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Nilotinib

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https://www.readbyqxmd.com/read/28074253/c-abl-inhibition-mitigates-diet-induced-obesity-through-improving-insulin-sensitivity-of-subcutaneous-fat-in-mice
#1
Rong Wu, Jian-Guang Sun, Ji-Qiu Wang, Binhua Li, Qingsong Liu, Guang Ning, Wanzhu Jin, Zengqiang Yuan
AIMS/HYPOTHESIS: High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance...
January 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#2
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28052354/evaluation-of-long-term-chronic-myeloid-leukemia-treatment-practices-with-tyrosine-kinase-inhibitors-in-a-national-cohort-of-veterans
#3
Eugene D Kreys, Christopher R Frei, Sarah M Villarreal, Mary J Bollinger, Xavier Jones, Jim M Koeller
STUDY OBJECTIVE: To evaluate nationwide chronic myeloid leukemia treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Health Administration (VHA) national database. PATIENTS: A total of 2,873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the approximately 150 VHA hospitals and 800 VHA clinics, had a diagnosis code for chronic myeloid leukemia, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010...
January 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#4
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28045960/modelling-predictors-of-molecular-response-to-frontline-imatinib-for-patients-with-chronic-myeloid-leukaemia
#5
Haneen Banjar, Damith Ranasinghe, Fred Brown, David Adelson, Trent Kroger, Tamara Leclercq, Deborah White, Timothy Hughes, Naeem Chaudhri
BACKGROUND: Treatment of patients with chronic myeloid leukaemia (CML) has become increasingly difficult in recent years due to the variety of treatment options available and challenge deciding on the most appropriate treatment strategy for an individual patient. To facilitate the treatment strategy decision, disease assessment should involve molecular response to initial treatment for an individual patient. Patients predicted not to achieve major molecular response (MMR) at 24 months to frontline imatinib may be better treated with alternative frontline therapies, such as nilotinib or dasatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28042454/exploratory-study-on-the-impact-of-switching-to-nilotinib-in-18-patients-with-chronic-myeloid-leukemia-in-chronic-phase-with-suboptimal-response-to-imatinib
#6
Sikander Ailawadhi, Luke P Akard, Carole B Miller, Anand Jillella, Daniel J DeAngelo, Solveig G Ericson, Felice Lin, Ghulam Warsi, Jerald Radich
BACKGROUND: The phase II, exploratory, open-label Exploring Nilotinib BCR-ABL Effects (ENABL) study [ClinicalTrials.gov identifier: NCT00644878] assessed the impact of switching to nilotinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) who had a suboptimal molecular response with imatinib. METHODS: Patients with CML-CP who had previously achieved a complete cytogenetic response (CCyR), but had a suboptimal molecular response, with frontline imatinib therapy (N = 18) were assigned to receive nilotinib 300 mg twice daily...
January 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28035939/could-mao-b-inhibitor-withdrawal-rather-than-nilotinib-benefit-explain-the-dopamine-metabolite-increase-in-parkinsonian-study-subjects
#7
Michael A Schwarzschild
No abstract text is available yet for this article.
December 23, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28011678/enhanced-targeting-of-cml-stem-and-progenitor-cells-by-inhibition-of-porcupine-acyltransferase-in-combination-with-tki
#8
Puneet Agarwal, Bin Zhang, Yinwei Ho, Amy Cook, Ling Li, Fady M Mikhail, Youzhen Wang, Margaret E McLaughlin, Ravi Bhatia
Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) has limited efficacy against leukemia stem cells (LSC) responsible for disease propagation, and most CML patients require continued TKI treatment to maintain remission. LSC maintenance is related, at least in part, to signals from the bone marrow microenvironment (BMM). Our previous studies have shown that Wnt signaling from the BMM contributes to preservation of CML LSC following TKI treatment. Secretion of Wnt ligands requires their modification by the O-acyl transferase Porcupine (PORCN)...
