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https://www.readbyqxmd.com/read/28534184/evaluation-of-cardiovascular-ischemic-event-rates-in-dasatinib-treated-patients-using-standardized-incidence-ratios
#1
Giuseppe Saglio, Philipp le Coutre, Jorge Cortes, Jiří Mayer, Philip Rowlings, François-Xavier Mahon, Glenn Kroog, Kyna Gooden, Milayna Subar, Neil P Shah
With high survival rates for chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs), emerging consequences, such as arterial ischemic events, require consideration when evaluating treatment options. Cardiovascular ischemic event incidence in clinical trials was evaluated in 2712 dasatinib-treated patients with Philadelphia chromosome-positive (Ph+) leukemias from 11 first- and second-line trials (pooled), newly diagnosed CML patients treated with dasatinib or imatinib (DASISION), and prostate cancer patients treated with dasatinib or placebo plus docetaxel/prednisone (READY)...
May 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#2
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28533646/image-findings-of-rare-case-of-peritoneal-carcinomatosis-from-non-small-cell-lung-cancer-and-response-to-erlotinib-in-f-18-fdg-positron-emission-tomography-computed-tomography
#3
Koramadai Karuppusamy Kamaleshwaran, Jephy Joseph, Radha Krishnan Kalarikal, Ajit Sugunan Shinto
Lung cancer is currently one of the most common malignancies in the world. Metastatic disease is observed in ~ 40% of patients with lung cancer, with the most common sites of metastasis being the bone, liver, brain and adrenal glands. Peritoneal carcinomatosis (PC) is defined as the progression of the primary cancer to the peritoneum. PC is a rare clinical event in lung cancer. Tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), such as erlotinib are used for the treatment of patients with advanced non-small cell lung cancer (NSCLC)...
April 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28533480/deregulated-expression-of-mir-29a-3p-mir-494-3p-and-mir-660-5p-affects-sensitivity-to-tyrosine-kinase-inhibitors-in-cml-leukemic-stem-cells
#4
Simona Salati, Valentina Salvestrini, Chiara Carretta, Elena Genovese, Sebastiano Rontauroli, Roberta Zini, Chiara Rossi, Samantha Ruberti, Elisa Bianchi, Greta Barbieri, Antonio Curti, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Micaela Bergamaschi, Agostino Tafuri, Enrico Tagliafico, Roberto Lemoli, Rossella Manfredini
The development of Imatinib mesylate (IM), which targets the oncogenic BCR-ABL fusion protein, has greatly improved the outcome of Chronic Myeloid Leukemia (CML) patients. However, BCR-ABL-positive progenitors can be detected in CML patients in complete cytogenetic response. Several evidence suggests that CML stem cells are intrinsically resistant to Tyrosine Kinase Inhibitors (TKI), and therefore they represent the most likely candidate responsible for disease relapse.In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28532501/pik3ca-hotspot-mutations-differentially-impact-responses-to-met-targeting-in-met-driven-and-non-driven-preclinical-cancer-models
#5
Lluís Nisa, Pascal Häfliger, Michaela Poliaková, Roland Giger, Paola Francica, Daniel Matthias Aebersold, Roch-Philippe Charles, Yitzhak Zimmer, Michaela Medová
BACKGROUND: The MET receptor tyrosine kinase represents a promising target in cancer. PIK3CA activating mutations are common in several tumor types and can potentially confer resistance to anti-receptor tyrosine kinase therapy. METHODS: MET and/or PI3K pathway inhibition was assessed in NIH3T3 cells harboring MET-activating point mutation with or without ectopic expression of PIK3CA(E545K) and PIK3CA(H1047R), as well as in MET-expressing head and neck cancer cells with endogenous PIK3CA mutations...
May 22, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28529741/pazopanib-induced-asymptomatic-radiological-acute-pancreatitis-a-case-report
#6
Iosune Baraibar, Almudena Quílez, Diego Salas, Marta Román, Christian Rolfo, José L Pérez-Gracia, Ignacio Gil-Bazo
The universal clinical use of multi-targeted tyrosine kinase inhibitors (TKIs) in patients diagnosed with advanced renal cell carcinoma (RCC) has significantly prolonged their estimated survival times and their quality of life. However, several adverse side-effects associated predominantly with the inhibition of the vascular endothelial growth factor receptor by these drugs may prove to be potentially life-threatening. One adverse event that is only rarely observed with the use of TKIs in this clinical setting is acute pancreatitis...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529640/lung-cancer-targeting-peptides-with-multi-subtype-indication-for-combinational-drug-delivery-and-molecular-imaging
#7
Yi-Hsuan Chi, Jong-Kai Hsiao, Ming-Huang Lin, Chen Chang, Chun-Hsin Lan, Han-Chung Wu
Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC)...
