keyword
MENU ▼
Read by QxMD icon Read
search

Spleen tyrosine kinase

keyword
https://www.readbyqxmd.com/read/28202166/m1-macrophage-triggered-by-mincle-leads-to-a-deterioration-of-acute-kidney-injury
#1
Tsuyoshi Inoue
In the early stage of acute kidney injury, M1 macrophages are proinflammatory and destructive. In this study, Lv et al. reveal that Mincle (macrophage-inducible C-type lectin, Clec4e) is expressed on M1 macrophages in acute kidney injury, and the kidney is protected in a murine model of cisplatin-induced renal injury by inhibiting Mincle expression on macrophages. Mincle expression is regulated by Toll-like receptor 4/nuclear factor κB signaling, and Mincle maintains the inflammatory phenotype through spleen tyrosine kinase signaling, leading to acute kidney injury...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28178664/identification-of-distinct-molecular-subtypes-of-uterine-carcinosarcoma
#2
Yang An, Haojie Wang, Jingyao Jie, Yitai Tang, Weijuan Zhang, Shaoping Ji, Xiangqian Guo
Uterine carcinosarcoma (UCS) is a rare but lethal neoplasm with high metastasis and recurrence rate, and to date, no molecular classification of UCS has been defined to achieve targeted therapies. In this study, we identified two distinct molecular subtypes of UCS with distinct gene expression patterns and clinicopathologic characteristics. Subtype I UCS recapitulates low-grade UCS, in contrast subtype II UCS represents high-grade UCS with higher tumor invasion rate and tumor weight. Interestingly, subtype I UCS is characterized by cell adhesion and apoptosis pathways, whereas genes over-expressed in subtype II UCS are more involved in myogenesis/muscle development...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173838/osteoarthritis-associated-basic-calcium-phosphate-crystals-activate-membrane-proximal-kinases-in-human-innate-immune-cells
#3
Emma M Corr, Clare C Cunningham, Laura Helbert, Geraldine M McCarthy, Aisling Dunne
BACKGROUND: Osteoarthritis (OA) is a chronic debilitating joint disorder of particularly high prevalence in the elderly population. Intra-articular basic calcium phosphate (BCP) crystals are present in the majority of OA joints and are associated with severe degeneration. They are known to activate macrophages, synovial fibroblasts, and articular chondrocytes, resulting in increased cell proliferation and the production of pro-inflammatory cytokines and matrix metalloproteases (MMPs)...
February 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28167651/contact-collaboration-and-conflict-signal-integration-of-syk-coupled-c-type-lectin-receptors
#4
REVIEW
Jenny Ostrop, Roland Lang
Several spleen tyrosine kinase-coupled C-type lectin receptors (CLRs) have emerged as important pattern recognition receptors for infectious danger. Because encounter with microbial pathogens leads to the simultaneous ligation of several CLRs and TLRs, the signals emanating from different pattern recognition receptors have to be integrated to achieve appropriate biological responses. In this review, we briefly summarize current knowledge about ligand recognition and core signaling by Syk-coupled CLRs. We then address mechanisms of synergistic and antagonistic crosstalk between different CLRs and with TLRs...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28160756/receptor-tyrosine-kinase-like-orphan-receptor-1-ror-1-an-emerging-target-for-diagnosis-and-therapy-of-chronic-lymphocytic-leukemia
#5
REVIEW
Leili Aghebati-Maleki, Mahdi Shabani, Behzad Baradaran, Morteza Motallebnezhad, Jafar Majidi, Mehdi Yousefi
Chronic lymphocytic leukemia (CLL) is characterized by reposition of malignant B cells in the blood, bone marrow, spleen and lymph nodes. It remains the most common leukemia in the Western world. Within the recent years, major breakthroughs have been made to prolong the survival and improve the health of patients. Despite these advances, CLL is still recognized as a disease without definitive cure. New treatment approaches, based on unique targets and novel drugs, are highly desired for CLL therapy. The Identification and subsequent targeting of molecules that are overexpressed uniquely in malignant cells not normal ones play critical roles in the success of anticancer therapeutic strategies...
