with several distinct chronic inflammatory disorders. Both the acquired genetic abnormalities and active chronic immunological responses play a critical role in the development of MALT lymphoma, interestingly by dysregulating similar molecular mechanisms. The three translocations seen in MALT lymphoma, namely t(14;18)(q32;q21)/IGH-MALT1, t(1;14)(p22;q32)/BCL10-IGH, and t(11;18)(q21;q21)/BIRC3 (API2)-MALT1 are capable of activating both canonical and non-canonical NF-κB pathways...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28283576/glucocorticoid-and-cytokine-crosstalk-feedback-feedforward-and-co-regulatory-interactions-determine-repression-or-resistance
#4
Robert Newton, Suharsh V Shah, Mohammed O Altonsy, Anthony N Gerber
Inflammatory signals induce complex feedback and feedforward systems that allow tight temporal control. Whereas glucocorticoids generally repress inflammatory gene expression, GR recruitment increases expression of negative feedback and feedforward regulators, including DUSP1, IRAK3, NFKBIA, TNFAIP3 or ZFP36. Moreover, GR cooperativity with factors, such as NF-κB, can enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, limit expression of the transcription factor IRF1, and the host defense gene, CXCL10, through a feedforward control mechanism...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28253718/tnfaip3-inhibits-migration-and-invasion-in-nasopharyngeal-carcinoma-by-suppressing-epithelial-mesenchymal-transition
#5
T Huang, L Yin, J Wu, J J Gu, K Ding, N Zhang, M Y Du, L X Qian, Z W Lu, X He
TNF alpha induced protein 3 (TNFAIP3), a member of zinc finger protein family, is a gene whose expression level is promptly induced by the tumor necrosis factor. In this study, the clinical significance of TNFAIP3 was analyzed based on available samples in The Cancer Genome Atlas database. TNFAIP3 downregulation was associated with distant metastasis and worse patient prognosis. TNFAIP3-overexpressing and TNFAIP3-knockdown NPC cell line models were established through plasmid-mediated overexpression and small interfering RNA (siRNA), respectively...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28231331/mesenchymal-stromal-cells-mscs-induce-ex-vivo-proliferation-and-erythroid-commitment-of-cord-blood-haematopoietic-stem-cells-cb-cd34-cells
#6
Simone Perucca, Andrea Di Palma, Pier Paolo Piccaluga, Claudia Gemelli, Elisa Zoratti, Giulio Bassi, Edoardo Giacopuzzi, Andrea Lojacono, Giuseppe Borsani, Enrico Tagliafico, Maria Teresa Scupoli, Simona Bernardi, Camilla Zanaglio, Federica Cattina, Valeria Cancelli, Michele Malagola, Mauro Krampera, Mirella Marini, Camillo Almici, Sergio Ferrari, Domenico Russo
A human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles. After 10 days of co-culture, non-adherent (SN-fraction) and adherent (AD-fraction) CD34+ stem cells were collected and analysed separately. In the presence of MSCs, a significant increase in CD34+ cell number was observed (fold increase = 14...
2017: PloS One
https://www.readbyqxmd.com/read/28199970/three-single-nucleotide-polymorphisms-of-tnfaip3-gene-increase-the-risk-of-rheumatoid-arthritis
#7
Nan Shen, Yuan Ruan, Yajun Lu, Xuefeng Jiang, Huiqing Sun, Gongming Gao, Luming Nong, Kewei Ren
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Stata 11...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197630/tnfaip3-overexpression-is-an-independent-factor-for-poor-survival-in-esophageal-squamous-cell-carcinoma
#8
Yuni Elsa Hadisaputri, Tatsuya Miyazaki, Takehiko Yokobori, Makoto Sohda, Makoto Sakai, Daigo Ozawa, Keigo Hara, Hiroaki Honjo, Yuji Kumakura, Hiroyuki Kuwano
Tumor necrosis factor α induced protein 3 (TNFAIP3) is a protein that is induced by TNF-mediated NF-κB activation and has a dual function in regulating NF-κB. TNFAIP3 is associated with inflammatory carcinogenesis in many cancer types. However, the clinical significance of TNFAIP3 expression and function in esophageal squamous cell carcinoma (ESCC) has not yet been reported. We examined 149 ESCC tissue specimens to determine the clinical significance of TNFAIP3 by immunohistochemistry. Western blot analyses were used to detect TNFAIP3 expression in TE-1, TE-8, TE-15 and KYSE-70 ESCC cells and in Het-1A, a non-cancerous esophageal cell line...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28178345/pi3k%C3%AE-inhibitor-idelalisib-in-combination-with-btk-inhibitor-ono-gs-4059-in-diffuse-large-b-cell-lymphoma-with-acquired-resistance-to-pi3k%C3%AE-and-btk-inhibitors
#9
Anella Yahiaoui, Sarah A Meadows, Rick A Sorensen, Zhi-Hua Cui, Kathleen S Keegan, Robert Brockett, Guang Chen, Christophe Quéva, Li Li, Stacey L Tannheimer
Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma...
