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https://www.readbyqxmd.com/read/29663334/the-rheumatic-disease-associated-fam167a-blk-locus-encodes-diora-1-a-novel-disordered-protein-highly-expressed-in-bronchial-epithelium-and-alveolar-macrophages
#1
Lara Mentlein, Gudny Ella Thorlacius, Lauro Meneghel, Lara A Aqrawi, Jorge I Ramírez Sepúlveda, Johan Grunewald, Alexander Espinosa, Marie Wahren-Herlenius
OBJECTIVES: Triggering of autoimmunity that leads to rheumatic disease has been suggested to depend on gene-environment interactions occurring in epithelial barriers and associated immune cells. Genetic studies have identified associations of the FAM167A-BLK locus with rheumatoid arthritis, SLE, and Sjögren's syndrome. While BLK (B lymphocyte kinase) has a well-established role in B cells, family with sequence similarity 167 member A (FAM167A) and its gene family remain uncharacterized...
April 17, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29567799/pan-src-kinase-inhibition-blocks-b-cell-receptor-oncogenic-signaling-in-non-hodgkin-lymphoma
#2
Elena Battistello, Natalya Katanayeva, Elie Dheilly, Daniele Tavernari, Maria C Donaldson, Luca Bonsignore, Margot Thome-Miazza, Amanda L Christie, Mark A Murakami, Olivier Michielin, Giovanni Ciriello, Vincent Zoete, Elisa Oricchio
In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of DLBCL patients. Here, we used lymphoma cells isolated from DLBCL patients to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC up-regulation...
March 22, 2018: Blood
https://www.readbyqxmd.com/read/29382514/-epigenetic-alterations-in-acute-lymphoblastic-leukemia
#3
REVIEW
María Del Pilar Navarrete-Meneses, Patricia Pérez-Vera
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL...
July 2017: Boletín Médico del Hospital Infantil de México
https://www.readbyqxmd.com/read/29377892/network-based-co-expression-analysis-for-exploring-the-potential-diagnostic-biomarkers-of-metastatic-melanoma
#4
Li-Xin Wang, Yang Li, Guan-Zhi Chen
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach...
2018: PloS One
https://www.readbyqxmd.com/read/29367740/combined-chemical-genetics-and-data-driven-bioinformatics-approach-identifies-receptor-tyrosine-kinase-inhibitors-as-host-directed-antimicrobials
#5
Cornelis J Korbee, Matthias T Heemskerk, Dragi Kocev, Elisabeth van Strijen, Omid Rabiee, Kees L M C Franken, Louis Wilson, Nigel D L Savage, Sašo Džeroski, Mariëlle C Haks, Tom H M Ottenhoff
Antibiotic resistance poses rapidly increasing global problems in combatting multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting for novel approaches including host-directed therapies (HDT). Intracellular pathogens like Salmonellae and Mycobacterium tuberculosis (Mtb) exploit host pathways to survive. Only very few HDT compounds targeting host pathways are currently known. In a library of pharmacologically active compounds (LOPAC)-based drug-repurposing screen, we identify multiple compounds, which target receptor tyrosine kinases (RTKs) and inhibit intracellular Mtb and Salmonellae more potently than currently known HDT compounds...
January 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64-cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#6
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64 Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29193869/cd4-and-b-lymphocyte-expression-quantitative-traits-at-rheumatoid-arthritis-risk-loci-in-patients-with-untreated-early-arthritis-implications-for-causal-gene-identification
#7
Nishanthi Thalayasingam, Nisha Nair, Andrew J Skelton, Jonathan Massey, Amy E Anderson, Alexander D Clark, Julie Diboll, Dennis W Lendrem, Louise N Reynard, Heather J Cordell, Stephen Eyre, John D Isaacs, Anne Barton, Arthur G Pratt
OBJECTIVE: Rheumatoid arthritis (RA) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus (eQTL) analysis of confirmed genetic risk loci in CD4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation. METHODS: RNA and DNA were isolated from purified B and/or CD4+ T cells obtained from the peripheral blood of 344 patients with early arthritis...
