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https://www.readbyqxmd.com/read/28918688/role-and-regulation-of-micrornas-targeting-btk-in-acute-myelogenous-leukemia
#1
Lara Rizzotto, Tzung-Huei Lai, Arianna Bottoni, Jennifer A Woyach, Rosa Lapalombella, Clara D Bloomfield, John C Byrd, Deepa Sampath
No abstract text is available yet for this article.
September 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28915637/btk-suppresses-myeloma-cellular-senescence-through-activating-akt-p27-rb-signaling
#2
Chunyan Gu, Hailin Peng, Yue Lu, Hongbao Yang, Zhidan Tian, Gang Yin, Wen Zhang, Sicheng Lu, Yi Zhang, Ye Yang
We previously explored the role of BTK in maintaining multiple myeloma stem cells (MMSCs) self-renewal and drug-resistance. Here we investigated the elevation of BTK suppressing MM cellular senescence, a state of irreversible cellular growth arrest. We firstly discovered that an increased expression of BTK in MM samples compared to normal controls by immunohistochemistry (IHC), and significant chromosomal gain in primary samples. In addition, BTK high-expressing MM patients are associated with poor outcome in both Total Therapy 2 (TT2) and TT3 cohorts...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905990/the-mtor-kinase-inhibitor-everolimus-synergistically-enhances-the-anti-tumor-effect-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-pls-123-on-mantle-cell-lymphoma
#3
Jiao Li, Xiaogan Wang, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Zhengying Pan, Ning Ding, Yuqin Song, Jun Zhu
Mantle cell lymphoma (MCL) is an aggressive and incurable malignant disease. Despite of general chemotherapy, relapse and mortality are common, highlighting the need for the development of novel targeted drugs or combination of therapeutic regimens. Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901789/cardiac-side-effects-of-bruton-tyrosine-kinase-btk-inhibitors
#4
Chloe Pek Sang Tang, Julie McMullen, Constantine Tam
The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects...
September 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28884985/staged-endovascular-repair-of-critical-limb-ischemia-in-high-risk-patients-the-procedural-and-clinical-outcomes
#5
Guang Liu, Chaoyi Cui, Minyi Yin, Kaichuang Ye, Xaiobing Liu, Jinbao Qin, Huihua Shi, Xintian Huang, Min Lu, Xinwu Lu, Weimin Li, Mier Jiang
PURPOSE: To retrospectively evaluate the procedural and clinical outcomes after staged angioplasty in high-risk, chronic, critical limb ischemia (CLI) patients. METHODS: Between 2013 and 2015, 29 patients (29 limbs) (mean age 77 years) were treated by staged revascularization procedures in (i) the iliac artery-DFA alone or with the femoropopliteal artery followed by (ii) the femoropopliteal artery and a below-the-knee artery. All patients had long-segment iliofemoral artery and below-the-knee artery (TASCII D) occlusions with abnormal serum myoglobin and ischemic lesions...
September 7, 2017: International Angiology: a Journal of the International Union of Angiology
https://www.readbyqxmd.com/read/28882879/acalabrutinib-acp-196-a-covalent-bruton-tyrosine-kinase-btk-inhibitor-with-a-differentiated-selectivity-and-in-vivo-potency-profile
#6
Tjeerd Barf, Todd Covey, Raquel Izumi, Bas van de Kar, Michael Gulrajani, Bart van Lith, Maaike van Hoek, Edwin de Zwart, Diana Mittag, Dennis Demont, Saskia Verkaik, Fanny Krantz, Paul G Pearson, Roger Ulrich, Allard Kaptein
Several small-molecule BTK inhibitors are in development for B-cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib (1, ACP-196). Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential...
