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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/28810340/-interstitial-pneumonia-induced-by-imatinib-in-patients-with-ph-acute-lymphoblastic-leukemia-a-case-report
#2
J F Ni, Y Liu, H M Guan, X D Wei
No abstract text is available yet for this article.
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28810322/-comparison-of-generic-and-original-imatinib-in-the-treatment-of-newly-diagnosed-patients-with-chronic-myelogenous-leukemia-in-chronic-phase-a-multicenter-retrospective-clinical-study
#3
H Jiang, L T Zhi, M Hou, J X Wang, D P Wu, X J Huang
Objective: To evaluate the efficacy and safety of generic imatinib (Genike, Chiatai Tianqing Pharmaceutical Group Co., Ltd.) and imatinib (Glevic, Novartis, Switzerland) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: A retrospective study of 323 CML-CP patients (205 in Glivec treatment group and 118 in Genike group) who were ≥ 18 years old receiving imatinib monotherapy over the period of June 2013 to March 2016 was done to compare the differences of cytogenetics, molecular curative effect, survival, and adverse reactions between the two groups...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#4
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/28807791/effects-of-bosutinib-treatment-on-renal-function-in-patients-with-philadelphia-chromosome-positive-leukemias
#5
Jorge E Cortes, Carlo Gambacorti-Passerini, Dong-Wook Kim, Hagop M Kantarjian, Jeff H Lipton, Amit Lahoti, Moshe Talpaz, Ewa Matczak, Elly Barry, Eric Leip, Tim H Brümmendorf, H Jean Khoury
BACKGROUND: The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. PATIENTS AND METHODS: Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. RESULTS: Time from the last patient's first dose to data cutoff was ≥ 48 months...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28803208/n-glucuronidation-catalyzed-by-ugt1a4-and-ugt2b10-in-human-liver-microsomes-assay-optimization-and-substrate-identification
#6
Danyi Lu, Qian Xie, Baojian Wu
N-glucuronidation is an important pathway for metabolism and disposition of tertiary amines in humans. This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N-glucuronidation are not fully clear. In this study, we first optimized in vitro reaction conditions for N-glucuronidation by using specific substrates (i.e., trifluoperazine for UGT1A4, cotinine and amitriptyline for UGT2B10). Furthermore, we found that hepatic N-glucuronidation showed significant species differences...
August 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#7
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/28801299/-effect-of-bortezomib-in-inducing-apoptosis-of-imatinib-resistant-k562-cells-and-the-mechanism
#8
Jia-Ye Hua, Xu-Hong Zhou, Shu-Ting Ouyang, Yong-Bin Wu
OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28799743/reducing-interstitial-fluid-pressure-ifp-and-inhibiting-pulmonary-metastasis-of-breast-cancer-by-gelatin-modified-cationic-lipid-nanoparticles
#9
Xuan Gao, Jun Zhang, Zun Huang, Tiantian Zuo, Qing Lu, Guangyu Wu, Qi Shen
Interstitial fluid pressure (IFP) in tumor is much higher than that in normal tissue and it constitutes a great obstacle for the delivery of anti-tumor drugs, which makes it a potential target for cancer therapy. In this study, cationic nanostructured lipid carriers (NLCs) were modified by gelatin with low molecular weight in order to achieve the desirable reduction of tumor IFP and improve the drug delivery as well as the chemotherapy on tumor proliferation and pulmonary metastasis. The nanoparticles were used to entrap three drugs - docetaxel (DTX), quercetin (Qu) and imatinib (IMA) - with high encapsulation efficiency of 89...
August 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#10
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/28796048/clinicopathologic-study-of-succinate-dehydrogenase-deficient-gastrointestinal-stromal-tumors-a-single-institutional-experience-in-china
#11
Weizhen Liu, Xiangyu Zeng, Xiuli Wu, Jun He, Jinbo Gao, Xiaoming Shuai, Guobin Wang, Peng Zhang, Kaixiong Tao
Gastrointestinal stromal tumors (GISTs) that are not driven by kinase mutations, as are most GISTs, often show loss of function of the succinate dehydrogenase (SDH) complex and are considered SDH-deficient GISTs. SDH-deficient GISTs share many distinct characteristics compared with conventional GISTs. However, data regarding these characteristics, particularly among Asian people, are relatively limited. The objective of this study was to characterize the clinicopathologic characteristics, treatment, and prognosis of these uncommon GISTs...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28795284/dermatofibrosarcoma-protuberans
#12
REVIEW
Alvaro E Acosta, Catalina Santa Vélez
Dermatofibrosarcoma protuberans (DFSP) is a slow growing tumor with a very low metastatic potential but with significant subclinical extension and great capacity for local destruction. Thus, the first surgeon approached with such challenging tumor must attempt to cure the patient with a method that spares healthy tissue and ensures an optimal oncological, functional, and esthetic result. The treatment of DFSP often requires a multidisciplinary approach. Depending on location, dermatologic surgeons, surgical oncologists, head and neck surgeons, neurosurgeons, plastic surgeons, and occasionally medical oncologists may be involved with the management...
August 10, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28791527/impact-of-imatinib-on-the-fertility-of-male-patients-with-chronic-myelogenous-leukaemia-in-the-chronic-phase
#13
Xiaohui Chang, Lin Zhou, Xiaoxia Chen, Baoli Xu, Yubin Cheng, Shujun Sun, Meiyun Fang, Yang Xiang
BACKGROUND: Imatinib is a first-line tyrosine kinase inhibitor for treating chronic myelogenous leukaemia (CML) and has greatly improved the prognosis of this disease. An increasing number of CML patients of reproductive age are diagnosed each year, and the impact of imatinib on fertility is a major concern. Providing useful advice to these patients regarding the choice of their therapeutic treatment is very important. OBJECTIVE: This study examined the impact of imatinib on the fertility of male patients with CML in the chronic phase...
