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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
#1
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/29438765/treatment-of-vitiligo-with-the-topical-janus-kinase-inhibitor-ruxolitinib-a-32-week-open-label-extension-study-with-optional-narrow-band-ultraviolet-b
#2
Deep Joshipura, Abdulaziz Alomran, Pedro Zancanaro, David Rosmarin
No abstract text is available yet for this article.
February 10, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29436642/synergistic-anticancer-effects-of-ruxolitinib-and-calcitriol-in-estrogen-receptor%C3%A2-positive-human-epidermal-growth-factor-receptor-2%C3%A2-positive-breast-cancer-cells
#3
Seung Taek Lim, Ye Won Jeon, Hongki Gwak, Se Young Kim, Young Jin Suh
The Janus kinase (JAK)1 and JAK2 inhibitor, ruxolitinib, and the active form of vitamin D (calcitriol) were previously reported to possess anticancer effects in breast cancer. The present study investigated the combined effects of ruxolitinib and calcitriol on an estrogen receptor (ER)‑positive, human epidermal growth factor receptor 2 (HER2)‑positive, breast cancer cell line. The ER and HER2‑positive MCF7‑HER18 breast cancer cell line was used to investigate the combination effect of ruxolitinib and calcitriol...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29417241/myxovirus-resistance-protein-a-inhibits-hepatitis-c-virus-replication-through-jak-stat-pathway-activation
#4
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/29399328/jak-inhibitors-for-the-treatment-of-myeloproliferative-neoplasms-and-other-disorders
#5
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
#6
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
#7
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/29388547/chlamydia-trachomatis-inhibits-the-production-of-pro-inflammatory-cytokines-in-human-pbmcs-through-induction-of-il-10
#8
Kun Du, Ming Zhou, Qi Li, Xue-Zheng Liu
PURPOSE: Previous research demonstrated that IL-10 was up-regulated in Chlamydia trachomatis-infected cells and that exogenous IL-10 was able to inhibit the secretion of pro-inflammatory cytokines by infected cells. However, the mechanisms are not well understood. The aim of this study was to investigate the mechanisms for up-regulation of IL-10 and inhibition of pro-inflammatory cytokine secretion in C. trachomatis-stimulated peripheral blood mononuclear cells (PBMCs). METHODOLOGY: Human PBMCs were isolated from the blood of healthy human donors by standard Ficoll-Hypaque density gradient centrifugation...
February 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29367708/ruxolitinib-a-steroid-sparing-agent-in-chronic-graft-versus-host-disease
#9
Hanna Jean Khoury, Amelia A Langston, Vamsi K Kota, Jennifer A Wilkinson, Iskra Pusic, Anand Jillella, Stephanie Bauer, Audrey S Kim, Danielle Roberts, Zaid Al-Kadhimi, Imre Bodo, Elliott Winton, Martha Arellano, John F DiPersio
Inhibition of the Janus-associated kinases (JAK) with ruxolitinib (RUX) reduces graft-versus-host disease (GVHD) in preclinical and clinical models. In total 19 allograft recipients with moderate/severe steroid-dependent chronic GVHD received RUX as ≥2nd line salvage. RUX was well tolerated, and led to complete/partial resolution of oral (92/7%), cutaneous (82/0%), hepatic (71/28%), gastro-intestinal (75/17%), musculoskeletal (33/67%), pulmonary (0/80%), scleroderma (0/75%), vaginal (0/75%), and ocular (0/100%) chronic GVHD...
January 24, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29363542/ruxolitinib-protects-skin-stem-cells-and-maintains-skin-homeostasis-in-murine-graft-versus-host-disease
#10
Shuichiro Takahashi, Daigo Hashimoto, Eiko Hayase, Reiki Ogasawara, Hiroyuki Ohigashi, Takahide Ara, Emi Yokoyama, Ko Ebata, Satomi Matsuoka, Geoffrey Hill, Junichi Sugita, Masahiro Onozawa, Takanori Teshima
Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT...
January 23, 2018: Blood
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#11
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29344542/ruxolitinib-for-essential-thrombocythemia
#12
EDITORIAL
Prithviraj Bose, Srdan Verstovsek
No abstract text is available yet for this article.
