1,142 results match your criteria Bruton Agammaglobulinemia
Cancer 2018 Dec 3. Epub 2018 Dec 3.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Background: In a proportion of patients with chronic lymphocytic leukemia (CLL), resistance to Bruton tyrosine kinase (BTK) inhibitors (BTKi) is attributed to acquired BTK/phospholipase C gamma 2 (PLCG2) mutations. However, knowledge regarding additional genetic lesions associated with BTK/PLCG2 mutations, and gene mutations in patients lacking BTK/PLCG2 mutations, is limited.
Methods: Using targeted deep sequencing, mutations in 29 genes associated with CLL and/or the BCR signaling pathway were assessed in patients with CLL who developed resistance to BTK inhibition with ibrutinib/acalabrutinib at a single institution. Read More
Br J Haematol 2018 Dec 2. Epub 2018 Dec 2.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Read More
Pharmacol Res 2018 Nov 27;139:395-411. Epub 2018 Nov 27.
Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742-8814, United States. Electronic address:
The EGFR family is among the most investigated receptor protein-tyrosine kinase groups owing to its general role in signal transduction and in oncogenesis. This family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). The ErbB proteins function as homo and heterodimers. Read More
Emerg Infect Dis 2018 Dec;24(12):2382-2386
We report a disseminated infection caused by Spiroplasma apis, a honeybee pathogen, in a patient in France who had X-linked agammaglobulinemia. Identification was challenging because initial bacterial cultures and direct examination by Gram staining were negative. Unexplained sepsis in patients with agammaglobulinemia warrants specific investigation to identify fastidious bacteria such as Spiroplasma spp. Read More
J Pharm Biomed Anal 2018 Nov 11;164:509-513. Epub 2018 Nov 11.
Drug Metabolism and Interactions Research Lab, Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India. Electronic address:
USFDA has approved a novel Bruton tyrosine kinase (BTK) inhibitor acalabrutinib (ACA) for the treatment of mantle cell lymphoma in adults. ACA is more potent and selective with fewer side effects compared to other Bruton tyrosine kinase inhibitors. In the current work a highly sensitive, selective and specific LC-MS/MS method for the estimation of acalabrutinib (ACA) in rat plasma was developed. Read More
Drug Metab Dispos 2018 Nov 15. Epub 2018 Nov 15.
Acerta Pharma, South San Francisco, CA.
Acalabrutinib is a targeted, covalent inhibitor of Bruton tyrosine kinase (BTK) with a unique 2-butynamide warhead that has relatively lower reactivity than other marketed acrylamide covalent inhibitors. A human [C] microtracer bioavailability study in healthy subjects revealed moderate intravenous clearance (39.4 l/h) and an absolute bioavailability of 25. Read More
Blood Adv 2018 Nov;2(21):3012-3024
Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL.
Although the treatment paradigm for chronic lymphocytic leukemia (CLL) is rapidly changing, the disease remains incurable, except with allogeneic bone marrow transplantation, and resistance, relapsed disease, and partial responses persist as significant challenges. Recent studies have uncovered roles for epigenetic modification in the regulation of mechanisms contributing to malignant progression of CLL B cells. However, the extent to which epigenetic modifiers can be targeted for therapeutic benefit in CLL patients remains poorly explored. Read More
Neuro Oncol 2018 Nov 13. Epub 2018 Nov 13.
Departments of Neurology and Radiation Oncology, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA.
Novel insights into the pathophysiology of Primary Central Nervous System Lymphoma (PCNSL) have identified the B-cell receptor and Toll-like receptor pathway as well as immune evasion and suppressed tumor immune microenvironment as a key mechanism in the pathogenesis of PCNSL. Small molecules and novel agents targeting these aberrant pathways have been introduced into clinical trials targeting the recurrent or refractory PCNSL patient population. Agents like the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting. Read More
Biomed Chromatogr 2018 Nov 13:e4435. Epub 2018 Nov 13.
Department of Pharmacy, The Research Hospital, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Ibrutinib is an oral inhibitor of Bruton tyrosine kinase, which is one of the key drugs used for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In this study, we aimed to develop a simple method for determining plasma ibrutinib concentration. The analysis required extraction of a 200 μL plasma sample and precipitation of proteins using solid-phase extraction. Read More
Infect Immun 2018 Nov 5. Epub 2018 Nov 5.
Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, The Netherlands
Antibody responses to () correlate with pulmonary clearance. However, -specific IgG antibodies can cross-react with the myelin glycolipid galactocerebroside (GalC) and cause neurologic disorders. We assessed whether anti-glycolipid antibody formation is part of the physiological immune response to We show that antibodies against -proteins and -glycolipids arise in serum of -infected children and mice. Read More
Cell Calcium 2018 Dec 5;76:87-100. Epub 2018 Oct 5.
Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address:
STIM1 and ORAI1 regulate store-operated Ca entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Read More
J Periodontol 2018 Nov 2. Epub 2018 Nov 2.
Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
Background: Periodontitis is not only one of the most prevalent inflammatory diseases among adults, but also commonly linked to numerous systemic conditions including cardiovascular diseases, stroke, and diabetes. Although osteoclasts are responsible for the alveolar bone resorption during periodontitis pathogenesis, the development of pharmacologic strategies targeting these cells has not been vastly fruitful.
Methods: Bone marrow macrophages were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) to examine the direct effect of acalabrutinib on osteoclastogenesis. Read More
Future Oncol 2018 Nov 1. Epub 2018 Nov 1.
UCI Medical Center, Orange, CA 92868, USA.
Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, Ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC) of 3 nM. Read More
Philos Trans A Math Phys Eng Sci 2018 Oct 29;376(2134). Epub 2018 Oct 29.
Curator of Technology and Engineering, Science Museum, London, UK
In May 1900, renowned General Post Office (GPO) engineer Arthur West Heaviside gave the Inaugural Address of the Institution of Electrical Engineers Newcastle local section. With a career spanning the pre-Telegraph Act private telegraph networks as well as the subsequent GPO management and licensing of British inland telecommunications, Arthur Heaviside outlined his innovative and experimental work with all three forms of telecommunication in his various GPO engineering roles based in Newcastle. Omitted from the address was the contribution made by Arthur's younger brother, Oliver Heaviside. Read More
Clin Immunol 2018 Dec 16;197:205-218. Epub 2018 Oct 16.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:
Lupus nephritis is a common disease manifestation of SLE, in which immune complex deposition and macrophage activation are important contributors to disease pathogenesis. Bruton's tyrosine kinase (BTK) plays an important role in both B cell and FcgammaR mediated myeloid cell activation. In the current study, we examined the efficacy of BI-BTK-1, a recently described irreversible BTK inhibitor, in the classical NZB × NZW F1 (NZB/W) and MRL/lpr spontaneous mouse models of SLE. Read More
Blood Adv 2018 Oct;2(20):2672-2680
Sickle Cell Branch and.
A key inflammatory mechanism recently identified in platelets involves the Nod-like receptor nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK), which control activation of caspase-1 within inflammasome complexes. We investigated platelet caspase-1 activity in the context of sickle cell disease (SCD) directly in platelets isolated from SCD patients (n = 24) and indirectly by incubating platelets from healthy subjects with plasma obtained from SCD patients (n = 20), both in steady state and during an acute pain crisis (paired samples). The platelet NLRP3 inflammasome was upregulated in SCD patients under steady state conditions compared with healthy controls, and it was further upregulated when patients experienced an acute pain crisis. Read More
J Clin Immunol 2018 Oct 11;38(7):748-752. Epub 2018 Oct 11.
Department of Immunology and Microbiology, Laboratory of inborn errors of immunity, KU Leuven, Leuven, Belgium.
Endocrinology 2018 Nov;159(11):3834-3847
Human Islet Transplant Laboratory, Department of Surgery, McGill University Health Centre, Montréal, Québec, Canada.
The autoimmune response that characterizes type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EVs) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EVs isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation. Read More
J Neurophysiol 2018 Oct 3. Epub 2018 Oct 3.
Exercise and Sport Science, The University of Sydney, Australia.
At face value, the term 'synergy' provides a unifying concept within a fractured field that encompasses complementary neural, computational and behavioral approaches. However, the term is not used synonymously by different researchers, but has substantially different meanings depending on the research approach. With so many operational definitions for the one term, it becomes difficult to use as either a descriptive or explanatory concept, yet it remains pervasive and apparently indispensable. Read More
Front Immunol 2018 13;9:1996. Epub 2018 Sep 13.
