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Autophagy leukemia

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https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#1
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28678742/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#2
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/28651104/autophagy-is-an-important-event-for-low-dose-cytarabine-treatment-in-acute-myeloid-leukemia-cells
#3
Liyun Chen, Pei Guo, Yunxiang Zhang, Xiaoyang Li, Peimin Jia, Jianhua Tong, Junmin Li
Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28641621/-effect-of-down-regulatory-nucleostemin-expression-on-autophagy-activities-in-p53-null-hl-60-leukemia-cells
#4
Yuan-Yu Wei, Zhao-Bo Li, Fan Zhang, Ning-Ning Wang, Shuai Liu, Bao-Hong Yue
OBJECTIVE: Based on previous microarry and bioinformatic analysis results, to investigate the effect of nucleostemin(NS) expression down-regulation on autophagy activity in p53 null HL-60 leukemia cells, so as to provide evidence for studying mechanisms of p53-independent signal pathway of NS in details. METHODS: The autophagy activity of HL-60 cells after down-regulation of NS expression was detected with acidine orange staining, Western blot and transmission electron mcrioscope technique...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28627682/microvesicles-released-from-human-embryonic-stem-cell-derived-mesenchymal-stem-cells-inhibit-proliferation-of-leukemia-cells
#5
Yuan Ji, Yongbin Ma, Xiang Chen, Xianyan Ji, Jianyi Gao, Lei Zhang, Kai Ye, Fuhao Qiao, Yao Dai, Hui Wang, Xiangmei Wen, Jiang Lin, Jiabo Hu
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay...
June 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28569787/inflammatory-mediator-ultra-low-molecular-weight-hyaluronan-triggers-necrosis-of-b-precursor-leukemia-cells-with-high-surface-cd44-expression
#6
Shin Kasai, Yoshiyuki Furuichi, Norie Ando, Keiko Kagami, Masako Abe, Takaya Nakane, Kumiko Goi, Takeshi Inukai, Sei Saitoh, Shinichi Ohno, Shogo Okazaki, Osamu Nagano, Hideyuki Saya, Kanji Sugita
Acute lymphoblastic leukemia (ALL) with mixed lineage leukemia (MLL) gene rearrangements (MLL+ALL) has a dismal prognosis and is characterized by high surface CD44 expression. Known that CD44 has the specific binding sites for a natural ligand hyaluronan (HA), we investigated biological effects of HA with different molecular sizes on MLL+ALL cell lines, and found that the addition of ultra-low-molecular-weight (ULMW)-HA strongly suppressed their thymidine uptakes. The MLL+ALL cell line lacking surface CD44 expression established by genome editing showed no suppression of thymidine uptake...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28553123/the-hiv-protease-inhibitor-nelfinavir-as-a-novel-therapeutic-approach-for-the-treatment-of-refractory-pediatric-leukemia
#7
Vanessa Meier-Stephenson, Justin Riemer, Aru Narendran
PURPOSE: Refractory pediatric leukemia remains one of the leading causes of death in children. Intensification of current chemotherapy regimens to improve the outcome in these children is often limited by the effects of drug resistance and cumulative toxicity. Hence, the search for newer agents and novel therapeutic approaches are urgently needed to formulate the next-generation early-phase clinical trials for these patients. MATERIALS AND METHODS: A comprehensive library of antimicrobials, including eight HIV protease inhibitors (nelfinavir [NFV], saquinavir, indinavir, ritonavir, amprenavir, atazanavir, lopinavir, and darunavir), was tested against a panel of pediatric leukemia cells by in vitro growth inhibition studies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28550181/acute-myeloid-leukemia-stem-cell-function-is-preserved-in-the-absence-of-autophagy
#8
Amy H Porter, Lucie Leveque-El Mouttie, Therese Vu, Claudia Bruedigam, Joanne Sutton, Sebastien Jacquelin, Geoffrey R Hill, Kelli P A MacDonald, Steven W Lane
No abstract text is available yet for this article.