December 23, 2016: Blood
https://www.readbyqxmd.com/read/28011145/a-functional-genomic-meta-analysis-of-clinical-trials-in-systemic-sclerosis-towards-precision-medicine-and-combination-therapy
#9
Jaclyn N Taroni, Viktor Martyanov, J Matthew Mahoney, Michael L Whitfield
Systemic sclerosis (SSc) is an orphan, systemic autoimmune disease with no FDA-approved treatments. Its heterogeneity and rarity often result in underpowered clinical trials making the analysis and interpretation of associated molecular data challenging. We performed a meta-analysis of gene expression data from skin biopsies of SSc patients treated with five therapies: mycophenolate mofetil (MMF), rituximab, abatacept, nilotinib, and fresolimumab. A common clinical improvement criterion of -20% OR -5 modified Rodnan Skin Score was applied to each study...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28006933/nilotinib-induces-er-stress-and-cell-death-in-h9c2-cells
#10
D Lekes, I Szadvari, O Krizanova, K Lopusna, I Rezuchova, M Novakova, Z Novakova, T Parak, P Babula
Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9c2 cells as a suitable cell model. We studied role of endoplasmic reticulum (ER) stress and apoptosis in nilotinib toxicity using a complex approach. Nilotinib impaired mitochondrial function and induced formation of ROS under clinically relevant concentrations...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27998488/stirring-controlled-solidified-floating-solid-liquid-drop-microextraction-as-a-new-solid-phase-enhanced-liquid-phase-microextraction-method-by-exploiting-magnetic-carbon-nanotube-nickel-hybrid
#11
Mehri Ghazaghi, Hassan Zavvar Mousavi, Hamid Shirkhanloo, Alimorad Rashidi
A specific technique is introduced to overcome limitations of classical solidification of floating organic drop microextraction, such as tedious and time-consuming centrifuge step and using disperser solvent, by facile and efficient participation of solid and liquid phases. In this proposed method of stirring-controlled solidified floating solid-liquid drop microextraction (SC-SF-SLDME), magnetic carbon nanotube-nickel hybrid (MNi-CNT) as a solid part of the extractors are dispersed ultrasonically in sample solution, and the procedure followed by dispersion of liquid phase (1-undecanol) through high-rate stirring and easily recollection of MNi-CNT in organic solvent droplets through hydrophobic force...
January 25, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27995880/-pharmacokinetics-of-generic-dasatinib-in-the-management-of-chronic-myeloid-leukemia-in-the-choronie-phase
#12
J Kong, N Chen, H X Fu, T J Hang, M Song, H Jiang
Objective: To evaluate the pharmacokinetics and bioequivalence of generic dasatinib in patients with chronic myeloid leukemia in the choronie phase (CML-CP). Methods: Using randomized, parallel, overlapping, self-control designed study, a 100 mg dose of the reference or test tablet was given to 12 CML-CP patients who were resistant or intolerant to Imatinib and Nilotinib in a randomized two-way crossover design, and the plasma concentration of the medicine was assayed by HPLC-MS-MS. The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated...
November 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27980759/extensive-intracranial-arterial-stenoses-in-conjunction-with-the-use-of-tyrosine-kinase-inhibitor-nilotinib
#13
Ruham Alshiekh-Nasany, Awss Zidan, Carmen Martinez
New-generation tyrosine kinase inhibitors (TKI) are promising agents for the treatment of chronic myeloid leukemia (CML), but the linkage to vascular diseases warrants a special attention from treating physicians, as it may carry major morbidity and mortality.
December 2016: Clinical Case Reports
https://www.readbyqxmd.com/read/27975299/nilotinib-a-tyrosine-kinase-inhibitor-exhibits-protection-against-acute-pancreatitis-induced-lung-and-liver-damage-in-rats
#14
Manar A Nader, Heba M Wagih
This investigation explored the nilotinib action in the management of acute pancreatitis (AP) and AP-induced lung and liver injury. AP was induced in Sprague Dawley (SD) rats with L-arginine. Treatment with nilotinib with or without L-arginine was applied for 7 days. Marked deterioration in serum amylase, lipase, aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), nitric oxide (NO), total protein content, and transforming growth factor beta1 (TGF-β1) along with pancreatic, hepatic, and pulmonary tissue lipid peroxidation (MDA) after induction of AP while significant reduction in tissues superoxide dismutase (SOD), glutathione (GSH) with marked edema, hemorrhage, and perivascular inflammation with acinar cell necrosis, along with elevated pancreatic percentage expression of TGF-β1 and nuclear factor kappa B (NF-κB), were observed in the AP group...
December 14, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27972529/cost-effectiveness-analysis-of-nilotinib-versus-imatinib-in-newly-diagnosed-chronic-myeloid-leukemia-from-the-health-insurance-perspective-in-egypt
#15
aS Abourawash, R Eldessouky, gH Elsisi
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27971690/modelling-the-economic-impact-of-implementing-treatment-free-remission-tfr-in-philadelphia-ph-chronic-myelogenous-leukemia-in-chronic-phase-cml-cp-patients-treated-in-first-line-1l-with-the-tyrosine-kinase-inhibitors-tki-imatinib-and-nilotinib
#16
E Sauvage, J Duco, S Nizard, S Arroum, F Mahon, P Kuizenga, J Ricci
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27966992/ugt1a10-is-a-high-activity-and-important-extrahepatic-enzyme-why-has-its-role-in-intestinal-glucuronidation-been-frequently-underestimated
#17
Johanna Troberg, Erkka Järvinen, Guang-Bo Ge, Ling Yang, Moshe Finel
The aim of this work was to highlight a considerable and broad problem in UGT1A10 activity assessment that has led to underestimation of its role in intestinal glucuronidation of drugs and other xenobiotics. The reason appears to be poor activity of the commercial UGT1A10 that is used by many laboratories, and here we have tested it by comparison with our recombinant His-tagged UGT1A10 (designated as UGT1A10-H), both expressed in insect cells. The glucuronidation rates of morphine, estradiol, estrone, SN-38, diclofenac, 4-methylumbelliferone, 7-amino-4-methylcoumarin, N-(3-carboxypropyl)-4-hydroxy-1,8-naphthalimide, and bavachinin were assayed...