September 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28880016/-5r-5-hydroxytriptolide-ameliorates-anti-glomerular-basement-membrane-glomerulonephritis-in-nzw-mice-by-regulating-fc%C3%AE-receptor-signaling
#7
Qing Qi, Heng Li, Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Yu-Ting Liu, Mei-Juan Shao, Lu-Yao Zhang, Yan-Sheng Xu, Yu-Xi Yan, Lan-Lan Sun, Shi-Jun He, Wei Tang, Jian-Ping Zuo
(5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic effect and possible mechanism of action of LLDT-8 in a murine anti-glomerular basement membrane (GBM) glomerulonephritis model. NZW mice were injected with rabbit anti-GBM serum (500 μL, ip). The mice were orally treated with LLDT-8 (0...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28879546/the-btk-dependent-pip5k1%C3%AE-lipid-kinase-activation-by-fas-counteracts-fasl-induced-cell-death
#8
Aurélie Rossin, Nadia Lounnas, Jérôme Durivault, Giorgia Miloro, Laurent Gagnoux-Palacios, Anne-Odile Hueber
The Fas/FasL system plays a critical role in death by apoptosis and immune escape of cancer cells. The Fas receptor being ubiquitously expressed in tissues, its apoptotic-inducing function, initiated upon FasL binding, is tightly regulated by several negative regulatory mechanisms to prevent inappropriate cell death. One of them, involving the non-receptor tyrosine kinase Btk, was reported mainly in B cells and only poorly described. We report here that Btk negatively regulates, through its tyrosine kinase activity, the FasL-mediated cell death in epithelial cell lines from colon cancer origin...
September 6, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28867612/achieving-a-graded-immune-response-btk-adopts-a-range-of-active-inactive-conformations-dictated-by-multiple-interdomain-contacts
#9
Raji E Joseph, Thomas E Wales, D Bruce Fulton, John R Engen, Amy H Andreotti
Capturing the functionally relevant forms of dynamic, multidomain proteins is extremely challenging. Bruton's tyrosine kinase (BTK), a kinase essential for B and mast cell function, has stubbornly resisted crystallization in its full-length form. Here, nuclear magnetic resonance and hydrogen-deuterium exchange mass spectrometry show that BTK adopts a closed conformation in dynamic equilibrium with open, active conformations. BTK lacks the phosphotyrosine regulatory tail of the SRC kinases, yet nevertheless achieves a phosphotyrosine-independent C-terminal latch...
August 10, 2017: Structure
https://www.readbyqxmd.com/read/28866449/fractional-flow-reserve-in-below-the-knee-arteries-with-critical-limb-ischemia-and-validation-against-gold-standard-morphologic-functional-measures-and-long-term-clinical-outcomes
#10
Zoltán Ruzsa, Szilárd Róna, Gábor G Tóth, Péter Sótonyi, Olivier F Bertrand, Balázs Nemes, Béla Merkely, Kálmán Hüttl
INTRODUCTION: The aim of this study was to assess the applicability of fractional flow reserve measurement (FFR) in below-the-knee (BTK) arteries and to evaluate its correlation with non-invasive functional parameters before and after angioplasty. METHODS: We enrolled 39 patients with severe BTK arterial lesions. Inclusion criteria were critical limb ischemia (Rutherford 4-6) and angiographically proven arterial stenosis of the distal lower limb (percent diameter stenosis ≥70%)...
July 18, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28864770/retraction-abstract-408-acp-196-an-orally-bioavailable-covalent-selective-inhibitor-of-btk-modulates-the-innate-tumor-microenvironment-exhibits-antitumor-efficacy-and-enhances-gemcitabine-activity-in-pancreatic-cancer
#11
https://www.readbyqxmd.com/read/28852581/one-year-primary-patency-of-infrapopliteal-angioplasty-using-drug-eluting-balloons-single-center-experience-at-king-hussein-medical-center
#12
Sizeph Edward Haddad, Jan Mohammad Shishani, Izzeddin Qtaish, Mohammad Abdelmajeed Rawashdeh, Belal Saleh Qtaishat
OBJECTIVE: Conventional percutaneous transluminal angioplasty (PTA) for long lesions in the below-the-knee (BTK) arteries in patients presenting with critical limb ischemia (CLI) has high restenosis rates at 1 year. Our goal is to evaluate whether paclitaxel drug-eluting balloons (DEB) have higher 1 year primary patency rates compared to conventional PTA. METHODS: This is a single-center, prospective, randomized trial that was conducted from June 2013 to December 2015...
