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Ruxolitinib

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https://www.readbyqxmd.com/read/28087229/disease-associated-mutations-identify-a-novel-region-in-human-sting-necessary-for-the-control-of-type-i-interferon-signaling
#1
Isabelle Melki, Yoann Rose, Carolina Uggenti, Lien Van Eyck, Marie-Louise Frémond, Naoki Kitabayashi, Gillian I Rice, Emma M Jenkinson, Anaïs Boulai, Nadia Jeremiah, Marco Gattorno, Sefano Volpi, Olivero Sacco, Suzanne W J Terheggen-Lagro, Harm A W M Tiddens, Isabelle Meyts, Marie-Anne Morren, Petra De Haes, Carine Wouters, Eric Legius, Anniek Corveleyn, Frederic Rieux-Laucat, Christine Bodemer, Isabelle Callebaut, Mathieu P Rodero, Yanick J Crow
BACKGROUND: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). OBJECTIVES: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease...
January 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28072602/-janus-kinase-ing-up-the-treatment-of-primary-myelofibrosis-building-better-combination-strategies
#2
Rita Assi, Srdan Verstovsek, Naval Daver
PURPOSE OF REVIEW: The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors-based combinatorial strategies in this setting. RECENT FINDINGS: Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of life, and an overall survival advantage with prolonged follow-up...
January 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28053127/potent-emt-and-csc-phenotypes-are-induced-by-oncostatin-m-in-pancreatic-cancer
#3
Jacob M Smigiel, Neetha Parameswaran, Mark W Jackson
: Pancreatic ductal adenocarcinoma (PDAC) is referred to as a silent killer due to the lack of clear symptoms, a lack of early detection methods, and a high frequency of metastasis at diagnosis. In addition, pancreatic cancer is remarkably resistant to chemotherapy, and clinical treatment options remain limited. The tumor microenvironment (TME) and associated factors are important determinants of metastatic capacity and drug resistance. Here, oncostatin M (OSM), an IL-6 cytokine family member, was identified as an important driver of mesenchymal and cancer stem cell (CSC) phenotypes...
January 4, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28042780/modulation-of-the-type-i-interferon-response-defines-the-sensitivity-of-human-melanoma-cells-to-oncolytic-measles-virus
#4
Ferdaous Allagui, Carole Achard, Clarisse Panterne, Chantal Combredet, Nathalie Labarrière, Brigitte Dréno, Amel Benammar Elgaaied, Daniel Pouliquen, Frédéric Tangy, Jean-François Fonteneau, Marcela Grégoire, Nicolas Boisgerault
BACKGROUND: Oncolytic viruses such as live-attenuated, vaccine strains of measles virus (MV) have recently emerged as promising cancer treatments, having shown significant antitumor activity against a large variety of human tumors. OBJECTIVE: Our study aims at determining which parameters define the sensitivity of human melanoma cells to oncolytic MV infection. METHOD: We analyzed both in vitro and in vivo the oncolytic activity of MV against a panel of human melanoma cell lines established in our laboratory...
January 2, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28042144/novel-bet-protein-proteolysis-targeting-chimera-bet-protac-exerts-superior-lethal-activity-than-bromodomain-inhibitor-beti-against-post-myeloproliferative-neoplasm-mpn-secondary-s-aml-cells
#5
D T Saenz, W Fiskus, Y Qian, T Manshouri, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, C P Mill, B Sun, P Qiu, T M Kadia, N Pemmaraju, C DiNardo, M-S Kim, A J Nowak, C Coarfa, C M Crews, S Verstovsek, K N Bhalla
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Whereas the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells...
January 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28035720/wp1066-suppresses-macrophage-cell-death-induced-by-inflammasome-agonists-independently-of-its-inhibitory-effect-on-stat3
#6
Shino Honda, Daichi Sadatomi, Yasuo Yamamura, Kazutaka Nakashioya, Susumu Tanimura, Kohsuke Takeda
The compound WP1066 was originally synthesized by modifying the structure of AG490, which inhibits the activation of signal transducer and activator of transcription 3 (STAT3) by directly targeting Janus kinases (JAKs). WP1066 exhibits stronger anti-cancer activity than AG490 against malignant glioma and other cancer cells and is regarded as a promising therapeutic agent. By screening a small library of target-known compounds, we identified WP1066 as an inhibitor of macrophage cell death induced by agonists of the NLRP3 inflammasome, an intracellular protein complex required for the processing of the proinflammatory cytokine interleukin (IL)-1β...
