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https://www.readbyqxmd.com/read/29121435/altered-intracellular-signaling-by-imatinib-increases-the-anti-cancer-effects-of-tyrosine-kinase-inhibitors-in-cml-cells
#1
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29118925/bardoxolone-methyl-cddo-me-or-rta402-induces-cell-cycle-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-erk1-2-signaling-pathways-in-k562-cells
#2
Xin-Yu Wang, Xue-Hong Zhang, Li Peng, Zheng Liu, Yin-Xue Yang, Zhi-Xu He, Hong-Wan Dang, Shu-Feng Zhou
Chronic myeloid leukemia (CML) treatment remains a challenge due to drug resistance and severe side effect, rendering the need on the development of novel therapeutics. CDDO-Me (Bardoxolone methyl), a potent Nrf2 activator and NF-κB inhibitor, is a promising candidate for cancer treatment including leukemia. However, the underlying mechanism for CDDO-Me in CML treatment is unclear. This study aimed to evaluate the molecular interactome of CDDO-Me in K562 cells using the quantitative proteomics approach stable-isotope labeling by amino acids in cell culture (SILAC) and explore the underlying mechanisms using cell-based functional assays...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118670/an-overview-of-the-role-of-platelets-in-angiogenesis-apoptosis-and-autophagy-in-chronic-myeloid-leukaemia
#3
REVIEW
Lisa Repsold, Roger Pool, Mohammed Karodia, Gregory Tintinger, Annie Margaretha Joubert
Amongst males, leukaemia is the most common cause of cancer-related death in individuals younger than 40 years of age whereas in female children and adolescents, leukaemia is the most common cause of cancer-related death. Chronic myeloid leukaemia (CML) is a chronic leukaemia of the haematopoietic stem cells affecting mostly adults. The disease results from a translocation of the Philadelphia chromosome in stem cells of the bone marrow. CML patients usually present with mild to moderate anaemia and with decreased, normal, or increased platelet counts...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28942039/comparative-effect-of-imatinib-and-ponatinib-on-autophagy-and-mirnome-in-chronic-myeloid-leukemia
#4
Cagla Kayabasi, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Aycan Asik, Sunde Yilmaz Susluer, Cigir Biray Avci, Guray Saydam, Cumhur Gunduz
BCR-ABL tyrosine kinase inhibitors (TKIs) are selective therapies for the patients with Chronic Myeloid Leukemia (CML). Imatinib and ponatinib have remarkable long-term efficacy on a major molecular response. Although TKI related induction of cytotoxicity and apoptosis have been clearly investigated in molecular levels, their comparative effect on autophagy and miRNome are largely unknown. This study aimed to investigate the involvement of alterations of miRNA expressions in CML progression, and how imatinib and ponatinib affect this process, by comparing CML, imatinib-resistant CML and leukemia stem cells (LSC)...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28905936/combing-oncolytic-adenovirus-expressing-beclin-1-with-chemotherapy-agent-doxorubicin-synergistically-enhances-cytotoxicity-in-human-cml-cells-in-vitro
#5
Li Li, Liang-Shun You, Li-Ping Mao, Shen-He Jin, Xiao-Hui Chen, Wen-Bin Qian
Cancer virotherapy provides a new strategy to treat cancer that can directly kill cancer cells by oncolysis. Insertion of therapeutic genes into the genome of a modified adenovirus, thereby creating a so-called gene-virotherapy that shares the advantages of gene therapy and virotherapy. In this study we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with the simultaneous expression of the autophagy gene Beclin-1 offered a therapeutic advantage for chronic myeloid leukemia (CML) cells with resistance to chemotherapy and evaluated the synergistic effects of SG511-BECN and doxorubicin (Dox) in human CML cells in vitro...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28678742/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#6
Angela Ianniciello, Amélie Guitart, Pierre-Yves Dumas, Claire Drullion, Arnaud Villacreces, Yan Peytour, Jean Chevaleyre, Philippe Brunet de la Grange, Isabelle Vigon, Vanessa Desplat, Muriel Priault, Persio Dello Sbarba, Zoran Ivanovic, François-Xavier Mahon, Jean-Max Pasquet
Albeit tyrosine kinase inhibitors anti-Abl used in Chronic Myeloid Leukemia (CML) block the deregulated activity of the Bcr-Abl tyrosine kinase and induce remission in 90% of patients, they do not eradicate immature hematopoietic compartments of leukemic stem cells. To elucidate if autophagy is important for stem cell survival and/or proliferation, we used culture in low oxygen concentration (0.1% O2 for 7 days) followed back by non-restricted O2 supply (normoxic culture) to mimic stem cell proliferation and commitment...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#7
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28366933/a-novel-ahi-1-bcr-abl-dnm2-complex-regulates-leukemic-properties-of-primitive-cml-cells-through-enhanced-cellular-endocytosis-and-ros-mediated-autophagy
#8
X Liu, K Rothe, R Yen, C Fruhstorfer, T Maetzig, M Chen, D L Forrest, R K Humphries, X Jiang
Tyrosine kinase inhibitor (TKI) therapies induce clinical remission with remarkable effects on chronic myeloid leukemia (CML). However, very few TKIs completely eradicate the leukemic clone and persistence of leukemic stem cells (LSCs) remains challenging, warranting new, distinct targets for improved treatments. We demonstrated that the scaffold protein AHI-1 is highly deregulated in LSCs and interacts with multiple proteins, including Dynamin-2 (DNM2), to mediate TKI-resistance of LSCs. We have now demonstrated that the SH3 domain of AHI-1 and the proline rich domain of DNM2 are mainly responsible for this interaction...
