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Bosutinib

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https://www.readbyqxmd.com/read/29018127/bosutinib-attenuates-inflammation-via-inhibiting-salt-inducible-kinases-in-experimental-model-of-intracerebral-hemorrhage-on-mice
#1
Li Ma, Anatol Manaenko, Yi-Bo Ou, An-Wen Shao, Shu-Xu Yang, John H Zhang
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. Pronounced inflammation plays a significant role in the development of the secondary brain injury after ICH. Recently, SIK-2 (salt-inducible kinase-2) was identified as an important component controlling inflammatory response. Here we sought to investigate the role of SIK-2 in post-ICH inflammation and potential protective effects of SIK-2 inhibition after ICH. METHODS: Two hundred and ninety-three male CD-1 mice were used...
October 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28990873/third-line-treatment-with-second-generation-tyrosine-kinase-inhibitors-dasatinib-or-nilotinib-in-patients-with-chronic-myeloid-leukemia-after-two-prior-tkis-real-life-data-on-a-single-center-experience-along-with-the-review-of-the-literature
#2
Seniz Ongoren, Ahmet Emre Eskazan, Veysel Suzan, Sercan Savci, Isil Erdogan Ozunal, Selin Berk, Fevzi Fırat Yalniz, Tugrul Elverdi, Ayse Salihoglu, Yucel Erbilgin, Sibel Aylin Iseri, Muhlis Cem Ar, Zafer Baslar, Yildiz Aydin, Nukhet Tuzuner, Ugur Ozbek, Teoman Soysal
OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated...
October 9, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28950062/integrating-transcriptomic-data-with-mechanistic-systems-pharmacology-models-for-virtual-drug-combination-trials
#3
Anne Marie Barrette, Mehdi Bouhaddou, Marc R Birtwistle
Monotherapy clinical trials with mutation-targeted kinase inhibitors, despite some success in other cancers, have yet to impact glioblastoma (GBM). Besides insufficient blood-brain barrier penetration, combinations are key to overcoming obstacles such as intratumoral heterogeneity, adaptive resistance, and the epistatic nature of tumor genomics that cause mutation-targeted therapies to fail. With now hundreds of potential drugs, exploring the combination space clinically and preclinically is daunting. We are building a simulation-based approach that integrates patient-specific data with a mechanistic computational model of pan-cancer driver pathways (receptor tyrosine kinases, RAS/RAF/ERK, PI3K/AKT/mTOR, cell cycle, apoptosis, and DNA damage) to prioritize drug combinations by their simulated effects on tumor cell proliferation and death...
October 6, 2017: ACS Chemical Neuroscience
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
#4
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/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#5
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28914582/express-a-case-of-worsening-pulmonary-arterial-hypertension-and-pleural-effusions-by-bosutinib-after-prior-treatment-with-dasatinib
#6
Karan Seegobin, Amit Babbar, Jason Ferreira, Brittany Lyons, James Cury, Vandana Seeram
No abstract text is available yet for this article.
January 1, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28891817/neutrophil-fc%C3%AE-riia-promotes-igg-mediated-glomerular-neutrophil-capture-via-abl-src-kinases
#7
Hiroshi Nishi, Kazuhiro Furuhashi, Xavier Cullere, Gurpanna Saggu, Mark J Miller, Yunfeng Chen, Florencia Rosetti, Samantha L Hamilton, Lihua Yang, Spencer P Pittman, Jiexi Liao, Jan M Herter, Jeffrey C Berry, Daniel J DeAngelo, Cheng Zhu, George C Tsokos, Tanya N Mayadas
The kidney glomerular capillaries are frequent sites of immune complex deposition and subsequent neutrophil accumulation in post-infectious and rapidly progressive glomerulonephritis. However, the mechanisms of neutrophil recruitment remain enigmatic, and there is no targeted therapeutic to avert this proximal event in glomerular inflammation. The uniquely human activating Fc receptor FcγRIIA promotes glomerular neutrophil accumulation and damage in anti-glomerular basement membrane-induced (anti-GBM-induced) glomerulonephritis when expressed on murine neutrophils...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28852787/exploring-the-binding-of-two-potent-anticancer-drugs-bosutinib-and-imatinib-mesylate-with-bovine-serum-albumin-spectroscopic-and-molecular-dynamic-simulation-studies
#8
Suma K Pawar, Roopa S Naik, J Seetharamappa
Bosutinib (BST) and imatinib mesylate (IMT) are tyrosine kinase inhibitors (TKIs). In view of the importance of these inhibitors in cancer treatment, we investigated the mechanism of interaction between BST/IMT and bovine serum albumin (BSA) using various spectroscopic and molecular docking methods. Fluorescence studies indicated that BST/IMT interacted with BSA without affecting the microenvironment around the residue Trp213 of BSA. The quenching mechanism associated with the BST-BSA and IMT-BSA interactions was determined by performing fluorescence measurements at different temperatures...
August 29, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28838955/bosutinib-versus-placebo-for-autosomal-dominant-polycystic-kidney-disease
#9
Vladimir Tesar, Kazimierz Ciechanowski, York Pei, Irina Barash, Megan Shannon, Ray Li, Jason H Williams, Matteo Levisetti, Steven Arkin, Andreas Serra
Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m(2), and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population)...
