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https://www.readbyqxmd.com/read/28643757/significance-of-expression-of-suppressor-of-cytokine-signaling-proteins-suppressor-of-cytokine-signaling-1-suppressor-of-cytokine-signaling-2-and-suppressor-of-cytokine-signaling-3-in-papillary-thyroid-cancer
#1
Toral Pundrik Kobawala, Trupti I Trivedi, Kinjal Kevin Gajjar, Girish H Patel, Nandita R Ghosh
PURPOSE: Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer. MATERIALS AND METHODS: SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643224/establishment-of-a-3d-cell-culture-model-of-primary-bovine-mammary-epithelial-cells-extracted-from-fresh-milk
#2
Maria Hillreiner, Nadine I Müller, Heiner M Koch, Christiane Schmautz, Bernhard Küster, Michael W Pfaffl, Heike Kliem
For the investigation of molecular processes underlying diseases of the bovine mammary gland, primary bovine mammary epithelial cells (pbMEC) are used. They are known to contribute to the innate immune system of the bovine mammary gland. The functionality of pbMEC depends on the maintenance of in vivo characteristics. So far, the optimization of pbMEC culture conditions was intended in a variety of experiments. For this purpose, most of the studies used stable cell lines or primary cells obtained from udder biopsies of slaughtered animals...
June 22, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28639898/targeting-interlukin-6-to-relieve-immunosuppression-in-tumor-microenvironment
#3
Qian Liu, Shengnan Yu, Anping Li, Hanxiao Xu, Xinwei Han, Kongming Wu
Immunotolerance is one of the hallmarks of malignant tumors. Tumor cells escape from host immune surveillance through various mechanisms resulting in tumor progression and therapeutic resistance. Interlukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes by integrating with multiple intracellular signaling pathways. Aberrant expression of interlukin-6 is associated with the growth, metastasis, and chemotherapeutic resistance in a wide range of cancers. Interlukin-6 exerts immunosuppressive capacity mostly by stimulating the infiltrations of myeloid-derived suppressor cells, tumor-associated neutrophils, and cancer stem-like cells via Janus-activated kinase/signal transducer and activator of transcription 3 pathway in tumor microenvironment...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639894/deregulated-expression-of-cdc6-as-bcr-abl-dependent-survival-factor-in-chronic-myeloid-leukemia-cells
#4
Jia-Hua Zhang, Yan-Li He, Rui Zhu, Wen Du, Jun-Hua Xiao
Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28637459/the-role-of-jak-stat-signaling-pathway-and-its-regulators-in-the-fate-of-t-helper-cells
#5
REVIEW
Farhad Seif, Majid Khoshmirsafa, Hossein Aazami, Monireh Mohsenzadegan, Gholamreza Sedighi, Mohammadali Bahar
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders...
June 21, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28635319/a-case-of-topical-ruxolitinib-treatment-failure-in-alopecia-areata
#6
Maya Deeb, Renée A Beach
Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#7
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28633283/janus-kinase-inhibitors-clear-to-land-janus-kinase-inhibitors-in-ra
#8
Martin Aringer
No abstract text is available yet for this article.
June 13, 2017: Rheumatology
https://www.readbyqxmd.com/read/28632888/excellent-response-to-tofacitinib-in-a-patient-with-alopecia-universalis
#9
Funda Erduran, Esra Adışen, Ahmet Burhan Aksakal
EAlopecia universalis (AU) is generally considered a variant of alopecia areata (AA), in which the treatment options seldom provide satisfactory results. However, successful treatment of several cases of AA and its variants with oral Janus kinase (JAK) inhibitors have been reported recently. Here we report a 23-year-old female patient with AU successfully treated with tofacitinib, a selective JAK-3 inhibitor. The initial tofacitinib dose was 5 mg twice daily. After 2 months of treatment, partial hair regrowth was seen on the scalp and eyebrows...
June 2017: Acta Dermatovenerologica Alpina, Panonica, et Adriatica
https://www.readbyqxmd.com/read/28631385/identification-of-glucose-kinase-dependent-and-independent-pathways-for-carbon-control-of-primary-metabolism-development-and-antibiotic-production-in-streptomyces-coelicolor-by-quantitative-proteomics
#10
Jacob Gubbens, Marleen M Janus, Bogdan I Florea, Herman S Overkleeft, Gilles P van Wezel
No abstract text is available yet for this article.
July 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28630047/update-on-anti-tumor-necrosis-factor-agents-and-other-new-drugs-for-inflammatory-bowel-disease
#11
REVIEW
Benjamin L Cohen, David B Sachar
The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs...
June 19, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28629666/treating-active-rheumatoid-arthritis-with-janus-kinase-inhibitors
#12
David L Scott, Matt D Stevenson
No abstract text is available yet for this article.