2017: PloS One
https://www.readbyqxmd.com/read/28158872/tnfaip3-downregulation-mediated-by-histone-modification-contributes-to-t-cell-dysfunction-in-systemic-lupus-erythematosus
#10
Hongjun Zhao, Lijing Wang, Hui Luo, Quan-Zhen Li, Xiaoxia Zuo
No abstract text is available yet for this article.
January 31, 2017: Rheumatology
https://www.readbyqxmd.com/read/28153771/b-cell-function-gene-mutations-in-diffuse-large-b-cell-lymphoma-a-retrospective-cohort-study
#11
Peng-Peng Xu, Hui-Juan Zhong, Yao-Hui Huang, Xiao-Dong Gao, Xia Zhao, Yang Shen, Shu Cheng, Jin-Yan Huang, Sai-Juan Chen, Li Wang, Wei-Li Zhao
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous subtype of non-Hodgkin lymphoma. In addition to clinical and immunophenotypic characteristics, recurrent gene mutations have recently been identified in patients with DLBCL using next-generation sequencing technologies. The aim of this study is to investigate the clinical relevance of B-cell function gene mutations in DLBCL. Clinical analysis was performed on 680 Chinese DLBCL patients (146 non-CR and 534 CR cases) treated with six cycles of 21-day R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), alone or followed by two additional doses of rituximab consolidation on patients' own intention...
January 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28152507/the-mutational-landscape-of-ocular-marginal-zone-lymphoma-identifies-frequent-alterations-in-tnfaip3-followed-by-mutations-in-tbl1xr1-and-crebbp
#12
Hyunchul Jung, Hae Yong Yoo, Seung Ho Lee, Sohyun Shin, Sang Cheol Kim, Sejoon Lee, Je-Gun Joung, Jae-Yong Nam, Daeun Ryu, Jae Won Yun, Jung Kyoon Choi, Ambarnil Ghosh, Kyeong Kyu Kim, Seok Jin Kim, Won Seog Kim, Woong-Yang Park, Young Hyeh Ko
Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-κB pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) were identified...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28116503/genetic-analysis-of-a-mouse-cross-implicates-an-anti-inflammatory-gene-in-control-of-atherosclerosis-susceptibility
#13
Norman E Garrett, Andrew T Grainger, Jing Li, Mei-Hua Chen, Weibin Shi
Nearly all genetic crosses generated from Apoe(-/-) or Lldlr(-/-) mice for genetic analysis of atherosclerosis have used C57BL/6 J (B6) mice as one parental strain, thus limiting their mapping power and coverage of allelic diversity. SM/J-Apoe (-/-) and BALB/cJ-Apoe (-/-) mice differ significantly in atherosclerosis susceptibility. 224 male F2 mice were generated from the two Apoe (-/-) strains to perform quantitative trait locus (QTL) analysis of atherosclerosis. F2 mice were fed 5 weeks of Western diet and analyzed for atherosclerotic lesions in the aortic root...
January 23, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#14
REVIEW
Thierry Lamy, Aline Moignet, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia has been recognized by the World Health Organization classifications amongst mature T-cell and natural killer (NK) cell neoplasms. There are 3 categories: chronic T-cell leukemia and NK-cell lymphocytosis, which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK-cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation, which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, phosphatidylinositol 3-kinase-Akt, Ras-Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid, and nuclear factor-κB...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28095483/association-between-nf-%C3%AE%C2%BAb-pathway-gene-variants-and-sicam1-levels-in-taiwanese
#15
Semon Wu, Ming-Sheng Teng, Leay-Kiaw Er, Wan-Yi Hsiao, Lung-An Hsu, Ching-Hua Yeh, Jeng-Feng Lin, Yi-Ying Lin, Cheng-Wen Su, Yu-Lin Ko
Intercellular adhesion molecule-1 (ICAM1) is crucial to the development and progression of atherosclerosis. Recent genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) in two of the nuclear factor-κB (NF-κB) pathway genes, NFKBIK and RELA, are associated with soluble ICAM1 (sICAM1) levels. However, neither of these two gene variants is found in the Asian populations. This study aimed to elucidate whether other candidate gene variants involved in the NF-κB pathway may be associated with sICAM1 levels in Taiwanese...
