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https://www.readbyqxmd.com/read/28634655/effect-of-adherence-on-pharmacokinetic-pharmacodynamic-relationships-of-oral-targeted-anticancer-drugs
#1
Evelina Cardoso, Chantal Csajka, Marie P Schneider, Nicolas Widmer
The emergence of oral targeted anticancer agents transformed several cancers into chronic conditions with a need for long-term oral treatment. Although cancer is a life-threatening condition, oncology medication adherence-the extent to which a patient follows the drug regimen that is intended by the prescriber-can be suboptimal in the long term, as in any other chronic disease. Poor adherence can impact negatively on clinical outcomes, notably because most of these drugs are given as a standard non-individualized dosage despite marked inter-individual variabilities that can lead to toxic or inefficacious drug concentrations...
June 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28629454/impact-of-pharmacy-channel-on-adherence-to-oral-oncolytics
#2
Michael Stokes, Carolina Reyes, Yu Xia, Veronica Alas, Hans-Peter Goertz, Luke Boulanger
BACKGROUND: Oral chemotherapy is increasingly prescribed to treat cancer. Despite its benefits, concerns have been raised regarding adherence to therapy. The study objective was to compare and measure adherence, persistence, and abandonment in patients filling prescriptions in traditional retail (TR) versus specialty pharmacy (SP) channels. METHODS: Using a retrospective cohort design, we selected newly treated patients aged ≥18 years with a prescription for erlotinib, capecitabine, or imatinib during 2007-2011 from a Medco population of both United States commercial and Medicare health plans...
June 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28629421/erratum-to-imatinib-relaxes-the-pulmonary-venous-bed-of-guinea-pigs
#3
Nina A Maihöfer, Said Suleiman, Daniela Dreymüller, Paul W Manley, Rolf Rossaint, Stefan Uhlig, Christian Martin, Annette D Rieg
No abstract text is available yet for this article.
June 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28627443/impact-of-the-bcr-abl1-fusion-transcripts-on-different-responses-to-imatinib-and-disease-recurrence-in-iranian-patients-with-chronic-myeloid-leukemia
#4
Golale Rostami, Mohammad Hamid, Hasan Jalaeikhoo
BACKGROUND: One genomic breakpoint can result in variable BCR-ABL1 transcript types due to alternative splicing. The influence of different BCR-ABL1 transcript types on clinical outcome is still controversial. AIM OF THE STUDY: The objective of this analysis was to determine the impact of transcript type on response, clinical outcome, recurrence risk after treatment with Imatinib mesylate in Chronic Myeloid Leukemia (CML) patients. METHODS: Sixty CML patients in chronic phase were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and banding standard protocols...
June 13, 2017: Gene
https://www.readbyqxmd.com/read/28626381/nilotinib-induced-acute-pancreatitis-in-a-patient-with-chronic-myeloid-leukemia
#5
Vihang Patel, Anil Pattisapu, Karim Attia, John Weiss
Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML); it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events...
May 2017: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28624905/reduced-intensity-allogeneic-hematopoietic-stem-cell-transplantation-combined-with-imatinib-has-comparable-event-free-survival-and-overall-survival-to-long-term-imatinib-treatment-in-young-patients-with-chronic-myeloid-leukemia
#6
Yanmin Zhao, Jiasheng Wang, Yi Luo, Jimin Shi, Weiyan Zheng, Yamin Tan, Zhen Cai, He Huang
The relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in imatinib era have not been evaluated. The study was designed to compare the outcomes of combination therapy of RIST plus imatinib (RIST + IM) vs. imatinib (IM) alone for young patients with early CP (ECP) and late CP (LCP). Of the patients, 130 were non-randomly assigned to treatment with IM alone (n = 88) or RIST + IM (n = 42). The 10-year overall survival (OS) and event-free survival (EFS) were comparable between RIST + IM and IM groups...
