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https://www.readbyqxmd.com/read/28548121/ebv-negative-aggressive-nk-cell-leukemia-lymphoma-a-clinical-and-pathological-study-from-a-single-institution
#1
Juehua Gao, Amir Behdad, Peng Ji, Kristy L Wolniak, Olga Frankfurt, Yi-Hua Chen
Aggressive natural killer (NK)-cell leukemia/lymphoma is a systemic NK-cell neoplasm that preferentially affects Asians with a fulminant clinical course and is almost always associated with Epstein-Barr virus (EBV). The data on EBV-negative aggressive NK-cell leukemia/lymphoma are limited. Here we report a series of three patients (two Caucasians, one African-American) with EBV-negative aggressive NK-cell leukemia/lymphoma from a single institution, including a case diagnosed on post-mortem examination. Similar to EBV-positive aggressive NK-cell leukemia/lymphoma, our patients presented with constitutional symptoms and hepatosplenomegaly, and followed a highly aggressive clinical course...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28544428/design-synthesis-and-evaluation-of-the-anti-cancer-activity-of-2-amino-aryl-7-aryl-benzoxazole-compounds
#2
Patcharaporn Khajondetchairit, Oraphan Phuangsawai, Praphasri Suphakun, Siriruk Rattanabunyong, Kiattawee Choowongkomon, M Paul Gleeson
A series of 2-aminoaryl-7-arylbenzoxazole derivatives have been designed, synthesized and evaluated as anti-cancer agents. Fourteen of the compounds exhibited cytotoxic effects towards Human A549 lung cancer cells. We found 12l was the most potent with an EC50 of 0.4 μM, equivalent to the anti-cancer drug doxorubicin, but had low selectivity following cross screening in monkey kidney Vero cells. Eight of the most potent or most selective compounds were further profiled in additional cell lines (MCF7, NCI-H187 and KB) to better understand their cytotoxic activity...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28537140/molecular-modeling-driven-approach-for-identification-of-janus-kinase-1-inhibitors-through-3d-qsar-docking-and-molecular-dynamics-simulations
#3
Ramesh Itteboina, Srilata Ballu, Sree Kanth Sivan, Vijjulatha Manga
Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5...
May 24, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28529955/identification-of-transcriptional-modules-and-key-genes-in-chickens-infected-with-salmonella-enterica-serovar-pullorum-using-integrated-coexpression-analyses
#4
Bao-Hong Liu, Jian-Ping Cai
Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA) and differential coexpression analysis (DCEA) to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28527256/-stat3-activation-by-hypoxia-in-in-vitro-models-of-cervix-cancer-and-endothelial-cells
#5
Óscar Ortega, Alejandro Ondo-Méndez, Ruth Garzón
INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28525837/differentially-expressed-jak-stat-signaling-pathway-genes-and-target-micrornas-in-the-spleen-of-necrotic-enteritis-afflicted-chicken-lines
#6
Anh Duc Truong, Deivendran Rengaraj, Yeojin Hong, Cong Thanh Hoang, Yeong Ho Hong, Hyun S Lillehoj
The JAK signal transducer and STAT signaling pathway is an important regulator of cell proliferation, differentiation, survival, motility, apoptosis, immune response, and development. In this study, we used RNA-Sequencing, qRT-PCR, and bioinformatics tools to investigate the differential expression of JAK-STAT pathway genes, their interactions, and regulators in the spleen of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and MD-susceptible line 7.2) induced necrotic enteritis (NE) disease by co-infection with Eimeria maxima and Clostridium perfringens...
May 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28518222/the-effect-of-initial-molecular-profile-on-response-to-recombinant-interferon-%C3%AE-rifn%C3%AE-treatment-in-early-myelofibrosis
#7
Richard T Silver, Ariella C Barel, Elena Lascu, Ellen K Ritchie, Gail J Roboz, Paul J Christos, Attilio Orazi, Duane C Hassane, Wayne Tam, Nicholas C P Cross
BACKGROUND: Although recombinant interferon-α (rIFNα) effectively treats patients with early myelofibrosis, the effect of driver and high molecular risk (HMR) mutations has not been considered. In this phase 2 study, for the first time, the authors correlate response to rIFNα treatment with driver and HMR mutations. METHODS: Patients were diagnosed using World Health Organization or International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria...
May 18, 2017: Cancer
https://www.readbyqxmd.com/read/28511114/bergapten-prevents-lipopolysaccharide-induced-inflammation-in-raw264-7-cells-through-suppressing-jak-stat-activation-and-ros-production-and-increases-the-survival-rate-of-mice-after-lps-challenge
#8
Yi Zhou, Jing Wang, Weidong Yang, Xiaowen Qi, Lei Lan, Lan Luo, Zhimin Yin
Bergapten (BG) is a cumarine-derivate compound in many medicinal plants. Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response. Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264...
