keyword
MENU ▼
Read by QxMD icon Read
search

Ibrutinib

keyword
https://www.readbyqxmd.com/read/29146136/identification-of-highly-potent-btk-and-jak3-dual-inhibitors-with-improved-activity-for-the-treatment-of-b-cell-lymphoma
#1
Yang Ge, Changyuan Wang, Shijie Song, Jiaxin Huang, Zhihao Liu, Yongming Li, Qiang Meng, Jianbin Zhang, Jihong Yao, Kexin Liu, Xiaodong Ma, Xiuli Sun
The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas. Here we report the identification of several classes of pyrimidine derivatives as potent BTK and JAK3 dual inhibitors. Among these molecules, approximately two thirds displayed strong inhibitory capacity at less than 10 nM concentration, and four compounds (7e, 7g, 7m and 7n) could significantly inhibit the phosphorylation of BTK and JAK3 enzymes at concentrations lower than 1 nM...
November 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29131376/method-development-for-quantification-of-quizartinib-in-rat-plasma-by-liquid-chromatography-tandem-mass-spectrometry-for-pharmacokinetic-application
#2
Essam Ezzelddin, Muzaffar Iqbal, Gamal Mostafa, Khalid A Al-Rashood, Toqa El Nahhas
Quizartinib is a highly potent inhibitor of the fms-like tyrosine kinase receptor, which is one of the most commonly mutated genes in acute myeloid leukemia (AML). Quizartinib has shown a significant antileukemic clinical influence among relapsed/refractory acute AML patients. This study aimed at developing and validating an analytical method for the measurement of quizartinib in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated according to FDA guidelines, and the results obtained in this work met the set criteria...
November 13, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29127086/mainstreaming-cryo-em-in-cancer-research
#3
(no author information available yet)
Cryo-electron microscopy, whose pioneers won the 2017 Nobel Prize in Chemistry, is gaining favor among scientists as a tool to probe cancer at the molecular level. To that end, the NCI recently launched a centralized, free service facility to better meet the needs of researchers interested in utilizing this otherwise highly expensive technology.
November 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29126867/allogeneic-hematopoietic-cell-transplantation-for-richter-syndrome-a-single-center-experience
#4
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Facundo E Stingo, Farhad Khimani, Mohammad Hussaini, Ernesto Ayala, Taiga Nishihori, Bijal Shah, Frederick L Locke, Javier Pinilla-Ibarz, Julio C Chavez
BACKGROUND: Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data. PATIENTS AND METHODS: We evaluated the efficacy of allogeneic transplantation in 10 patients, median age of 63 (range, 50-74) years, allografted at a median of 5 (range, 4-25) months from diagnosis of Richter syndrome...
October 12, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#5
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
November 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29125406/bruton-s-tyrosine-kinase-inhibitors-first-and-second-generation-agents-for-patients-with-chronic-lymphocytic-leukemia-cll
#6
Philip A Thompson, Jan A Burger
The BTK inhibitor ibrutinib is effective in both low- and high-risk CLL patients, achieving durable remissions with continuous therapy in the majority of patients. Ibrutinib lacks myelotoxicity and is generally well tolerated by older and unfit patients; however, side effects, such as atrial fibrillation or hemorrhage, can result in treatment interruption or discontinuation. Given the high efficacy and overall safety, ibrutinib is increasingly used in untreated and previously treated CLL patients. Second-generation BTK inhibitors are being developed, with different and generally more BTK-selective kinase inhibition profiles, which may increase the safety and/or efficacy...
November 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#7
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29117640/functional-characterization-of-22-cyp3a4-protein-variants-to-metabolize-ibrutinib-in-vitro
#8
Ren-Ai Xu, Jian Wen, Pengfei Tang, Chenchen Wang, Saili Xie, Bo-Wen Zhang, Quan Zhou, Jian-Ping Cai, Guo-Xin Hu
Cytochrome P450 3A4 (CYP3A4) is quantitatively the most important P450 enzyme in adults. It is suggested that CYP3A4 genetic polymorphisms may influence the rate of the metabolism and elimination of CYP3A4 substrates in humans. Ibrutinib is an anti-cancer drug and primarily metabolized by CYP3A4. The aim of this study was to systematically investigate the effects of 22 CYP3A4 protein variants on the metabolism of ibrutinib in vitro. When compared with wild-type CYP3A4.1, two variants (CYP3A4.17 and CYP3A4.24) had no detectable enzyme activity; five variants (CYP3A4...
November 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29115892/management-of-patients-with-chronic-lymphocytic-leukemia-at-high-risk-of-relapse-on-ibrutinib-therapy
#9
Ayed O Ayed, Sameer A Parikh
The past two decades have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL), particularly with the introduction of targeted therapies to clinical practice. Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has shown significant efficacy and tolerability, even in heavily treated patients. Despite improvement in outcomes, patients do ultimately relapse. Those who develop disease progression on ibrutinib are a particularly high-risk population with poor outcomes...
