keyword
MENU ▼
Read by QxMD icon Read
search

Tyrosine kinase inhibitors

keyword
https://www.readbyqxmd.com/read/28930482/diagnostic-and-prognostic-cytogenetics-of-chronic-myeloid-leukaemia-an-update
#1
Matteo Molica, Fulvio Massaro, Massimo Breccia
Despite the advent of molecular assessment, banding cytogenetics and fluorescence in situ hybridization (FISH) still have a significant role in diagnostic and prognostic approaches to chronic myeloid leukaemia (CML). Area covered. At diagnosis and duringtreatment with tyrosine kinase inhibitors (TKIs), cytogenetics is used to detect the Philadelphia chromosome, with its typical translocation t(9;22)(q34;q11.2), and any additional or other chromosomal aberrations (ACAs and OCAs) that may arise in 5-10% of cases, the latter associated to transformation of the disease in blast phases...
September 20, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28929822/genetic-and-ethnic-modulation-of-cardiovascular-toxicity-of-vascular-endothelial-growth-factor-inhibitors
#2
Yen-Chou Chen, Cheng-Chih Chung, Yung-Kuo Lin, Yi-Jen Chen
Vascular endothelial growth factor (VEGF) inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are important as anticancer treatments through curbing tumor angiogenesis and growth. VEGF inhibitors have significant cardiovascular effects. By blocking VEGF receptors, ligands, or signal pathways, VEGF inhibitors disturb the balance between vasodilation and vasoconstriction, undermine endothelial cell integrity, and activate cardiomyocyte apoptosis. VEGF inhibitors increase risks of hypertension, heart failure, thromboembolism, and arrhythmia...
September 20, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#3
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928160/quantitative-and-mechanistic-understanding-of-azd1775-penetration-across-human-blood-brain-barrier-in-glioblastoma-patients-using-an-ivive-pbpk-modeling-approach
#4
Jing Li, Jianmei Wu, Xun Bao, Norissa Honea, Youming Xie, Seongho Kim, Alex Sparreboom, Nader Sanai
PURPOSE: AZD1775, a first-in-class, small molecule inhibitor of the Wee1 tyrosine kinase, is under evaluation as a potential chemo- and radio-sensitizer for treating glioblastoma. This study was to prospectively, quantitatively, and mechanistically investigate the penetration of AZD1775 across human blood-brain barrier (BBB). EXPERIMENTAL DESIGN: AZD1775 plasma and tumor pharmacokinetics were evaluated in 20 glioblastoma patients. The drug metabolism, transcellular passive permeability, and interactions with efflux and uptake transporters were determined using human derived in vitro systems...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#5
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#6
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#7
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#8
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925954/quantitative-structure-activity-relationship-modeling-of-kinase-selectivity-profiles
#9
Sandeepkumar Kothiwale, Corina Borza, Ambra Pozzi, Jens Meiler
The discovery of selective inhibitors of biological target proteins is the primary goal of many drug discovery campaigns. However, this goal has proven elusive, especially for inhibitors targeting the well-conserved orthosteric adenosine triphosphate (ATP) binding pocket of kinase enzymes. The human kinome is large and it is rather difficult to profile early lead compounds against around 500 targets to gain an upfront knowledge on selectivity. Further, selectivity can change drastically during derivatization of an initial lead compound...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28925739/synthesis-of-piperazine-based-thiazolidinones-as-vegfr2-tyrosine-kinase-inhibitors-inducing-apoptosis
#10
Mostafa Mm El-Miligy, Heba A Abd El Razik, Marwa M Abu-Serie
AIM: VEGFR2 tyrosine kinase is a main target in suppressing cancer growth and metastasis. Materials & methods: Piperazine-based thiazolidinones were synthesized and screened for their anticancer and VEGFR2 tyrosine kinase inhibitory activity. Results: Compounds 11, 13 and 16 displayed potent anticancer activity against HepG-2 with IC50 values 0.03-0.06 μM. They were safe on normal human fibroblasts with selectivity indices 8.09, 11.40 and 4.37, respectively. Also, these compounds showed VEGFR2 tyrosine kinase inhibitory activities more than the reference staurosporine with IC50 values <0...