March 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29175418/src-family-kinase-tyrosine-phosphorylates-toll-like-receptor-4-to-dissociate-myd88-and-mal-tirap-suppressing-lps-induced-inflammatory-responses
#8
Jonathon Mitchell, Su Jin Kim, Alexandra Seelmann, Brendan Veit, Brooke Shepard, Eunok Im, Sang Hoon Rhee
Src family kinases (SFKs) are a family of protein tyrosine kinases containing nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK activation is a major immediate signaling event in LPS/Toll-like receptor 4 (TLR4) signaling, its precise role has remained elusive due to various contradictory results obtained from a certain SFK member-deficient mice or cells. The observed inconsistencies may be due to the compensation or redundancy by other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to induce temporal and precise SFK activation in living cells, thereby limiting the chance of cellular adaption to a SFK-deficient condition...
January 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29098351/the-roles-of-genetic-factors-in-kawasaki-disease-a-systematic-review-and-meta-analysis-of-genetic-association-studies
#9
REVIEW
Xiaochuan Xie, Xiaohan Shi, Meilin Liu
This systematic review and meta-analysis aimed to better elucidate the roles of genetic factors in Kawasaki disease (KD), and determine the potential genetic biomarkers of KD. The systematic literature search of PubMed, Medline, Embase, Web of Science and CNKI identified 164 eligible studies. The qualitative synthesis revealed that 62 genes may be correlated with the susceptibility to KD, and 47 genes may be associated with the incidence of coronary artery lesions (CALs) in KD. A total of 53 polymorphisms in 34 genes were investigated in further quantitative synthesis...
February 2018: Pediatric Cardiology
https://www.readbyqxmd.com/read/29070082/sex-influences-eqtl-effects-of-sle-and-sj%C3%A3-gren-s-syndrome-associated-genetic-polymorphisms
#10
Magdalena Lindén, Jorge I Ramírez Sepúlveda, Tojo James, Gudny Ella Thorlacius, Susanna Brauner, David Gómez-Cabrero, Tomas Olsson, Ingrid Kockum, Marie Wahren-Herlenius
BACKGROUND: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects...
October 25, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28960790/color-of-bulk-fill-composite-resin-restorative-materials
#11
Çağatay Barutcigil, Kubilay Barutcigil, Mehmet Mustafa Özarslan, Ayşe Dündar, Burak Yilmaz
OBJECTIVE: To evaluate the color stability of novel bulk-fill composite resins. MATERIALS AND METHODS: Color measurements of a nanohybrid composite resin (Z550) and 3 bulk-fill composite resins (BLK, AFX, XTF; n = 45) were performed before polymerization. After polymerization, color measurements were repeated and specimens were immersed in distilled water or red wine, or coffee. Color change [CIEDE2000 (ΔE00 )] was calculated after 24 h, 1 and 3 weeks. Data were analyzed with Kruskal-Wallis, Mann-Whitney U and Wilcoxon tests (α = 0...
September 28, 2017: Journal of Esthetic and Restorative Dentistry
https://www.readbyqxmd.com/read/28925718/interaction-analysis-between-blk-rs13277113-polymorphism-and-bank1-rs3733197-polymorphism-mmel1-tnfrsf14-rs3890745-polymorphism-in-determining-susceptibility-to-rheumatoid-arthritis
#12
Hua Huang, Si-Chao Huang, Dong-Jin Hua, Qing-Qing Sun, Han Cen, Xia-Fei Xin
Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population...
September 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28885337/b-cell-lymphocyte-kinase-polymorphisms-rs13277113-rs2736340-and-rs4840568-and-risk-of-autoimmune-diseases-a-meta-analysis
#13
Chang Zeng, Cheng Fang, Hong Weng, Xiaoqing Xu, Tianyang Wu, Wenhua Li
BACKGROUND: B-cell lymphocyte kinase (BLK) is an inhibitor of B cells that has an important influence on several autoimmune diseases, but there is a lack of comprehensive analysis of its association with autoimmune diseases. Hence, it is meaningful to conduct a comprehensive analysis. METHODS: A systematic literature search was performed on the PubMed, ScienceDirect, and Web of Science databases up to June 30, 2016. The data were extracted and quality-assessed before conducting the meta-analysis...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28876896/differential-kinobeads-profiling-for-target-identification-of-irreversible-kinase-inhibitors
#14
Lars Dittus, Thilo Werner, Marcel Muelbaier, Marcus Bantscheff
Chemoproteomics profiling of kinase inhibitors with kinobeads enables the assessment of inhibitor potency and selectivity for endogenously expressed protein kinases in cell lines and tissues. Using a small panel of targeted covalent inhibitors, we demonstrate the importance of measuring covalent target binding in live cells. We present a differential kinobeads profiling strategy for covalent kinase inhibitors where a compound is added either to live cells or to a cell extract that enables the comprehensive assessment of inhibitor selectivity for covalent and noncovalent targets...