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
Chronic lymphocytic leukemia (CLL) can be divided into prognostically distinct subsets with stereotyped or non-stereotyped, mutated or unmutated B cell receptors (BCRs). Individual subsets vary in antigen specificity and origin, but the impact of antigenic pressure on the CLL BCR repertoire remains unknown. Here, we employed μ mice that spontaneously develop CLL, expressing mostly unmutated BCRs of which ~35% harbor V11-2/Vκ14-126 and recognize phosphatidylcholine. Read More
Sci Eng Ethics 2018 Sep 26. Epub 2018 Sep 26.
School of Humanities, The University of Southern Mississippi, 118 College Drive #5037, Hattiesburg, MS, 39406, USA.
The current study sought to determine research scientists' sensitivity to various justifications for engaging in behaviors typically considered to be questionable research practices (QRPs) by asking them to evaluate the appropriateness and ethical defensibility of each. Utilizing a within-subjects design, 107 National Institutes of Health principal investigators responded to an invitation to complete an online survey in which they read a series of research behaviors determined, in prior research, to either be ambiguous or unambiguous in their ethical defensibility. Additionally, each behavior was paired with either an ostensibly sound or unsound reason for the behavior. Read More
Clin Lymphoma Myeloma Leuk 2018 Dec 18;18(12):803-813.e7. Epub 2018 Aug 18.
The Leeds Teaching Hospitals, St. James University Hospital, Leeds, United Kingdom.
Background: Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Patients And Methods: Measures of well-being were assessed in RESONATE, where previously treated patients with CLL/SLL were randomized to receive ibrutinib 420 mg/day (n = 195) or ofatumumab (n = 196) for up to 24 weeks. Endpoints included hematologic function, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), disease-related symptoms, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30), and medical resource utilization. Read More
Am Soc Clin Oncol Educ Book 2018 May(38):604-615
From the Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Neurology, Weill Cornell Medical College, New York, NY.
Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid (CSF) without evidence of systemic spread. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. The prognosis of patients with PCNSL has improved during the past few decades with the introduction of high-dose methotrexate (HD-MTX), which now serves as the backbone of all first-line treatment regimens. Read More
J Allergy Clin Immunol 2018 Nov 7;142(5):1441-1443. Epub 2018 Sep 7.
McMaster Immunology Research Centre (MIRC), Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address:
Hematol Oncol Clin North Am 2018 Oct 19;32(5):853-864. Epub 2018 Jul 19.
Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address:
Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma that is heavily dependent on Bruton tyrosine kinase (BTK) hyperactivation. Ibrutinib is a first-generation BTK inhibitor that has shown high activity and durable responses in patients with relapsed/refractory WM. Newer and more selective BTK inhibitors are currently being tested in several clinical trials and are expected to address the toxicity and the acquired resistance observed in patients receiving ibrutinib. Read More
EBioMedicine 2018 Sep 30;35:222-232. Epub 2018 Aug 30.
Biology Platform, Sunnybrook Research Institute, Toronto M4N 3M5, Canada.
The intrinsic humoral immunodeficiency of chronic lymphocytic leukemia (CLL) is often managed with immunoglobulin replacement therapy (IgRT) to maintain IgG levels in the low-normal range (6-8 g/L) but optimal targets for IgG and timing to commence IgRT are unclear. IgG levels fell near 6 g/L at rates of -0.85±0. Read More
Health Expect 2018 Dec 30;21(6):1134-1141. Epub 2018 Aug 30.
School of Public Health, Imperial College London, London, UK.
Background: Successes in biomedicine have transformed HIV from a debilitating and frequently fatal infection to a chronic, manageable condition.
Objective: To explore how the contemporary metanarrative of HIV as a chronic condition is understood by patients and how it varies depending on when they were diagnosed.
Design: Qualitative interviews with 52 people living with HIV who were diagnosed during different phases in the history of the epidemic. Read More
Br J Haematol 2018 Oct 20;183(2):212-224. Epub 2018 Aug 20.
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
In chronic lymphocytic leukaemia (CLL) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes (LN) to peripheral blood (PB). Here, we characterized in depth the dynamics of ibrutinib-induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Read More
Rheumatology (Oxford) 2018 Dec;57(12):2149-2157
Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Solna, Sweden.
Objectives: To investigate the expression of IL-18 in symptomatic and asymptomatic muscle tissues of patients with PM and DM and the effects of conventional immunosuppressive treatment on such expression.
