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https://www.readbyqxmd.com/read/29348870/n%C3%AE%C2%B5-carboxymethyl-lysine-promotes-calcium-deposition-in-vsmcs-via-intracellular-oxidative-stress-induced-pdk4-activation-and-alters-glucose-metabolism
#1
Wen-Qi Ma, Xi-Qiong Han, Ying Wang, Xin Wang, Yi Zhu, Nai-Feng Liu
Diabetes and vascular calcification are intrinsically linked. We previously reported that advanced glycation end products (AGEs) accelerate calcium deposition in vascular smooth muscle cells (VSMCs) via excessive oxidative stress. However, the underlying mechanism remains poorly understood. Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy metabolism. Since hyperactivation of PDK4 has been reported in calcified vessels and in patients with diabetes mellitus, inhibition of PDK4 expression may be a strategy for the prevention of diabetic vascular calcification...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29344896/a-robust-optimization-approach-to-cancer-treatment-under-toxicity-uncertainty
#2
Junfeng Zhu, Hamidreza Badri, Kevin Leder
The design of optimal protocols plays an important role in cancer treatment. However, in clinical applications, the outcomes under the optimal protocols are sensitive to variations of parameter settings such as drug effects and the attributes of age, weight, and health conditions in human subjects. One approach to overcoming this challenge is to formulate the problem of finding an optimal treatment protocol as a robust optimization problem (ROP) that takes parameter uncertainty into account. In this chapter, we describe a method to model toxicity uncertainty...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344194/chronic-myeloid-leukemia-following-repeated-diagnostic-x-ray-exposure-for-the-treatment-of-recurrent-spontaneous-pneumothorax-in-a-patient-with-ankylosing-spondylitis-a-case-report-and-literature-review
#3
Fang-He Ju, Xu-Bo Gong, Ting-Zhen Xu, Li-Bin Jiang, Hui-Hua Hong, Zhen Wang
Previous studies have indicated that X-ray irradiation may increase the risk of chronic myeloid leukemia (CML), and the incidence of spontaneous pneumothorax in patients with ankylosing spondylitis (AS) is higher than in the general population. Patients with AS usually develop spontaneous pneumothorax several years after the diagnosis of AS. The present study reports the unusual case and complicated clinical history of a 29-year-old man with recurrent pneumothorax and AS, who developed CML following repeated exposure to low doses of radiation via diagnostic X-rays and chest computed tomography imaging...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344183/a-patient-with-chronic-myeloid-leukemia-and-situs-inversus-totalis-a-case-report
#4
Yunxia Sun, Xiaoli Li, Lijun Li, Huan Liu, Qian Xu, Bei Liu
In the present study, a case of chronic myeloid leukemia (CML) with complete situs inversus in a 68-year-old female patient was reported. The patient presented with general weakness, abdominal distension and tenderness in the right hypochondrium. A chest X-ray revealed a right-sided heart. Ultrasonography revealed situs inversus totalis. A bone marrow smear demonstrated CML in the accelerated phase. Imatinib mesylate was subsequently administered; the patient stopped taking imatinib mesylate following discharge from the hospital...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343154/dasatinib-induced-pulmonary-arterial-hypertension-a-rare-late-complication
#5
Uroosa Ibrahim, Amina Saqib, Vidhya Dhar, Marcel Odaimi
Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#6
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342166/effects-of-vitamin-d-on-insulin-resistance-and-myosteatosis-in-diet-induced-obese-mice
#7
Elisa Benetti, Raffaella Mastrocola, Fausto Chiazza, Debora Nigro, Giuseppe D'Antona, Valentina Bordano, Roberto Fantozzi, Manuela Aragno, Massimo Collino, Marco Alessandro Minetto
Epidemiological studies pointed out to a strong association between vitamin D deficiency and type 2 diabetes prevalence. However, the role of vitamin D supplementation in the skeletal muscle, a tissue that play a crucial role in the maintenance of glucose homeostasis, has been scarcely investigated so far. On this basis, this study aimed to evaluate the effect of vitamin D supplementation in a murine model of diet-induced insulin resistance with particular attention to the effects evoked on the skeletal muscle...
2018: PloS One
https://www.readbyqxmd.com/read/29341317/apoptosis-induction-in-k562-human-myelogenous-leukaemia-cells-is-connected-to-the-modulation-of-wnt-%C3%AE-catenin-signalling-by-bhx-a-novel-pyrazoline-derivative
#8
Hanmei Bao, Qing Zhang, Yibo Du, Cai Zhang, Hui Xu, Zhongling Zhu, Zhao Yan
OBJECTIVES: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed...
January 16, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#9
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334406/dasatinib-induced-pulmonary-arterial-hypertension
#10
REVIEW
Nurgül Özgür Yurttaş, Ahmet Emre Eşkazan
Drug-induced (Group 1) pulmonary hypertension (PH) is an important subgroup of PH involving dasatinib as a likely related agent, which is a second-generation tyrosine kinase inhibitor (TKI), that is used in the treatment of chronic myeloid leukemia (CML). The mechanism of dasatinib-induced pulmonary arterial hypertension (PAH) is unclear. However, the occurence of PAH at a late onset in CML patients suggests a chronic pathological mechanism with an insidious onset rather than an acute inflammatory or cardiac etiology...
