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https://www.readbyqxmd.com/read/27589085/the-cancer-drug-dasatinib-increases-pgc-1%C3%AE-in-adipose-tissue-but-has-adverse-effects-on-glucose-tolerance-in-obese-mice
#1
Lykke Sylow, Jonathan Z Long, Isha A Lokurkar, Xing Zeng, Erik A Richter, Bruce M Spiegelman
Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia. In this study, we identify dasatinib as a potent inducer of Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes...
November 2016: Endocrinology
https://www.readbyqxmd.com/read/25975582/therapeutic-effects-of-dasatinib-in-mouse-model-of-multiple-sclerosis
#2
Gholamreza Azizi, Mahdi Goudarzvand, Sanaz Afraei, Reza Sedaghat, Abbas Mirshafiey
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS...
June 2015: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/24794907/dasatinib
#3
REVIEW
Hesham M Korashy, A F M Motiur Rahman, Mohammed Gabr Kassem
Dasatinib (Sprycel®), a second-generation TKI, has been shown to be effective as an anticancer drug in the treatment of patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of dasatinib showed a λmax of approximately 320-330nm, and IR spectroscopy principal peaks were observed at 3418 (NH), 3200 (OH), 1620 (CO), 1582 (CC and CN), 1513 (CHCH) cm(-1)...
2014: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/24455114/treatment-recommendations-for-chronic-myeloid-leukemia
#4
REVIEW
Michele Baccarani, Fausto Castagnetti, Gabriele Gugliotta, Francesca Palandri, Gianantonio Rosti
The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy...
January 2, 2014: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/23564552/-adequate-supportive-treatment-in-therapeutic-use-of-biologicals-for-gi-tumours-in-oncosurgery-what-does-the-surgeon-need-to-know
#5
REVIEW
E Kettner, H Hütten, J Ricke, F Meyer
BACKGROUND: Along with the increasing use and inauguration of novel antineoplastic substances (inhibitors, antibodies [Ab]) at various levels of the tumour cell-specific intracellular signalling (transduction cascade) on the cell surface and within the cell as well as messengers ["biologicals", "targeted therapy"]), a new quality, intensity and complexity of adverse effects was simultaneously developed, which have become more and more relevant even to oncosurgeons. AIM: A summary is given of clinically obtained expertise including recommendations for a competent approach, management and use of biologicals for targeted therapy in case of abnormal or adverse effects as well as toxic reactions, which are compared with available data from the literature and provided as systematic short review on the clinically used substances and drugs in GI tumour lesions...
April 2013: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/23549840/dasatinib-a-guide-to-its-use-in-chronic-myeloid-leukemia-in-the-eu
#6
REVIEW
Gillian M Keating, Katherine A Lyseng-Williamson, Paul L McCormack, Susan J Keam
Oral dasatinib (Sprycel(®)) is effective in the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML) or imatinib-resistant or imatinib-intolerant chronic-phase, accelerated-phase, or blast-phase CML. In particular, dasatinib is associated with better and faster responses than imatinib in patients with newly diagnosed chronic-phase CML. The response to dasatinib appears to be maintained in the longer-term. Dasatinib has an acceptable tolerability profile; it is associated with myelosuppression, with fluid retention being the most common nonhematologic adverse event...
June 2013: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/23175995/is-imatinib-still-an-acceptable-first-line-treatment-for-cml-in-chronic-phase
#7
John M Goldman, David Marin
The introduction of the tyrosine kinase inhibitor (TKI) imatinib (Gleevec) into clinical practice resulted in a very dramatic prolongation of survival for most, but not all, patients with chronic myeloid leukemia in chronic phase (CML-CP). A leukemia with a median survival of about 5 years was transformed into one for which the survival in many cases promises to be comparable to that of normal persons of similar age. The more recently available TKIs, namely nilotinib (Tasigna) and dasatinib (Sprycel), produce more rapid responses but have not yet shown any overall survival advantage compared with long-term administration of imatinib...
October 2012: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/22975544/pulmonary-arterial-hypertension-caused-by-treatment-with-dasatinib-for-chronic-myeloid-leukemia-critical-alert
#8
Makoto Sano, Masao Saotome, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Kazunori Ohnishi, Hideharu Hayashi
We present a case of pulmonary arterial hypertension (PAH), which is potentially related to treatment with dasatinib (Sprycel(®)). A 61-year-old woman, who had been treated with dasatinib for 27 months for chronic myeloid leukemia (CML), visited our hospital complaining of dyspnea. In right heart catheterization, her mean pulmonary arterial pressure was 35 mmHg. After other possible etiologies to cause PAH were excluded, the patient was diagnosed as a dasatinib-related PAH. As notified by U.S. Food and Drug Administration (FDA) in October 2011, we recommend routine cardiopulmonary evaluation before and during treatment with dasatinib in CML patients in terms of the adverse effects of PAH...