May 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28505169/molecular-basis-of-targeted-therapy-in-t-nk-cell-lymphoma-leukemia-a-comprehensive-genomic-and-immunohistochemical-analysis-of-a-panel-of-33-cell-lines
#9
Rufino Mondejar, Cristina Pérez, Arantza Onaindia, Nerea Martinez, Julia González-Rincón, Helena Pisonero, Jose Pedro Vaqué, Laura Cereceda, Miguel Santibañez, Margarita Sánchez-Beato, Miguel Angel Piris
T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28500170/jak2-inhibitors-for-myeloproliferative-neoplasms-what-is-next
#10
Prithviraj Bose, Srdan Verstovsek
Since its approval in 2011, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant/intolerant polycythemia vera (PV) is steadily increasing. A number of other JAK2 inhibitors have entered clinical testing, but none has been approved yet, and many discontinued. Importantly, the activity of these agents is not restricted to patients with JAK2 V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical benefit, their disease-modifying activity is limited, and rational combinations with other targeted agents are needed, particularly in MF, where survival is short...
May 12, 2017: Blood
https://www.readbyqxmd.com/read/28498099/synthekines-are-surrogate-cytokine-and-growth-factor-agonists-that-compel-signaling-through-non-natural-receptor-dimers
#11
Ignacio Moraga, Jamie B Spangler, Juan L Mendoza, Milica Gakovic, Tom S Wehrman, Peter Krutzik, K Christopher Garcia
Cytokine and growth-factor ligands typically signal through homo- or hetero-dimeric cell surface receptors via Janus Kinase (JAK/TYK), or Receptor Tyrosine Kinase (RTK)-mediated trans-phosphorylation. However, the number of receptor dimer pairings occurring in nature is limited to those driven by natural ligands encoded within our genome. We have engineered synthethic cytokines (synthekines) that drive formation of cytokine receptor dimer pairings that are not formed by endogenous cytokines and that are not found in nature, and which activate distinct signaling programs...
May 12, 2017: ELife
https://www.readbyqxmd.com/read/28496202/inhibition-of-jak-stat-signaling-reduces-the-activation-of-pancreatic-stellate-cells-in-vitro-and-limits-caerulein-induced-chronic-pancreatitis-in-vivo
#12
Hannah M Komar, Gregory Serpa, Claire Kerscher, Erin Schwoegl, Thomas A Mace, Ming Jin, Ming-Chen Yang, Ching-Shih Chen, Mark Bloomston, Michael C Ostrowski, Phil A Hart, Darwin L Conwell, Gregory B Lesinski
Chronic pancreatitis (CP) is a fibro-inflammatory disease leading to pain, maldigestion, and pancreatic insufficiency. No therapeutic options exist due to a limited understanding of the biology of CP pathology. Recent findings implicate pancreatic stellate cells (PSC) as prominent mediators of inflammatory and fibrotic processes during CP. Here, we utilized primary and immortalized PSC obtained from mice and patients with CP or pancreatic cancer to examine the effect of Jak/STAT and MAPK pathway inhibition in vitro...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28496097/hepatitis-b-virus-e-antigen-activates-the-suppressor-of-cytokine-signaling-2-to-repress-interferon-action
#13
Yi Yu, Pin Wan, Yanhua Cao, Wei Zhang, Junbo Chen, Li Tan, Yan Wang, Zhichen Sun, Qi Zhang, Yushun Wan, Ying Zhu, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma (HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally indicates ongoing viral replication and disease progression. However, the mechanism by which HBeAg regulates HBV infection remains unclear. Interferons (IFNs) are pleiotropic cytokines that participate in host innate immunity. After binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression of IFN-stimulated genes (ISGs), leading to induction of antiviral responses...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494922/analysis-of-jak-stat-signaling-pathway-genes-and-their-micrornas-in-the-intestinal-mucosa-of-genetically-disparate-chicken-lines-induced-with-necrotic-enteritis
#14
Anh Duc Truong, Deivendran Rengaraj, Yeojin Hong, Cong Thanh Hoang, Yeong Ho Hong, Hyun S Lillehoj
The JAK-STAT signaling pathway plays a key role in cytokine and growth factor activation and is involved in several cellular functions and diseases. The main objective of this study was to investigate the expression of candidate JAK-STAT pathway genes and their regulators and interactors in the intestinal mucosal layer of two genetically disparate chicken lines [Marek's disease (MD)-resistant line 6.3 and MD-susceptible line 7.2] induced with necrotic enteritis (NE). Through RNA-sequencing, we investigated 116 JAK-STAT signaling pathway-related genes that were significant and differentially expressed between the intestinal mucosa of the two lines compared with respective uninfected controls...
