keyword
MENU ▼
Read by QxMD icon Read
search

Jak-inhibitor

keyword
https://www.readbyqxmd.com/read/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#1
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#2
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28402197/minimal-residual-disease-or-cure-in-mpns-rationales-and-perspectives-on-combination-therapy-with-interferon-alpha2-and-ruxolitinib
#3
Mads Emil Bjørn, Hans Carl Hasselbalch
The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28395559/management-of-myelofibrosis-jak-inhibition-and-beyond
#4
Maximilian Stahl, Amer M Zeidan
Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF. Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. We provide clinical trial evidence behind using the JAK2 inhibitor ruxolitinib, erythropoiesis stimulating agents, androgens, immunomodulatory drugs, interferon, cytoreductive drugs and hypomethylating agents in MF...
April 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28389709/-familial-chilblain-lupus-type-1-interferonopathy-with-model-character
#5
REVIEW
C Fiehn
Familial chilblain lupus belongs to the group of type 1 interferonopathies and is particularly characterized by typical skin manifestations and ischemia of the acra. There are various mutations that can lead to this autosomal dominant disease. A mutation in the TREX-1 gene has been most frequently found; however, families with mutations in the SAMHD1 gene and recently in the gene which codes for the stimulator of interferon genes (STING) protein were also described. A common feature of these genetic defects is that they are all involved in the process of detection of intracellular free DNA, which as a result leads to increased production of type 1 interferons and the induced gene products...
April 7, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28378336/review-of-treatment-for-alopecia-totalis-and-alopecia-universalis
#6
REVIEW
Sama Kassira, Dorota Z Korta, Lance W Chapman, Francis Dann
Alopecia areata (AA) is an autoimmune disease directed at the hair follicle. Although usually limited to patchy hair loss over the scalp (focalis), AA can present as total loss of scalp hair (totalis; AT) or as total loss of both scalp and body hair (universalis; AU). Management of AT and AU can be challenging, and although multiple treatment modalities have been explored, no therapy is currently FDA-approved. This review focuses on the evidence for current treatment options for AT and AU. The PubMed database was searched from January 1, 2000, to September 1, 2016, for clinical trials, retrospective studies, and case reports of treatments for AT and AU...
April 5, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28371574/tofacitinib-suppresses-disease-activity-and-febrile-attacks-in-a-patient-with-coexisting-rheumatoid-arthritis-and-familial-mediterranean-fever
#7
Kevser Gök, Gizem Cengiz, Kemal Erol, Salih Ozgocmen
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA)...
January 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28370306/is-allogeneic-stem-cell-transplantation-for-myelofibrosis-still-indicated-at-the-time-of-molecular-markers-and-jak-inhibitors-era
#8
Elsa Lestang, Pierre Peterlin, Yannick Le Bris, Viviane Dubruille, Jacques Delaunay, Catherine Godon, Olivier Theisen, Nicolas Blin, Beatrice Mahe, Thomas Gastinne, Alice Garnier, Cyrille Touzeau, Maud Voldoire, Marie C Bene, Steven Le Gouill, Noel Milpied, Mohamad Mohty, Philippe Moreau, Thierry Guillaume, Patrice Chevallier
OBJECTIVE: The role of allogenic stem cell transplantation (ASCT) is still debated in myelofibrosis. METHOD: A retrospective analyzed was performed to compare the outcome of 71 patients with intermediate-2 or high-risk Dynamic International Prognosis Scoring System+ (DIPSS+) primary (PMF) or secondary (SMF) myelofibrosis with an indication of ASCT as they ultimately underwent the procedure (n=34) or not (n=37). RESULTS: Five-year overall survival (OS) was not statistically different between both groups (allograft: 52% vs no allograft: 34%, p=0,12)...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28369741/janus-kinase-inhibitors-prevent-migration-of-rheumatoid-arthritis-neutrophils-towards-interleukin-8-but-do-not-inhibit-priming-of-the-respiratory-burst-or-reactive-oxygen-species-production
#9
T S Mitchell, R J Moots, H L Wright
Neutrophils play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via the release of reactive oxygen species (ROS), proteases and cytokines. Orally active Janus kinase (JAK) inhibitors (JAKi), e.g. baricitinib and tofacitinib, have high clinical efficacy in RA but are linked with neutropenia and increased infections. Our aim was to determine the effect of JAK inhibition with baricitinib and tofacitinib on healthy control and RA neutrophil lifespan and function. RA (n = 7) and healthy control (n = 7) neutrophils were treated with baricitinib or tofacitinib for 30 min, prior to incubation in the absence or presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon (IFN)-γ...
April 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28360424/the-emerging-safety-profile-of-jak-inhibitors-in-rheumatic-disease
#10
Kevin L Winthrop
No abstract text is available yet for this article.
March 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28356514/cytokine-receptor-signaling-is-required-for-the-survival-of-alk-anaplastic-large-cell-lymphoma-even-in-the-presence-of-jak1-stat3-mutations
#11
Jing Chen, Yong Zhang, Michael N Petrus, Wenming Xiao, Alina Nicolae, Mark Raffeld, Stefania Pittaluga, Richard N Bamford, Masao Nakagawa, Sunny Tianyi Ouyang, Alan L Epstein, Marshall E Kadin, Annarose Del Mistro, Richard Woessner, Elaine S Jaffe, Thomas A Waldmann
Activating Janus kinase (JAK) and signal transducer and activator of transcription (STAT) mutations have been discovered in many T-cell malignancies, including anaplastic lymphoma kinase (ALK)(-) anaplastic large cell lymphomas (ALCLs). However, such mutations occur in a minority of patients. To investigate the clinical application of targeting JAK for ALK- ALCL, we treated ALK- cell lines of various histological origins with JAK inhibitors. Interestingly, most exogenous cytokine-independent cell lines responded to JAK inhibition regardless of JAK mutation status...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28337870/jak2-tyrosine-kinase-inhibitor-ag490-suppresses-cell-growth-and-invasion-of-gallbladder-cancer-cells-via-inhibition-of-jak2-stat3-signaling
#12
L X Fu, Q W Lian, J D Pan, Z L Xu, T M Zhou, B Ye
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28323260/mechanisms-and-consequences-of-jak-stat-signaling-in-the-immune-system
#13
REVIEW
Alejandro V Villarino, Yuka Kanno, John J O'Shea
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs...
