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https://www.readbyqxmd.com/read/29772037/a-review-of-fabry-disease
#1
A Cinats, E Heck
The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia...
May 2018: Skin Therapy Letter
https://www.readbyqxmd.com/read/29765973/complete-regrowth-of-beard-hair-with-ruxolitinib-in-an-alopecia-universalis-patient
#2
Yuval Ramot, Abraham Zlotogorski
While most alopecia areata (AA) cases resolve spontaneously, the more severe types of AA, alopecia totalis (AT) and alopecia universalis (AU), can be highly resistant to therapy. We report on a 33-year-old ultraorthodox Jewish man with an 11-year history of AA that resulted in complete loss of the scalp and body hair 7 years ago. Previous treatments with intralesional and systemic corticosteroids had only partial and temporary effects. The patient was treated with ruxolitinib, 20 mg twice daily, resulting in complete growth of the beard after 4 months of treatment...
April 2018: Skin Appendage Disorders
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#3
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29765118/ifn-%C3%AE-s-inhibit-hantaan-virus-infection-through-the-jak-stat-pathway-and-expression-of-mx2-protein
#4
Ning Li, Fan Luo, Qingzhou Chen, Ni Zhu, Hui Wang, Linlin Xie, Hairong Xiong, Ming Yue, Yun Zhang, Yong Feng, Wei Hou
Hantaan virus (HTNV), member of the newly defined Hantaviridae family, within the order Bunyavirales, can cause a hemorrhagic fever with renal syndrome with high fatality rates in humans. However, no specific antiviral agents are currently available for HTNV infection approved by the US Food and Drug Administration. Although interferon lambdas (IFN-λs) have been shown to induce an antiviral state against HTNV, the molecular mechanisms remain to be determined. In this study, we found that IFN-λs exerted its anti-HTNV effect by activating Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway-mediated antiviral immunity in A549 cells...
May 15, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#5
Daniel G Stover, Carlos R Gil Del Alcazar, Jane Brock, Hao Guo, Beth Overmoyer, Justin Balko, Qiong Xu, Aditya Bardia, Sara M Tolaney, Rebecca Gelman, Maxwell Lloyd, Yu Wang, Yaomin Xu, Franziska Michor, Vivian Wang, Eric P Winer, Kornelia Polyak, Nancy U Lin
Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study enrolling patients with refractory, metastatic triple-negative breast cancer. The primary endpoint was objective response by RECIST 1.1. The study was designed to enroll patients whose archival tumor tissue was pSTAT3-positive ( T -score >5) by central immunohistochemistry...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29757976/fatty-acid-%C3%AE-oxidation-is-essential-in-leptin-mediated-oocytes-maturation-of-yellow-catfish-pelteobagrus-fulvidraco
#6
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755657/regulatory-effect-of-anti-gp130-functional-mab-on-il-6-mediated-rankl-and-wnt5a-expression-through-jak-stat3-signaling-pathway-in-fls
#7
Ping Miao, Xiao Wei Zhou, Ping Wang, Rong Zhao, Ninan Chen, Chao Ying Hu, Xue Hua Chen, Liu Qian, Qi Wen Yu, Ji Ying Zhang, Rong Xu, Dong Yi He, Lian Bo Xiao, Pu Li, Mason Lu, Dong Qing Zhang
We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined the interleukin 6 (IL-6), IL-6 receptor α (IL-6Rα), gp130, receptor activator of nuclear factor κB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Rα; WNT5A and RANKL levels were detected...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29751177/activation-of-the-il-6-jak2-stat3-pathway-induces-plasma-cell-mastitis-in-mice
#8
Yang Liu, Jian Zhang, Yu-Hui Zhou, Hui-Min Zhang, Ke Wang, Yu Ren, Yi-Na Jiang, Shui-Ping Han, Jian-Jun He, Xiao-Jiang Tang
Plasma cell mastitis (PCM) is a chronic mastitis with limited treatment options and common recurrence. A histopathological hallmark of PCM is the infiltration of numerous plasma cells surrounding the mammary duct. Our previous study showed that the activity of the IL-6/STAT3 signaling pathway was elevated in patients with PCM. However, the etiology of PCM remains largely unclear. In this study, we sought to explore the effects of IL-6/JAK2/STAT3 signaling pathway in the pathogenesis of PCM. Histological analysis showed that the mammary glands of mice that received human breast tissue homogenates, followed by an injection of IL-6, exhibited features of PCM similar to human PCM...