June 17, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28624216/gold-nanoparticles-for-bcr-abl1-gene-silencing-improving-tyrosine-kinase-inhibitor-efficacy-in-chronic-myeloid-leukemia
#7
Raquel Vinhas, Alexandra R Fernandes, Pedro V Baptista
Introduction of tyrosine kinase inhibitors for chronic myeloid leukemia treatment is associated with a 63% probability of maintaining a complete cytogenetic response, meaning that over 30% patients require an alternative methodology to overcome resistance, tolerance, or side effects. Considering the potential of nanotechnology in cancer treatment and the benefits of a combined therapy with imatinib, a nanoconjugate was designed to achieve BCR-ABL1 gene silencing. Gold nanoparticles were functionalized with a single-stranded DNA oligonucleotide that selectively targets the e14a2 BCR-ABL1 transcript expressed by K562 cells...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623111/reversal-of-abcb1-mediated-efflux-by-imatinib-and-nilotinib-in-cells-expressing-various-transporter-levels
#8
Petr Mlejnek, Petr Kosztyu, Petr Dolezel, Susan E Bates, Eliska Ruzickova
Recently, it has been suggested that imatinib (IM) and nilotinib (NIL) could be studied beyond their original application, as inhibitors of the drug efflux pump ABCB1 (P-glycoprotein, MDR1). Since the reversal of ABCB1-mediated resistance has never been successfully demonstrated in the clinic, we addressed the question of whether IM and NIL may actually serve as efficient inhibitors of ABCB1. Here we define an efficient inhibitor as a compound that achieves full (90-100%) reversal of drug efflux at a concentration that does not exhibit significant off-target toxicity in vitro...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28622526/extragastrointestinal-stromal-tumour-of-the-lesser-omentum-a-case-report-and-literature-review
#9
I E Katsoulis, A Tzortzopoulou, P Tziakou, N Arnogiannaki, I Kostoglou-Athanassiou, G Lypas, I G Karaitianos
INTRODUCTION: Extragastrointestinal stromal tumours (EGISTs) are very uncommon compared to their gastrointestinal counterparts. Most of them originate from the intestinal mesentery and the omentum. CASE REPORT: A 70 year-old Caucasian woman presented with a bulky abdominal mass which on laparotomy was found to originate from the lesser omentum and was completely resected. Histological examination revealed spindle cells with severe pleomorphism and high mitotic activity...
June 8, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28621487/simultaneous-quantification-of-imatinib-and-its-main-metabolite-n-demethyl-imatinib-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry-and-its-application-to-therapeutic-drug-monitoring-in-patients-with-gastrointestinal-stromal-tumor
#10
Wei Zhuang, Hai-Bo Qiu, Xin-Meng Chen, Xiu-Hong Yuan, Li-Fang Yang, Xiao-Wei Sun, Xiao-Jun Zhou, Min Huang, Xue-Ding Wang, Zhi-Wei Zhou
AIM: To improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of Imatinib and its metabolite N-demethyl-Imatinib (NDI) in human plasma. METHODS: Separation of analytes was performed on a Waters XTerra RP18 column (50mm×2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol/acetonitrile/ water (65:20:15, v/v/v) with 0.05% formic acid at a flow-rate of 0...
June 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28620185/c-abl-regulates-gastrointestinal-muscularis-propria-homeostasis-via-erks
#11
Jinnan Xiang, Yiqun Zhang, Dandan Bao, Na Cao, Xin Zhang, Ping Li, Shoutao Qiu, Jigang Guo, Dan He, Baojie Li, Liqing Yao, Huijuan Liu
The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl (-/-) mice developed megaesophagus and rectal prolapse...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618035/population-pharmacokinetics-of-imatinib-in-nigerians-with-chronic-myeloid-leukemia-clinical-implications-for-dosing-and-resistance
#12
Babatunde Ayodeji Adeagbo, Tiwalade Adewale Olugbade, Muheez Alani Durosinmi, Rahman Ayodele Bolarinwa, Kayode Ogungbenro, Oluseye Oladotun Bolaji
Imatinib, a tyrosine kinase inhibitor, is the drug of choice for the treatment of chronic myeloid leukemia in Nigeria. Several studies have established interindividual and interpopulation variations in imatinib disposition although no pharmacokinetic study have been conducted in an African population since the introduction of the drug. This study explored a population pharmacokinetic approach to investigate the disposition of imatinib in Nigerians and examined the involvement of some covariates including genetic factors in the variability of the drug disposition with a view to optimize the use of the drug in this population...