Methods: Two cohorts of patients were included in this study. The first cohort consisted of 10 new-onset myositis patients. Read More
J Pest Sci (2004) 2018 22;91(4):1251-1267. Epub 2018 Jun 22.
Invasive Insect Biocontrol and Behavior Laboratory, Agricultural Research Service, United States Department of Agriculture, Bldg. 007, Rm. 312, BARC-W, Beltsville, MD 20705 USA.
, commonly known as the spotted wing drosophila (SWD), is an exotic fruit fly from Southeast Asia that was introduced to the temperate regions of North America and Europe in 2008. It attacks a wide variety of fruits and has become a devastating pest of soft-skinned fruit crops. Due to the rapid spread of SWD across the newly invaded continents, fresh fruit markets have a zero-tolerance policy regarding infestation. Read More
Cancer Discov 2018 Oct 9;8(10):1300-1315. Epub 2018 Aug 9.
Department of Internal Medicine, Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
Targeted inhibition of Bruton tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL). Here, we describe preclinical investigations of ARQ 531, a potent, reversible inhibitor of BTK with additional activity against Src family kinases and kinases related to ERK signaling. We hypothesized that targeting additional kinases would improve global inhibition of signaling pathways, producing more robust responses. Read More
Br J Haematol 2018 Oct 6;183(2):196-211. Epub 2018 Aug 6.
Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL, USA.
CD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti-CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells. In vitro Dara treatment of WM cells (including ibrutinib-resistant lines) elicited antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cell phagocytosis (ADCP) and direct apoptosis. Read More
Clin Lymphoma Myeloma Leuk 2018 Nov 1;18(11):755-761. Epub 2018 Aug 1.
Division of Hematology-Oncology, Department of Medicine and Cancer Center, University of Virginia Health System, Charlottesville, VA.
Background: The Bruton tyrosine kinase inhibitor, ibrutinib, is an effective therapy against mature B-cell malignancies. Although generally well tolerated, serious bleeding emerged during developmental clinical trials as an unexpected, although uncommon, adverse event. As the use of ibrutinib increases outside of the clinical trial setting and in patients with more comorbidities, the rate of major bleeding could be greater. Read More
Allergol Immunopathol (Madr) 2018 Jul 30. Epub 2018 Jul 30.
Department of Medical Genetics, Çukurova University Faculty of Medicine, Adana, Turkey.
Background: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA.
Methods: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Read More
Clin Lymphoma Myeloma Leuk 2018 Oct 28;18(10):648-657.e15. Epub 2018 Jun 28.
Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
Background: Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's tyrosine kinase has become a standard treatment for patients with CLL and MCL.
Patients And Methods: We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators. Read More
Expert Rev Hematol 2018 Sep 2;11(9):749-756. Epub 2018 Aug 2.
b Department of Hematology and Hematopoietic Cell Transplantation , City of Hope National Medical Center , Duarte , CA , USA.
Introduction: Despite recent prognostic improvements, mantle cell lymphoma (MCL) remains incurable. Bruton tyrosine kinase (BTK) is a key receptor in B-cell tumorigenesis, and the benefits of the first BTK inhibitor, ibrutinib, are becoming clear in MCL. However, off-target activities, which contribute to ibrutinib-related adverse events, suggest potential for further improvement of this drug class. Read More
Leukemia 2018 Sep 23;32(9):1883-1898. Epub 2018 Jul 23.
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. Read More
Eur J Haematol 2018 Jul 20. Epub 2018 Jul 20.
Pharmacyclics, LLC, an AbbVie Company, Sunnyvale, CA, USA.
Objectives: Bruton's tyrosine kinase (BTK) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) are expressed by human platelets. These kinases participate in platelet activation through the collagen receptor glycoprotein VI and may perform overlapping functions. In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear. Read More
BMJ Case Rep 2018 Jul 18;2018. Epub 2018 Jul 18.
Infectious Diseases and Microbiology, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
We report a case of pulmonary infection complicated by empyema in a 79-year-old man with diffuse large B-cell lymphoma treated with R-CHOP and ibrutinib. A literature review identified 25 cases of cryptococcal pleural disease published since 1980. Most cases were caused by the species in immunocompromised hosts with an exudative pleural effusion and lymphocyte-predominant infiltrate. Read More
Blood 2018 Sep 17;132(10):1039-1049. Epub 2018 Jul 17.
Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center.
