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https://www.readbyqxmd.com/read/28802860/upregulation-of-il-9-and-jak-stat-signaling-pathway-in-children-with-autism
#1
Sheikh F Ahmad, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Laila Yousef Al-Ayadhi, Sabry M Attia
Autism spectrum disorder (ASD) gradually develops predominantly neurodevelopmental disorders, which are socially diagnosed in early childhood. Though the etiopathology of ASD is not clear, immune alteration has been suggested as autism's pathophysiological mechanism. Previous studies found that several cytokines and transcription factor activation pathways were significantly increased in ASD. IL-9 has been confirmed to play a significant role in the central nervous system (CNS). The aim of the present study was to investigate the understudied role of pro- and anti-inflammatory cytokines and the JAK-STAT signaling pathway in ASD...
August 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28794380/tumor-lysis-syndrome-after-the-administration-of-ruxolitinib-in-a-patient-with-post-polycythemia-vera-myelofibrosis
#2
Megumi Koshiishi, Yuki Sueki, Ichiro Kawashima, Kei Nakajima, Toru Mitsumori, Keita Kirito
The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28794072/ruxolitinib-versus-best-available-therapy-for-et-intolerant-or-resistant-to-hydroxycarbamide-in-a-randomized-trial
#3
Claire N Harrison, Adam J Mead, Anesh Panchal, Sonia Fox, Christina Yap, Emmanouela Gbandi, Aimee Houlton, Samah Alimam, Joanne Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Ruben Scherber, Amylou C Dueck, Nicholas C P Cross, Ruben Mesa, Mary Frances McMullin
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28790099/gsk2586184-a-jak1-selective-inhibitor-in-two-patients-with-ulcerative-colitis
#4
Leonie C S De Vries, Valerie J Ludbrook, Kirsty J Hicks, Geert R D'Haens
Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus...
August 7, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28783722/identification-of-essential-genes-for-cancer-immunotherapy
#5
Shashank J Patel, Neville E Sanjana, Rigel J Kishton, Arash Eidizadeh, Suman K Vodnala, Maggie Cam, Jared J Gartner, Li Jia, Seth M Steinberg, Tori N Yamamoto, Anand S Merchant, Gautam U Mehta, Anna Chichura, Ophir Shalem, Eric Tran, Robert Eil, Madhusudhanan Sukumar, Eva Perez Guijarro, Chi-Ping Day, Paul Robbins, Steve Feldman, Glenn Merlino, Feng Zhang, Nicholas P Restifo
Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8(+) T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas...
August 7, 2017: Nature
https://www.readbyqxmd.com/read/28780423/cinnamic-acid-derivatives-inhibit-hepatitis-c-virus-replication-via-the-induction-of-oxidative-stress
#6
Ryota Amano, Atsuya Yamashita, Hirotake Kasai, Tomoka Hori, Sayoko Miyasato, Setsu Saito, Hiromasa Yokoe, Kazunori Takahashi, Tomohisa Tanaka, Teruhime Otoguro, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi
Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr(705) in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2...
August 2, 2017: Antiviral Research
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
#7
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/28770966/inhibition-of-mir-221-influences-bladder-cancer-cell-proliferation-and-apoptosis
#8
H Liu, J-K Chang, J-Q Hou, Z-H Zhao, L-D Zhang
OBJECTIVE: Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway participate in cell proliferation and apoptosis. Suppressors of cytokine signaling 3 (SOCS3) are negative regulators of JAK-STAT3. SOCS3 was found significantly declined, while microRNA-221 (miR-221) obviously up-regulated in bladder cancer tissue. Bioinformatics analysis revealed the complementary binding site between miR-221 and 3'-UTR of SOCS3. This study investigated the role of miR-221 in regulating SOCS3/JAK-STAT3 signaling pathway and bladder cancer cell proliferation and apoptosis...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28770377/1-6-o-o-diacetylbritannilactone-inhibits-eotaxin-1-and-alox15-expression-through-inactivation-of-stat6-in-a549-cells
#9
Xi Chen, Ning Ji, Nan Qin, Sheng-An Tang, Ran Wang, Yuling Qiu, Hongquan Duan, Dexin Kong, Meihua Jin
1,6-O,O-Diacetylbritannilactone (OODBL), a plant sesquiterpene lactone, was previously reported to show multiple pharmacological effects such as anti-cancer and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effect of OODBL on interleukin (IL)-4-induced signal transducer and activator of transcription 6 (STAT6) signaling pathway in human lung A549 cells. We found that OODBL dramatically inhibited IL-4-induced messenger RNA (mRNA) expression of eotaxin-1 and arachidonate 15-lipoxygenase-1 (ALOX15) in a dose-dependent manner...
August 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#10
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28757617/nilotinib-induced-vasculopathy-identification-of-vascular-endothelial-cells-as-a-primary-target-site
#11
E Hadzijusufovic, K Albrecht-Schgoer, K Huber, G Hoermann, F Grebien, G Eisenwort, W Schgoer, S Herndlhofer, C Kaun, M Theurl, W R Sperr, U Rix, I Sadovnik, B Jilma, G H Schernthaner, J Wojta, D Wolf, G Superti-Furga, R Kirchmair, P Valent
The BCR/ABL1 inhibitor Nilotinib is increasingly used to treat patients with chronic myeloid leukemia (CML). Although otherwise well-tolerated, Nilotinib has been associated with the occurrence of progressive arterial occlusive disease (AOD). Our objective was to determine the exact frequency of AOD and examine in vitro and in vivo effects of Nilotinib and Imatinib on endothelial cells to explain AOD-development. In contrast to Imatinib, Nilotinib was found to upregulate pro-atherogenic adhesion-proteins (ICAM-1, E-selectin, VCAM-1) on human endothelial cells...
