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https://www.readbyqxmd.com/read/28815757/first-line-treatment-selection-and-early-monitoring-patterns-in-chronic-phase-chronic-myeloid-leukemia-in-routine-clinical-practice-simplicity
#1
Stuart L Goldberg, Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010-September 02 2015) are reported...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#2
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#3
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28806182/nilotinib-induced-ocular-toxicity-a-case-report
#4
Donald C Moore, Alaa Muslimani, Pamela Sinclair
No abstract text is available yet for this article.
August 8, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28803825/cardiovascular-events-after-exposure-to-nilotinib-in-chronic-myeloid-leukemia-long-term-follow-up
#5
Nazanin Aghel, Jeffrey Howard Lipton, Eshetu G Atenafu, Dennis Dong Hwan Kim, Diego Hernan Delgado
INTRODUCTION: Nilotinib is a highly effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML). However, reports of cardiovascular toxicities caused by nilotinib have recently raised critical concerns. The aim of the present study was to evaluate the incidence of cardiovascular events (CVEs) and frequency of asymptomatic peripheral arterial disease (PAD) after long-term exposure to nilotinib. PATIENTS AND METHODS: In the present retrospective cohort, we evaluated the incidence of CVEs in 63 CML patients treated with nilotinib...
July 15, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#6
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#7
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28757617/nilotinib-induced-vasculopathy-identification-of-vascular-endothelial-cells-as-a-primary-target-site
#8
E Hadzijusufovic, K Albrecht-Schgoer, K Huber, G Hoermann, F Grebien, G Eisenwort, W Schgoer, S Herndlhofer, C Kaun, M Theurl, W R Sperr, U Rix, I Sadovnik, B Jilma, G H Schernthaner, J Wojta, D Wolf, G Superti-Furga, R Kirchmair, P Valent
The BCR/ABL1 inhibitor Nilotinib is increasingly used to treat patients with chronic myeloid leukemia (CML). Although otherwise well-tolerated, Nilotinib has been associated with the occurrence of progressive arterial occlusive disease (AOD). Our objective was to determine the exact frequency of AOD and examine in vitro and in vivo effects of Nilotinib and Imatinib on endothelial cells to explain AOD-development. In contrast to Imatinib, Nilotinib was found to upregulate pro-atherogenic adhesion-proteins (ICAM-1, E-selectin, VCAM-1) on human endothelial cells...
July 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28757432/genetic-risk-of-prediabetes-and-diabetes-development-in-chronic-myeloid-leukemia-patients-treated-with-nilotinib
#9
Bruno Martino, Corrado Mammì, Claudia Labate, Silvia Rodi, Domenica Ielo, Manuela Priolo, Maurizio Postorino, Giovanni Tripepi, Francesca Ronco, Carmelo Laganà, Caterina Musolino, Marianna Greco, Giorgio La Nasa, Giovanni Caocci
Impaired fasting glucose (IFG) and type 2 diabetes (T2D) represents adverse events in Chronic Myeloid Leukemia (CML) patients treated with the second-generation tyrosine kinase inhibitor (TKI) nilotinib. A genetic risk score (uGRS) for the prediction of insulin resistance, consisting of 10 multiple single-nucleotide polymorphisms (SNPs), has been proposed. We evaluated the uGRS predictivity in 61 CML patients treated with nilotinib. Patients were genotyped for IRS1, GRB14, ARL15, PPARG, PEPD, ANKRD55/MAP3K1, PDGFC, LYPLAL1, RSPO3, and FAM13A1 genes...
July 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28756527/synergistic-tumor-suppression-by-a-perilla-frutescens-derived-methoxyflavanone-and-anti-cancer-tyrosine-kinase-inhibitors-in-a549-human-lung-adenocarcinoma
#10
Amer Ali Abd El-Hafeez, Takashi Fujimura, Rikiya Kamei, Noriko Hirakawa, Kenji Baba, Kazuhisa Ono, Seiji Kawamoto
Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of cancers including non-small cell lung cancer, while appearance of TKI-resistant tumors suggests a need for the development of their potentiation strategies. We have previously shown that a methoxyflavanone derivative from the Asian medicinal herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and ponatinib) synergistically suppress proliferation of A549 cells...