December 14, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27960086/integrated-epi-genomic-analyses-identify-subgroup-specific-therapeutic-targets-in-cns-rhabdoid-tumors
#18
Jonathon Torchia, Brian Golbourn, Shengrui Feng, King Ching Ho, Patrick Sin-Chan, Alexandre Vasiljevic, Joseph D Norman, Paul Guilhamon, Livia Garzia, Natalia R Agamez, Mei Lu, Tiffany S Chan, Daniel Picard, Pasqualino de Antonellis, Dong-Anh Khuong-Quang, Aline C Planello, Constanze Zeller, Dalia Barsyte-Lovejoy, Lucie Lafay-Cousin, Louis Letourneau, Mathieu Bourgey, Man Yu, Deena M A Gendoo, Misko Dzamba, Mark Barszczyk, Tiago Medina, Alexandra N Riemenschneider, A Sorana Morrissy, Young-Shin Ra, Vijay Ramaswamy, Marc Remke, Christopher P Dunham, Stephen Yip, Ho-Keung Ng, Jian-Qiang Lu, Vivek Mehta, Steffen Albrecht, Jose Pimentel, Jennifer A Chan, Gino R Somers, Claudia C Faria, Lucia Roque, Maryam Fouladi, Lindsey M Hoffman, Andrew S Moore, Yin Wang, Seung Ah Choi, Jordan R Hansford, Daniel Catchpoole, Diane K Birks, Nicholas K Foreman, Doug Strother, Almos Klekner, Laszló Bognár, Miklós Garami, Péter Hauser, Tibor Hortobágyi, Beverly Wilson, Juliette Hukin, Anne-Sophie Carret, Timothy E Van Meter, Eugene I Hwang, Amar Gajjar, Shih-Hwa Chiou, Hideo Nakamura, Helen Toledano, Iris Fried, Daniel Fults, Takafumi Wataya, Chris Fryer, David D Eisenstat, Katrin Scheinemann, Adam J Fleming, Donna L Johnston, Jean Michaud, Shayna Zelcer, Robert Hammond, Samina Afzal, David A Ramsay, Nongnuch Sirachainan, Suradej Hongeng, Noppadol Larbcharoensub, Richard G Grundy, Rishi R Lulla, Jason R Fangusaro, Harriet Druker, Ute Bartels, Ronald Grant, David Malkin, C Jane McGlade, Theodore Nicolaides, Tarik Tihan, Joanna Phillips, Jacek Majewski, Alexandre Montpetit, Guillaume Bourque, Gary D Bader, Alyssa T Reddy, G Yancey Gillespie, Monika Warmuth-Metz, Stefan Rutkowski, Uri Tabori, Mathieu Lupien, Michael Brudno, Ulrich Schüller, Torsten Pietsch, Alexander R Judkins, Cynthia E Hawkins, Eric Bouffet, Seung-Ki Kim, Peter B Dirks, Michael D Taylor, Anat Erdreich-Epstein, Cheryl H Arrowsmith, Daniel D De Carvalho, James T Rutka, Nada Jabado, Annie Huang
We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27942835/pregnancy-outcome-among-partners-of-male-patients-receiving-imatinib-dasatinib-or-nilotinib-in-chronic-myeloid-leukemia-reports-collected-by-the-french-network-pharmacovigilance-centers
#19
Patrick Carlier, Nathalie Bernard, Laurence Lagarce, Anne Dautriche, Johana Béné, Nathalie Fouilhé Sam-Lai, Pirayeh Eftekhari
No abstract text is available yet for this article.
December 10, 2016: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/27942623/effects-of-nilotinib-on-leukaemia-cells-using-vibrational-microspectroscopy-and-cell-cloning
#20
M R Siddique, A V Rutter, K Wehbe, G Cinque, G Bellisola, J Sulé-Suso
Over the last few years, both synchrotron-based FTIR (S-FTIR) and Raman microspectroscopies have helped to better understand the effects of drugs on cancer cells. However, cancer is a mixture of cells with different sensitivity/resistance to drugs. Furthermore, the effects of drugs on cells produce both chemical and morphological changes, the latter could affect the spectra of cells incubated with drugs. Here, we successfully cloned sensitive and resistant leukaemia cells to nilotinib, a drug used in the management of leukaemia...
December 12, 2016: Analyst
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