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https://www.readbyqxmd.com/read/28721333/pulmonary-cryptococcosis-in-a-ruxolitinib-treated-patient-with-primary-myelofibrosis
#1
Anna Hirano, Masahiro Yamasaki, Naomi Saito, Koji Iwato, Wakako Daido, Kunihiko Funaishi, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi
We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28712096/myeloproliferative-neoplasms-translating-new-discoveries-into-better-outcomes-better-quality-of-life
#2
REVIEW
Leslie Padrnos, Ruben A Mesa
Despite the identification of JAK mutations and the development of targeted inhibitors, there remain significant unmet needs for patients with myeloproliferative neoplasms. Identification of the myeloproliferative neoplasm populations not currently benefiting from JAK inhibitor therapy highlights the therapeutic deficits still present in this heterogeneous stem cell malignancy. While JAK inhibition has provided significant benefits for patients with intermediate-2 or high-risk myelofibrosis and in patients with polycythemia vera in the second-line setting, JAK inhibitor monotherapy is not approved and not appropriate for all patients with myeloproliferative neoplasms...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28711084/herpes-zoster-in-psoriasis-patients-treated-with-tofacitinib
#3
Kevin L Winthrop, Mark Lebwohl, Arnon D Cohen, Jeffrey M Weinberg, Stephen K Tyring, Scott T Rottinghaus, Pankaj Gupta, Kaori Ito, Huaming Tan, Mandeep Kaur, Alexander Egeberg, Lotus Mallbris, Hernan Valdez
BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models...
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28690841/new-frontiers-in-the-treatment-of-systemic-juvenile-idiopathic-arthritis
#4
REVIEW
Susan Canny, Elizabeth Mellins
Systemic juvenile idiopathic arthritis (sJIA) and its most significant complication, macrophage activation syndrome (MAS), have traditionally been treated with steroids and non-steroidal anti-inflammatory medications. However, the introduction of biologic medications that inhibit specific cytokines, such interleukins 1 and 6, has changed the treatment paradigm for sJIA patients. In this review, we discuss the therapies currently used in the treatment of sJIA as well as novel targets and approaches under consideration, including mesenchymal stromal cell therapy and JAK inhibitors...
2017: F1000Research
https://www.readbyqxmd.com/read/28677733/sulforaphane-inhibits-the-interferon-%C3%AE-induced-expression-of-mig-ip-10-and-i-tac-in-ins%C3%A2-1-pancreatic-%C3%AE-cells-through-the-downregulation-of-irf-1-stat-1-and-pkb
#5
Yu-Kyoung Park, Mahesh Ramalingam, Shin Kim, Byeong-Churl Jang, Jong Wook Park
Sulforaphane (SFN) is a dietary isothiocyanate abundantly available in cruciferous vegetables and has been shown to possess anti-inflammatory and immunomodulatory activities. Chemokines are important mediators of inflammation and immune responses due to their ability to recruit and activate macrophages and leukocytes. To date, little is known about the SFN-mediated regulation of chemokine expression in pancreatic β-cells. In this study, we investigated the inhibitory effects and mechanisms of SFN on the interferon-γ (IFN-γ)-induced expression of a subset of chemokines, including monokine induced by IFN-γ (MIG), IFN-inducible protein of 10 kDa (IP-10) and IFN-inducible T‑cell alpha chemoattractant (I-TAC), in INS‑1 cells, a rat pancreatic β-cell line...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28677265/epigenetics-in-myeloproliferative-neoplasms
#6
REVIEW
Suzanne McPherson, Mary Frances McMullin, Ken Mills
A decade on from the description of JAK2 V617F, the MPNs are circumscribed by an increasingly intricate landscape. There is now evidence that they are likely the result of combined genetic dysregulation, with several mutated genes involved in the regulation of epigenetic mechanisms. Epigenetic changes are not due to a change in the DNA sequence but are reversible modifications that dictate the way in which genes may be expressed (or silenced). Among the epigenetic mechanisms, DNA methylation is probably the best described...