2012: Internal Medicine
https://www.readbyqxmd.com/read/22829108/the-tyrosine-kinase-inhibitor-dasatinib-sprycel-inhibits-chondrocyte-activity-and-proliferation
#9
K Vandyke, S Fitter, A C W Zannettino
No abstract text is available yet for this article.
February 2011: Blood Cancer Journal
https://www.readbyqxmd.com/read/22233429/spotlight-on-dasatinib-in-chronic-myeloid-leukemia-and-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#10
Paul L McCormack, Susan J Keam
Dasatinib (Sprycel®) is an orally administered small molecule inhibitor of multiple tyrosine kinases, including BCR-ABL and SRC family kinases, which is indicated for the treatment of adults with newly diagnosed chronic-phase chronic myeloid leukemia (CML), CML (chronic-, accelerated- or blast-phase) with resistance or intolerance to prior therapy, including imatinib, or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. Dasatinib is ≈325-fold more active than imatinib in inhibiting wild-type BCR-ABL kinase in vitro and is active against a wide variety of imatinib-resistant BCR-ABL mutants, except for T315I...
February 1, 2012: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/21982905/a-validated-lc-ms-ms-assay-for-the-simultaneous-determination-of-the-anti-leukemic-agent-dasatinib-and-two-pharmacologically-active-metabolites-in-human-plasma-application-to-a-clinical-pharmacokinetic-study
#11
Michael T Furlong, Shruti Agrawal, Dara Hawthorne, Michael Lago, Steve Unger, Linda Krueger, Bruce Stouffer
Dasatinib (Sprycel) is a potent antitumor agent prescribed for patients with chronic myeloid leukemia (CML). To enable reliable quantification of dasatinib and its pharmacologically active metabolites in human plasma during clinical testing, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. Samples were prepared using solid phase extraction on Oasis HLB 96-well plates. Chromatographic separation was achieved isocratically on a Luna phenyl-hexyl analytical column...
January 25, 2012: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/21902298/dasatinib-a-review-of-its-use-in-the-treatment-of-chronic-myeloid-leukaemia-and-philadelphia-chromosome-positive-acute-lymphoblastic-leukaemia
#12
REVIEW
Paul L McCormack, Susan J Keam
Dasatinib (Sprycel®) is an orally administered small molecule inhibitor of multiple tyrosine kinases, including BCR-ABL and SRC family kinases, which is indicated for the treatment of adults with newly diagnosed chronic-phase chronic myeloid leukaemia (CML), CML (chronic-, accelerated- or blast-phase) with resistance or intolerance to prior therapy, including imatinib, or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) with resistance or intolerance to prior therapy. Dasatinib is ≈325-fold more active than imatinib in inhibiting wild-type ABL kinase in vitro and is active against a wide variety of imatinib-resistant BCR-ABL mutants, except for T315I...
September 10, 2011: Drugs
https://www.readbyqxmd.com/read/21226671/dasatinib-an-anti-tumour-agent-via-src-inhibition
#13
REVIEW
Antonio Gnoni, Ilaria Marech, Nicola Silvestris, Angelo Vacca, Vito Lorusso
Dasatinib (BMS-354825, Sprycel®) is an oral, multitargeted inhibitor of receptor tyrosine kinases (RTKs), including BCR-ABL fusion protein, stem cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGFR), and Src family kinases (SFKs). Several early- and late-phase clinical trials for chronic myelogeneous leukaemia (CML) have demonstrated the direct inhibition of BCR-ABL fusion protein and SFKs, which led to dasatinib approval by the Food and Drug Administration (FDA) and the European Union for the treatment of imatinib-resistant or -intolerant CML, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)...
April 2011: Current Drug Targets
https://www.readbyqxmd.com/read/20962097/variola-and-monkeypox-viruses-utilize-conserved-mechanisms-of-virion-motility-and-release-that-depend-on-abl-and-src-family-tyrosine-kinases
#14
Patrick M Reeves, Scott K Smith, Victoria A Olson, Steve H Thorne, William Bornmann, Inger K Damon, Daniel Kalman
Vaccinia virus (VacV) enters mammalian cells, replicates extranuclearly, and produces virions that move to the cell surface along microtubules, fuse with the plasma membrane, and move from infected cells toward apposing cells on actin-filled membranous protrusions or actin tails. To form actin tails, cell-associated enveloped virions (CEV) require Abl and Src family tyrosine kinases. Furthermore, release of CEV from the cell requires Abl but not Src family tyrosine kinases and is blocked by imatinib mesylate (STI-571; Gleevec), an Abl family kinase inhibitor used to treat chronic myelogenous leukemia in humans...