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29321520/essential-thrombocythemia-treatment-algorithm-2018
#13
REVIEW
Ayalew Tefferi, Alessandro M Vannucchi, Tiziano Barbui
Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29316837/ruxolitinib-for-the-treatment-of-patients-with-steroid-refractory-gvhd-an-introduction-to-the-reach-trials
#14
Madan Jagasia, Robert Zeiser, Michael Arbushites, Patricia Delaite, Brian Gadbaw, Nikolas von Bubnoff
For patients with hematologic malignancies and disorders, allogeneic hematopoietic stem cell transplantation offers a potentially curative treatment option. Many patients develop graft-versus-host disease (GVHD), a serious complication and leading cause of nonrelapse mortality. Corticosteroids are the standard first-line treatment for GVHD; however, patients often become steroid-refractory or remain corticosteroid-dependent. New second-line treatment options are needed to improve patient outcomes. Here we review the role of JAK1 and JAK2 in acute and chronic GVHD...
January 10, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29296819/impact-of-genomic-alterations-on-outcomes-in-myelofibrosis-patients-undergoing-jak1-2-inhibitor-therapy
#15
Jay Y Spiegel, Caroline McNamara, James A Kennedy, Tony Panzarella, Andrea Arruda, Tracy Stockley, Mahadeo Sukhai, Mariam Thomas, Justyna Bartoszko, Jenny Ho, Nancy Siddiq, Dawn Maze, Aaron Schimmer, Andre Schuh, Hassan Sibai, Karen Yee, Jamie Claudio, Rebecca Devlin, Mark D Minden, Suzanne Kamel-Reid, Vikas Gupta
In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296813/oncogenic-role-and-therapeutic-targeting-of-abl-class-and-jak-stat-activating-kinase-alterations-in-ph-like-all
#16
Kathryn G Roberts, Yung-Li Yang, Debbie Payne-Turner, Wenwei Lin, Jacob K Files, Kirsten Dickerson, Zhaohui Gu, Jack Taunton, Laura J Janke, Taosheng Chen, Mignon L Loh, Stephen P Hunger, Charles G Mullighan
New therapies for Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) patients are urgently needed. The genetic landscape of Ph-like ALL is characterized by a diverse array of kinase-activating alterations (including rearrangements, sequence mutations, and copy number alterations), suggesting that patients with Ph-like ALL are candidates for targeted therapy, similar to BCR-ABL1 ALL. We sought to investigate the functional role and targetability of the spectrum of kinase-activating alterations identified in Ph-like ALL...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296794/ruxolitinib-for-treatment-of-refractory-hemophagocytic-lymphohistiocytosis
#17
Larisa Broglie, Lauren Pommert, Sridhar Rao, Monica Thakar, Rachel Phelan, David Margolis, Julie Talano
Optimal salvage therapy for refractory HLH is unknown.In our patient, ruxolitinib treatment led to clinical remission of refractory HLH.
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295936/gene-regulation-and-suppression-of-type-i-interferon-signaling-by-stat3-in-diffuse-large-b-cell-lymphoma
#18
Li Lu, Fen Zhu, Meili Zhang, Yangguang Li, Amanda C Drennan, Shuichi Kimpara, Ian Rumball, Christopher Selzer, Hunter Cameron, Ashley Kellicut, Amanda Kelm, Fangyu Wang, Thomas A Waldmann, Lixin Rui
STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29285836/disease-and-treatment-characteristics-of-polycythaemia-vera-patients-in-belgium-results-from-a-scientific-survey
#19
Timothy Devos, Yves Beguin, Lucien Noens, Koen Van Eygen, Pierre Zachée, Philippe Mineur, Laurent Knoops, Chantal Doyen, Koen Theunissen, Fleur Samantha Benghiat, Michael Reusens, Wim Pluymers
OBJECTIVE: The current survey aimed to gather pre-defined disease parameters and treatment strategies to characterize the polycythaemia vera (PV) patient population in Belgium METHODS: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analysed descriptively and quantitatively RESULTS: Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age...
December 29, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29280197/fulminant-cryptococcus-neoformans-infection-with-fatal-pericardial-tamponade-in-a-patient-with-chronic-myelomonocytic-leukemia-who-was-treated-with-ruxolitinib-case-report-and-review-of-fungal-pericarditis
#20
Jing Liu, Elie Mouhayar, Jeffrey J Tarrand, Dimitrios P Kontoyiannis
Cryptococcus neoformans is a saprophytic fungal pathogen that can cause serious illness in immune-compromised hosts and it presents with a wide variety of clinical symptoms. We present a fatal case of fulminant C. neoformans infection presenting as pericardial tamponade in a 71-year-old male with chronic myelomonocytic leukemia undergoing chemotherapy with the JAK-STAT inhibitor ruxolitinib. We also review the published cases of fungal pericarditis/tamponade. In addition to illustrating an atypical presentation of C...
December 27, 2017: Mycoses
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