January 15, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29334300/the-impact-of-early-molecular-response-in-children-and-adolescents-with-chronic-myeloid-leukemia-treated-with-imatinib-a-single-center-study-from-china
#11
Haigang Shao, Zhao Zeng, Jiannong Cen, Jun Zhang, Shuxiao Bai, Chunxiao Wu, Yanlei Gong, Yong Wang, Huiying Qiu, Suning Chen, Jinlan Pan
Chronic myeloid leukemia (CML) is rare among children and adolescents. The early molecular response (EMR) is an important prognostic significance for adult CML patients. This study explored the impact of EMR on the prognosis in 40 children and adolescents with CML-CP treated with imatinib (IM). Our results showed that a high proportion of patients failed to achieve the BCR-ABL1/ABL1 International Scale (IS) ≤ 10% at 3 months. Children with a BCR-ABL1/ABL1 ≤ 10% at 3 months and <1% at 6 months increased the rate of achieving complete cytogenetic response (CCyR) and/or major molecular response (MMR) at 12 months compared to those with BCR-ABL1/ABL1 > 10%...
January 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29332352/puerarin-leads-to-k562-cell-apoptosis-of-chronic-myelogenous-leukemia-via-induction-of-autophagy
#12
Da Gao, Zhen Xiao, Hui-Ping Li
PURPOSE: To study the effects of puerarin on the viability, apoptosis and autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of human CML were taken as the study material and puerarin was applied in different concentrations. The effect of puerarin on cell viability was detected via cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were used to detect the cell autophagy level...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29328387/rhus-verniciflua-stokes-extract-induces-inhibition-of-cell-growth-and-apoptosis-in-human-chronic-myelogenous-leukemia-k562-cells
#13
Kyung-Wook Lee, Eun-Sik Um, Bo-Bae Jung, Eun-Sol Choi, Eun-Young Kim, Seungbo Lee, Eungyeong Jang, Jang-Hoon Lee, Youngchul Kim
Rhus verniciflua Stokes has been widely used as a traditional medicinal plant with a variety of pharmacological activities. We investigated the mechanisms involved in mediating the effects of Rhus verniciflua Strokes (R. verniciflua) extract in human chronic myelogenous leukemia K562 cells, including caspase-dependent apoptotic pathways related to cell-cycle arrest, as well as the inhibition of nuclear factor NF-κB activation and upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328378/liposome%C3%A2-delivered-baicalein-induction-of-myeloid-leukemia-k562-cell-death-via-reactive-oxygen-species-generation
#14
Scarlet Xiaoyan Wang, Xuesong Wen, Celia Bell, Sandra Appiah
Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long‑circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#15
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29325229/dual-drug-targeting-of-mutant-bcr-abl-induces-inactive-conformation-new-strategy-for-the-treatment-of-chronic-myeloid-leukemia-and-overcoming-monotherapy-resistance
#16
Ahmed A El Rashedy, Fisayo A Olotu, Mahmoud E S Soliman
Bcr-Abl is an oncogenic fusion protein which expression enhances tumorigenesis, and has been highly associated with chronic myeloid leukemia (CML). Acquired drug resistance in mutant Bcr-Abl has enhanced pathogenesis with the use of single therapy agents such as Nilotinib. Moreover, allosteric targeting has been identified to consequentially inhibit Bcr-Abl activity, which led to the recent development of ABL-001 (asciminib) that selectively binds the myristoyl pocket. Experimental studies have revealed that the combination of Nilotinib and ABL-001 induced a "bent" conformation in the C-terminal helix of Bcr-Abl; a benchmark of inhibition, thereby exhibiting a greater potency in the treatment of CML, surmounting the setbacks of drug resistance, disease regression and relapse...
January 11, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29323237/racial-differences-in-four-leukemia-subtypes-comprehensive-descriptive-epidemiology
#17
Yinjun Zhao, Yu Wang, Shuangge Ma
Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321163/antitumor-effects-of-blocking-protein-neddylation-in-t315i-bcr-abl-leukemia-cells-and-leukemia-stem-cells
#18
Chang Liu, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Jingfeng Zhou, Yanli Jin, Jingxuan Pan
Imatinib (IM) revolutionized the treatment of chronic myeloid leukemia (CML) but drug resistance and disease recurrence remain a challenge. In this study, we suggest a novel strategy based on blocking protein neddylation to address BCR-ABL point mutations and leukemia stem cells (LSCs) that lie at the root of IM-resistant recurrences. Based on the finding that the NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, we hypothesized that the function of certain neddylation-dependent protein substrates might be targeted to therapeutic ends in IM-resistant CML cells and LSCs...
January 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29316665/towards-comprehension-of-the-abcb1-p-glycoprotein-role-in-chronic-myeloid-leukemia
#19
REVIEW
Raquel C Maia, Flavia C Vasconcelos, Paloma S Souza, Vivian M Rumjanek
Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs-dasatinib, nilotinib, and bosutinib-and the third-generation TKI-ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29316372/can-therapeutic-drug-monitoring-increase-the-safety-of-imatinib-in-gist-patients
#20
Wei Zhuang, Jing-Dun Xie, Shan Zhou, Zhi-Wei Zhou, Yi Zhou, Xiao-Wei Sun, Xiu-Hong Yuan, Min Huang, Si Liu, Shuang Xin, Qi-Biao Su, Hai-Bo Qiu, Xue-Ding Wang
Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin ) with adverse effects (AEs) was described here...
January 7, 2018: Cancer Medicine
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