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https://www.readbyqxmd.com/read/28817464/biologics-for-idiopathic-inflammatory-myopathies
#1
Siamak Moghadam-Kia, Rohit Aggarwal, Chester V Oddis
PURPOSE OF REVIEW: As treatment of refractory cases of idiopathic inflammatory myopathies (IIMs) has been challenging, there is growing interest in assessing novel biologics that target various pathways implicated in the pathogenesis of IIM. RECENT FINDINGS: In the largest clinical trial in adult and juvenile IIM assessing the effectiveness of rituximab, the primary outcome was not met but 83% of this refractory group of IIM patients met a predefined definition of improvement and rituximab demonstrated a significant glucocorticoid-sparing effect...
August 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#2
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28794380/tumor-lysis-syndrome-after-the-administration-of-ruxolitinib-in-a-patient-with-post-polycythemia-vera-myelofibrosis
#3
Megumi Koshiishi, Yuki Sueki, Ichiro Kawashima, Kei Nakajima, Toru Mitsumori, Keita Kirito
The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28794072/ruxolitinib-versus-best-available-therapy-for-et-intolerant-or-resistant-to-hydroxycarbamide-in-a-randomized-trial
#4
Claire N Harrison, Adam J Mead, Anesh Panchal, Sonia Fox, Christina Yap, Emmanouela Gbandi, Aimee Houlton, Samah Alimam, Joanne Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Ruben Scherber, Amylou C Dueck, Nicholas C P Cross, Ruben Mesa, Mary Frances McMullin
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28791654/pharmacotherapy-of-myelofibrosis
#5
REVIEW
Douglas Tremblay, Bridget Marcellino, John Mascarenhas
Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors...
August 8, 2017: Drugs
https://www.readbyqxmd.com/read/28791626/fatal-ruxolitinib-related-jc-virus-meningitis
#6
Begoña Ballesta, Héctor González, Vicente Martín, Juan J Ballesta
We report a possible association between ruxolitinib and JC virus meningitis. A 72-year-old man with myelofibrosis started treatment with ruxolitinib. Fourteen days later, the patient presented to the emergency department with fever and nausea. HIV test was negative. Ruxolitinib was suspended. Symptoms progressed with neck stiffness, cognitive impairment, and motor aphasia. CSF was positive for JC virus. MRI showed nonspecific abnormal findings. Five days after the clinical debut, the patient died. The clinical picture, MRI imaging, and positive JC virus PCR in CSF strongly suggest ruxolitinib-related JC virus meningitis...
August 8, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28776046/jak-inhibitors-modulate-production-of-replication-competent-zika-virus-in-human-hofbauer-trophoblasts-and-neuroblastoma-cells
#7
Christina Gavegnano, Leda C Bassit, Bryan D Cox, Hui-Mien Hsiao, Erica L Johnson, Mehul Suthar, Rana Chakraborty, Raymond F Schinazi
Zika Virus (ZIKV) is a flavivirus that has been implicated in causing brain deformations, birth defects, and microcephaly in fetuses, and associated with Guillain-Barre syndrome. Mechanisms responsible for transmission of ZIKV across the placenta to the fetus are incompletely understood. Herein, we define key events modulating infection in clinically relevant cells, including primary placental macrophages (human Hofbauer cells; HC), trophoblasts, and neuroblastoma cells. Consistent with previous findings, HC and trophoblasts are permissive to ZIKV infection...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#8
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#9
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28751937/myricitrin-modulates-nadph-oxidase-dependent-ros-production-to-inhibit-endotoxin-mediated-inflammation-by-blocking-the-jak-stat1-and-nox2-p47-phox-pathways
#10
Shimei Qi, Zunyong Feng, Qiang Li, Zhilin Qi, Yao Zhang
Myricitrin, a naturally occurring polyphenol hydroxy flavonoid, has been reported to possess anti-inflammatory properties. However, the precise molecular mechanism of myricitrin's effects on LPS-induced inflammation is unclear. In the present study, myricitrin significantly alleviated acute lung injury in mice. Myricitrin also markedly suppressed the production of NO, TNF-α, IL-6, and MCP-1 in RAW264.7 macrophage cells. The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of iNOS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28749919/philadelphia-chromosome-like-acute-lymphoblastic-leukemia-progress-in-a-new-cancer-subtype
#11
Julia Wells, Nitin Jain, Marina Konopleva
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a newly described, high-risk subtype of B-cell ALL. It is characterized by a gene expression profile similar to that of Ph-positive ALL; however, the BCR-ABL1 fusion is not present. The World Health Organization classification of myeloid neoplasms and acute leukemia recently was updated to include the Ph-like or BCR-ABL1-like ALL subtype of B-cell ALL as a provisional entity. Unlike Ph-positive ALL, which is characterized by the pathognomonic BCR-ABL1 fusion, Ph-like ALL is characterized by a multitude of different genetic rearrangements and mutations...