December 30, 2016: Cancer Science
https://www.readbyqxmd.com/read/28031554/enhanced-mapk-signaling-is-essential-for-csf3r-induced-leukemia
#7
S Rohrabaugh, M Kesarwani, Z Kincaid, E Huber, J Leddonne, Z Siddiqui, Y Khalifa, K Komurov, H L Grimes, M Azam
Both membrane-proximal and truncation mutations in CSF3R have recently been reported to drive the onset of chronic neutrophilic leukemia (CNL). Here we show that although truncation mutation alone can not induce leukemia, both proximal and compound mutations (proximal and truncation mutations on same allele) are leukemogenic with a disease latency of 90 and 23 days, respectively. Comparative whole-genome expression profiling and biochemical experiments revealed that induced expression of Mapk adaptor protein Ksr1 and enhanced Mapk signaling are crucial to leukemogenesis by CSF3R proximal and compound mutants...
December 29, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28031182/does-ruxolitinib-prolong-the-survival-of-patients-with-myelofibrosis
#8
Francisco Cervantes, Arturo Pereira
No abstract text is available yet for this article.
December 28, 2016: Blood
https://www.readbyqxmd.com/read/28028027/emerging-treatments-for-classical-myeloproliferative-neoplasms
#9
Alessandro M Vannucchi, Claire Harrison
There has been a major revolution in the management of patients with myeloproliferative neoplasms (MPN), in particular those with myelofibrosis and extensive splenomegaly and symptomatic burden, following the introduction of the JAK1 and JAK2 inhibitor ruxolitinib. The drug has been later approved also as second line therapy for polycythemia vera (PV). However, the therapeutic armamentarium for MPN is still largely inadequate to cope with the major unmet patients' needs, that include normalization of life span (MF and some PV patients), reduction of cardiovascular complications (mainly PV and essential thrombocythemia (ET)), prevention of hematological progression and improved quality of life (all MPN)...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28024126/janus-kinase-jak-inhibitors-for-the-treatment-of-skin-and-hair-disorders-a-review-of-literature
#10
Aniseh Samadi, Saman Ahmad Nasrollahi, Ashkan Hashemi, Mansour Nassiri-Kashani, Alireza Firooz
Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are U.S. FDA approved drugs in this family approved for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. We overview the JAK/STAT signaling pathway and its involvement in skin diseases...
December 26, 2016: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28011890/idiopathic-myelofibrosis-with-disseminated-hepatosplenic-mesenteric-renal-and-pulmonary-extramedullary-haematopoeisis-portal-hypertension-and-tuberculosis-initial-presentation-and-2%C3%A2-years-follow-up
#11
Ananya Panda, Sheragaru Hanumanthappa Chandrashekhara, Aruna Nambirajan, Pravas Mishra
A 35-year-old man with a 12-year history of idiopathic myelofibrosis (IMF) presented in 2014 with fatigue and abdominal distension. CT scan revealed massive hepatosplenomegaly with focal splenic lesions, soft tissue around renal pelvis, mesenteric masses compressing bowel loops and perilymphatic nodules in lungs. There was portal hypertension, ascites, pleural effusion, bilateral psoas abscesses and necrotic retroperitoneal lymphadenopathy. MRI additionally revealed hypointense periportal infiltrative lesions in liver, not seen on CT scan...
December 23, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/28007736/cervantes-f-vannucchi-am-kiladjian-j-j-et-al-three-year-efficacy-safety-and-survival-findings-from-comfort-ii-a-phase-3-study-comparing-ruxolitinib-with-best-available-therapy-for-myelofibrosis-blood-2013-122-25-4047-4053
#12
https://www.readbyqxmd.com/read/27998278/janus-kinase-inhibition-suppresses-pkc-induced-cytokine-release-without-affecting-hiv-1-latency-reversal-ex-vivo
#13
Adam M Spivak, Erin T Larragoite, McKenna L Coletti, Amanda B Macedo, Laura J Martins, Alberto Bosque, Vicente Planelles
BACKGROUND: Despite the durable viral suppression afforded by antiretroviral therapy, HIV-1 eradication will require strategies to target latently infected cells that persist in infected individuals. Protein kinase C (PKC) activation is a promising strategy to reactivate latent proviruses and allow for subsequent recognition and clearance of infected cells by the immune system. Ingenol derivatives are PKC agonists that induce latency reversal but also lead to T cell activation and the release of pro-inflammatory cytokines, which would be undesirable in vivo...