May 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28492557/cryptotanshinone-inhibits-human-glioma-cell-proliferation-in-vitro-and-in-vivo-through-shp-2-dependent-inhibition-of-stat3-activation
#15
Liang Lu, Sulin Zhang, Cuixian Li, Chun Zhou, Dong Li, Peiqing Liu, Min Huang, Xiaoyan Shen
Malignant gliomas (MGs) are one of the most common primary brain cancers in adults with a high mortality rate and relapse rate. Thus, finding better effective approaches to treat MGs has become very urgent. Here, we studied the effects of cryptotanshinone (CTS) on MGs in vitro and in vivo, and explored the underlying mechanisms. Effects of CTS in vitro on cell proliferation, cycle, migration and invasion were evaluated. The activation of JAK/STATs signaling was detected by western blot and immunofluorescenc staining...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28484267/microrna-146a-reduces-mhc-ii-expression-via-targeting-jak-stat-signaling-in-dendritic-cells-after-stem-cell-transplantation
#16
N Stickel, K Hanke, D Marschner, G Prinz, M Köhler, W Melchinger, D Pfeifer, A Schmitt-Graeff, T Brummer, A Heine, P Brossart, D Wolf, N von Bubnoff, J Finke, J Duyster, J Ferrara, U Salzer, R Zeiser
Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant-recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a(-/-) dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected-DCs ameliorated disease...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28484265/jak-stat-pathway-inhibition-overcomes-il7-induced-glucocorticoid-resistance-in-a-subset-of-human-t-cell-acute-lymphoblastic-leukemias
#17
C Delgado-Martin, L K Meyer, B J Huang, K A Shimano, M S Zinter, J V Nguyen, G A Smith, J Taunton, S S Winter, J R Roderick, M A Kelliher, T M Horton, B L Wood, D Teachey, M L Hermiston
While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. Additionally, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28483666/docosahexaenoic-acid-inhibits-il-6-expression-via-ppar%C3%AE-mediated-expression-of-catalase-in-cerulein-stimulated-pancreatic-acinar-cells
#18
Eun Ah Song, Joo Weon Lim, Hyeyoung Kim
Cerulein pancreatitis mirrors human acute pancreatitis. In pancreatic acinar cells exposed to cerulein, reactive oxygen species (ROS) mediate inflammatory signaling by Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, and cytokine induction. Docosahexaenoic acid (DHA) acts as an agonist of peroxisome proliferator activated receptor γ (PPARγ), which mediates the expression of some antioxidant enzymes. We hypothesized that DHA may induce PPARγ-target catalase expression and reduce ROS levels, leading to the inhibition of JAK2/STAT3 activation and IL-6 expression in cerulein-stimulated acinar cells...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28476581/tumour-associated-macrophages-activate-migration-and-stat3-in-pancreatic-ductal-adenocarcinoma-cells-in-co-cultures
#19
Aino Salmiheimo, Harri Mustonen, Sanna Vainionpää, Zhanlong Shen, Esko Kemppainen, Pauli Puolakkainen, Hanna Seppänen
OBJECTIVES: Tumour-associated macrophages participate in tumour development and progression. The aim of this study was to assess the interactions of pancreatic cancer cells and pro-inflammatory M1 and anti-inflammatory M2 macrophages, specifically their effect on pancreatic cancer cell migration and the changes in STAT-signalling. METHODS: Monocytes were isolated from healthy subjects and differentiated into macrophages with M-CSF. The macrophages were polarized towards M1 by IL-12 and towards M2 by IL-10...
April 24, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28476239/defective-il-4-signaling-in-t-cells-defines-severe-common-variable-immunodeficiency
#20
Eli Taraldsrud, Børre Fevang, Silje F Jørgensen, Kristine Moltu, Vera Hilden, Kjetil Taskén, Pål Aukrust, June H Myklebust, Johanna Olweus
Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and B-cell dysfunction, with significant clinical and immunological heterogeneity. Severe non-infectious complications, such as autoimmunity, granulomatous disease and splenomegaly, constitute a major cause of morbidity in CVID patients. T cells are generally regarded important for development of these clinical features. However, while T-cell abnormalities have been found in CVID patients, functional characteristics of T cells corresponding to well-defined clinical subtypes have not been identified...
May 2, 2017: Journal of Autoimmunity
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