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https://www.readbyqxmd.com/read/28306714/reconstruction-and-signal-propagation-analysis-of-the-syk-signaling-network-in-breast-cancer-cells
#1
Aurélien Naldi, Romain M Larive, Urszula Czerwinska, Serge Urbach, Philippe Montcourrier, Christian Roy, Jérôme Solassol, Gilles Freiss, Peter J Coopman, Ovidiu Radulescu
The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk) protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells...
March 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#2
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28298521/the-interaction-of-pneumocystis-with-the-c-type-lectin-receptor-mincle-exerts-a-significant-role-in-host-defense-against-infection
#3
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Vijayalakshmi Nandakumar, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Bernd Lepenies, Andrew H Limper
Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28294121/a-bacterial-aromatic-aldehyde-dehydrogenase-critical-for-the-efficient-catabolism-of-syringaldehyde
#4
Naofumi Kamimura, Takayuki Goto, Kenji Takahashi, Daisuke Kasai, Yuichiro Otsuka, Masaya Nakamura, Yoshihiro Katayama, Masao Fukuda, Eiji Masai
Vanillin and syringaldehyde obtained from lignin are essential intermediates for the production of basic chemicals using microbial cell factories. However, in contrast to vanillin, the microbial conversion of syringaldehyde is poorly understood. Here, we identified an aromatic aldehyde dehydrogenase (ALDH) gene responsible for syringaldehyde catabolism from 20 putative ALDH genes of Sphingobium sp. strain SYK-6. All these genes were expressed in Escherichia coli, and nine gene products, including previously characterized BzaA, BzaB, and vanillin dehydrogenase (LigV), exhibited oxidation activities for syringaldehyde to produce syringate...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293439/proteomic-analysis-of-hdac3-selective-inhibitor-in-the-regulation-of-inflammatory-response-of-primary-microglia
#5
Mingxu Xia, Qiuchen Zhao, He Zhang, Yanting Chen, Zengqiang Yuan, Yun Xu, Meijuan Zhang
HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28291124/myc-protein-positive-diffuse-large-b-cell-lymphoma-features-an-activated-b-cell-receptor-signal-pathway
#6
Wei-Ge Wang, Xiang-Nan Jiang, Ze-Bing Liu, Xiao-Yan Zhou, Xiao-Qiu Li
Components of the B-cell receptor (BCR) signaling pathway represent promising therapeutic targets in diffuse large B-cell lymphoma (DLBCL) and other B-cell malignancies. MYC, a transcriptional factor and oncoprotein, is overexpressed in a fraction of DLBCL and indicates poor prognosis and aggressive clinical course when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, BCR signaling status in MYC-positive DLBCL cases and the potential efficacy of BCR signal inhibitors in treating this aggressive disease are unknown...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28283589/tula-2-protein-phosphatase-suppresses-activation-of-syk-through-the-gpvi-platelet-receptor-for-collagen-by-dephosphorylating-tyr-p-346-a-regulatory-site-of-syk
#7
Kevin Reppschläger, Jeanne Gosselin, Carol A Dangelmaier, Dafydd H Thomas, Nick Carpino, Steven E McKenzie, Satya P Kunapuli, Alexander Y Tsygankov
No abstract text is available yet for this article.
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28275138/distinct-expression-and-function-of-fc%C3%AE%C2%B5rii-in-human-b-cells-and-monocytes
#8
Wenming Peng, William Grobe, Gisela Walgenbach-Brünagel, Sabine Flicker, Chunfeng Yu, Marc Sylvester, Jean-Pierre Allam, Johannes Oldenburg, Natalio Garbi, Rudolf Valenta, Natalija Novak
FcεRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FcεRII-mediated functions are being increasingly recognized, the consequences of FcεRII activation are not completely understood. In this study, we evaluated the expression of FcεRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FcεRIIb isoform on B cells and monocytes, the expression of the FcεRIIa isoform was not dependent on IL-4...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28268139/discovery-of-new-syk-inhibitors-through-structure-based-virtual-screening
#9
Yahui Huang, Youjun Zhang, Kexin Fan, Guoqiang Dong, Bohua Li, Wannian Zhang, Jian Li, Chunquan Sheng
Spleen tyrosine kinase (Syk) is an attractive target for the discovery of new treatments for inflammatory and autoimmune disorders. Structure-based virtual screening was performed for identifying novel scaffolds of Syk inhibitors. A total of 16 hits were discovered in the enzyme assay and 8 compounds had an IC50 value lower than 10μM. In particular, compound 11 (IC50=3.2μM) was active in the cellular Syk assay and could inhibit lymphocytes proliferation in a dose-dependent manner, which could be used as a good starting point for the discovery of new class of Syk inhibitors...