August 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28807791/effects-of-bosutinib-treatment-on-renal-function-in-patients-with-philadelphia-chromosome-positive-leukemias
#10
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...
October 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#11
REVIEW
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...
October 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28774214/the-safety-of-bosutinib-for-the-treatment-of-chronic-myeloid-leukemia
#12
REVIEW
Jee Hyun Kong, H J Khoury, Audrey Sunwha Kim, Brittany Gray Hill, Vamsi Kota
Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered: This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion: Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy...
October 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28756527/synergistic-tumor-suppression-by-a-perilla-frutescens-derived-methoxyflavanone-and-anti-cancer-tyrosine-kinase-inhibitors-in-a549-human-lung-adenocarcinoma
#13
Amer Ali Abd El-Hafeez, Takashi Fujimura, Rikiya Kamei, Noriko Hirakawa, Kenji Baba, Kazuhisa Ono, Seiji Kawamoto
Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of cancers including non-small cell lung cancer, while appearance of TKI-resistant tumors suggests a need for the development of their potentiation strategies. We have previously shown that a methoxyflavanone derivative from the Asian medicinal herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and ponatinib) synergistically suppress proliferation of A549 cells...
July 29, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28639957/pulmonary-arterial-hypertension-induced-by-tyrosine-kinase-inhibitors
#14
Jason Weatherald, Marie-Camille Chaumais, David Montani
PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several neoplastic conditions; however, pulmonary arterial hypertension (PAH) has been reported as a complication of TKIs, predominantly with dasatinib. Recent studies have elucidated the potential mechanisms of TKI-induced PAH and have better clarified the long-term outcomes. RECENT FINDINGS: In addition to the known association between dasatinib and PAH, several other TKIs have recently been reported to cause PAH, including ponatinib, bosutinib and lapatinib...
September 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28637715/tyrosine-kinase-inhibitors-protect-the-salivary-gland-from-radiation-damage-by-inhibiting-activation-of-protein-kinase-c-%C3%AE
#15
Sten M Wie, Elizabeth Wellberg, Sana D Karam, Mary E Reyland
In patients undergoing irradiation (IR) therapy, injury to nontumor tissues can result in debilitating, and sometimes permanent, side effects. We have defined protein kinase C-δ (PKCδ) as a regulator of DNA damage-induced apoptosis and have shown that phosphorylation of PKCδ by c-Abl and c-Src activates its proapoptotic function. Here, we have explored the use of tyrosine kinase inhibitors (TKI) of c-Src and c-Abl to block activation of PKCδ for radioprotection of the salivary gland. Dasatinib, imatinib, and bosutinib all suppressed tyrosine phosphorylation of PKCδ and inhibited IR-induced apoptosis in vitro To determine whether TKIs can provide radioprotection of salivary gland function in vivo, mice were treated with TKIs and a single or fractionated doses of irradiation...
September 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28599428/bosutinib-as-a-fourth-line-therapy-for-a-patient-with-t315i-positive-lymphoid-blastic-phase-chronic-myeloid-leukemia-a-case-report
#16
Yukiko Komeno, Naoyuki Uchida, Yumiko Satoh, Hideki Uryu, Yuko Iwata, Akiko Masuda, Kuniko Iihara, Yutaka Yatomi, Shuichi Taniguchi, Tomiko Ryu
A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28560147/bosutinib-induced-pleural-effusions-case-report-and-review-of-tyrosine-kinase-inhibitors-induced-pulmonary-toxicity
#17
Natalia I Moguillansky, Hafiz Abdul Moiz Fakih, John R Wingard
Tyrosine kinase inhibitors are known to cause pulmonary complications. We report a case of bosutinib related bilateral pleural effusions in a patient with chronic myeloid leukemia. Characteristics of the pleural fluid are presented. We also discuss other tyrosine kinase inhibitors induced pulmonary toxicities, including pulmonary hypertension and interstitial lung disease.
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#18
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28475010/computational-analysis-of-abl-kinase-mutations-allows-predicting-drug-sensitivity-against-selective-kinase-inhibitors
#19
Swapna Kamasani, Sravani Akula, Sree Kanth Sivan, Vijjulatha Manga, Justus Duyster, Dashavantha Reddy Vudem, Rama Krishna Kancha
The ABL kinase inhibitor imatinib has been used as front-line therapy for Philadelphia-positive chronic myeloid leukemia. However, a significant proportion of imatinib-treated patients relapse due to occurrence of mutations in the ABL kinase domain. Although inhibitor sensitivity for a set of mutations was reported, the role of less frequent ABL kinase mutations in drug sensitivity/resistance is not known. Moreover, recent reports indicate distinct resistance profiles for second-generation ABL inhibitors. We thus employed a computational approach to predict drug sensitivity of 234 point mutations that were reported in chronic myeloid leukemia patients...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28470980/aprepitant-and-fosaprepitant-drug-interactions-a-systematic-review
#20
Priya Patel, J Steven Leeder, Micheline Piquette-Miller, L Lee Dupuis
AIMS: Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant. METHODS: We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant...
October 2017: British Journal of Clinical Pharmacology
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