January 2011: Journal of Virology
https://www.readbyqxmd.com/read/20956938/dasatinib-sensitizes-kras-mutant-colorectal-tumors-to-cetuximab
#15
E F Dunn, M Iida, R A Myers, D A Campbell, K A Hintz, E A Armstrong, C Li, D L Wheeler
KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). This study sought to determine if KRAS mutant CRC lines could be sensitized to cetuximab using dasatinib (BMS-354825, Sprycel), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases (SFKs). We analyzed 16 CRC lines for: (1) KRAS mutation status, (2) dependence on mutant KRAS signaling and (3) expression level of epidermal growth factor receptor (EGFR) and SFKs...
February 3, 2011: Oncogene
https://www.readbyqxmd.com/read/20537386/bcr-abl-tyrosine-kinase-inhibitors-in-the-treatment-of-philadelphia-chromosome-positive-chronic-myeloid-leukemia-a-review
#16
REVIEW
Xin An, Amit K Tiwari, Yibo Sun, Pei-Rong Ding, Charles R Ashby, Zhe-Sheng Chen
Chronic Myeloid Leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia (Ph+) chromosome and its oncogenic product, BCR-ABL, a constitutively active tyrosine kinase, that is present in >90% of the patients. Epidemiologic data indicates that almost 5000 new cases are reported every year and 10% of these patients eventually succumb to the disease. The treatment of CML was revolutionized by the introduction of imatinib mesylate (IM, Gleevec), a BCR-ABL tyrosine kinase inhibitor (TKI)...
October 2010: Leukemia Research
https://www.readbyqxmd.com/read/19854117/development-of-a-high-performance-liquid-chromatographic-mass-spectrometric-method-for-the-determination-of-cellular-levels-of-the-tyrosine-kinase-inhibitors-lapatinib-and-dasatinib
#17
Sandra Roche, Gillian McMahon, Martin Clynes, Robert O'Connor
A highly sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed to quantify cellular levels of the tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and lapatinib (Tykerb, Tyverb). Cellular samples were extracted with a tert-butyl methyl ether:acetonitrile (3:1, v/v):1 M ammonium formate pH 3.5 (8:1, v/v) mixture. Separation was achieved on a Hyperclone BDS C18 (150 mm x 2.0 mm 3 microm) column with isocratic elution using a mobile phase of acetonitirile-10 mM ammonium formate, pH 4 (54:46, v/v), at a flow rate of 0...
December 1, 2009: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/19786067/dasatinib-inhibits-the-secretion-of-tnf-alpha-following-tlr-stimulation-in-vitro-and-in-vivo
#18
Cara K Fraser, Erin L Lousberg, Raman Kumar, Timothy P Hughes, Kerrilyn R Diener, John D Hayball
OBJECTIVE: Dasatinib (SPRYCEL, BMS-354825) is a small molecule Src/Abl tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, kinases inhibited by dasatinib are also involved in the induction and regulation of innate immunity. The purpose of this study was to evaluate the effect of dasatinib on cytokine secretion in response to toll-like receptor (TLR) stimulation. MATERIALS AND METHODS: Dasatinib-treated mice were administered intraperitoneally with lipopolysaccharide (LPS) and serum cytokine (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-10, and IL-6) levels and neutrophil accumulation in the lungs were analyzed...
December 2009: Experimental Hematology
https://www.readbyqxmd.com/read/19749489/pharmacological-properties-and-clinical-efficacy-of-dasatinib-hydrate-sprycel-an-anticancer-drug-for-chronic-myelogenous-leukemia-and-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#19
REVIEW
Yutaka Fujii, Manabu Amano, Taku Seriu
No abstract text is available yet for this article.
September 2009: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/19662183/ns-187-inno-406-a-bcr-abl-lyn-dual-tyrosine-kinase-inhibitor
#20
Tomoko Niwa, Tetsuo Asaki, Shinya Kimura
Protein kinases catalyze the transfer of the gamma-phosphoryl group of adenosine triphosphate (ATP) to the hydroxyl groups of protein side chains, and they play critical roles in regulating cellular signal transduction and other biochemical processes. They are attractive targets for today's drug discovery and development, and many pharmaceutical companies are intensively developing various kinds of protein kinase inhibitors. A good example is the recent success with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (Gleevec) in the treatment of chronic myeloid leukemia...
November 14, 2007: Analytical Chemistry Insights
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