June 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28616912/-the-roles-of-glut5-in-imatinib-resistance-in-the-ph-acute-lymphoblastic-leukemia-cell
#13
Tian-You Yan, Duo-Lan Naren, Yu-Ping Gong
OBJECTIVES: To explore the possible roles of glucose transport 5 (Glut5) in imatinib resistance in the Ph(+) acute lymphoblastic leukemia cell (Ph(+) ALL). METHODS: The gene chip technique was used to detect different gene expression between Ph(+) ALL cell line SUP-B15/R (imatinib resistant cell line) and SUP-B15/S (imatinib sensitive cell line), the gene of solute carrier family 2 member 5 (SLC2A5) and its coded protein Glut5 were screened out and were reconfirmed by qPCR and Western blot assay...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28615625/anti-leukemia-activity-of-a-hsp70-inhibitor-and-its-hybrid-molecules
#14
Seong-Hyun Park, Won-Je Kim, Hui Li, Wonil Seo, Sang-Hyun Park, Hwan Kim, Sang Chul Shin, Erik R P Zuiderweg, Eunice EunKyeong Kim, Taebo Sim, Nak-Kyoon Kim, Injae Shin
In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615132/identification-of-a-secondary-mutation-in-the-kit-kinase-domain-correlated-with-imatinib-resistance-in-a-canine-mast-cell-tumor
#15
Yuko Nakano, Masato Kobayashi, Makoto Bonkobara, Masamine Takanosu
Imatinib-resistance is a major therapeutic problem in human chronic myeloid leukemia, human gastrointestinal stromal tumors, and canine mast cell tumors. In the present study, we identified the secondary mutation c.2006C>T in c-KIT exon 14 in a mast cell tumor obtained from a dog carrying c.1663-1671del in exon 11 and showing resistance to imatinib. The mutation in exon 14 resulted in substitution of threonine with isoleucine at position 669, which was located at the center of the ATP binding site as a gatekeeper and played an important role in binding to imatinib...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28612534/-associations-of-preoperative-platelet-to-lymphocyte-ratio-and-derived-neutrophil-to-lymphocyte-ratio-with-theprognosis-of-gastrointestinal-stromal-tumor
#16
Xiao-Nan Yin, Su-Min Tang, Yuan Yin, Chao-Yong Shen, Bo Zhang, Zhi-Xin Chen
OBJECTIVES: To determine the associations of preoperative platelet-to-lymphocyte ratio (PLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) with the prognosis of gastrointestinal stromal tumor (GIST). METHODS: GIST patients with surgical treatment from June 2005 to February 2015 in West China Hospital of Sichuan University were enrolled in the study. The results of blood routine tests of the patients within one week prior to surgery and their clinical data were extracted...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28612529/-the-mechanism-of-combination-using-mtorc1-2-inhibitor-and-imatinib-to-suppress-cell-proliferation-of-ph-all-cell-line
#17
Jia-Hui Wu, Fang-Fang Shi, Yu-Ping Gong, Rui Shi
OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#18
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28609680/characterization-and-targeting-of-platelet-derived-growth-factor-receptor-alpha-pdgfra-in-inflammatory-breast-cancer-ibc
#19
Madhura Joglekar-Javadekar, Steven Van Laere, Michael Bourne, Manal Moalwi, Pascal Finetti, Peter B Vermeulen, Daniel Birnbaum, Luc Y Dirix, Naoto Ueno, Monique Carter, Justin Rains, Abhijit Ramachandran, Francois Bertucci, Kenneth L van Golen
PURPOSE: Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth factor receptor alpha (PDGFRA) as being uniquely expressed and active in IBC patient tumor cells...
June 10, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28607207/lncrna-uca1-in-anti-cancer-drug-resistance
#20
REVIEW
Haohao Wang, Zhonghai Guan, Kuifeng He, Jiong Qian, Jiang Cao, Lisong Teng
The pivotal role of the long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in anti-cancer drug resistance has been confirmed in many cancers. Overexpression of lncRNA UCA1 correlates with resistance to chemotherapeutics such as cisplatin, gemcitabine, 5-FU, tamoxifen, imatinib and EGFR-TKIs, whereas lncRNA UCA1 knockdown restores drug sensitivity. These studies highlight the potential of lncRNA UCA1 as a diagnostic and prognostic biomarker, and a therapeutic target in malignant tumors. In this review, we address the role of lncRNA UCA1 in anti-cancer drug resistance and discuss its potential in future clinical applications...
June 2, 2017: Oncotarget
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