September 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#11
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923937/direct-engagement-of-the-pi3k-pathway-by-mutant-kit-dominates-oncogenic-signaling-in-gastrointestinal-stromal-tumor
#12
Benedikt Bosbach, Ferdinand Rossi, Yasemin Yozgat, Jennifer Loo, Jennifer Q Zhang, Georgina Berrozpe, Katherine Warpinski, Imke Ehlers, Darren Veach, Andrew Kwok, Katia Manova, Cristina R Antonescu, Ronald P DeMatteo, Peter Besmer
Gastrointestinal stromal tumors (GISTs) predominantly harbor activating mutations in the receptor tyrosine kinase KIT. To genetically dissect in vivo the requirement of different signal transduction pathways emanating from KIT for tumorigenesis, the oncogenic Kit(V558Δ) mutation was combined with point mutations abrogating specific phosphorylation sites on KIT. Compared with single-mutant Kit(V558Δ/+) mice, double-mutant Kit(V558Δ;Y567F/Y567F) knock-in mice lacking the SRC family kinase-binding site on KIT (pY567) exhibited attenuated MAPK signaling and tumor growth...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923922/trkb-neurotrophic-activities-are-blocked-by-%C3%AE-synuclein-triggering-dopaminergic-cell-death-in-parkinson-s-disease
#13
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Matthew J Benskey, Xuebing Cao, Jun Xu, Yi E Sun, Keqiang Ye
BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson's disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923853/adaptation-to-tki-treatment-reactivates-erk-signaling-in-tyrosine-kinase-driven-leukemias-and-other-malignancies
#14
Joshua K Bruner, Hayley S Ma, Li Li, Alice Can Ran Qin, Michelle A Rudek, Richard J Jones, Mark J Levis, Keith W Pratz, Christine A Pratilas, Donald Small
FLT3 tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia. We hypothesized that FLT3/ITD leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared to either drug alone...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923179/drugs-and-hyperglycemia-a-practical-guide
#15
REVIEW
Vandana Jain, Ronak Kumar Patel, Zaureen Kapadia, Sneha Galiveeti, Maryann Banerji, Lisel Hope
Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha)...
October 2017: Maturitas
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#16
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28921872/first-line-therapy-with-dacomitinib-an-orally-available-pan-her-tyrosine-kinase-inhibitor-for-locally-advanced-or-metastatic-penile-squamous-cell-carcinoma-results-of-an-open-label-single-arm-single-center-phase-2-study
#17
A Necchi, S Lo Vullo, F Perrone, D Raggi, P Giannatempo, G Calareso, N Nicolai, L Piva, D Biasoni, M Catanzaro, T Torelli, S Stagni, E Togliardi, M Colecchia, A Busico, A Gloghini, A Testi, L Mariani, R Salvioni
OBJECTIVE: To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. PATIENTS AND METHODS: In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (TNM 2009), and no prior chemotherapy administration...
September 16, 2017: BJU International
https://www.readbyqxmd.com/read/28921811/a-role-for-the-non-receptor-tyrosine-kinase-ack1-in-tnf-alpha-mediated-apoptosis-and-proliferation-in-human-intestinal-epithelial-caco-2-cells
#18
Xinmei Zhao, Chaolan Lv, Shenbo Chen, Fachao Zhi
The roles of tumor necrosis factor alpha (TNF-alpha) and its mediators in cellular processes related to intestinal diseases remain elusive. In this study, we aimed to determine the biological role of activated Cdc42-associated kinase 1 (ACK1) in TNF-alpha-mediated apoptosis and proliferation in Caco-2 cells. ACK1 expression was knocked down using ACK1-specific siRNAs, and ACK1 activity was disrupted using a small molecule ACK1 inhibitor. The Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) and the BrdU incorporation assays were used to measure apoptosis and cell proliferation, respectively...
September 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28921623/one-step-synthesis-of-18-f-cabozantinib-for-use-in-positron-emission-tomography-imaging-of-c-met
#19
Vegard Torp Lien, Jo Klaveness, Dag Erlend Olberg
Cabozantinib is an FDA approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c-Met. Non-invasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. Based on cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor...
September 18, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28920960/long-noncoding-rna-egfr-as1-mediates-epidermal-growth-factor-receptor-addiction-and-modulates-treatment-response-in-squamous-cell-carcinoma
#20
Daniel S W Tan, Fui Teen Chong, Hui Sun Leong, Shen Yon Toh, Dawn P Lau, Xue Lin Kwang, Xiaoqian Zhang, Gopinath M Sundaram, Gek San Tan, Mei Mei Chang, Boon Tin Chua, Wan Teck Lim, Eng Huat Tan, Mei Kim Ang, Tony K H Lim, Prabha Sampath, Balram Chowbay, Anders J Skanderup, Ramanuj DasGupta, N Gopalakrishna Iyer
Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes...
September 18, 2017: Nature Medicine
keyword
keyword
2815
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"