May 8, 2018: Cytokine
https://www.readbyqxmd.com/read/29750040/a-phase-ib-study-of-ruxolitinib-gemcitabine-%C3%A2-nab-paclitaxel-in-patients-with-advanced-solid-tumors
#9
Todd M Bauer, Manish R Patel, Andres Forero-Torres, Thomas J George, Albert Assad, Yining Du, Herbert Hurwitz
Purpose: Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients and methods: Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29741608/jak-inhibitor-improves-type-i-interferon-induced-damage-proof-of-concept-in-dermatomyositis
#10
Leandro Ladislau, Xavier Suárez-Calvet, Ségolène Toquet, Océane Landon-Cardinal, Damien Amelin, Marine Depp, Mathieu P Rodero, Denisa Hathazi, Darragh Duffy, Vincent Bondet, Corinna Preusse, Boris Bienvenu, Flore Rozenberg, Andreas Roos, Claudia F Benjamim, Eduard Gallardo, Isabel Illa, Vincent Mouly, Werner Stenzel, Gillian Butler-Browne, Olivier Benveniste, Yves Allenbach
Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy and vasculopathy. Dermatomyositis patients display an upregulation of type I interferon-inducible genes in muscle fibres, endothelial cells, skin and peripheral blood. However, the effect of type I interferon on muscle tissue has not yet been determined. Our aim was to study the pathogenicity of type I interferon in vitro and to evaluate the efficacy of the type I interferon pathway blockade for therapeutic purposes...
May 8, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29741513/myelofibrosis-clinicopathologic-features-prognosis-and-management
#11
Jennifer M O'Sullivan, Claire N Harrison
Myelofibrosis is one of the BCR-ABL-negative clonal disorders that collectively are known as myeloproliferative neoplasms (MPNs). It is caused by the proliferation of clonal hematopoietic stem cells, which over time leads to characteristic clinical features. The disease presentation is heterogeneous, however, with 30% of patients initially asymptomatic. This variation in clinical phenotype warrants careful risk stratification to guide appropriate management, and prognostic risk scores are continually being refined...
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741224/angiotensin-ii-enhances-the-acetylation-and-release-of-hmgb1-in-raw264-7-macrophage
#12
Shanshan Zhou, Hongxiang Lu, Rong Chen, Yu Tian, YuanYuan Jiang, Shiqing Zhang, Daobing Ni, Zhaoliang Su, Xiaoyi Shao
The high-mobility group box-1 (HMGB1), as a highly conserved ubiquitous DNA-binding protein, has been widely studied in various diseases, including inflammation and tumor; however, fewer studies were focused on the mechanisms controlling HMGB1 release compared with the function of HMGB1. Previous studies have proven that ANG II can act as a pro-inflammatory cytokine, both of HMGB1 and ANG II were significantly upregulated in autoimmune diseases, however, the exact role of ANG II in regulating HMGB1 release have not been shown...
May 9, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29738047/tofacitinib-represses-the-janus-kinase-signal-transducer-and-activators-of-transcription-signalling-pathway-in-keratinocytes
#13
Ankit Srivastava, Mona Ståhle, Andor Pivarcsi, Enikö Sonkoly
Tofacitinib is a Janus kinase (JAK) inhibitor, which has shown efficacy in treating psoriasis. The mode of action of tofacitinib is not completely understood but it has been thought to be mediated by the inhibition of CD4+ T-cell activation. Here, we investigated whether the molecular targets of tofacitinib are expressed in keratinocytes, and whether tofacitinib can modulate the activity of the JAK/Signal Transducer and Activators of Transcription (STAT)-pathway in keratinocytes. Transcriptomic profiling of human keratinocytes treated with IL-22 in combination with tofacitinib revealed that tofacitinib could prevent the majority of IL-22-mediated gene expression changes...
May 8, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29737092/-study-of-kinase-inhibitor-wp1066-on-the-stat3-jak2-of-prostate-stromal-cells
#14
Yun-Xiang Li, Jin-Ming Li, Qiang Wei, Zong-Ping Zhang, Ji Wu, An-Guo Wang
OBJECTIVE: To study the role of JAK2 signaling pathway in prostate stromal cells and the effect of inhibitor WP1066 on its expression. METHODS: The phosphorylation of JAK2 and STAT3 in prostate tissues of patients with benign prostatic hyperplasia (BHP) ( n =4) and severe histological prostatitis (HP) plus BPH ( n =4) was tested by using Western blot to verify the activation of their mediated signaling pathway. Kinase inhibitor WP1066 was added to prostate stromal cells to detect inhibition of the JAK2 and STAT3 activation launched by IL-6...