July 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28737134/nephrotic-syndrome-in-primary-myelofibrosis-with-renal-extramedullary-hematopoiesis-and-glomerulopathy-in-the-jak-inhibitor-era
#12
Rachele Del Sordo, Rachele Brugnano, Carla Covarelli, Gioia Fiorucci, Franca Falzetti, Giorgio Barbatelli, Emidio Nunzi, Angelo Sidoni
Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure...
July 24, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#13
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721333/pulmonary-cryptococcosis-in-a-ruxolitinib-treated-patient-with-primary-myelofibrosis
#14
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/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#15
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28711920/baseline-factors-associated-with-response-to-ruxolitinib-an-independent-study-on-408-patients-with-myelofibrosis
#16
REVIEW
Francesca Palandri, Giuseppe Alberto Palumbo, Massimiliano Bonifacio, Mario Tiribelli, Giulia Benevolo, Bruno Martino, Elisabetta Abruzzese, Mariella D'Adda, Nicola Polverelli, Micaela Bergamaschi, Alessia Tieghi, Francesco Cavazzini, Adalberto Ibatici, Monica Crugnola, Costanza Bosi, Roberto Latagliata, Ambra Di Veroli, Luigi Scaffidi, Federico de Marchi, Elisa Cerqui, Barbara Anaclerico, Giovanna De Matteis, Marco Spinsanti, Elena Sabattini, Lucia Catani, Franco Aversa, Francesco Di Raimondo, Umberto Vitolo, Roberto Massimo Lemoli, Renato Fanin, Francesco Merli, Domenico Russo, Antonio Cuneo, Maria Letizia Bacchi Reggiani, Michele Cavo, Nicola Vianelli, Massimo Breccia
In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk (p=0...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710306/ruxolitinib-treatment-in-an-infant-with-jak2-polycythaemia-vera-associated-budd-chiari-syndrome
#17
Mehmet Enes Coskun, Sue Height, Anil Dhawan, Nedim Hadzic
Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction commonly seen with myeloproliferative neoplasms (MPNs). Polycythaemia vera (PV) is a very rare MPN in childhood. This is the youngest reported patient diagnosed with PV and BCS secondary to JAK V617F mutation.A 26-month-old girl was admitted with a 5-month history of abdominal distension, hepatosplenomegaly and ascites. Imaging studies revealed occlusion of the right hepatic vein and marked attenuation of the middle and left hepatic veins...
July 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28701183/ruxolitinib-found-to-cause-eyelash-growth-a-case-report
#18
Julia Song, Alice Song, Trisa Palmares, Michael Song, Harold Song
BACKGROUND: Hypereosinophilic syndrome is a hematologic disorder in which the eosinophils proliferate. Oral Janus kinase inhibitors are known to be effective treating hypereosinophilic syndrome. Janus kinase inhibitors have also demonstrated efficacy in alopecia. Madarosis is a condition in which the eyelashes are missing or absent and can been seen in alopecia patients. CASE PRESENTATION: We present the case of a 77-year-old Asian man who was diagnosed with hypereosinophilic syndrome, refractive to all medications except ruxolitinib...
July 12, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28687621/cancer-associated-fibroblasts-share-characteristics-and-pro-tumorigenic-activity-with-mesenchymal-stromal-cells
#19
Lucia Borriello, Rie Nakata, Michael A Sheard, G Esteban Fernandez, Richard Sposto, Jemily Malvar, Laurence Blavier, Hiroyuki Shimada, Shahab Asgharzadeh, Robert C Seeger, Yves A DeClerck
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship to MSC is not clear. Here we have isolated from primary human neuroblastoma (NB) tumors a population of αFAP- and FSP-1-expressing CAF that share phenotypic and functional characteristics with bone marrow-derived MSC (BM-MSC). Analysis of human NB tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28684419/versican-g1-domain-enhances-adenoviral-mediated-transgene-expression-and-can-be-modulated-by-inhibitors-of-the-janus-kinase-jak-stat-and-src-family-kinase-pathways
#20
Patricia Y Akinfenwa, Wesley S Bond, Cristhian J Ildefonso, Mary Y Hurwitz, Richard L Hurwitz
To examine the biochemical influences that may contribute to the success of gene therapy for ocular disorders, the role of versican, a vitreous component, in adenoviral-mediated transgene expression was examined. Versican is a large chondroitin sulfate-containing, hyaluronic acid-binding proteoglycan present in the extracellular matrix and in ocular vitreous body. Y79 retinoblastoma cells and CD44-negative SK-N-DZ neuroblastoma cells transduced with adenoviral vectors in the presence of versican respond with an activation of transgene expression...
July 6, 2017: Journal of Biological Chemistry
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