June 15, 2017: Lancet
https://www.readbyqxmd.com/read/28629665/efficacy-and-safety-of-tofacitinib-monotherapy-tofacitinib-with-methotrexate-and-adalimumab-with-methotrexate-in-patients-with-rheumatoid-arthritis-oral-strategy-a-phase-3b-4-double-blind-head-to-head-randomised-controlled-trial
#13
Roy Fleischmann, Eduardo Mysler, Stephen Hall, Alan J Kivitz, Robert J Moots, Zhen Luo, Ryan DeMasi, Koshika Soma, Richard Zhang, Liza Takiya, Svitlana Tatulych, Christopher Mojcik, Sriram Krishnaswami, Sujatha Menon, Josef S Smolen
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate. METHODS: ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, randomised controlled trial in patients aged 18 years or older with active rheumatoid arthritis despite methotrexate therapy...
June 15, 2017: Lancet
https://www.readbyqxmd.com/read/28629517/erythropoietin-mediated-neuroprotection-in-insects-suggests-a-prevertebrate-evolution-of-erythropoietin-like-signaling
#14
Ralf Heinrich, Verena Günther, Natasa Miljus
The cytokine erythropoietin (Epo) mediates protective and regenerative functions in mammalian nervous systems via activation of poorly characterized receptors that differ from the "classical" homodimeric Epo receptor expressed on erythroid progenitor cells. Epo genes have been identified in vertebrate species ranging from human to fish, suggesting that Epo signaling evolved earlier than the vertebrate lineage. Studies on insects (Locusta migratoria, Chorthippus biguttulus, Tribolium castaneum) revealed Epo-mediated neuroprotection and neuroregeneration...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28629512/erythropoietin-receptor-structural-domains
#15
Qingxin Li, CongBao Kang
Erythropoietin (EPO) is a hormone that is important for regulating red blood cell production. It is functional through binding to its receptor-EpoR. EpoR is a single-span membrane protein. It contains an extracellular region, a transmembrane domain, and a C-terminus. The extracellular region is important for binding to EPO, and its conformation is critical for signal transduction. The transmembrane domain contains 21 residues forming a helix which plays an important role in transferring ligand-induced conformational changes of the extracellular domain across the cell membrane...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628689/aggressive-skin-cancers-occurring-in-patients-treated-with-the-janus-kinase-inhibitor-ruxolitinib
#16
Adam B Blechman, Christine E Cabell, Christine H Weinberger, Anna Duckworth, Justin J Leitenberger, Fiona O Zwald, Mark A Russell
<p>The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28626521/identification-and-characterization-of-jak2-pseudokinase-domain-small-molecule-binders
#17
David E Puleo, Kaury Kucera, Henrik M Hammarén, Daniela Ungureanu, Ana S Newton, Olli Silvennoinen, William L Jorgensen, Joseph Schlessinger
Janus kinases (JAKs) regulate hematopoiesis via the cytokine-mediated JAK-STAT signaling pathway. JAKs contain tandem C-terminal pseudokinase (JH2) and tyrosine kinase (JH1) domains. The JAK2 pseudokinase domain adopts a protein kinase fold and, despite its pseudokinase designation, binds ATP with micromolar affinity. Recent evidence shows that displacing ATP from the JAK2 JH2 domain alters the hyperactivation state of the oncogenic JAK2 V617F protein while sparing the wild type JAK2 protein. In this study, small molecule binders of JAK2 JH2 were identified via an in vitro screen...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28626517/janus-associated-kinase-1-jak1-inhibitors-as-potential-treatment-for-immune-disorders
#18
EDITORIAL
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28625126/enhanced-risk-for-specific-somatic-myeloproliferative-neoplastic-mutations-in-patients-with-stroke
#19
Chih-Cheng Chen, Chia-Chen Hsu, Cih-En Huang, Yi-Yang Chen, Jrhau Lung, Hsing-Ying Ho, Chian-Pei Li, Jiann-Der Lee
BACKGROUND: Somatic mutations of Janus kinase 2 (JAK2V617F), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are the major clonal molecules that drive the pathogenesis of myeloproliferative neoplasms (MPN). It is well recognized that MPN patients carry an excessive risk of thrombohemorrhagic complications. However, little is known about the prevalence of these clonal markers in patients with cerebral vascular disease. METHODS: To address this issue, 153 consecutive stroke patients in Taiwan were enrolled in the study...
June 18, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28622463/efficacy-safety-pharmacokinetics-and-pharmacodynamics-of-filgotinib-a-selective-janus-kinase-1-inhibitor-after-short-term-treatment-of-rheumatoid-arthritis-results-of-two-randomized-phase-iia-trials
#20
Frédéric Vanhoutte, Minodora Mazur, Oleksandr Voloshyn, Mykola Stanislavchuk, Annegret Van der Aa, Florence Namour, René Galien, Luc Meuleners, Gerben van 't Klooster
OBJECTIVE: Janus kinase (JAK) inhibitors have shown efficacy in rheumatoid arthritis (RA). We hypothesized that selective inhibition of JAK1 would combine good efficacy with a differentiated safety profile versus less selective JAK inhibitors. METHODS: In two 4-week exploratory, double-blind, placebo-controlled Phase IIA trials, 127 RA patients with insufficient response to methotrexate received filgotinib (GLPG0634, GS-6034) oral capsules (twice-daily 100 mg, or once-daily 30, 75, 150, 200, or 300 mg) or placebo, added on to a stable regimen of methotrexate, to evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of filgotinib...
June 16, 2017: Arthritis & Rheumatology
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