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https://www.readbyqxmd.com/read/28199182/one-reporter-for-in-cell-activity-profiling-of-majority-of-protein-kinase-oncogenes
#1
Iva Gudernova, Silvie Foldynova-Trantirkova, Barbora El Ghannamova, Bohumil Fafilek, Miroslav Varecha, Lukas Balek, Eva Hruba, Lucie Jonatova, Iva Jelinkova, Michaela Kunova Bosakova, Lukas Trantirek, Jiri Mayer, Pavel Krejci
In-cell profiling enables the evaluation of receptor tyrosine activity in a complex environment of regulatory networks that affect signal initiation, propagation and feedback. We used FGF-receptor signaling to identify EGR1 as a locus that strongly responds to the activation of a majority of the recognized protein kinase oncogenes, including 30 receptor tyrosine kinases and 154 of their disease-associated mutants. The EGR1 promoter was engineered to enhance trans-activation capacity and optimized for simple screening assays with luciferase or fluorescent reporters...
February 15, 2017: ELife
https://www.readbyqxmd.com/read/28191543/the-third-time-chronic-myeloid-leukemia-in-lymphoblastic-crisis-with-abl1-kinase-mutation-induced-by-decitabine-dexamethason-combined-with-nilotinib-and-dasatinib
#2
Suli Wang, Chun Qiao, Yu Zhu, Wenyi Shen, Guangsheng He, Jianyong Li
Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28190859/renal-artery-stenosis-following-nilotinib-administration-in-a-patient-with-chronic-myelogenous-leukemia
#3
Mayumi Hatsuse, Yuka Daikoku, Yuta Tamoto, Masahiro Uehara, Takashi Kitani, Keiichi Tamagaki, Shin-Ichi Fuchida, Akira Okano, Satoshi Murakami, Chihiro Shimazaki
A 63-year-old male was diagnosed as having chronic phase CML in 2001. He obtained a major molecular response with imatinib (IM). In 2012, amulodipin was started for hypertension. In January 2013, IM was switched to nilotinib (NIL) in a clinical trial, and in February 2015, NIL was discontinued because MR(4.5) had been maintained for two years. One month later, he was admitted to our hospital because of headache and high blood pressure (194/108 mmHg). His urine test showed protein 3+ and occult blood 2+. His eGFR rapidly deteriorated from 45...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28185798/quality-of-life-and-adherence-to-therapy-in-patients-with-chronic-myeloid-leukemia-treated-with-nilotinib-as-a-second-line-therapy-a%C3%A2-multicenter-prospective-observational-study
#4
Tomasz Sacha, Joanna Góra-Tybor, Ewa Wąsak-Szulkowska, Sławomira Kyrcz-Krzemień, Ewa Mędraś, Rafał Becht, Grażyna Bober, Aneta Kotowska, Joanna Wącław, Andrzej Hellmann
INTRODUCTION: The aim of this study was to evaluate quality of life (QOL) and adherence to the therapy in patients with chronic myeloid leukemia in chronic phase treated with nilotinib as second-line therapy. PATIENTS AND METHODS: A multicenter, prospective, observational trial with 6 time points was conducted; 177 patients were recruited in 23 centers in Poland who were treated with nilotinib as second-line therapy because of the ineffectiveness or intolerance of their previous therapy...
January 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28135648/current-approach-to-the-treatment-of-chronic-myeloid-leukaemia
#5
REVIEW
Ivan Pasic, Jeffrey H Lipton
Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28135325/early-bcr-abl1-transcript-decline-after-1-month-of-tyrosine-kinase-inhibitor-therapy-as-an-indicator-for-treatment-response-in-chronic-myeloid-leukemia
#6
Mohamed El Missiry, Henrik Hjorth-Hansen, Johan Richter, Ulla Olson-Strömberg, Leif Stenke, Kimmo Porkka, Anna Kreutzman, Satu Mustjoki
In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response...
2017: PloS One
https://www.readbyqxmd.com/read/28125915/modulation-of-d-galactosamine-lipopolysacharride-induced-fulminant-hepatic-failure-by-nilotinib
#7
D S El-Agamy, A M Shebl, A A Shaaban
This investigation was undertaken to test the effect of nilotinib against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF). Male Swiss albino mice were orally treated with nilotinib for 3 days prior to GalN/LPS challenge. The results revealed that administration of GalN/LPS caused elevation in the mortality rate. GalN/LPS-induced severe hepatic injury was manifested by increased serum transaminases and alkaline phosphatase (ALP) levels as well as histopathological hepatic necrosis and inflammation...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28121203/chronic-myeloid-leukemia-with-a-novel-e8a1-bcr-abl1-fusion-rapid-molecular-response-with-nilotinib
#8
Mireille Crampe, Fatima Shakkak, Johanna Kelly, Andrew Hodgson, Stephen E Langabeer
No abstract text is available yet for this article.
January 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28117336/cd5-molecule-like-and-transthyretin-as-putative-biomarkers-of-chronic-myeloid-leukemia-an-insight-from-the-proteomic-analysis-of-human-plasma
#9
Iram Fatima, Saima Sadaf, Syed Ghulam Musharraf, Naghma Hashmi, Muhammad Waheed Akhtar
Better and sensitive biomarkers are needed to help understand the mechanism of disease onset, progression, prognosis and monitoring of the therapeutic response. Aim of this study was to identify the candidate circulating markers of chronic-phase chronic myeloid leukemia (CP-CML) manifestations, having potential to develop into predictive- or monitoring-biomarkers. A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose. Based on the spot intensity measurements, six proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28109974/incidences-and-outcomes-of-therapy-related-chronic-myeloid-leukemia-in-the-era-of-tyrosine-kinase-inhibitors-surveillance-of-the-cml-cooperative-study-group
#10
Noriyoshi Iriyama, Michihide Tokuhira, Tomoiku Takaku, Eriko Sato, Maho Ishikawa, Tomonori Nakazato, Kei-Ji Sugimoto, Hiroyuki Fujita, Isao Fujioka, Yoshihiro Hatta, Masahiro Kizaki, Norio Komatsu, Norio Asou, Tatsuya Kawaguchi
This study was performed to investigate the features and outcome of patients with therapy-related chronic myeloid leukemia (TR-CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 308 patients with CML in the chronic phase who were extracted from the CML Cooperative Study Group database. Of these patients, 11 (3.6%) were identified as having TR-CML. No differences in age, sex, white blood cell count, hemoglobin level, platelet count, or European Treatment and Outcome Study risk were observed between patients with TR-CML vs...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#11
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28093990/insight-to-pharmacokinetics-of-tkis-optimizing-practical-guidelines-for-individualized-therapy
#12
Ruiqing Wang, Chaoqin Zhong, Chen Zhang, Mingqiang Hua, Daoxin Ma
Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavailability and stable blood concentration in humans. TKIs pharmacokinetics has close relationships with the clinical response and clinical treatment of CML. We conducted a systematic PubMed search to look for studies relating to TKIs pharmacokinetics with proper inclusion/exclusion criteria...
January 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28074253/c-abl-inhibition-mitigates-diet-induced-obesity-through-improving-insulin-sensitivity-of-subcutaneous-fat-in-mice
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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