February 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28260035/screening-of-potential-gene-markers-for-predicting-carotid-atheroma-plaque-formation-using-bioinformatics-approaches
#10
Guiming Wang, Dong Kuai, Yudong Yang, Gaochao Yang, Zhigang Wei, Wenbo Zhao
The present study aimed to investigate potential gene markers for predicting the formation of carotid atheroma plaques using high‑throughput bioinformatics methods. The GSE43292 gene expression profile was downloaded from the Gene Expression Omnibus database. Following data processing, differentially expressed genes (DEGs) were screened using a paired t‑test in the Linear Models for Microarray Data package with the criteria of a false discovery rate of P<0.05 and |log2 fold‑change| ≥0.58, followed by functional enrichment, protein‑protein interaction (PPI) network construction, key node and module analysis, and prediction of transcription factors (TFs) targeting genes in the significant modules...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259713/jte-852-a-novel-spleen-tyrosine-kinase-inhibitor-blocks-mediator-secretion-from-mast-cells-with-immunoglobulin-e-crosslinking
#11
Toshinobu Kato, Hidenori Iwasaki, Hatsue Kobayashi, Naoki Miyagawa, Akira Matsuo, Takahiro Hata, Mutsuyoshi Matsushita
Mast cells stimulated by immunoglobulin E (IgE)-crosslinking secrete mediators, which are mainly categorized into three groups: granule contents, arachidonate metabolites, and cytokines. These mediators play important roles in pathogenesis of allergic diseases; indeed, some conventional drugs which target the mediators are used in clinical practices. However, these drugs are not yet sufficient enough in their efficacy. That is because most of them are blockers of single mediators and are unable to prevent simultaneously various reactions caused by the three group mediators...
March 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28259446/syk-expression-and-ige-mediated-histamine-release-in-basophils-as-biomarkers-for-predicting-the-clinical-efficacy-of-omalizumab
#12
Donald W MacGlashan, Sarbjit S Saini
No abstract text is available yet for this article.
March 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28255536/central-role-of-pi3k-syk-interaction-in-fibrinogen-induced-lamellipodia-and-filopodia-formation-in-platelets
#13
Raghvendra Singh
The WAVE complex-1, a complex of WAVE, Abi1, NAP1, PIR121, HSPC300, RacGTP and Arp2/3 proteins, and WASP complex-1, a complex of WASP, Cdc42, PIP2, and Arp2/3 proteins, are involved in lamellipodia and filopodia formation, respectively. It is known that the two complexes have opposite dynamics. Furthermore, Rac has two guanine nucleotide exchange factors, Vav and Sos, whose role in activating Rac is not well understood. In this work, by the construction of signaling network, analysis, and mathematical modeling, I show that Sos generates a pulse of WAVE complex-1, decreasing the response time of WAVE complex-1 formation upon the stimulation of platelets by fibrinogen...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28245410/-research-progress-of-novel-small-molecule-drugs-in-the-treatment-of-chronic-lymphocytic-leukemia-review
#14
Jing-Qiao Qiao, Miao He, Shu-Ting Zhang, Hai Bai
Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western population, is characterized by accumulation of mature-looking CD5(+)/19(+)/23(+) B cells in peripheral blood, bone marrow, and lymphatic organs. Over the last 20 years, there has been a dramatic change in therapy for CLL, the complete response rate increased from the initial <5% to the current 40%-50%, this remarkable improvement has been attributable to combination of chemoimmunotherapy agents that have contributed to the backbone of therapy for patients with CLL...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28225025/specific-pathways-mediating-inflammasome-activation-by-candida-parapsilosis
#15
Adél Tóth, Erik Zajta, Katalin Csonka, Csaba Vágvölgyi, Mihai G Netea, Attila Gácser