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28545761/ultrastructural-analysis-of-human-leukemia-u-937-cells-after-apoptosis-induction-localization-of-proteasomes-and-perichromatin-fibers
#9
Ekaterina S Snigirevskaya, Yan Yu Komissarchik
We studied the ultrastructure of human histiocytic lymphoma U-937cells after apoptosis induction with two external agents, hypertonic shock and etoposide. Appearance of aggregates of particles of nuclear origin within the nuclei and cytoplasm of the induced cells was the first and the most prominent morphological sign of apoptosis. These aggregates were not coated by a membrane, had variable shape, density and size. Two types of particles dominated in the aggregates: perichromatin fibers (PFs) and proteasomes (PRs)...
May 22, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28483400/autophagy-a-necessary-event-during-erythropoiesis
#10
REVIEW
Rubén Grosso, Claudio M Fader, María I Colombo
Autophagy is a well-known cellular process involved in many physiological and pathological processes. During erythropoiesis, autophagy plays an important role participating in the clearance of unnecessary organelles such as ribosomes and mitochondria (mitophagy) allowing the correct formation of mature red blood cells. The dysfunction of autophagy proteins hamper the correct erythroid maturation, leading to anemia, the release of immature cells from the bone marrow and other hematological abnormalities. Autophagy plays different roles depending on the type of pathology...
April 22, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28446269/-expression-of-death-associated-protein-kinase-1-in-chronic-lymphocytic-leukemia
#11
Guan-Ting Zhang, Xiao-Jing Liu, Lin Lu, Fei-Yue Zhao
OBJECTIVE: To explore the expression of death-associated protein kinase 1(DAPK1) in chronic lymphocytic leukemia(CLL). METHODS: The DAPK1 expression was studied by means of MEC1 cells and B lymphocytes from blood samples of the patients with CLL. The quantitative detection of mRNA and Western blot were used to detecte the expression of DAPK1 and autophagy-related genes at both mRNA and protein levels. RESULTS: mRNA quantitative detection and Western blot displayed that the DAPK1 expression in the patients with CLL was silenced...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445844/upregulation-of-mir-142-3p-improves-drug-sensitivity-of-acute-myelogenous-leukemia-through-reducing-p-glycoprotein-and-repressing-autophagy-by-targeting-hmgb1
#12
Yuan Zhang, Yufeng Liu, Xueju Xu
miR-142-3p was reported to be downregulated in acute myelogenous leukemia (AML) and acted as a novel diagnostic marker. However, the regulatory effect of miR-142-3p on drug resistance of AML cells and its underlying mechanism have not been elucidated. Here, we found that miR-142-3p was significantly downregulated and high mobility group box 1 (HMGB1) was dramatically upregulated in AML samples and cells, as well as drug-resistant AML cells. P-gp level and autophagy were markedly enhanced in HL-60/ADR and HL-60/ATRA cells...
June 2017: Translational Oncology
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
#13
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/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#14
Jiaqiu Li, Ping Song, Liyuan Zhu, Neelum Aziz, Qiyin Zhou, Yulong Zhang, Wenxia Xu, Lifeng Feng, Dingwei Chen, Xian Wang, Hongchuan Jin
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415750/xanthohumol-induces-paraptosis-of-leukemia-cells-through-p38-mitogen-activated-protein-kinase-signaling-pathway
#15
Xiangquan Mi, Chunming Wang, Chao Sun, Xu Chen, Xiang Huo, Yiming Zhang, Gang Li, Bo Xu, Jun Zhang, Jianxin Xie, Zhenhua Wang, Ji Li
Xanthohumol as a natural polyphenol demonstrates an anticancer activity, but its underlying mechanism remains unclear. In this study, we showed that xanthohumol (XN) induces paraptosis of leukemia cells. The paraptosis is one cell death which is characterized by dilation of the endoplasmic reticulum and/or mitochondria. The results demonstrated that XN treatment significantly inhibited cell proliferation and triggered extensive cytoplasmic vacuolation of HL-60 leukemia cells, but it did not cause the cleavage of caspase-3 protein or apoptosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407594/trifluoromethyl-arylamides-with-antileukemia-effect-and-intracellular-inhibitory-activity-over-serine-arginine-rich-protein-kinases-srpks
#16
Raoni Pais Siqueira, Marcus Vinícius de Andrade Barros, Éverton de Almeida Alves Barbosa, Thiago Souza Onofre, Victor Hugo Sousa Gonçalves, Higor Sette Pereira, Abelardo Silva Júnior, Leandro Licursi de Oliveira, Márcia Rogéria Almeida, Juliana Lopes Rangel Fietto, Róbson Ricardo Teixeira, Gustavo Costa Bressan
The serine/arginine-rich protein kinases (SRPKs) have frequently been found with altered activity in a number of cancers, suggesting they could serve as potential therapeutic targets in oncology. Here we describe the synthesis of a series of twenty-two trifluoromethyl arylamides based on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and the evaluation of their antileukemia effects. Some derivatives presented superior cytotoxic effects against myeloid and lymphoid leukemia cell lines compared to SRPIN340...