November 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28339029/hydroxychloroquine-sensitizes-chronic-myeloid-leukemia-cells-to-v%C3%AE-9v%C3%AE-2-t-cell-mediated-lysis-independent-of-autophagy
#9
Biqing Han, Yanmin Zhao, Yu Lin, Shan Fu, Limengmeng Wang, Mingming Zhang, Ruxiu Tie, Binsheng Wang, Yi Luo, Lizhen Liu, Jian Yu, He Huang
Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28283035/inhibition-of-autophagy-enhances-the-selective-anti-cancer-activity-of-tigecycline-to-overcome-drug-resistance-in-the-treatment-of-chronic-myeloid-leukemia
#10
Ziyuan Lu, Na Xu, Bolin He, Chengyun Pan, Yangqing Lan, Hongsheng Zhou, Xiaoli Liu
BACKGROUND: Drug resistance and disease progression are still the major obstacles in the treatment of chronic myeloid leukemia (CML). Increasing researches have demonstrated that autophagy becomes activated when cancer cells are subjected to chemotherapy, which is involved in the development of drug resistance. Therefore, combining chemotherapy with inhibition of autophagy serves as a new strategy in cancer treatment. Tigecycline is an antibiotic that has received attention as an anti-cancer agent due to its inhibitory effect on mitochondrial translation...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28094938/in-vitro-and-in-vivo-evaluation-of-fully-substituted-5-3-ethoxy-3-oxopropynyl-4-ethoxycarbonyl-1-2-3-triazolyl-glycosides-as-original-nucleoside-analogues-to-circumvent-resistance-in-myeloid-malignancies
#11
Hella Amdouni, Guillaume Robert, Mohsine Driowya, Nathan Furstoss, Camille Métier, Alix Dubois, Maeva Dufies, Marwa Zerhouni, François Orange, Sandra Lacas-Gervais, Khalid Bougrin, Anthony R Martin, Patrick Auberger, Rachid Benhida
A series of nucleoside analogues bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27853367/caveolin-1-contributes-to-realgar-nanoparticle-therapy-in-human-chronic-myelogenous-leukemia-k562-cells
#12
Dan Shi, Yan Liu, Ronggang Xi, Wei Zou, Lijun Wu, Zhiran Zhang, Zhongyang Liu, Chao Qu, Baoli Xu, Xiaobo Wang
Chronic myelogenous leukemia (CML) is characterized by the t(9;22) (q34;q11)-associated Bcr-Abl fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs) have been prepared with an average particle size of <100 nm in a previous work. Compared with coarse realgar, the realgar NPs have higher bioavailability. As a principal constituent protein of caveolae, caveolin-1 (Cav-1) participates in regulating various cellular physiological and pathological processes including tumorigenesis and tumor development...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27852045/different-bcr-abl-protein-suppression-patterns-as-a-converging-trait-of-chronic-myeloid-leukemia-cell-adaptation-to-energy-restriction
#13
Silvia Bono, Matteo Lulli, Vito Giuseppe D'Agostino, Federico Di Gesualdo, Rosa Loffredo, Maria Grazia Cipolleschi, Alessandro Provenzani, Elisabetta Rovida, Persio Dello Sbarba
BCR/Abl protein drives the onset and progression of Chronic Myeloid Leukemia (CML). We previously showed that BCR/Abl protein is suppressed in low oxygen, where viable cells retain stem cell potential. This study addressed the regulation of BCR/Abl protein expression under oxygen or glucose shortage, characteristic of the in vivo environment where cells resistant to tyrosine kinase inhibitors (TKi) persist. We investigated, at transcriptional, translational and post-translational level, the mechanisms involved in BCR/Abl suppression in K562 and KCL22 CML cells...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27645552/celecoxib-suppresses-autophagy-and-enhances-cytotoxicity-of-imatinib-in-imatinib-resistant-chronic-myeloid-leukemia-cells
#14
Ying Lu, Ling-Ling Liu, Shou-Sheng Liu, Zhi-Gang Fang, Yong Zou, Xu-Bin Deng, Zi-Jie Long, Quentin Liu, Dong-Jun Lin
BACKGROUND: Chronic myelogenous leukemia (CML) is a hematological stem cell disorder. Tyrosine kinase inhibitors (TKIs) are the standard treatments for CML, but a number of patients fail to respond effectively due to gene mutations. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been shown to have anti-tumor effect on solid tumor whereas the anti-CML effect and its underlying mechanism have not been completely elucidated. METHODS: The cytotoxic effects of celecoxib and/or imatinib were evaluated by MTT assay...