July 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28674362/the-amelioration-of-myelofibrosis-with-thrombocytopenia-by-a-jak1-2-inhibitor-ruxolitinib-in-a-post-polycythemia-vera-myelofibrosis-patient-with-a-jak2-exon-12-mutation
#7
Kazuhiko Ikeda, Koki Ueda, Takahiro Sano, Kazuei Ogawa, Takayuki Ikezoe, Yuko Hashimoto, Soji Morishita, Norio Komatsu, Hitoshi Ohto, Yasuchika Takeishi
Less than 5% of patients with polycythemia vera (PV) show JAK2 exon 12 mutations. Although PV patients with JAK2 exon 12 mutations are known to develop post-PV myelofibrosis (MF) as well as PV with JAK2V617F, the role of JAK inhibitors in post-PV MF patients with JAK2 exon 12 mutations remains unknown. We describe how treatment with a JAK1/2 inhibitor, ruxolitinib, led to the rapid amelioration of marrow fibrosis, erythrocytosis and thrombocytopenia in a 77-year-old man with post-PV MF who carried a JAK2 exon 12 mutation (JAK2H538QK539L)...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28665978/testosterone-suppresses-uropathogenic-escherichia-coli-invasion-and-colonization-within-prostate-cells-and-inhibits-inflammatory-responses-through-jak-stat-1-signaling-pathway
#8
Chen-Hsun Ho, Chia-Kwung Fan, Hong-Jeng Yu, Chia-Chang Wu, Kuan-Chou Chen, Shih-Ping Liu, Po-Ching Cheng
Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies...
2017: PloS One
https://www.readbyqxmd.com/read/28656316/apigenin-overcomes-drug-resistance-by-blocking-the-signal-transducer-and-activator-of-transcription-3-signaling-in-breast-cancer-cells
#9
Hye-Sook Seo, Jin Mo Ku, Hyeong Sim Choi, Jong-Kyu Woo, Byung Hoon Lee, Doh Sun Kim, Hyun Jong Song, Bo-Hyoung Jang, Yong Cheol Shin, Seong-Gyu Ko
Drug resistance in chemotherapy is a serious obstacle for the successful treatment of cancer. Drug resistance is caused by various factors, including the overexpression of P‑glycoprotein (P‑gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in vivo and in vitro. In the present study, we investigated whether apigenin is able to reverse drug resistance using adriamycin‑resistant breast cancer cells (MCF‑7/ADR)...
June 26, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28654918/serum-human-beta-defensin-2-is-a-possible-biomarker-for-monitoring-response-to-jak-inhibitor-in-psoriasis-patients
#10
Tingting Jin, Ziwen Sun, Xixue Chen, Yun Wang, Ruoyu Li, Suzhen Ji, Yi Zhao
AIMS: To analyse the correlation between serum human beta-defensin-2 (hBD-2) levels and response to JAK inhibitor in psoriasis. METHODS: We evaluated the psoriasis area and severity index (PASI) and serum hBD-2 levels of 18 psoriasis patients randomized to receive placebo or tofacitinib 5 or 10 mg b.i.d. at baseline, week 8, and week 16. Serum hBD-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The PASI achieved a dramatic reduction after tofacitinib 5 or 10 mg b...
June 28, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28652245/unpaired-extracellular-cysteine-mutations-of-csf3r-mediate-gain-or-loss-of-function
#11
Haijiao Zhang, Sophie Means, Anna Reister Schultz, Kevin Watanabe-Smith, Bruno C Medeiros, Daniel Bottomly, Beth Wilmot, Shannon K McWeeney, Tim Kükenshöner, Oliver Hantschel, Jeffrey W Tyner
Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g. T618I), functionally defective mutations in the extracellular domain of the granulocyte colony-stimulating factor receptor (CSF3R) have been reported only in severe congenital and idiopathic neutropenia patients. Here we describe the first activating mutation in the fibronectin like type III domain of the extracellular region of CSF3R (W341C) in a leukemia patient. This mutation transformed cells via cysteine-mediated intermolecular disulfide bonds, leading to receptor dimerization...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28646676/multicenter-phase-2-study-of-combination-therapy-with-ruxolitinib-and-danazol-in-patients-with-myelofibrosis
#12
K Gowin, H Kosiorek, A Dueck, J Mascarenhas, R Hoffman, C Reeder, J Camoriano, R Tibes, K Gano, J Palmer, R Mesa
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol...