August 8, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28790106/kit-signaling-is-dispensable-for-human-mast-cell-progenitor-development
#14
Joakim S Dahlin, Maria Ekoff, Jennine Grootens, Liza Löf, Rose-Marie Amini, Hans Hagberg, Johanna S Ungerstedt, Ulla Olsson-Strömberg, Gunnar Nilsson
Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28781815/preliminary-data-on-microrna-expression-profiles-in-a-group-of-south-african-patients-diagnosed-with-chronic-myeloid-leukaemia
#15
Andrea Prinsloo, Roger Pool, Chantal Van Niekerk
Micro-ribonucleic acids (miRNAs) are small functional non-coding RNAs that downregulate gene expression at the post-transcriptional level. Abnormal expression of specific miRNAs has been recorded in chronic lymphocytic leukaemia, other non-Hodgkin B-cell lymphomas, lung cancer and chronic myeloid leukaemia (CML). The aim of this study was to compare miRNA expression profiles among patients with newly diagnosed CML, those on established therapy with imatinib mesylate, and healthy individuals. The expression of 88 miRNAs was evaluated in a total of nine samples divided into three groups: Group 1 comprised three samples collected from newly diagnosed CML patients; group 2 consisted of three samples collected from patients on therapy; the remaining three samples were collected from healthy volunteers (control group)...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28780584/platelet-derived-growth-factor-alpha-pdgfr%C3%AE-induces-the-activation-of-cardiac-fibroblasts-by-activating-c-kit
#16
Lexun Wang, Yuan Yue, Xiao Yang, Tian Fan, Bo Mei, Jian Hou, Mengya Liang, Guangxian Chen, Zhongkai Wu
BACKGROUND Enhanced platelet-derived growth factor receptor a (PDGFRα) signaling pathway activity leads to cardiac fibrosis. However, because of the pleiotropic effects of PDGFR signaling, its role in mediating the cardiac fibrotic response remains poorly understood. This study aimed to investigate the regulatory effect of c-Kit in cardiac fibroblasts activated by PDGFRa signaling. MATERIAL AND METHODS A cardiac fibrosis mice model was induced using isoproterenol, and the heart tissues of mice were tested through western blotting and real-time quantitative PCR (RT-qPCR)...
August 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28777148/new-mechanisms-of-mtor-pathway-activation-in-kit-mutant-malignant-gists
#17
Jerzy Lasota, Artur Kowalik, Anna Felisiak-Golabek, Sebastian Zięba, Zeng-Feng Wang, Markku Miettinen
A great majority of gastrointestinal stromal tumors (GISTs) are primarily driven by gain-of-function KIT receptor tyrosine kinase mutations that subsequently lead to activation of phosphatidiylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, a downstream effector of KIT signaling. KIT tyrosine kinase inhibitor, imatinib mesylate, has been successfully used for the treatment of primary, advanced, and disseminated GISTs. Recently, activation of mTOR pathway independent of KIT signaling was demonstrated in imatinib mesylate naïve malignant GISTs and treatment-resistant metastatic tumors...
August 2, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28770635/natural-history-and-treatment-of-cutaneous-and-systemic-mastocytosis
#18
Michelle Le, Barbara Miedzybrodzki, Tim Olynych, Hugo Chapdelaine, Moshe Ben-Shoshan
INTRODUCTION: Mastocytosis, a heterogeneous group of disorders, is characterized by an abnormal increase in the number of mast cells that is limited to the skin (cutaneous mastocytosis), involving extracutaneous tissues (systemic mastocytosis), or presenting as solid tumours (mastocytoma and mast cell sarcoma). Recent studies estimate that 1 in 10,000 people are diagnosed with mastocytosis. Although prompt diagnosis and appropriate management are crucial, little is known about the natural history and currently there are no established management guidelines...
August 3, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28768491/succinate-dehydrogenase-deficiency-in-a-pdgfra-mutated-gist
#19
Martin G Belinsky, Kathy Q Cai, Yan Zhou, Biao Luo, Jianming Pei, Lori Rink, Margaret von Mehren
BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor mutually exclusive gain of function mutations in the receptor tyrosine kinase (RTK) KIT (70-80%) or in the related receptor PDGFRA (~10%). These GISTs generally respond well to therapy with the RTK inhibitor imatinib mesylate (IM), although initial response is genotype-dependent. An alternate mechanism leading to GIST oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex resulting from genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX)...
August 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28767619/women-administered-standard-dose-imatinib-for-chronic-myeloid-leukemia-have-higher-dose-adjusted-plasma-imatinib-and-norimatinib-concentrations-than-men
#20
Sarah L Belsey, Robin Ireland, Kathryn Lang, Aytug Kizilors, Aloysius Ho, Ghulam J Mufti, Alessandra Bisquera, Hugues De Lavallade, Robert J Flanagan
BACKGROUND: The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg d. A pre-dose plasma imatinib concentration of >1 mg L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with CML administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. METHODS: We evaluated data from a cohort of patients treated between 2008-2014 with respect to dose, age, sex, body weight, and response...
July 31, 2017: Therapeutic Drug Monitoring
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