March 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28404874/identification-of-jl1037-as-a-novel-specific-reversible-lysine-specific-demethylase-1-inhibitor-that-induce-apoptosis-and-autophagy-of-aml-cells
#17
Shuang Liu, Wenting Lu, Shouyun Li, Saisai Li, Jia Liu, Yuanyuan Xing, Shuzu Zhang, Joe Zhongxiang Zhou, Haiyan Xing, Yingxi Xu, Qing Rao, Chengjun Deng, Min Wang, Jianxiang Wang
Lysine-specific demethylase 1 (LSD1) has been recognized as a potential therapeutic target for acute myeloid leukemia (AML). Herein, we identified a novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037 is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.1 μM and >1.5 μM for LSD1 and monoamine oxidases A/B (MAO-A/B), respectively. Treatment of THP-1 and Kasumi-1 cell lines with JL1037 resulted in dose dependent accumulation of H3K4me1 and H3K4me2, the major substrates of LSD1, as well as inhibition of cell proliferation, blockade of cell cycle and induction of apoptosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401217/activation-of-autophagy-by-elevated-reactive-oxygen-species-rather-than-released-silver-ions-promotes-cytotoxicity-of-polyvinylpyrrolidone-coated-silver-nanoparticles-in-hematopoietic-cells
#18
Lingying Zhu, Dawei Guo, Lili Sun, Zhihai Huang, Xiuyan Zhang, Wenjuan Ma, Jie Wu, Lun Xiao, Yun Zhao, Ning Gu
Silver nanoparticles (AgNPs) are the most commonly used engineered nanomaterials in commercialized products because of their antimicrobial activity. Previously, we have shown that polyvinylpyrrolidone (PVP)-coated AgNPs have an anti-leukemia effect against human myeloid leukemia cells; however, whether AgNPs are able to trigger autophagy in normal hematopoietic cells and the role of autophagy in AgNP-induced cytotoxicity remain unclear. In the current study, we observed that AgNPs were taken up by murine pro-B cells (Ba/F3), and then promoted accumulation of autophagosomes, which resulted from the induction of autophagy rather than the blockade of autophagic flux...
May 4, 2017: Nanoscale
https://www.readbyqxmd.com/read/28392570/human-t-cell-lymphotropic-virus-type-1-and-its-oncogenesis
#19
REVIEW
Lan-Lan Zhang, Jing-Yun Wei, Long Wang, Shi-le Huang, Ji-Long Chen
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), a rapidly progressing clonal malignancy of CD4+ T lymphocytes. Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficient therapies against the viral infection and associated leukemia/lymphoma. It has been demonstrated to date that several HTLV-1 proteins play key roles in the cellular transformation and immortalization of infected T lymphocytes...
April 10, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28390196/pi3k-isoform-inhibition-associated-with-anti-bcr-abl-drugs-shows-in-vitro-increased-anti-leukemic-activity-in-philadelphia-chromosome-positive-b-acute-lymphoblastic-leukemia-cell-lines
#20
Simona Ultimo, Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Camilla Evangelisti, Claudio Celeghini, James A McCubrey, Giorgia Marisi, Paola Ulivi, Silvano Capitani, Luca M Neri
B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein...
April 4, 2017: Oncotarget
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