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https://www.readbyqxmd.com/read/28223148/stat3-activation-in-infection-and-infection-associated-cancer
#1
Rong Lu, Yong-Guo Zhang, Jun Sun
The Janus kinase/signal transducers and activators for transcription (JAK/STAT) pathway plays crucial roles in regulating apoptosis, proliferation, differentiation, and the inflammatory response. The JAK/STAT families are composed of four JAK family members and seven STAT family members. STAT3 plays a key role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment. Recent evidence suggests that STAT3 regulates diverse biological functions in pathogenesis of diseases, such as infection and cancer...
February 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28218042/doxorubicin-has-a-synergistic-cytotoxicity-with-cucurbitacin-b-in-anaplastic-thyroid-carcinoma-cells
#2
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
In this study, the combined effect of doxorubicin with cucurbitacin B on survival of anaplastic thyroid carcinoma cells was evaluated. For experiments, 8505C and CAL62 human anaplastic thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, and cytotoxic activity were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, multiplexed cytotoxicity assay, and cytotoxicity assay, respectively. Reactive oxygen species production was measured. In experiments, doxorubicin and cucurbitacin B reduced cell viability in a dose- and time-dependent manner...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#3
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28214598/three-stats-are-involved-in-the-regulation-of-the-expression-of-antimicrobial-peptides-in-the-triangle-sail-mussel-hyriopsis-cumingii
#4
Yun-Jia Dai, Kai-Min Hui, Ying-Hao Zhang, Yan Liu, Yu-Qing Wang, Li-Juan Zhao, Li Lin, Lian-Qin Chai, Shun Wei, Jiang-Feng Lan
Janus kinase (Jak) and signal transducers and activators of transcription (STAT) signaling pathway is associated in antiviral and antibacterial immune response. Previous studies primarily investigated the function of STATs in mammals. For most invertebrates, only one STAT was found in each species, such as STAT92E was found in Drosophila melanogaster. The studies, which focus on the functional difference between various STATs in the same species of invertebrate, are limited. In the present study, three STATs (HcSTAT1, HcSTAT2 and HcSTAT3) were identified in triangle shell pearl mussel, Hyriopsis cumingii...
February 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28209624/tofacitinib-for-induction-and-maintenance-therapy-of-crohn-s-disease-results-of-two-phase-iib-randomised-placebo-controlled-trials
#5
Julian Panés, William J Sandborn, Stefan Schreiber, Bruce E Sands, Séverine Vermeire, Geert D'Haens, Remo Panaccione, Peter D R Higgins, Jean-Frederic Colombel, Brian G Feagan, Gary Chan, Michele Moscariello, Wenjin Wang, Wojciech Niezychowski, Amy Marren, Paul Healey, Eric Maller
OBJECTIVE: Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). DESIGN: We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks...
February 16, 2017: Gut
https://www.readbyqxmd.com/read/28204819/lncrna-co-expression-network-model-for-the-prognostic-analysis-of-acute-myeloid-leukemia
#6
Jia-Qi Pan, Yan-Qing Zhang, Jing-Hua Wang, Ping Xu, Wei Wang
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA‑lncRNA co-expression network (LLCN) was constructed...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28199814/baricitinib-versus-placebo-or-adalimumab-in-rheumatoid-arthritis
#7
Peter C Taylor, Edward C Keystone, Désirée van der Heijde, Michael E Weinblatt, Liliana Del Carmen Morales, Jaime Reyes Gonzaga, Sergey Yakushin, Taeko Ishii, Kahaku Emoto, Scott Beattie, Vipin Arora, Carol Gaich, Terence Rooney, Douglas Schlichting, William L Macias, Stephanie de Bono, Yoshiya Tanaka
Background Baricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis. Methods We conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti-tumor necrosis factor α monoclonal antibody) every other week...
16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28193636/evaluation-of-jak3-biology-in-autoimmune-disease-using-a-highly-selective-irreversible-jak3-inhibitor
#8
Fiona Elwood, David Witter, Jennifer Piesvaux, Brian Kraybill, Nathan Bays, Carla Alpert, Peter Goldenblatt, Yujie Qu, Irena Ivanovska, Hyun-Hee Lee, Chi-Sung Chiu, Hao Tang, Mark E Scott, Sujal Deshmukh, Mark Zielstorff, Alan Byford, Kalyan Chakravarty, Lauren Dorosh, Alexy Rivkin, Joel Klappenbach, Bo-Sheng Pan, Ilona Kariv, Christopher Dinsmore, Deborah Slipetz, Peter Dandliker
Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012)...