Candida albicans and C. parapsilosis are human pathogens causing severe infections. The NLRP3 inflammasome plays a crucial role in host defence against C. albicans, but it has been previously unknown whether C. parapsilosis activates this complex. Here we show that C. parapsilosis induces caspase-1 activation and interleukin-1β (IL-1β) secretion in THP-1, as well as primary, human macrophages. IL-1β secretion was dependent on NLRP3, K(+)-efflux, TLR4, IRAK, Syk, caspase-1, caspase-8 and NADPH-oxidase. Importantly, while C...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217127/cell-intrinsic-galectin-3-attenuates-neutrophil-ros-dependent-killing-of-candida-by-modulating-cr3-downstream-syk-activation
#16
Sheng-Yang Wu, Juin-Hua Huang, Wen-Yu Chen, Yi-Chen Chan, Chun-Hung Lin, Yee-Chun Chen, Fu-Tong Liu, Betty A Wu-Hsieh
Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control of candidiasis. While recombinant galectin-3 enhances neutrophil phagocytosis of Candida, we found that intracellular galectin-3 downregulates neutrophil fungicidal functions. Co-immunoprecipitation and immunofluorescence staining reveal that cytosolic gal3 physically interacts with Syk in neutrophils after Candida stimulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209719/adaptive-nk-cells-can-persist-in-patients-with-gata2-mutation-depleted-of-stem-and-progenitor-cells
#17
Heinrich Schlums, Moonjung Jung, Hongya Han, Jakob Theorell, Venetia Bigley, Samuel C C Chiang, David S J Allan, Jan K Davidson-Moncada, Rachel E Dickinson, Tim D Holmes, Amy P Hsu, Danielle Townsley, Thomas Winkler, Weixin Wang, Pål Aukrust, Ingvild Nordøy, Katherine R Calvo, Steve M Holland, Matthew Collin, Cynthia E Dunbar, Yenan T Bryceson
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and NK cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor PLZF, as well as expression of intracellular signaling proteins FcϵRγ, SYK, and EAT-2 in a variegated manner...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28202529/aberrant-syk-kinase-signaling-is-essential-for-tumorigenesis-induced-by-tsc2-inactivation
#18
Ye Cui, Wendy K Steagall, Anthony M Lamattina, Gustavo Pacheco-Rodriguez, Mario Stylianou, Pranav Kidambi, Benjamin Stump, Fernanda Golzarri, Ivan O Rosas, Carmen Priolo, Elizabeth P Henske, Joel Moss, Souheil El-Chemaly
Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis, a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogenic growth factor VEGF-D are elevated significantly in lymphangioleiomyomatosis. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in lymphangioleiomyomatosis. Here, we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from lymphangioleiomyomatosis patients contributes to tumor growth...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28190762/optimal-fractionation-of-preoperative-radiotherapy-and-timing-to-surgery-for-rectal-cancer-stockholm-iii-a-multicentre-randomised-non-blinded-phase-3-non-inferiority-trial
#19
Johan Erlandsson, Torbjörn Holm, David Pettersson, Åke Berglund, Björn Cedermark, Calin Radu, Hemming Johansson, Mikael Machado, Fredrik Hjern, Olof Hallböök, Ingvar Syk, Bengt Glimelius, Anna Martling
BACKGROUND: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. METHODS: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible...
February 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28179537/early-tyrosine-phosphorylation-events-following-adenosine-a2a-receptor-in-human-neutrophils-identification-of-regulated-pathways
#20
Miriam S Giambelluca, Marc Pouliot
Activation of the adenosine 2A receptor (A2AR) elevates intracellular levels of cAMP and acts as a physiologic inhibitor of inflammatory neutrophil functions. In this study, we looked into the impact of A2AR engagement on early phosphorylation events. Neutrophils were stimulated with well-characterized proinflammatory agonists in the absence or presence of an A2AR agonist {3-[4-[2-[ [6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino] ethyl] phenyl] propanoic acid (CGS 21680)}, PGE2, or a mixture of the compounds RO 20-1724 and forskolin...
February 8, 2017: Journal of Leukocyte Biology
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