Read by QxMD icon Read


Robert Campbell, Geoffrey Chong, Eliza A Hawkes
Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies...
March 21, 2018: Journal of Clinical Medicine
Maria Gavriatopoulou, Efstathios Kastritis, Meletios Athanasios Dimopoulos
No abstract text is available yet for this article.
February 27, 2018: Oncotarget
Kristina Busygina, Janina Jamasbi, Till Seiler, Hans Deckmyn, Christian Weber, Richard Brandl, Reinhard Lorenz, Wolfgang Siess
Interaction of Von Willebrand factor (VWF) with platelet glycoprotein (GP) Ib and of collagen with GPVI is essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk) which can irreversibly be blocked by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long term safety. We found that ibrutinib and the novel Btk-inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid...
March 20, 2018: Blood
Prachi Jani, Megan B Vissing, Salman Ahmed, Jason C Sluzevich, Sonikpreet Aulakh, Victoria Alegria, Meghna Ailawadhi, Asher Chanan-Khan, Sikander Ailawadhi
No abstract text is available yet for this article.
March 20, 2018: Journal of Oncology Practice
Fevzi F Yalniz, Mohammad H Murad, Stephanie J Lee, Steven Z Pavletic, Nandita Khera, Nilay D Shah, Shahrukh K Hashmi
Given the increasing incidence of cGVHD and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost effectiveness analysis (CEA) for the frequently utilized agents in SR-cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis (ECP), pomalidomide and methotrexate...
March 14, 2018: Biology of Blood and Marrow Transplantation
Xiaojun Huang, Lugui Qiu, Jie Jin, Daobin Zhou, Xiequn Chen, Ming Hou, Jianda Hu, Yu Hu, Xiaoyan Ke, Junmin Li, Yingmin Liang, Ting Liu, Yue Lv, Hanyun Ren, Aining Sun, Jianmin Wang, Chunting Zhao, Mariya Salman, Steven Sun, Angela Howes, Jingzhao Wang, Peng Wu, Jianyong Li
In the Asia-Pacific region, treatment options are limited for patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Rituximab is widely used in this setting when purine analog-based therapies are not appropriate. We evaluated the efficacy and safety of ibrutinib compared with rituximab in a randomized, open-label phase 3 study in predominantly Asian patients with relapsed/refractory CLL/SLL. Patients (N = 160) were randomly assigned 2:1 to receive 420 mg ibrutinib (n = 106) until disease progression (PD) or unacceptable toxicity or up to six cycles of rituximab (n = 54)...
March 13, 2018: Cancer Medicine
Alexandra Smith, Eve Roman, Simon Appleton, Debra Howell, Rod Johnson, Cathy Burton, Russell Patmore
The treatment landscape for mantle cell lymphoma (MCL) has changed dramatically in recent years, with findings from clinical trials reporting improvements in survival. Data on the general patient population are, however, sparse; and it is unclear whether the effects observed in clinical trials have translated into the real-world setting. To investigate this, we examined first-line and relapsed/refractory (RR) disease management in 335 MCL patients diagnosed between 2004 and 2015 in an established population-based patient cohort, along with data on demographic, diagnostic and prognostic factors...
March 13, 2018: British Journal of Haematology
Yangyang Gu, Bo Huang, Yanfei Yang, Mengdie Qi, Guohua Lu, Dajing Xia, Hequan Li
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung...
March 13, 2018: Inflammation
Yuta Ito, Shinichi Makita, Akiko Miyagi Maeshima, Shunsuke Hatta, Tomotaka Suzuki, Sayako Yuda, Suguru Fukuhara, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Koji Izutsu
Paraneoplastic pemphigus (PNP) is a severe autoimmune blistering disease associated with an underlying malignancy, and its prognosis is poor. We herein report the first patient with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL)-associated PNP successfully treated with the Bruton's tyrosine kinase inhibitor ibrutinib and rituximab. Although his PNP lesions did not improve with ibrutinib monotherapy, the combination of ibrutinib and rituximab was effective against B-CLL/SLL-associated PNP...
March 9, 2018: Internal Medicine
Madeliene Parrott, Simon Rule
Mantle cell lymphoma (MCL) is a rare but often aggressive B-cell non-Hodgkin lymphoma (NHL). Initial therapy can achieve high response rates but invariably patients relapse and die from their disease. Incorporating a maintenance phase into the treatment strategy may prolong remission duration and ultimately prolong survival. Areas covered: The current literature incorporating a maintenance phase into treatment strategies for newly diagnosed and pre-treated MCL patients has been summarized. A literature search was performed using search terms "mantle cell lymphoma", "indolent NHL", "maintenance", "interferon", "rituximab", "lenalidomide", "bortezomib" and "ibrutinib"...
March 9, 2018: Expert Review of Hematology
Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Sandra A Davis, Michael A Matthay, Anna K Kurdowska
Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza infected patients. Previous experiments in our laboratory indicated that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury (ALI) in mice, therefore we sought to determine if blocking Btk activity had a protective effect in the lung during influenza induced inflammation. A Btk inhibitor (Btk Inh...