February 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28191885/molecular-definition-of-a-metastatic-lung-cancer-state-reveals-a-targetable-cd109-janus-kinase-stat-axis
#9
Chen-Hua Chuang, Peyton G Greenside, Zoë N Rogers, Jennifer J Brady, Dian Yang, Rosanna K Ma, Deborah R Caswell, Shin-Heng Chiou, Aidan F Winters, Barbara M Grüner, Gokul Ramaswami, Andrew L Spencley, Kimberly E Kopecky, Leanne C Sayles, E Alejandro Sweet-Cordero, Jin Billy Li, Anshul Kundaje, Monte M Winslow
Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival...
February 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28188673/socs-potential-immune-checkpoint-molecules-for-cancer-immunotherapy
#10
REVIEW
Shunsuke Chikuma, Mitsuhiro Kanamori, Setsuko Mise-Omata, Akihiko Yoshimura
Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals, respectively. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine Interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway...
February 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28188131/momelotinib-inhibits-acvr1-alk2-decreases-hepcidin-production-and-ameliorates-anemia-of-chronic-disease-in-rodents
#11
Malte Asshoff, Verena Petzer, Matthew R Warr, David Haschka, Piotr Tymoszuk, Egon Demetz, Markus Seifert, Wilfried Posch, Manfred Nairz, Pat Maciejewski, Peter Fowles, Christopher J Burns, Gregg Smith, Kay-Uwe Wagner, Guenter Weiss, J Andrew Whitney, Igor Theurl
Patients with myelofibrosis (MF) often develop anemia and frequently become dependent on red blood cell transfusions. Results from a phase 2 study for the treatment of MF with the Janus kinase1/2 (JAK1/2) inhibitor momelotinib (MMB) demonstrated that MMB treatment ameliorated anemia, unexpected for a JAK1/2 inhibitor, as erythropoietin-mediated JAK2 signaling is essential for erythropoiesis. Using a rat model of anemia of chronic disease (ACD), we now demonstrate that MMB treatment can normalize hemoglobin and red blood cell numbers...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28186964/il-6-secreted-by-cancer-associated-fibroblasts-promotes-epithelial-mesenchymal-transition-and-metastasis-of-gastric-cancer-via-jak2-stat3-signaling-pathway
#12
Xiongyan Wu, Pan Tao, Quan Zhou, Jie Li, Zhenjia Yu, Xiaofeng Wang, Jiaanfang Li, Chen Li, Min Yan, Zhenggang Zhu, Bingya Liu, Liping Su
Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Here, we show that CAFs isolated from gastric cancer produce significant amounts of interleukin-6 (IL-6). CAFs enhances the migration and EMT of gastric cancer cells through the secretion of IL-6 that activates Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in gastric cancer cells, while deprivation of IL-6 using a neutralizing antibody or inhibition of JAK/STAT3 pathway with specific inhibitor AG490 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184222/canonical-and-non-canonical-aspects-of-jak-stat-signaling-lessons-from-interferons-for-cytokine-responses
#13
REVIEW
Andrea Majoros, Ekaterini Platanitis, Elisabeth Kernbauer-Hölzl, Felix Rosebrock, Mathias Müller, Thomas Decker
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28182037/janus-kinase-2-mutations-in-cases-with-bcr-abl-negative-chronic-myeloproliferative-disorders-from-turkey
#14
Ismail Yildiz, Osman Yokuş, Habip Gedik
OBJECTIVE: We aimed to investigate the frequency of Janus kinase 2 (JAK2) mutations in cases with chronic myeloproliferative disorders (CMDs), and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. MATERIALS AND METHODS: Patients, who were diagnosed with BCR-ABL-negative CMDs according to diagnosis criteria of the World Health Organization and followed up at the hematology clinic between 2013 and 2015, were investigated in terms of the frequency of JAK2 mutation in cases with CMDs, and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively...