July 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28753783/gene-expression-profiling-of-advanced-penile-squamous-cell-carcinoma-receiving-cisplatin-based-chemotherapy-improves-prognostication-and-identifies-potential-therapeutic-targets
#12
Andrea Necchi, Bernhard J Eigl, Eddy Shih-Hsin Yang, Sejong Bae, Darshan Chandrashekar, Dongquan Chen, Gurudatta Naik, Amitkumar Mehta, Patrizia Giannatempo, Maurizio Colecchia, Jennifer Gordetsky, Shi Wei, Tiffiny Cooper, Sooryanarayana Varambally, Guru Sonpavde
In men with advanced penile squamous cell carcinoma receiving first-line chemotherapy, visceral metastases (VM) and Eastern Cooperative Oncology Group performance status ≥1 are poor prognostic factors for overall survival (OS). We hypothesized that tumor gene expression profiling may enhance prognostic stratification and identify potential therapeutic targets. In this retrospective study, RNA extracted from macrodissected tumors underwent profiling for the expression of 738 genes using NanoString. Univariate and multivariate analyses assessed the association of genes, VM, and performance status with OS...
August 27, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28751891/deconvolution-of-the-response-to-bacillus-calmette-gu%C3%A3-rin-reveals-nf-%C3%AE%C2%BAb-induced-cytokines-as-autocrine-mediators-of-innate-immunity
#13
Aurélie Bisiaux, Jeremy Boussier, Darragh Duffy, Lluis Quintana-Murci, Magnus Fontes, Matthew L Albert
Bacillus Calmette-Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28748833/identification-and-characterization-of-differentially-expressed-genes-from-human-microglial-cell-samples-infected-with-japanese-encephalitis-virus
#14
Manoj Kumar Gupta, Santosh Kumar Behera, Budheswar Dehury, Namita Mahapatra
BACKGROUND & OBJECTIVES: Limited studies have been reported on Japanese encephalitis (JE) with reference to microarray data analysis. The present study involved an in silico approach for identification and characterization of differentially expressed genes in human microglial cell (CHME3) samples, infected with P20778 strain of Japanese encephalitis virus (JEV). METHODS: Gene expression data (GSE57330) belonging to mRNA expression profile of CHME3 cells infected with JEV, was downloaded from the gene expression omnibus (GEO) database, processed and normalized by robust multichip averaging (RMA) method using affy packages of R...
April 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/28744013/the-t-cell-leukemia-associated-ribosomal-rpl10-r98s-mutation-enhances-jak-stat-signaling
#15
T Girardi, S Vereecke, S O Sulima, Y Khan, L Fancello, J W Briggs, C Schwab, J O de Beeck, J Verbeeck, J Royaert, E Geerdens, C Vicente, S Bornschein, C J Harrison, J P Meijerink, J Cools, J D Dinman, K R Kampen, K De Keersmaecker
Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10-R98S) found in T-ALL. The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. A proteome screen revealed overexpression of several Jak-Stat signaling proteins in engineered RPL10-R98S mouse lymphoid cells, which we confirmed in hematopoietic cells from transgenic Rpl10-R98S mice and T-ALL xenograft samples...
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28737053/efficacy-of-baricitinib-in-the-treatment-of-rheumatoid-arthritis
#16
Christophe Richez, Marie-Elise Truchetet, Marie Kostine, Thierry Schaeverbeke, Bernard Bannwarth
although the outcome for patients with rheumatoid arthritis (ra) has improved in the past decades, adequate disease control cannot be achieved in a substantial proportion of patients. new drugs with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Areas covered: This review focuses on the pharmacodynamics and pharmacokinetics of baricitinib. Furthermore, the article summarizes and comments the drug's efficacy and safety profile in RA patients. Expert opinion: Baricitinib is an oral targeted synthetic (ts) disease-modifying antirheumatic drug (DMARD) that mainly inhibits JAK1 and JAK2...
July 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28730475/characterization-of-ligand-binding-to-pseudokinases-using-a-thermal-shift-assay
#17
Isabelle S Lucet, James M Murphy
The protocol herein describes a robust and proven method for the measurement of pseudokinase-ligand interaction using a fluorescence-based thermal shift assay (TSA). Pseudokinases are kinase-like proteins that have recently emerged as crucial regulatory modules of signal transduction pathways and may well represent a novel class of drug targets. However, unlike kinases, the regulatory activity of pseudokinases is mainly conferred through protein-protein interactions. Understanding the mechanisms that underlie pseudokinase conformational changes through ligand binding and how such conformational changes can tune signaling pathways is a necessary step to unravel their biological functions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729401/jak1-stat3-activation-through-a-proinflammatory-cytokine-pathway-leads-to-resistance-to-molecularly-targeted-therapy-in-non-small-cell-lung-cancer
#18
Kazuhiko Shien, Vassiliki A Papadimitrakopoulou, Dennis Ruder, Carmen Behrens, Li Shen, Neda Kalhor, Juhee Song, J Jack Lee, Jing Wang, Ximing Tang, Roy S Herbst, Shinichi Toyooka, Luc Girard, John D Minna, Jonathan M Kurie, Ignacio I Wistuba, Julie G Izzo
Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine interleukin-6 (IL6) and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAFs)...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#19
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28720093/solanum-nigrum-unripe-fruit-fraction-attenuates-adriamycin-resistance-by-down-regulating-multi-drug-resistance-protein-mdr-1-through-jak-stat-pathway
#20
Sankar Jagadeeshan, Diana David, S Jisha, S Manjula, S Asha Nair
BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S...
July 18, 2017: BMC Complementary and Alternative Medicine
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