July 29, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28753128/imatinib-induced-interstitial-pneumonitis-successfully-switched-to-nilotinib-in-a-patient-with-prior-history-of-mycobacterium-tuberculosis-infection
#11
Zhuan Bo Luo, Ning Xu, Xiao Ping Huang, Guifang Ouyang
No abstract text is available yet for this article.
July 28, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28749622/understanding-and-challenges-in-taking-tyrosine-kinase-inhibitors-among-malaysian-chronic-myeloid-leukemia-patients-a-qualitative-study
#12
Yik Ming Lim, Wei Lerk Eng, Huan Keat Chan
Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis approach...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28744011/nk-cell-dynamics-and-association-with-molecular-response-in-early-chronic-phase-chronic-myelogenous-leukemia-cml-cp-patients-treated-with-nilotinib
#13
S Sopper, S Mustjoki, B T Gjertsen, F Giles, A Hochhaus, J J W M Janssen, K Porkka, D Wolf
Leukemia accepted article preview online, 24 July 2017. doi:10.1038/leu.2017.235.
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28735458/the-efficacy-of-lapatinib-and-nilotinib-in-combination-with-radiation-therapy-in-a-model-of-nf2-associated-peripheral-schwannoma
#14
Iddo Paldor, Sara Abbadi, Nicolas Bonne, Xiaobu Ye, Fausto J Rodriguez, David Rowshanshad, MariaLisa Itzoe, Veronica Vigilar, Marco Giovannini, Henry Brem, Jaishri O Blakeley, Betty M Tyler
Neurofibromatosis type 2 (NF2), a neurogenetic condition manifest by peripheral nerve sheath tumors (PNST) throughout the neuroaxis for which there are no approved therapies. In vitro and in vivo studies presented here examine agents targeting signaling pathways, angiogenesis, and DNA repair mechanisms. In vitro dose response assays demonstrated potent activity of lapatinib and nilotinib against the mouse schwannoma SC4 (Nf2 (-/-)) cell line. We then examined the efficacy of everolimus, nilotinib, lapatinib, bevacizumab and radiation (RT) as mono- and combination therapies in flank and sciatic nerve in vivo NF2-PNST models...
July 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28723754/an-economic-analysis-of-high-dose-imatinib-dasatinib-and-nilotinib-for-imatinib-resistant-chronic-phase-chronic-myeloid-leukemia-in-china-a-cheers-compliant-article
#15
Bin Wu, Maobai Liu, Te Li, Houwen Lin, Hua Zhong
BACKGROUND: The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). METHODS: A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28720666/inactivation-of-receptor-tyrosine-kinases-reverts-aberrant-dna-methylation-in-acute-myeloid-leukemia
#16
Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Lai-Chu Wu, Ann M Bode, Aref Al-Kali, Mark R Litzow, Shujun Liu
Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.<br />Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene specific DNA methylation were examined...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#17
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28706179/nilotinib-induced-recurrent-gastric-polyps-case-report-and-review-of-literature
#18
Nancy Kassem, Omar M Ismail, Halima Elomri, Mohamad A Yassin
BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment...
July 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28703026/placental-transfer-of-tyrosine-kinase-inhibitors-used-for-chronic-myeloid-leukemia-treatment
#19
Ekaterina Chelysheva, Anna Turkina, Evgenia Polushkina, Roman Shmakov, Alexey Zeifman, Sergey Aleshin, Igor Shokhin, Dorel Guranda, Oksana Oksenjuk, Sergey Mordanov, Khamida Kazakbaeva, Ghermes Chilov
Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs...
July 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#20
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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