January 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28182002/rapamycin-upregulates-glutamate-transporter-and-il-6-expression-in-astrocytes-in-a-mouse-model-of-parkinson-s-disease
#15
Yunlong Zhang, Xiaoliang He, Xiaojuan Wu, Ming Lei, Zhiyun Wei, Xiuping Zhang, Lei Wen, Pingyi Xu, Shaomin Li, Shaogang Qu
Rapamycin protects mice against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons, which is an established model for Parkinson's disease. We demonstrated that rapamycin preserves astrocytic expression of glutamate transporters and glutamate reuptake. The protective effect was also observed in astrocyte cultures, indicating that rapamycin acts directly on astrocytes. In the MPTP model, rapamycin caused reduced expression of the E3 ubiquitin ligase Nedd4-2 (neuronal precursor cell expressed developmentally downregulated 4-2) and reduced colocalization of glutamate transporters with ubiquitin...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28177684/aegle-marmelos-l-corr-impedes-onset-of-insulin-resistance-syndrome-in-rats-provided-with-drinking-fructose-from-weaning-to-adulthood-stages-of-development-a-mechanistic-study
#16
Rajani Mathur, Ratika Sehgal, Preeti Rajora, Shveta Sharma, Rajesh Kumar, Sandeep Mathur
To explore the effect of aqueous extract of leaves of Aegle marmelos (AM) on hepatic carbohydrate metabolism and insulin downstream signalling in rats provided with drinking fructose (15%) from weaning to adulthood. Wistar albino rats (4week) were randomly divided into Normal Control (NC), Fructose Control (FC) and treatment (AMT) groups and provided over 8 weeks, chow + water, chow + fructose (15%) and chow + fructose (15%) + AM (500 mg/kg/d, p.o.), respectively. Significantly (p<0.05) raised levels of Fasting Blood Glucose, lipid, visceral weight, plasma insulin and leptin, glycogen, gluconeogenesis enzyme levels but decreased glycolytic enzyme activity was recorded in FC as compared to NC...
December 17, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28172756/p469-safety-tolerability-and-pharmacokinetics-of-the-intestine-restricted-oral-pan-janus-kinase-inhibitor-td-1473-after-single-and-multiple-oral-doses-in-healthy-subjects
#17
B Ferslew, C Sherman, D Nguyen, R Graham
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28169015/janus-kinase-inhibitors-in-dermatology-a-systematic-review
#18
REVIEW
Rony Shreberk-Hassidim, Yuval Ramot, Abraham Zlotogorski
BACKGROUND: Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. OBJECTIVE: Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. METHODS: This is a systematic review of PubMed and ClinicalTrials.gov. RESULTS: One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events...
February 3, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28167129/jak-stat-signaling-in-the-therapeutic-landscape-of-myeloproliferative-neoplasms
#19
Jennifer M O'Sullivan, Claire N Harrison
Myeloproliferative neoplasms (MPN) are a group of disorders defined by clonal proliferation of mature myeloid cells with overlapping clinical features. The driver mutations of these disorders, namely JAK2 (Janus Kinase), MPL (Myeloproliferative Leukaemia Virus) and CALR (Calreticulin) upregulate JAK-STAT signaling with increase in downstream transcription and gene expression. Epigenetic mutations are prevalent in MPNs but their interplay with aberrant JAK-STAT signaling is not known. This understanding lead to development of first targeted treatment in MPN; ruxolitinib for primary myelofibrosis...
February 3, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28164762/regulation-of-ion-channels-cellular-carriers-and-na-k-atpase-by-janus-kinase-3
#20
Mentor Sopjani, Shpëtim Thaçi, Berat Krasniqi, Miranda Selmonaj, Mark Rinnerthaler, Miribane Dërmaku-Sopjani
Janus kinase-3 (JAK3), a tyrosine kinase, is expressed in a variety of tissues, including the brain, and is involved in the signaling of cytokine receptors. JAK3 participates in numerous functions, among other the cell survival and proliferation, neuroprotection, apoptosis, as well as cellular response to hypoxia and ischemia-reperfusion. This kinase further contributes in the signaling of hematopoietic cell cytokine receptors, dendritic cells activation, maturation, and immune suppression as well as to cell volume regulation...
February 3, 2017: Current Medicinal Chemistry
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