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Jak-inhibitor

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https://www.readbyqxmd.com/read/29471605/-emerging-therapies-what-are-promising-in-the-near-future
#1
REVIEW
Geom Seog Seo, Sung Hee Lee
The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective...
February 25, 2018: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/29470611/osteoporosis-in-rheumatic-diseases-anti-rheumatic-drugs-and-the-skeleton
#2
REVIEW
Alanna M Dubrovsky, Mie Jin Lim, Nancy E Lane
Osteoporosis in rheumatic diseases is a very well-known complication. Systemic inflammation results in both generalized and localized bone loss and erosions. Recently, increased knowledge of inflammatory process in rheumatic diseases has resulted in the development of potent inhibitors of the cytokines, the biologic DMARDs. These treatments reduce systemic inflammation and have some effect on the generalized and localized bone loss. Progression of bone erosion was slowed by TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab...
February 22, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29466675/emerging-drugs-for-alopecia-areata-jak-inhibitors
#3
Matilde Iorizzo, Antonella Tosti
Alopecia Areata is a common form of non-scarring hair loss that usually starts abruptly with a very high psychological impact. Due to the still not completely understood etiopathogenesis, at present there is no treatment that can induce a permanent remission and there is no drug approved for the treatment of this disorder. Areas covered: Leading existing treatment are briefly overviewed and then ongoing research on Janus Kinases Inhibitors is discussed, reviewing trials with oral and topical formulations so as new opportunities for other forms of alopecia, such as cicatricial alopecia...
February 21, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29458040/pharmacological-inhibition-of-jak3-enhances-the-antitumor-activity-of-imatinib-in-human-chronic-myeloid-leukemia
#4
Kenta Yagi, Akira Shimada, Toshiaki Sendo
Imatinib (IMA) is the standard treatment for CML; however, stopping IMA sometimes results in disease relapse, which suggests that leukemic stem cells (LSCs) remain in such patients, even after complete molecular remission has been achieved. Therefore, new strategies will be required to eradicate LSCs. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is part of the BCR-ABL signaling network, and it is activated in CML, especially in LSCs. JAK2 is known to be associated with CML survival, but the role of JAK3 in CML remains unknown...
February 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#5
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
February 14, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29454012/immunologic-effects-of-chronic-administration-of-tofacitinib-a-janus-kinase-inhibitor-in-cynomolgus-monkeys-and-rats-comparison-of-juvenile-and-adult-responses
#6
Mark Collinge, Douglas J Ball, Christopher J Bowman, Andrea L Nilson, Zaher A Radi, W Mark Vogel
Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3 inhibition impairs gamma common chain cytokine receptor signaling, important in lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus monkey and rat studies were conducted and the impact of tofacitinib on immune parameters (lymphoid tissues and lymphocyte subsets) and function (T-dependent antibody response (TDAR), mitogen-induced T cell proliferation) assessed...
February 14, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29452121/an-open-label-pilot-study-to-evaluate-the-efficacy-of-tofacitinib-in-moderate-to-severe-patch-type-alopecia-areata-totalis-and-universalis
#7
A Jabbari, F Sansaricq, J Cerise, J C Chen, A Bitterman, G Ulerio, J Borbon, R Clynes, A M Christiano, J Mackay-Wiggan
Alopecia areata (AA) is a common autoimmune disease, with a lifetime risk of ∼2%. In AA, the immune systems targets the hair follicle, resulting in clinical hair loss. AA prognosis is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Since these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors...
February 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29444362/the-use-of-jak-inhibitors-in-the-treatment-of-progressive-systemic-sclerosis
#8
Sandhya Chowdary Deverapalli, David Rosmarin
Systemic sclerosis is a connective tissue disorder characterized by fibrosis. Patients may have restricted movement of the joints, Raynaud's phenomenon, self-amputation of the digits, dyspnea, and upper gastrointestinal symptoms. Excessive production of extracellular matrix (ECM) proteins such as type I collagen via transforming growth factor β (TGF β) are thought to be responsible for the fibrosis. 1 This article is protected by copyright. All rights reserved.
February 14, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29441552/jak-inhibitors-appear-to-have-a-bright-future-in-the-treatment-of-atopic-dermatitis
#9
R Bissonnette
No abstract text is available yet for this article.
February 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29439310/lncrna-ab073614-induces-epithelial-mesenchymal-transition-of-colorectal-cancer-cells-via-regulating-the-jak-stat3-pathway
#10
Jinfang Xue, Liya Liao, Fang Yin, Haoyu Kuang, Xiaojun Zhou, Yanan Wang
BACKGROUND: LncRNAs are involved in the metastasis and recurrence of human tumors, including colorectal cancer (CRC). We previously reported that lncRNA AB073614 promotes tumor proliferation and metastasis and predicted a poor clinical outcome of CRC patients. Herein, we investigated the underlying mechanism of lncRNA AB073614-related metastasis in CRC. MATERIAL AND METHODS: The expression of lncRNA AB073614 in CRC tissues were evaluated by quantitative real-time PCR (qRT-PCR)...
January 26, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29433635/-current-and-upcoming-treatments-of-adult-atopic-dermatitis
#11
J-P Lacour
The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP...