October 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28855716/a-genome-wide-association-analysis-identifies-nmnat2-and-hcp5-as-susceptibility-loci-for-kawasaki-disease
#15
Jae-Jung Kim, Sin Weon Yun, Jeong Jin Yu, Kyung Lim Yoon, Kyung-Yil Lee, Hong-Ryang Kil, Gi Beom Kim, Myung-Ki Han, Min Seob Song, Hyoung Doo Lee, Kee Soo Ha, Sejung Sohn, Todd A Johnson, Atsushi Takahashi, Michiaki Kubo, Tatsuhiko Tsunoda, Kaoru Ito, Yoshihiro Onouchi, Young Mi Hong, Gi Young Jang, Jong-Keuk Lee
Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1...
December 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28780099/effect-of-recombinant-bovine-somatotropin-on-leukocyte-mrna-expression-for-genes-related-to-cell-energy-metabolism-cytokine-production-phagocytosis-oxidative-burst-and-adaptive-immunity
#16
P R B Silva, C D Nelson, J P Driver, W W Thatcher, R C Chebel
Objectives of the current experiment were to evaluate the effects of treatment of periparturient dairy cows with recombinant bovine somatotropin (rbST) on mRNA expression in peripheral leukocytes for genes related to the somatotropic axis, cell energy metabolism, and innate and adaptive immune responses. Cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to an untreated control group (n = 98) or to receive 125 mg of rbST weekly from -21 to 21 d relative to calving (rbST125; n = 98)...
August 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28713926/association-between-tnfsf4-and-blk-gene-polymorphisms-and-susceptibility-to-allergic-rhinitis
#17
Yang Shen, Yun Liu, Xiao-Qiang Wang, Xia Ke, Hou-Yong Kang, Su-Ling Hong
Allergic rhinitis (AR) is a common inflammatory disease of the upper airway. Recent evidence suggests that gene‑gene interactions between tumor necrosis factor receptor superfamily 4 (TNFSF4) and B cell lymphocyte kinase (BLK) may have a synergistic effect on T and B cells in determining immunologic aberration, via the nuclear factor‑κB pathway. The present study was performed to evaluate the potential association between specific single nucleotide polymorphisms (SNPs) in the TNFSF4 and BKL genes with susceptibility to AR in Chinese subjects...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28670978/a-novel-blk-induced-tumor-model
#18
David Leander Petersen, Jens Berthelsen, Andreas Willerslev-Olsen, Simon Fredholm, Sally Dabelsteen, Charlotte Menné Bonefeld, Carsten Geisler, Anders Woetmann
B-lymphoid tyrosine kinase (BLK) is a non-receptor tyrosine kinase belonging to the SRC family kinases. BLK is known to be functionally involved in B-cell receptor signaling and B-cell development. New evidence suggests that B-lymphoid tyrosine kinase is ectopically expressed and is a putative oncogene in cutaneous T-cell lymphoma and other T-cell malignancies. However, little is known about the role of BLK in lymphomagenesis, and the oncogenic function seems to depend on the cellular context. Importantly, BLK is also ectopically expressed in other hematological and multiple non-hematological malignancies including breast, kidney, and lung cancers, suggesting that BLK could be a new potential target for therapy...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638728/gene-expression-analysis-in-cutaneous-t-cell-lymphomas-ctcl-highlights-disease-heterogeneity-and-potential-diagnostic-and-prognostic-indicators
#19
Ivan V Litvinov, Michael T Tetzlaff, Philippe Thibault, Pamela Gangar, Linda Moreau, Andrew K Watters, Elena Netchiporouk, Kevin Pehr, Victor G Prieto, Elham Rahme, Nathalie Provost, Martin Gilbert, Denis Sasseville, Madeleine Duvic
Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28552732/integrating-genome-wide-association-study-and-expression-quantitative-trait-loci-data-identifies-multiple-genes-and-gene-set-associated-with-neuroticism
#20
Qianrui Fan, Wenyu Wang, Jingcan Hao, Awen He, Yan Wen, Xiong Guo, Cuiyan Wu, Yujie Ning, Xi Wang, Sen Wang, Feng Zhang
Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software...
May 25, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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