2017: Journal of Clinical Imaging Science
https://www.readbyqxmd.com/read/28838994/the-btk-inhibitor-cc-292-shows-activity-in-mantle-cell-lymphoma-and-synergizes-with-lenalidomide-and-nik-inhibitors-depending-on-the-nf-%C3%AE%C2%BAb-mutational-status
#13
Anna Vidal-Crespo, Vanina Rodriguez, Alba Matas-Céspedes, Eriong Lee, Alfredo Rivas-Delgado, Eva Giné, Alba Navarro, Sílvia Beà, Elías Campo, Armando López-Guillermo, Mónica López-Guerra, Gaël Roué, Dolors Colomer, Patricia Pérez-Galán
No abstract text is available yet for this article.
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28830912/mapping-genetic-vulnerabilities-reveals-btk-as-a-novel-therapeutic-target-in-oesophageal-cancer
#14
Irene Yushing Chong, Lauren Aronson, Hanna Bryant, Aditi Gulati, James Campbell, Richard Elliott, Stephen Pettitt, Paul Wilkerson, Maryou B Lambros, Jorge S Reis-Filho, Anisha Ramessur, Michael Davidson, Ian Chau, David Cunningham, Alan Ashworth, Christopher J Lord
OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations...
August 22, 2017: Gut
https://www.readbyqxmd.com/read/28807838/large-btk-gene-mutation-in-a-child-with-x-linked-agammaglobulinemia-and-polyarthritis
#15
Dhrubajyoti Sharma, Aman Gupta, Shubham Goel, Madhubala Sharma, Amit Rawat, Surjit Singh
No abstract text is available yet for this article.
August 12, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28792217/kinase-crystal-miner-a-powerful-approach-to-repurposing-3d-hinge-binding-fragments-and-its-application-to-finding-novel-bruton-tyrosine-kinase-inhibitors
#16
Prasenjit Mukherjee, Jörg Bentzien, Todd Bosanac, Wang Mao, Michael Burke, Ingo Muegge
Protein kinases represent an important target class for drug discovery because of their role in signaling pathways involved in disease areas such as oncology and immunology. A key element of many ATP-competitive kinase inhibitors is their hinge-binding motif. Here, we describe Kinase Crystal Miner (KCM)-a new approach developed at Boehringer Ingelheim (BI) that harvests the existing crystallographic information on kinase-inhibitor co-crystal structures from internal and external databases. About 1000 unique three-dimensional kinase inhibitor hinge binding motifs have been extracted from structures covering more than 180 different protein kinases...
August 28, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#17
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28789968/b-cell-phenotypes-signaling-and-their-roles-in-secretion-of-antibodies-in-systemic-lupus-erythematosus
#18
Yoshiya Tanaka, Satoshi Kubo, Shigeru Iwata, Maiko Yoshikawa, Shingo Nakayamada
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5(+) IgM memory B cells to CXCR3(+) class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features...
August 5, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28783468/evaluation-of-experimental-infection-with-l-l-amazonensis-in-x-linked-immunodeficient-mice
#19
Wagner Francisco Kennerly Marcondes Gonzaga, Mariana Marques Geraldo, Bruno Camolese Vivanco, Ana Flavia Popi, Mario Mariano, Wagner Luiz Batista, Patricia Xander
B-1 cells are a subtype of B cells with peculiar characteristics. These cells are distinct from B-2 lymphocytes in their morphology, ontogeny, tissue distribution and phenotypic functional features. B-1 cells can participate in the immune response in several ways, for example, by being recruited to inflammatory foci, producing large amounts of IL-10 cytokine, and differentiating into IgM-secreting cells or phagocytes. Nevertheless, the role of B-1 cells in the pathogenesis of experimental leishmaniasis has not been fully elucidated...
August 7, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28769069/autosomal-recessive-agammaglobulinemia-due-to-defect-in-%C3%AE-heavy-chain-caused-by-a-novel-mutation-in-the-ighm-gene
#20
P Silva, A Justicia, A Regueiro, S Fariña, J M Couselo, L Loidi
Agammaglobulinemia is a primary immunodeficiency disorder characterized by profoundly low or absent serum antibodies and low or absent circulating B cells. The most common form is X-linked agammaglobulinemia (XLA) caused by mutations in BTK gene. The remaining cases, clinically similar to XLA, are autosomal recessive agammaglobulinemia (ARA). Nearly 30% of ARA cases present mutations in the μ heavy constant region gene IGHM. Here, we present a 7-month-old patient, born from non-consanguineous parents, who is affected by ARA due to defect in the μ heavy chain...
August 3, 2017: Genes and Immunity
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