December 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29424301/novel-therapeutic-approaches-in-rheumatoid-arthritis-role-of-janus-kinases-inhibitors
#12
Felice Rivellese, Antonio Lobasso, Letizia Barbieri, Bianca Liccardo, Amato De Paulis, Francesca Wanda Rossi
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29417241/myxovirus-resistance-protein-a-inhibits-hepatitis-c-virus-replication-through-jak-stat-pathway-activation
#13
Hailong Wang, Xiu Xin, Mingzhen Wang, Lingling Han, Jiadai Li, Yao Hao, Congyi Zheng, Chao Shen
The interferon-inducible dynamin-like GTPase myxovirus resistance protein A (MxA) exhibits activity against multiple viruses. However, its role in the life cycle of hepatitis C virus (HCV) is unclear, and the mechanisms underlying the anti-HCV activity of MxA require further investigation. In this study, we demonstrated that exogenous MxA expression in the Huh7 and Huh7.5.1 hepatoma cell lines significantly decreased the levels of HCV RNA and core proteins, whereas MxA knockdown exerted the opposite effect...
February 7, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29408565/in-vitro-induced-m2-type-macrophages-induces-the-resistance-of-prostate-cancer-cells-to-cytotoxic-action-of-nk-cells
#14
Lijun Xu, Mingjing Shen, Xiaodong Chen, Dong-Rong Yang, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells...
January 31, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29399328/jak-inhibitors-for-the-treatment-of-myeloproliferative-neoplasms-and-other-disorders
#15
REVIEW
William Vainchenker, Emilie Leroy, Laure Gilles, Caroline Marty, Isabelle Plo, Stefan N Constantinescu
JAK inhibitors have been developed following the discovery of the JAK2 V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL ) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity...
2018: F1000Research
https://www.readbyqxmd.com/read/29397859/-research-progress-on-effect-of-jak-inhibitors-on-myelofibrosis-review
#16
Jun-Xiu Liu, Wei Chen, Kai-Lin Xu
Myelofibrosis(MF) is a type of myeloprolifirative neoplasms which is difficult to be treated. With the discovery of V617F mutation site in Janus kinase 2 (JAK2), JAK inhibitor provides a new treatment strategy for patients with myelofibrosis. Since 2011 the FDA in USA approved the first generation of JAK inhibitor Ruxolitinib for marketing, a growing number of JAK inhibitors have been entering into the clinical trials and showed a certain clinical efficacy. On the one hand, some JAK inhibitors for single application can effectively relieve the clinical symptoms of patients with myelofibrosis, slow down disease progression, and prolong the survival; on the other hand, JAK inhibitor can also be applied in combination with traditional or other new targeted drugs for MF patients, even during the allogenetic hematopoietic stem cell transplantation, thus providing more choices for targeted therapy on the patients with myelofibrosis...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29396713/efficacy-and-safety-of-ruxolitinib-after-and-versus-interferon-use-in-the-response-studies
#17
Jean-Jacques Kiladjian, Paola Guglielmelli, Martin Griesshammer, Guray Saydam, Tamas Masszi, Simon Durrant, Francesco Passamonti, Mark Jones, Huiling Zhen, Jingjin Li, Brian Gadbaw, Julian Perez Ronco, Mahmudul Khan, Srdan Verstovsek
Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients...
February 2, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29383118/phosphoproteome-profiling-reveals-critical-role-of-jak-stat-signaling-in-maintaining-chemoresistance-in-breast-cancer
#18
Augusto S Nascimento, Luisa L Peres, Alessandra V S Fari, Renato Milani, Rodrigo A Silva, Celio Jr da Costa Fernandes, Maikel P Peppelenbosch, Carmen V Ferreira-Halder, Willian F Zambuzzi
Breast cancer is responsible for 25% of cancer cases and 15% of cancer death among women. Treatment is usually prolonged and hampered by the development of chemoresistance. The molecular mechanisms maintaining the chemoresistant phenotype remains, however, largely obscure. As kinase signaling in general is highly drugable, identification of kinases essential for maintaining chemoresistance could prove therapeutically useful. Hence we compared cellular kinase activity in chemotherapy resistant MCF7Res cells to chemotherapy-sensitive MCF cells using a peptide array approach that provides an atlas of cellular kinase activities and consequently, predominant pathways can be identified...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29377257/exposure-response-characterisation-of-tofacitinib-efficacy-in-moderate-to-severe-ulcerative-colitis-results-from-a-dose-ranging-phase-2-trial
#19
Arnab Mukherjee, Anasuya Hazra, Mike K Smith, Steven W Martin, Diane R Mould, Chinyu Su, Wojciech Niezychowski
BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule JAK inhibitor being investigated for UC. In a phase 2 dose-ranging study, tofacitinib demonstrated efficacy vs placebo as UC induction therapy. In this post-hoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC. METHODS: One- and two-compartment pharmacokinetic models, with first-order absorption and elimination, were evaluated to describe plasma tofacitinib concentration-time data at baseline and week 8...
January 28, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29352846/the-janus-kinase-inhibitor-tofacitinib-inhibits-tnf-%C3%AE-induced-gliostatin-expression-in-rheumatoid-fibroblast-like-synoviocytes
#20
Yohei Kawaguchi, Yuko Waguri-Nagaya, Naoe Tatematsu, Yusuke Oguri, Masaaki Kobayashi, Masahiro Nozaki, Kiyofumi Asai, Mineyoshi Aoyama, Takanobu Otsuka
OBJECTIVES: Gliostatin (GLS) is known to have angiogenic and arthritogenic activity, and GLS expression levels in serum from patients with rheumatoid arthritis (RA) are significantly correlated with the disease activity. Tofacitinib is a novel oral Janus kinase (JAK) inhibitor and is effective in treating RA. However, the mechanism of action of tofacitinib in fibroblast-like synoviocytes (FLSs) has not been elucidated. The purpose of this study was to investigate the modulatory effects of tofacitinib on serum GLS levels in patients with RA and GLS production in FLSs derived from patients with RA...
January 15, 2018: Clinical and Experimental Rheumatology
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