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29113297/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#10
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108275/functional-imaging-in-combination-with-mutation-status-aids-prediction-of-response-to-inhibiting-b-cell-receptor-signaling-in-lymphoma
#11
Laura Jacobs, Stefan Habringer, Jolanta Slawska, Katharina Huber, Elke Hauf, Zhoulei Li, Yosef Refaeli, Markus Schwaiger, Martina Rudelius, Axel Walch, Ulrich Keller
Aberrant B-cell receptor (BCR) signaling is known to contribute to malignant transformation. Two small molecule inhibitors targeting BCR pathway signaling include ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and idelalisib, a specific Phosphatidylinositol-4,5-bisphosphate 3-kinase delta (PI3Kδ) inhibitor, both of which have been approved for use in haematological malignancies. Despite the identification of various diffuse large B-cell lymphoma (DLBCL) subtypes, mutation status alone is not sufficient to predict patient response and therapeutic resistance can arise...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100012/targeting-glioma-stem-cell-derived-pericytes-disrupts-the-blood-tumor-barrier-and-improves-chemotherapeutic-efficacy
#12
Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q Ke, Yi-Fang Ping, Hua Feng, Jeremy N Rich, Jennifer S Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29099493/pharmacodynamics-and-proteomic-analysis-of-acalabrutinib-therapy-similarity-of-on-target-effects-to-ibrutinib-and-rationale-for-combination-therapy
#13
V K Patel, B Lamothe, M L Ayres, J Gay, J Cheung, K Balakrishnan, C Ivan, J Morse, M Nelson, M J Keating, W G Wierda, J R Marszalek, V Gandhi
Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL), however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation, and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29097160/clinical-practice-guidelines-for-diagnosis-and-treatment-of-chronic-lymphocytic-leukemia-cll-in-the-netherlands
#14
Sabina Kersting, Suzanne I M Neppelenbroek, Hein P J Visser, Michel van Gelder, Mark-David Levin, Rogier Mous, Ward Posthuma, Hanneke M van der Straaten, Arnon P Kater
INTRODUCTION: In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. MATERIALS AND METHODS: The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline...
September 25, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29096668/observational-study-of-lenalidomide-in-patients-with-mantle-cell-lymphoma-who-relapsed-progressed-after-or-were-refractory-intolerant-to-ibrutinib-mcl-004
#15
Michael Wang, Stephen J Schuster, Tycel Phillips, Izidore S Lossos, Andre Goy, Simon Rule, Mehdi Hamadani, Nilanjan Ghosh, Craig B Reeder, Evelyn Barnett, Marie-Laure Casadebaig Bravo, Peter Martin
BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment...
November 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29094220/ibrutinib-associated-nail-plate-abnormalities-case-reports-and-review
#16
Lucas A Heldt Manica, Philip R Cohen
Chronic lymphocytic leukemia is a lymphoproliferative disorder characterized by a gradual accumulation of neoplastic B-lymphocytes. Ibrutinib is a novel therapy for chronic lymphocytic leukemia. Ibrutinib therapy has been associated with nail plate abnormalities. Other common cutaneous adverse events caused by ibrutinib appear to be bruising, hair changes, pruritus, and rashes. We describe the clinical features of two patients with chronic lymphocytic leukemia: a 79-year-old woman and a 53-year-old man who developed nail plate abnormalities approximately 6 and 4 months, respectively, after beginning ibrutinib therapy...
November 1, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29082795/treatment-approach-for-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#17
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29081253/rapid-flare-of-immune-thrombocytopenia-after-stopping-ibrutinib-in-a-patient-with-chronic-lymphocytic-leukemia
#18
Rino Sato, Jillian Jacob, Sameh Gaballa
No abstract text is available yet for this article.
October 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29080970/ibrutinib-does-not-prolong-the-corrected-qt-interval-in-healthy-subjects-results-from-a-thorough-qt-study
#19
Jan de Jong, Peter Hellemans, James Juhui Jiao, Yuhan Huang, Sofie Mesens, Juthamas Sukbuntherng, Daniele Ouellet
PURPOSE: Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. METHODS: Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval...
October 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29079592/inhibition-of-focal-adhesion-kinase-overcomes-resistance-of-mantle-cell-lymphoma-to-ibrutinib-in-the-bone-marrow-microenvironment
#20
Martina Rudelius, Mathias Tillmann Rosenfeldt, Ellen Leich, Hilka Rauert-Wunderlich, Antonio Giovanni Solimando, Andreas Beilhack, German Ott, Andreas Rosenwald
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells cocultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi based focal adhesion kinase silencing was performed...
October 27, 2017: Haematologica
keyword
keyword
166
1
2
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"