The clinical success of ibrutinib validates Bruton tyrosine kinase (BTK) inhibition as an effective strategy for treating hematologic malignancies, including chronic lymphocytic leukemia (CLL). Despite ibrutinib's ability to produce durable remissions in patients, acquired resistance can develop, mostly commonly by mutation of C481 of BTK in the ibrutinib binding site. Here, we characterize a novel BTK inhibitor, GDC-0853, to evaluate its preclinical efficacy in ibrutinib-naive and ibrutinib-resistant CLL. Read More
Curr Opin Allergy Clin Immunol 2018 Oct;18(5):425-431
Department of Dermatology and Allergy, Charité - Universitätsmedizin, Berlin, Germany.
Purpose Of Review: Symptomatic management of chronic spontaneous urticaria (CSU) basically depends on second-generation H1 antihistamines and omalizumab. Omalizumab is a game changer in the management, but still there is a need for new targets and new biologics targeting new pathways in the treatment which will provide long-lasting remission, which will be given orally and which will be cheaper. This review will focus on new biologics that are underway of production or are already under use for different disorders but could be beneficial for the treatment of Chronic urticaria. Read More
J Oncol Pharm Pract 2018 Jan 1:1078155218786037. Epub 2018 Jan 1.
1 Grand Strand Regional Medical Center, Myrtle Beach, USA.
Bruton tyrosine kinase plays a critical role in hastening cell proliferation. Bruton tyrosine kinase inhibitors are a class of immunotheraputic agents that disrupt this signaling pathway. Ibrutinib, a novel Bruton tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of Waldenstrom macroglobulinemia in patients who have failed treatment with other agents, has emerged as an important therapeutic agent in the management of Waldenstrom macroglobulinemia and other plasma cell dyscrasias. Read More
Blood 2018 Aug 9;132(7):681-688. Epub 2018 Jul 9.
Department of Hematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal non- Hodgkin lymphoma. Although high remission rates can be achieved with high-dose methotrexate-based immunochemotherapy, risk of relapse and associated death is still substantial in at least a third of patients. Novel agents for treating lymphoid malignancies have substantially enriched treatment options for PCNSL. Read More
Oncotarget 2018 Jun 19;9(47):28547-28560. Epub 2018 Jun 19.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, Saga, Japan.
Despite the development of the novel Bruton tyrosine kinase inhibitor ibrutinib, mantle cell lymphoma (MCL) remains an incurable B-cell non-Hodgkin lymphoma. BMI-1 is required for the self-renewal and maintenance of MCL-initiating stem cells. Upregulation of BMI-1 has been reported in MCL patients, especially in those with refractory/relapsed disease. Read More
Br J Haematol 2018 Sep 5;182(5):654-669. Epub 2018 Jul 5.
Northern Blood Research Centre, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, Sydney, Australia.
Despite significant advances in treatment, chronic lymphocytic leukaemia (CLL) remains an incurable disease. Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway. IBL-202 is a dual inhibitor of the PIM and PI3 kinases. Read More
J Biol Chem 2018 Aug 20;293(31):12149-12166. Epub 2018 Jun 20.
From the Leicester Institute of Structural and Chemical Biology and
Dickkopf (Dkk) family proteins are important regulators of Wnt signaling pathways, which play key roles in many essential biological processes. Here, we report the first detailed structural and dynamics study of a full-length mature Dkk protein (Dkk4, residues 19-224), including determination of the first atomic-resolution structure for the N-terminal cysteine-rich domain (CRD1) conserved among Dkk proteins. We discovered that CRD1 has significant structural homology to the Dkk C-terminal cysteine-rich domain (CRD2), pointing to multiple gene duplication events during Dkk family evolution. Read More
Int J Mol Sci 2018 Jun 13;19(6). Epub 2018 Jun 13.
Department of Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Read More
Future Oncol 2018 Sep 5;14(22):2229-2237. Epub 2018 Jun 5.
CCC Ulm, University Hospital Ulm, Ulm, Germany.
Waldenström macroglobulinemia (WM), an incurable B-cell malignancy, is sensitive to Bruton tyrosine kinase (BTK) inhibition with ibrutinib, a first-generation BTK inhibitor. Off-target effects of ibrutinib against TEC- and EGFR-family kinases are implicated in some adverse events. Patients with CXCR4 and MYD88 mutations or who are MYD88 have less sensitivity to ibrutinib than those with MYD88 and CXCR4 disease. Read More