2017: Theranostics
https://www.readbyqxmd.com/read/28528977/imatinib-induces-autophagy-via-upregulating-xiap-in-gist882%C3%A2-cells
#8
Qingqing Xie, Qi Lin, Dezhi Li, Jianming Chen
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528264/baseline-and-longitudinal-variability-of-normal-tissue-uptake-values-of-18-f-fluorothymidine-pet-images
#9
Matthijs C F Cysouw, Gerbrand M Kramer, Virginie Frings, Adrianus J De Langen, Mariëlle J Wondergem, Laura M Kenny, Eric O Aboagye, Carsten Kobe, Jürgen Wolf, Otto S Hoekstra, Ronald Boellaard
PURPOSE: [(18)F]-fluorothymidine ([(18)F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution. METHODS: (18)F-FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated...
May 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28527959/systemic-treatment-patterns-with-advanced-or-recurrent-non-small-cell-lung-cancer-in-japan-a-retrospective-hospital-administrative-database-study
#10
Feng Wang, Sari Mishina, Shinji Takai, T Kim Le, Kenya Ochi, Kotaro Funato, Shozo Matsuoka, Yuichiro Ohe
PURPOSE: Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. METHODS: This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed...
May 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#11
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28527565/-advancement-in-the-treatment-of-renal-carcinoma
#12
Arnaud Méjean
Partial nephrectomy is the gold standard for the renal tumours less than 7 to 10cm whenever feasible in order to preserve renal function. The extension of nephron-sparing surgery using a mini-invasive approach is possible by robotic surgery. Radical nephrectomy is mandatory in the other situations and especially in case of locally advanced renal carcinoma. The place of cytoreductive nephrectomy in metastatic renal cell carcinoma is the purpose of the CARMENA trial. Tyrosine kinase inhibitors are currently the first line treatment; but in the near future new immunotherapy by checkpoints molecules could crucially change the treatment of metastatic renal cell carcinoma...
May 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28526956/erratum-to-role-of-complexity-of-variant-philadelphia-chromosome-in-chronic-myeloid-leukemia-in-the-era-of-tyrosine-kinase-inhibitor-therapy
#13
Zimu Gong, Lan Zheng, Zhenya Tang, Zi Chen, Wei Wang, Shi Bai, Guilin Tang, L Jeffrey Medeiros, Shimin Hu
No abstract text is available yet for this article.
May 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#14
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28525890/a-novel-egfr-tki-inhibitor-camp-h3bo3%C3%A2-complex-combined-with-thermal-therapy-is-a-promising-strategy-to-improve-lung-cancer-treatment-outcomes
#15
Yongpeng Tong, Chunliu Huang, Junfang Zhang
PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524780/role-of-cost-sharing-subsidies-on-the-initiation-of-and-adherence-to-tyrosine-kinase-inhibitor-therapy-by-medicare-beneficiaries-with-chronic-myeloid-leukemia
#16
Ellen K Ritchie, Annie Guerin, Johannes Wolff, George Joseph
No abstract text is available yet for this article.
May 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#17
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28524213/-update-on-the-treatment-of-rasopathies
#18
A Duat-Rodriguez, A Hernandez-Martin
INTRODUCTION: The term 'RASopathies' covers a series of diseases that present mutations in the genes that code for the proteins of the RAS/MAPK pathway. These diseases include neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome. Involvement of the RAS/MAPK pathway not only increases predisposition to develop tumours, but also determines the presence of phenotypic anomalies and alterations in learning processes...
May 17, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28523104/3-aroyl-1-4-diarylpyrroles-inhibit-chronic-myeloid-leukemia-cell-growth-through-an-interaction-with-tubulin
#19
Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sara Passacantilli, Valentina Naccarato, Giorgio Ortar, Carmela Mazzoccoli, Vitalba Ruggieri, Francesca Agriesti, Claudia Piccoli, Tiziana Tataranni, Marianna Nalli, Andrea Brancale, Stefania Vultaggio, Ciro Mercurio, Mario Varasi, Concetta Saponaro, Sara Sergio, Michele Maffia, Addolorata Maria Luce Coluccia, Ernest Hamel, Romano Silvestri
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#20
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
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