December 20, 2016: Retrovirology
https://www.readbyqxmd.com/read/27983880/how-ruxolitinib-modified-the-outcome-in-myelofibrosis-focus-on-overall-survival-allele-burden-reduction-and-fibrosis-changes
#14
Fulvio Massaro, Matteo Molica, Massimo Breccia
Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor that has shown superiority as compared to available conventional chemotherapies, in terms of reduction in splenomegaly and improvement of symptoms and quality of life. Areas covered: Data published about overall survival in the major randomized sponsored trials and in independent series of patients were detailed. Indeed, data regarding action of ruxolitinib on allele burden reduction and potential activity of the drug on pathogenetic mechanisms involved in increased fibrosis has been reviewed...
December 16, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27971738/cost-effectiveness-of-ruxolitinib-versus-best-available-therapy-for-the-treatment-of-myelofibrosis-from-public-health-perspective-in-chile
#15
R Rojas, C Balmaceda, C Vargas, M A Espinoza
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27971666/real-world-evidence-of-ruxolitinib-in-the-treatment-of-myelofibrosis-experince-of-a-portuguese-hospital-center
#16
A Almeida, K Alnajjar, D Viriato
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27971662/off-label-use-of-ruxolitinib-in-refractory-graft-versus-host-disease-after-allogenic-stem-cell-transplantation
#17
L L Poyatos-Ruiz, M D Vega-Coca, S Flores-Moreno, A Garcia-Avello, L Abdel-Kader-Martin, C Calderon-Cabrera
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27966016/austrian-recommendations-for-the-management-of-primary-myelofibrosis-post-polycythemia-vera-myelofibrosis-and-post-essential-thrombocythemia-myelofibrosis-an-expert-statement
#18
Thamer Sliwa, Christine Beham-Schmid, Sonja Burgstaller, Veronika Buxhofer-Ausch, Günther Gastl, Klaus Geissler, Maria Krauth, Peter Krippl, Alois Lang, Andreas Petzer, Stefan Wöhrer, Albert Wölfler, Heinz Gisslinger
The entity "myelofibrosis" represents a subgroup of the Philadelphia chromosome-negative myeloproliferative neoplasms. It comprises primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. This heterogeneous disease is characterized by clonal myeloproliferation, dysregulated kinase signalling and the abnormal expression of several proinflammatory cytokines. Clinically, patients present with symptoms related to thrombocytosis/leukocytosis, anemia and/or progressive splenomegaly...
December 13, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27956543/drug-development-pipeline-for-myeloproliferative-neoplasms-potential-future-impact-on-guidelines-and-management
#19
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of ruxolitinib in myelofibrosis (MF) has paved the way for the development of other Janus kinase (JAK) inhibitors and other agents representing diverse drug classes and mechanisms of action in myeloproliferative neoplasms (MPNs). In particular, the symptomatic benefits afforded by ruxolitinib have led to the recognition of "clinical improvement" in symptoms and the spleen in international consensus response criteria for MF. Ruxolitinib is also approved for the second-line treatment of polycythemia vera and is being developed for essential thrombocythemia...
December 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27930945/a-phase-ii-study-of-panobinostat-in-patients-with-primary-myelofibrosis-pmf-and-post-polycythemia-vera-essential-thrombocythemia-myelofibrosis-post-pv-et-mf
#20
John Mascarenhas, Lonette Sandy, Min Lu, James Yoon, Bruce Petersen, David Zhang, Fei Ye, Carrie Newsom, Vesna Najfeld, Tsivia Hochman, Judith D Goldberg, Ronald Hoffman
Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis...
November 30, 2016: Leukemia Research
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