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https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#1
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445830/overexpression-of-heme-oxygenase-1-in-bone-marrow-stromal-cells-promotes-microenvironment-mediated-imatinib-resistance-in-chronic-myeloid-leukemia
#2
Ping Liu, Dan Ma, Zhengyu Yu, Nana Zhe, Mei Ren, Ping Wang, Meisheng Yu, Jun Huang, Qin Fang, Jishi Wang
Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445529/ductular-reaction-correlates-with-fibrogenesis-but-does-not-contribute-to-liver-regeneration-in-experimental-fibrosis-models
#3
András Rókusz, Dániel Veres, Armanda Szücs, Edina Bugyik, Miklós Mózes, Sándor Paku, Péter Nagy, Katalin Dezső
BACKGROUND AND AIMS: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models. METHODS: Liver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration...
2017: PloS One
https://www.readbyqxmd.com/read/28445102/journey-of-generic-imatinib-a-case-study-in-oncology-drug-pricing
#4
Christopher T Chen, Aaron S Kesselheim
No abstract text is available yet for this article.
April 26, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28444623/treatment-adherence-in-chronic-myeloid-leukaemia-patients-receiving-tyrosine-kinase-inhibitors
#5
Anna Rychter, Piotr Jerzmanowski, Adam Hołub, Zofia Specht-Szwoch, Violetta Kalinowska, Urszula Tęgowska, Ilona Seferyńska, Agnieszka Kołkowska-Leśniak, Ewa Lech-Marańda, Joanna Góra-Tybor
Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#6
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28438191/continuous-diphenhydramine-infusion-and-imatinib-for-kit-d816v-negative-mast-cell-activation-syndrome-a-case-report
#7
Faizan Malik, Naveed Ali, Syed Imran Mustafa Jafri, Ali Ghani, Mohsin Hamid, Margot Boigon, Christian Fidler
BACKGROUND: We present the first full case report of the treatment of mast cell activation syndrome with continuous diphenhydramine infusion, which resulted in the improvement of anaphylactic reactions and a decrease in hospital readmission. Furthermore, the patient received imatinib in the absence of the KIT-D816V mutation, which led to further improvement of quality of life. Currently, we are trying to wean this patient off diphenhydramine; if successful, this attempt will represent the first reported case...
April 24, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28437552/bcr-abl1-transcript-types-showed-distinct-laboratory-characteristics-in-patients-with-chronic-myeloid-leukemia
#8
A P Vasconcelos, I F Azevedo, F C B C Melo, W B Neves, A C A C Azevedo, R A M Melo
In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent...
April 20, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28435517/inhibition-of-the-platelet-derived-growth-factor-receptor-beta-pdgfrb-using-gene-silencing-crenolanib-besylate-or-imatinib-mesylate-hampers-the-malignant-phenotype-of-mesothelioma-cell-lines
#9
Ombretta Melaiu, Calogerina Catalano, Chiara De Santi, Monica Cipollini, Gisella Figlioli, Lucia Pellè, Elisa Barone, Monica Evangelista, Alice Guazzelli, Laura Boldrini, Elisa Sensi, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Luciano Mutti, Gabriella Fontanini, Federica Gemignani, Stefano Landi
Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25)...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435469/interleukin-3-receptor-targeted-exosomes-inhibit-in-vitro-and-in-vivo-chronic-myelogenous-leukemia-cell-growth
#10
Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents...
2017: Theranostics
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#11
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433749/novel-sulphur-containing-imatinib-metabolites-found-by-untargeted-lc-hrms-analysis
#12
Ivo Vrobel, David Friedecký, Edgar Faber, Lukáš Najdekr, Kateřina Mičová, Radana Karlíková, Tomáš Adam
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure...
April 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28433494/patterns-of-care-and-clinical-outcomes-in-primary-oesophageal-gastrointestinal-stromal-tumours-gist-a-retrospective-study-of-the-french-sarcoma-group-fsg
#13
F Duffaud, P Meeus, F Bertucci, J-B Delhorme, E Stoeckle, N Isambert, E Bompas, J Gagniere, O Bouché, M Toulmonde, S Salas, J-Y Blay, S Bonvalot
BACKGROUND: Oesophageal GIST (ESOGIST) are very rare tumours requiring special consideration regarding diagnosis, surgical management, and perioperative treatment. METHODS: A retrospective study was conducted across 9 centres in the French Sarcoma Group (FSG) to characterize all patients in the years 2000-2014. RESULTS: Seventeen patients (pts) with primary localized ESOGIST were identified, with median age 69 years (36-81) and 11 females...
April 1, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#14
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28425854/rationale-design-synthesis-cytotoxicity-evaluation-and-molecular-docking-studies-of-1-3-4-oxadiazole-analogues
#15
Mohamed Jawed Ahsan, Arun Choupra, Rakesh Kumar Sharma, Surender Singh Jadav, Mohd Zaheen Hassan, Mohammed Afroz Bakht, Pannala Padmaja, Abdulmalik Bin Saleh Al-Tamimi, Mohammed H Geesi
We report herein, the synthesis of two new series of oxadiazole analogues, and their cytotoxicity evaluation. The oxadiazole analogues (5a-h and 12a-h) were structurally related to the heterocyclic (1,3,4- oxadiazole) linked aryl core of IMC-038525 (tubulin polymerization inhibitor), NSC 776715, and NSC 776716, with further modification by incorporating methylene linker. The title compounds (5a-h and 12a-h) were synthesized in good yields, and were characterized by IR, NMR, and mass spectral data. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI US) Protocol against NCI-60 human cell lines derived from nine different panels...
April 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28424749/development-of-asymmetric-facial-depigmentation-in-a-patient-treated-with-dasatinib-with-new-onset-hypovitaminosis-d-case-report-and-review-of-the-literature
#16
Kirsten C Webb, Magdalena Harasimowicz, Monica Janeczek, Jodi Speiser, James Swan, Rebecca Tung
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#17
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28423649/stellettin-b-induces-apoptosis-in-human-chronic-myeloid-leukemia-cells-via-targeting-pi3k-and-stat5
#18
Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423367/imatinib-dose-escalation-versus-sunitinib-as-a-second-line-treatment-against-advanced-gastrointestinal-stromal-tumors-a-nationwide-population-based-cohort-study
#19
Jun-Te Hsu, Puo-Hsien Le, Chang-Fu Kuo, Meng-Jiun Chiou, Chia-Jung Kuo, Tsung-Hsing Chen, Chun-Jung Lin, Jen-Shi Chen, Huang-Pin Yu, Chun-Nan Yeh, Yi-Yin Jan, Ta-Sen Yeh
BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421416/emergence-of-ctnnb1-mutation-at-acquired-resistance-to-kit-inhibitor-in-metastatic-melanoma
#20
J Cho, S Y Kim, Y J Kim, M H Sim, S T Kim, N K D Kim, K Kim, W Park, J H Kim, K-T Jang, J Lee
PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. The mechanisms of acquired resistance to imatinib in melanoma remain unclear. METHODS: We analyzed biopsy samples from paired baseline and post-treatment tumor lesions in one patient with KIT-mutated melanoma who had had an initial objective tumor regression in response to imatinib treatment followed by disease progression 8 months later...
April 18, 2017: Clinical & Translational Oncology
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