March 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Giuseppe Boriani, Paolo Corradini, Antonio Cuneo, Anna Falanga, Robin Foà, Gianluca Gaidano, Paolo Prospero Ghia, Maurizio Martelli, Roberto Marasca, Massimo Massaia, Francesca Romana Mauro, Giorgio Minotti, Stefano Molica, Marco Montillo, Antonio Pinto, Alessandra Tedeschi, Umberto Vitolo, Pier Luigi Zinzani
The Bruton tyrosine kinase inhibitor ibrutinib (IB) has attained an important role in the treatment of patients with chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia, significantly improving clinical outcomes. However, IB therapy has been associated with an increased risk of atrial fibrillation (AF) and bleeding. We report on the expert opinion that a group of Italian haematologists, cardiologists, and pharmacologists jointly released to improve the practical management of patients at risk for AF and bleeding during treatment with IB...
March 7, 2018: Hematological Oncology
Tilly Varughese, Ying Taur, Nina Cohen, M Lia Palomba, Susan K Seo, Tobias M Hohl, Gil Redelman-Sidi
Background: Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used for the treatment of lymphoid malignancies, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia and mantle cell lymphoma (MCL). Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid malignancies at Memorial Sloan Kettering Cancer Center who received ibrutinib during a five-year period from January 1, 2012 to December 31, 2016...
March 2, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Bijal Shah, Xiaohong Zhao, Ariosto S Silva, Kenneth H Shain, Jianguo Tao
Ibrutinib resistance, as a result of coordinated rewiring of signaling networks and enforced tumor microenvironment (TME)-lymphoma interactions, drives unrestrained proliferation and disease progression. To combat resistance mechanisms, we must identify the compensatory resistance pathways and the central modulators of reprogramming events. Targeting the transcriptome and kinome reprogramming of lymphoma cells represents a rational approach to mitigate ibrutinib resistance in B cell malignancies. However, with the apparent heterogeneity and plasticity of tumors shown in therapy response, a one size fits all approach may be unattainable...
March 2018: Trends in Cancer
Jiaji G Chen, Xia Liu, Manit Munshi, Lian Xu, Nicholas Tsakmaklis, Maria G Demos, Amanda Kofides, Maria Luisa Guerrera, Gloria G Chan, Christopher J Patterson, Kirsten E Meid, Joshua Gustine, Toni Dubeau, Patricia Severns, Jorge J Castillo, Zachary R Hunter, Jinhua Wang, Sara J Buhrlage, Nathanael S Gray, Steven P Treon, Guang Yang
Acquired ibrutinib resistance due to BTKCys481 mutations occurs in B-cell malignancies, including those with MYD88 mutations. BTKCys481 mutations are usually sub-clonal, and their relevance to clinical progression remains unclear. Moreover, the signaling pathways that promote ibrutinib resistance remain to be clarified. We therefore engineered BTKCys481Ser and BTKWT expressing MYD88 mutated WM and ABC DLBCL cells, and observed re-activation of BTK-PLCγ2-ERK1/2 signaling in the presence of ibrutinib in only the former...
March 1, 2018: Blood
Sarah P Hammond, Kaiwen Chen, Alisha Pandit, Matthew S Davids, Nicolas C Issa, Francisco M Marty
No abstract text is available yet for this article.
February 28, 2018: Blood
Idanna Innocenti, Davide Rossi, Giulio Trapè, Francesco Autore, Luigi Maria Larocca, Vincenzo Gomes, Michaela Cerri, Paolo Falcucci, Simona Sica, Gianluca Gaidano, Luca Laurenti
Richter syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a diffuse large B-cell lymphoma, is a rare complication of patients treated with chemo-immunotherapy. Richter syndrome might be both clonally related or unrelated to the underlying CLL and often showed mutations of the TP53 and NOTCH1 genes. Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation. The clinical picture, pathology, and genetics of Richter transformation after IBR treatment are largely unknown...
February 27, 2018: Hematological Oncology
Jiyu Guan, Dan Huang, Konstantin Yakimchuk, Sam Okret
Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL). The tumor microenvironment often impacts negatively on drug response. Here we demonstrate that stromal cells protect MCL cells from ibrutinib-induced apoptosis and support MCL cell regrowth after drug removal by impairing ibrutinib-mediated down-regulation of phosphoinositide-3-kinase (PI3K)/AKT signaling...
February 26, 2018: Molecular Cancer Therapeutics
Inhye E Ahn, Mohammed Z H Farooqui, Xin Tian, Janet Valdez, Clare Sun, Susan Soto, Jennifer Lotter, Stephanie Housel, Maryalice Stetler-Stevenson, Constance M Yuan, Irina Maric, Katherine R Calvo, Pia Nierman, Thomas E Hughes, Nakhle S Saba, Gerald E Marti, Stefania Pittaluga, Sarah E M Herman, Carsten U Niemann, Lone B Pedersen, Christian H Geisler, Richard Childs, Georg Aue, Adrian Wiestner
Safety and efficacy of ibrutinib (420mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase II study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled for age ≥ 65 years (elderly cohort). Both cohorts included patients with treatment-naïve (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20...
February 26, 2018: Blood
Li Li, Min Tong, Yi-Ting Zhao, Yun He, Hong-Yu Zhou, Guo-Fu Zhang, Yuan-Jin Zhang
Using bone biopsy samples, we examined whether osteolytic cytokine profile is changed in situ in bone samples of metastatic multiple myeloma, and whether this creates an environment of lysis within the bone to which it has spread. This also produces the clinical features of increased circulating plasma calcium, and deleterious effects on the kidney.Using multiple myeloma biopsy and cell extracts from bone metastatic lesions, Bruton kinase, a tyrosine kinase, was demonstrated to be translocated to the membrane...
January 2018: Medicine (Baltimore)
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"