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28318222/selective-downregulation-of-jak2-and-jak3-by-an-atp-competitive-pan-jak-inhibitor
#14
S Denise Field, Jacob Arkin, Jing Li, Lyn H Jones
PF-956980 has been used previously as a JAK3-selective chemical probe in numerous cell-based experiments. Here, we report that not only is PF-956980 a pan-JAK ATP-competitive inhibitor, but it also causes selective reduction of endogenous JAK2 and JAK3 protein levels in human primary immune cells (in a time-dependent manner), leaving the other JAK family members (JAK1 and TYK2) unchanged. We found that PF-956980 selectively downregulated JAK2 and JAK3 mRNA, corresponding to changes observed at the protein level...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28301084/the-effect-of-verapamil-a-p-glycoprotein-inhibitor-on-the-pharmacokinetics-of-peficitinib-an-orally-administered-once-daily-jak-inhibitor
#15
Tong Zhu, Corrie Howieson, Tomasz Wojtkowski, Jay P Garg, David Han, Ogert Fisniku, James Keirns
Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14...
March 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28295194/anti-leukaemic-activity-of-the-tyk2-selective-inhibitor-ndi-031301-in-t-cell-acute-lymphoblastic-leukaemia
#16
Koshi Akahane, Zhaodong Li, Julia Etchin, Alla Berezovskaya, Evisa Gjini, Craig E Masse, Wenyan Miao, Jennifer Rocnik, Rosana Kapeller, Jeremy R Greenwood, Hong Tiv, Takaomi Sanda, David M Weinstock, A Thomas Look
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage...
April 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28290136/baricitinib-first-global-approval
#17
Anthony Markham
Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. JAKs transduce intracellular signals from cell surface receptors for various cytokines and growth factors involved in inflammation and immune function, suggesting JAK inhibitors may be of therapeutic benefit in inflammatory conditions. In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs)...
March 13, 2017: Drugs
https://www.readbyqxmd.com/read/28277287/the-promise-of-janus-kinase-inhibitors-in-the-treatment-of-hematological-malignancies
#18
REVIEW
Emilee Senkevitch, Scott Durum
The Janus kinases (JAK) are a family of kinases that play an essential role in cytokine signaling and are implicated in the pathogenesis of autoimmune diseases and hematological malignancies. As a result, the JAKs have become attractive therapeutic targets. The discovery of a JAK2 point mutation (JAK2 V617F) as the main cause of polycythemia vera lead to the development and FDA approval of a JAK1/2 inhibitor, ruxolitinib, in 2011. This review focuses on the various JAK and associated components aberrations implicated in myeloproliferative neoplasms, leukemias, and lymphomas...
October 27, 2016: Cytokine
https://www.readbyqxmd.com/read/28264816/eular-recommendations-for-the-management-of-rheumatoid-arthritis-with-synthetic-and-biological-disease-modifying-antirheumatic-drugs-2016-update
#19
Josef S Smolen, Robert Landewé, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, Sofia Ramiro, Marieke Voshaar, Ronald van Vollenhoven, Daniel Aletaha, Martin Aringer, Maarten Boers, Chris D Buckley, Frank Buttgereit, Vivian Bykerk, Mario Cardiel, Bernard Combe, Maurizio Cutolo, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Cem Gabay, Juan Gomez-Reino, Laure Gossec, Jacques-Eric Gottenberg, Johanna M W Hazes, Tom Huizinga, Meghna Jani, Dmitry Karateev, Marios Kouloumas, Tore Kvien, Zhanguo Li, Xavier Mariette, Iain McInnes, Eduardo Mysler, Peter Nash, Karel Pavelka, Gyula Poór, Christophe Richez, Piet van Riel, Andrea Rubbert-Roth, Kenneth Saag, Jose da Silva, Tanja Stamm, Tsutomu Takeuchi, René Westhovens, Maarten de Wit, Désirée van der Heijde
Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib)...
March 6, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28260257/a-case-based-discussion-of-clinical-problems-in-the-management-of-patients-treated-with-ruxolitinib-for-myelofibrosis
#20
P Joy Ho, Ashish Bajel, Kate Burbury, Lindsay Dunlop, Simon Durrant, Cecily Forsyth, Andrew C Perkins, David M Ross
Ruxolitinib is a dual janus kinase 1 (JAK1)/JAK2 inhibitor used to treat splenomegaly and symptoms associated with myelofibrosis (MF). Current therapeutic options for symptomatic MF include supportive care, myelosuppressive therapy (such as hydroxycarbamide) and janus kinase (JAK) inhibitors (in particular ruxolitinib). Allogeneic stem cell transplantation remains the only potentially curative treatment for MF, and younger transplant-eligible patients should still be considered for allogeneic stem cell transplantation; however, this is applicable only to a small proportion of patients...
March 2017: Internal Medicine Journal
keyword
keyword
85922
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"