January 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29731464/-diagnosis-and-treatment-of-rheumatoid-arthritis-toward-the-best-practice-best-practice-with-jak-inhibitors
#15
Kunihiro Yamaoka
Janus kinase(JAK)inhibitor is a new orally available disease modifying anti-rheumatic drug that has shown anti-rheumatic effect resembling biologics. Clinical trials for autoinflammatory and autoimmune diseases are under investigation. Administration route is convenient compared to biologics and possess high anti-rheumatic effect, however specific side effects considered as a class-effect exists. I would like to offer the best conceivable practice with JAK inhibitors based on evidence from clinical trials and real world experiences...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29731458/-diagnosis-and-treatment-of-rheumatoid-arthritis-toward-the-best-practice-new-therapeutic-target-for-rheumatoid-arthritis
#16
Toshihiro Nanki
For rheumatoid arthritis, biological DMARDs, such as TNF inhibitors, and JAK inhibitors have been widely used as a targeted therapy. These drugs show higher effect compared to conventional therapy. New molecular targeted drugs are also developing. Clinical trials of anti-GM-CSF and -chemokine monoclonal antibodies, and inhibitors of intracellular signals are underway. We anticipate new drugs with higher efficacy and safety.
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29725131/interleukin-6-designing-specific-therapeutics-for-a-complex-cytokine
#17
REVIEW
Christoph Garbers, Sylvia Heink, Thomas Korn, Stefan Rose-John
Interleukin-6 (IL-6) is a pivotal cytokine with a diverse repertoire of physiological functions that include regulation of immune cell proliferation and differentiation. Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders such as rheumatoid arthritis and Castleman disease, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. So far, monoclonal antibodies against IL-6 or IL-6 receptor (IL-6R) and Janus kinases (JAK) inhibitors have been successfully developed for the treatment of autoimmune diseases such as rheumatoid arthritis...
May 4, 2018: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29709516/cancer-associated-fibroblasts-stimulated-interleukin-11-promotes-metastasis-of-gastric-cancer-cells-mediated-by-upregulation-of-muc1
#18
Xiaoxun Wang, Xiaofang Che, Chang Liu, Yibo Fan, Ming Bai, Kezuo Hou, Xiaonan Shi, Xiaojie Zhang, Bofang Liu, Chunlei Zheng, Yunpeng Liu, Xiujuan Qu
Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma and regulators of tumor progression. However, the molecular mechanism by which CAFs promote gastric cancer progression should be further explored. In our study, we found that interleukin-11 (IL-11) secretion was significantly increased when CAFs were co-cultured with gastric cancer cells. Co-culture system-derived IL-11 promoted the migration and invasion of gastric cancer cells, whereas the increase of migration and invasion was attenuated by a neutralizing antibody of IL-11 or inhibition of JAK/STAT3 and MAPK/ERK pathways with specific inhibitors...
April 27, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29702085/tnf-%C3%AE-sensitive-brain-pericytes-activate-microglia-by-releasing-il-6-through-cooperation-between-i%C3%AE%C2%BAb-nf%C3%AE%C2%BAb-and-jak-stat3-pathways
#19
Junichi Matsumoto, Shinya Dohgu, Fuyuko Takata, Takashi Machida, Funda F Bölükbaşi Hatip, Izzettin Hatip-Al-Khatib, Atsushi Yamauchi, Yasufumi Kataoka
Interleukin (IL)-6 is an important mediator of neurovascular dysfunction, neurodegeneration and/or neuroinflammation. We previously reported that brain pericytes released higher levels of IL-6 than did glial cells (astrocytes and microglia) in response to tumor necrosis factor (TNF)-α. Moreover, pericytes stimulated with TNF-α enhanced activation of BV-2 microglia. In this study, we investigated the mechanisms of TNF-α mediated induction of IL-6 release from brain pericytes and astrocytes and whether pericyte-derived IL-6 would facilitate activation of BV-2 microglia...
April 24, 2018: Brain Research
https://www.readbyqxmd.com/read/29701124/the-use-of-tofacitinib-in-the-treatment-of-inflammatory-bowel-disease
#20
Roni Weisshof, Maya Aharoni Golan, Olivia V Yvellez, David T Rubin
Janus kinases (JAK) play a major role in the immunologic pathways and specifically in signal transduction in inflammatory bowel disease. Thus, they can serve as a target for new therapeutic options. Tofacitinib is a novel, first-in-class, pan-Janus kinase inhibitor. It has been found to be effective and safe in the treatment of moderate-to-severe ulcerative colitis. In this review, we will describe the drug's mechanism of action as well as the clinical evidence for its effectiveness in treating patients with inflammatory bowel disease...
April 27, 2018: Immunotherapy
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