2017: PloS One
https://www.readbyqxmd.com/read/28088970/-tnfaip3-deletion-status-in-classical-hodgkin-lymphoma-and-its-relation-to-epstein-barr-virus
#16
Y F Shi, Z F Gao, C L Liu, M Li, D M Lin, L X Zhou, Y M Lai, X L Liu, X Huang
Objective: To investigate the TNFAIP3/A20 abnormalities and its association with Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (CHL). Methods: Formalin-fixed, paraffinembedded tissue blocks of 54 CHL patients were collected and subjected to the construction of tissue microarray (TMA) for further analyses. EBV status was evaluated by in situ hybridization (ISH) for EBER1/2 and immunohistochemistry (IHC) with anti-LMP-1 antibody. Fluorescence in situ hybridization (FISH) and IHC were performed to determine the copy number alterations of TNFAIP3 and A20 protein expression respectively...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28073005/simultaneous-inhibition-of-pi3k%C3%AE-and-pi3k%C3%AE-induces-abc-dlbcl-regression-by-blocking-bcr-dependent-and-independent-activation-of-nf-%C3%AE%C2%BAb-and-akt
#17
Juliane Paul, Maurice Soujon, Antje M Wengner, Sabine Zitzmann-Kolbe, Andrea Sturz, Katja Haike, Koh Hui Keng Magdalene, Sze Huey Tan, Martin Lange, Soo Yong Tan, Dominik Mumberg, Soon Thye Lim, Karl Ziegelbauer, Ningshu Liu
Compared with follicular lymphoma, high PI3Kα expression was more prevalent in diffuse large B cell lymphoma (DLBCL), although both tumor types expressed substantial PI3Kδ. Simultaneous inhibition of PI3Kα and PI3Kδ dramatically enhanced the anti-tumor profile in ABC-DLBCL models compared with selective inhibition of PI3Kδ, PI3Kα, or BTK. The anti-tumor activity was associated with suppression of p-AKT and a mechanism of blocking nuclear factor-κB activation driven by CD79(mut), CARD11(mut), TNFAIP3(mut), or MYD88(mut)...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28039105/long-acting-%C3%AE-2-agonists-promote-glucocorticoid-mediated-repression-of-nf-%C3%AE%C2%BAb-by-enhancing-expression-of-the-feedback-regulator-tnfaip3
#18
Mohammed Omar Altonsy, Mahmoud M Mostafa, Anthony N Gerber, Robert Newton
Glucocorticoids, or corticosteroids, are effective treatments for many chronic inflammatory diseases and, in mild/moderate asthma, long-acting β2-adrenoceptor agonists (LABAs) enhance the efficacy of inhaled corticosteroids (ICSs) more than increasing the ICS dose. In human bronchial epithelial, BEAS-2B, cells, expression of TNFα-induced protein 3 (TNFAIP3), or A20, a dual-ubiquitin ligase that provides feedback inhibition of NF-κB, was induced by budesonide, an ICS, formoterol, a LABA, and was further enhanced by budesonide/formoterol combination...
December 29, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28013313/increased-intestinal-inflammation-and-digestive-dysfunction-in-preterm-pigs-with-severe-necrotizing-enterocolitis
#19
Ann Cathrine F Støy, Peter M H Heegaard, Kerstin Skovgaard, Stine B Bering, Mette Bjerre, Per T Sangild
BACKGROUND: The risk factors for necrotizing enterocolitis (NEC) are well known, but the factors involved in the different NEC presentations remain unclear. OBJECTIVES: We hypothesized that digestive dysfunction and intestinal inflammation are mainly affected by severe NEC lesions. METHODS: In 48 preterm pigs, the association between the macroscopic NEC score (range 1-6) and the expression of 48 genes related to inflammation, morphological, and digestive parameters in the distal small intestine was investigated...
December 24, 2016: Neonatology
https://www.readbyqxmd.com/read/27991929/mir-19a-promotes-colitis-associated-colorectal-cancer-by-regulating-tumor-necrosis-factor-alpha-induced-protein-3-nf-%C3%AE%C2%BAb-feedback-loops
#20
T Wang, X Xu, Q Xu, J Ren, S Shen, C Fan, Y Hou
Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3)...
December 19, 2016: Oncogene
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