February 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28135325/early-bcr-abl1-transcript-decline-after-1-month-of-tyrosine-kinase-inhibitor-therapy-as-an-indicator-for-treatment-response-in-chronic-myeloid-leukemia
#6
Mohamed El Missiry, Henrik Hjorth-Hansen, Johan Richter, Ulla Olson-Strömberg, Leif Stenke, Kimmo Porkka, Anna Kreutzman, Satu Mustjoki
In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response...
2017: PloS One
https://www.readbyqxmd.com/read/28131718/spleen-tyrosine-kinase-mediates-the-actions-of-epo-and-gm-csf-and-coordinates-with-tgf-%C3%AE-in-erythropoiesis
#7
Hua-Ching Chang, Duen-Yi Huang, Mai-Szu Wu, Ching-Liang Chu, Shiang-Jong Tzeng, Wan-Wan Lin
Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis...
January 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28114285/hsp90-stabilizes-b-cell-receptor-kinases-in-a-multi-client-interactome-pu-h71-induces-cll-apoptosis-in-a-cytoprotective-microenvironment
#8
A Guo, P Lu, J Lee, C Zhen, G Chiosis, Y L Wang
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells in the hematopoietic system and lymphoid tissues. Although inhibitors targeting the B-cell receptor (BCR) pathway have been successful in the treatment of the disease, the underlying mechanisms leading to BCR over-activity in CLL are not fully understood. In this study, we found that HSP90, a highly conserved molecular chaperone, is overexpressed in CLL compared with resting B cells. HSP90 overexpression is accompanied by the overexpression of several BCR kinases including LYN, spleen tyrosine kinase, Bruton tyrosine kinase and AKT...
January 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28100269/a-spleen-tyrosine-kinase-inhibitor-attenuates-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#9
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Eunhyun Choi, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay...
January 18, 2017: Biological Research
https://www.readbyqxmd.com/read/28097631/force-dependent-calcium-signaling-and-its-pathway-of-human-neutrophils-on-p-selectin-in-flow
#10
Bing Huang, Yingchen Ling, Jiangguo Lin, Xin Du, Ying Fang, Jianhua Wu
P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy...
February 2017: Protein & Cell
https://www.readbyqxmd.com/read/28064214/hsp90-promotes-burkitt-lymphoma-cell-survival-by-maintaining-tonic-b-cell-receptor-signaling
#11
Roland Walter, Kuan-Ting Pan, Carmen Doebele, Federico Comoglio, Katarzyna Tomska, Hanibal Bohnenberger, Ryan M Young, Laura Jacobs, Ulrich Keller, Halvard Bönig, Michael Engelke, Andreas Rosenwald, Henning Urlaub, Louis M Staudt, Hubert Serve, Thorsten Zenz, Thomas Oellerich
Burkitt lymphoma (BL) is an aggressive B cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Due to their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#12
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28054556/phosphorylation-impact-on-spleen-tyrosine-kinase-conformation-by-surface-enhanced-raman-spectroscopy
#13
Maximilien Cottat, Ryohei Yasukuni, Yo Homma, Nathalie Lidgi-Guigui, Nadine Varin-Blank, Marc Lamy de la Chapelle, Christine Le Roy
Spleen Tyrosine Kinase (Syk) plays a crucial role in immune cell signalling and its altered expression or activation are involved in several cancers. Syk activity relies on its phosphorylation status and its multiple phosphorylation sites predict several Syk conformations. In this report, we characterized Syk structural changes according to its phosphorylation/activation status by Surface Enhanced Raman Spectroscopy (SERS). Unphosphorylated/inactive and phosphorylated/active Syk forms were produced into two expression systems with different phosphorylation capability...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28011996/the-kinase-inhibitors-r406-and-gs-9973-impair-t-cell-functions-and-macrophage-mediated-anti-tumor-activity-of-rituximab-in-chronic-lymphocytic-leukemia-patients
#14
Ana Colado, María Belén Almejún, Enrique Podaza, Denise Risnik, Carmen Stanganelli, Esteban Enrique Elías, Patricia Dos Santos, Irma Slavutsky, Horacio Fernández Grecco, María Cabrejo, Raimundo Fernando Bezares, Mirta Giordano, Romina Gamberale, Mercedes Borge
Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011623/sunitinib-treatment-enhances-metastasis-of-innately-drug-resistant-breast-tumors
#15
Joseph W Wragg, Victoria L Heath, Roy Bicknell
Antiangiogenic therapies have failed to confer survival benefits in patients with metastatic breast cancer (mBC). However, to date, there has not been an inquiry into the roles for acquired versus innate drug resistance in this setting. In this study, we report roles for these distinct phenotypes in determining therapeutic response in a murine model of mBC resistance to the antiangiogenic tyrosine kinase inhibitor sunitinib. Using tumor measurement and vascular patterning approaches, we differentiated tumors displaying innate versus acquired resistance...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28000738/immunomodulatory-and-antitumor-effects-of-a-novel-tlr7-agonist-combined-with-lapatinib
#16
Ningning Gao, Jingjing Zhong, Xiaodong Wang, Zhenchao Jin, Wang Li, Yu Liu, Yuwen Diao, Zhulin Wang, Wenqi Jiang, Guangyi Jin
As new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance. We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27994755/carboxamide-spleen-tyrosine-kinase-syk-inhibitors-leveraging-ground-state-interactions-to-accelerate-optimization
#17
J Michael Ellis, Michael D Altman, Brandon Cash, Andrew M Haidle, Rachel L Kubiak, Matthew L Maddess, Youwei Yan, Alan B Northrup
Optimization of a series of highly potent and kinome selective carbon-linked carboxamide spleen tyrosine kinase (Syk) inhibitors with favorable drug-like properties is described. A pervasive Ames liability in an analogous nitrogen-linked carboxamide series was obviated by replacement with a carbon-linked moiety. Initial efforts lacked on-target potency, likely due to strain induced between the hinge binding amide and solvent front heterocycle. Consideration of ground state and bound state energetics allowed rapid realization of improved solvent front substituents affording subnanomolar Syk potency and high kinome selectivity...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27966556/mv140-a-sublingual-polyvalent-bacterial-preparation-to-treat-recurrent-urinary-tract-infections-licenses-human-dendritic-cells-for-generating-th1-th17-and-il-10-responses-via-syk-and-myd88
#18
C Benito-Villalvilla, C Cirauqui, C M Diez-Rivero, M Casanovas, J L Subiza, O Palomares
Recurrent urinary tract infections (RUTIs) are one of the most common bacterial infectious diseases, especially in women. Antibiotics remain the mainstay of treatment, but their overuse is associated with antibiotic-resistant infections and deleterious effects in the microbiota. Therefore, alternative approaches are fully demanded. Sublingual immunization with MV140 (Uromune), a polyvalent bacterial preparation (PBP) of whole heat-inactivated bacteria, demonstrated clinical efficacy for the treatment of RUTIs, but the involved immunological mechanisms remain unknown...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27942010/limited-impact-of-imatinib-in-a-murine-model-of-sclerodermatous-chronic-graft-versus-host-disease
#19
Ludovic Belle, Gilles Fransolet, Joan Somja, Marilène Binsfeld, Philippe Delvenne, Pierre Drion, Muriel Hannon, Yves Beguin, Grégory Ehx, Frédéric Baron
BACKGROUND: Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β) play a significant role in the fibrosing process occurring in scl-cGVHD. This prompted us to assess the impact of the PDGF-r and c-Abl tyrosine kinase inhibitor imatinib on scl-cGVHD. METHODS: To assess the impact of imatinib on T cell subset proliferation in vivo, Balb/cJ recipient mice were lethally (7 Gy) irradiated and then injected with 10x106 bone marrow cells from B10...
2016: PloS One
https://www.readbyqxmd.com/read/27906453/spleen-tyrosine-kinase-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling
#20
C Tabeling, J Herbert, A C Hocke, D J Lamb, S L Wollin, K J Erb, E Boiarina, H Movassagh, J Scheffel, J M Doehn, S Hippenstiel, M Maurer, A S Gounni, W M Kuebler, N Suttorp, M Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
keyword
keyword
51188
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"