September 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27581142/detecting-autophagy-and-autophagy-flux-in-chronic-myeloid-leukemia-cells-using-a-cyto-id-fluorescence-spectrophotometric-assay
#15
Sujuan Guo, Kevin J Pridham, Zhi Sheng
Autophagy is a catabolic process whereby cellular components are degraded to fuel cells for longer survival during stress. Hence, autophagy plays a vital role in determining cell fate and is central for homeostasis and pathogenesis of many human diseases including chronic myeloid leukemia (CML). It has been well established that autophagy is important for the leukemogenesis as well as drug resistance in CML. Thus, autophagy is an intriguing therapeutic target. However, current approaches that detect autophagy lack reliability and often fail to provide quantitative measurements...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27575313/discovery-and-optimization-of-n-4-3-aminophenyl-thiazol-2-yl-acetamide-as-a-novel-scaffold-active-against-sensitive-and-resistant-cancer-cells
#16
Antoine Millet, Magali Plaisant, Cyril Ronco, Michaël Cerezo, Patricia Abbe, Emilie Jaune, Elisa Cavazza, Stéphane Rocchi, Rachid Benhida
Cancer is the second cause of deaths worldwide and is forecasted to affect more that 22 million people in 2020. Despite dramatic improvement in its care over the last two decades, the treatment of resistant forms of cancer is still an unmet challenge. Thus, innovative and efficient treatments are still needed. In this context, we report herein the synthesis and the evaluation of a new class of bioactive molecules belonging to the N-(4-(3-aminophenyl(thiazol-2-yl)acetamide family. Structure-activity relationships could be driven and resulted in the discovery of lead compound 6b...
September 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27499639/lapatinib-induces-autophagic-cell-death-and-differentiation-in-acute-myeloblastic-leukemia
#17
Yu-Jen Chen, Li-Wen Fang, Wen-Chi Su, Wen-Yi Hsu, Kai-Chien Yang, Huey-Lan Huang
Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27278818/the-antineoplastic-agent-%C3%AE-bisabolol-promotes-cell-death-by-inducing-pores-in-mitochondria-and-lysosomes
#18
Antonella Rigo, Fabrizio Vinante
The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis...
August 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27168493/atg7-regulates-energy-metabolism-differentiation-and-survival-of-philadelphia-chromosome-positive-cells
#19
Maria Karvela, Pablo Baquero, Elodie M Kuntz, Arunima Mukhopadhyay, Rebecca Mitchell, Elaine K Allan, Edmond Chan, Kamil R Kranc, Bruno Calabretta, Paolo Salomoni, Eyal Gottlieb, Tessa L Holyoake, G Vignir Helgason
A major drawback of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is that primitive CML cells are able to survive TKI-mediated BCR-ABL inhibition, leading to disease persistence in patients. Investigation of strategies aiming to inhibit alternative survival pathways in CML is therefore critical. We have previously shown that a nonspecific pharmacological inhibition of autophagy potentiates TKI-induced death in Philadelphia chromosome-positive cells. Here we provide further understanding of how specific and pharmacological autophagy inhibition affects nonmitochondrial and mitochondrial energy metabolism and reactive oxygen species (ROS)-mediated differentiation of CML cells and highlight ATG7 (a critical component of the LC3 conjugation system) as a potential specific therapeutic target...
June 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27070592/distinct-dasatinib-induced-mechanisms-of-apoptotic-response-and-exosome-release-in-imatinib-resistant-human-chronic-myeloid-leukemia-cells
#20
Juan Liu, Yujing Zhang, Aichun Liu, Jinghua Wang, Lianqiao Li, Xi Chen, Xinyu Gao, Yanming Xue, Xiaomin Zhang, Yao Liu
Although dasatinib is effective in most imatinib mesylate (IMT)-resistant chronic myeloid leukemia (CML) patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562R(IMT)). Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling and autophagic activity were increased significantly in K562R(IMT) cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells...
April 8, 2016: International Journal of Molecular Sciences
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