June 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#13
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646393/the-changing-landscape-of-alopecia-areata-the-therapeutic-paradigm
#14
REVIEW
Yael Renert-Yuval, Emma Guttman-Yassky
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use...
June 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28635319/a-case-of-topical-ruxolitinib-treatment-failure-in-alopecia-areata
#15
Maya Deeb, Renée A Beach
Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28632888/excellent-response-to-tofacitinib-treatment-in-a-patient-with-alopecia-universalis
#16
Funda Erduran, Esra Adışen, Ahmet Burhan Aksakal
Alopecia universalis (AU) is generally considered a variant of alopecia areata (AA), in which the treatment options seldom provide satisfactory results. However, successful treatment of several cases of AA and its variants with oral Janus kinase (JAK) inhibitors have been reported recently. Here we report a 23-year-old female patient with AU successfully treated with tofacitinib, a selective JAK-3 inhibitor. The initial tofacitinib dose was 5 mg twice daily. After 2 months of treatment, partial hair regrowth was seen on the scalp and eyebrows...
June 2017: Acta Dermatovenerologica Alpina, Panonica, et Adriatica
https://www.readbyqxmd.com/read/28630047/update-on-anti-tumor-necrosis-factor-agents-and-other-new-drugs-for-inflammatory-bowel-disease
#17
REVIEW
Benjamin L Cohen, David B Sachar
The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs...
June 19, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28628689/aggressive-skin-cancers-occurring-in-patients-treated-with-the-janus-kinase-inhibitor-ruxolitinib
#18
Adam B Blechman, Christine E Cabell, Christine H Weinberger, Anna Duckworth, Justin J Leitenberger, Fiona O Zwald, Mark A Russell
<p>The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28622463/efficacy-safety-pharmacokinetics-and-pharmacodynamics-of-filgotinib-a-selective-janus-kinase-1-inhibitor-after-short-term-treatment-of-rheumatoid-arthritis-results-of-two-randomized-phase-iia-trials
#19
Frédéric Vanhoutte, Minodora Mazur, Oleksandr Voloshyn, Mykola Stanislavchuk, Annegret Van der Aa, Florence Namour, René Galien, Luc Meuleners, Gerben van 't Klooster
OBJECTIVE: Janus kinase (JAK) inhibitors have shown efficacy in rheumatoid arthritis (RA). We hypothesized that selective inhibition of JAK1 would combine good efficacy with a differentiated safety profile versus less selective JAK inhibitors. METHODS: In two 4-week exploratory, double-blind, placebo-controlled Phase IIA trials, 127 RA patients with insufficient response to methotrexate received filgotinib (GLPG0634, GS-6034) oral capsules (twice-daily 100 mg, or once-daily 30, 75, 150, 200, or 300 mg) or placebo, added on to a stable regimen of methotrexate, to evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of filgotinib...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28622305/the-thrombopoietin-mpl-axis-is-activated-in-the-gata1-low-mouse-model-of-myelofibrosis-and-is-associated-with-a-defective-rps14-signature
#20
M Zingariello, L Sancillo, F Martelli, F Ciaffoni, M Marra, L Varricchio, R A Rana, C Zhao, J D Crispino, A R Migliaccio
Myelofibrosis (MF) is characterized by hyperactivation of thrombopoietin (TPO) signaling, which induces a RPS14 deficiency that de-regulates GATA1 in megakaryocytes by hampering its mRNA translation. As mice carrying the hypomorphic Gata1(low) mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model. Gata1(low) mice contained two times more Tpo mRNA in liver and TPO in plasma than wild-type littermates. Furthermore, Gata1(low) LSKs expressed levels of Mpl mRNA (five times greater than normal) and protein (two times lower than normal) similar to those expressed by LSKs from TPO-treated wild-type mice...
June 16, 2017: Blood Cancer Journal
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