Suppressor substance produced by the K562 cell line in vitro

1983 ◽  
Vol 23 (1) ◽  
pp. 16-20 ◽  
Author(s):  
J. M. Korzelius ◽  
P. M. Bealmear ◽  
O. A. Holtermann
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
K562 Cell Line

scholarly journals Absorption Characteristics of Combination Medication of Realgar and Indigo Naturalis: In Vitro Transport across MDCK-MDR1 Cells and In Vivo Pharmacokinetics in Mice after Oral Administration

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Miao Zhang ◽  
Lin Guo ◽  
Long-Fei Lin ◽  
Chang-Hai Qu ◽  
Xing-Bin Yin ◽  
...  
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
Computational Study ◽  
Arsenic Concentration ◽  
K562 Cells ◽  
Cell Permeability ◽  
K562 Cell Line ◽  
Apparent Permeability ◽  
Indigo Naturalis

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4…Indirubin] involves noncovalent interaction that changes the concentration of arsenic.

scholarly journals Functional Evaluation of T-Cells Generated from WT1-TCR Transduced Human Hematopoietic Stem Cells Using the OP9-DL1 Coculture System

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2152-2152
Author(s):  
Sarah Bonte ◽  
Sylvia Snauwaert ◽  
Jasper Van Heuverswyn ◽  
Glenn Goetgeluk ◽  
Mirjam H.M. Heemskerk ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Line ◽  
K562 Cell ◽  
K562 Cell Line ◽  
Agonist Peptide ◽  
Release Assay

Abstract Introduction: Chemotherapy leads to cure of acute myeloid leukemia (AML) in less than half of the patients. Stem cell transplantation can be used as an immunotherapeutic treatment to cure the patient, but carries a high risk of toxicity and mortality. Moreover, not all patients have a suitable donor. We have developed a novel immunotherapeutic treatment, in which we generate in vitro, starting from hematopoietic precursor cells, T-cells that recognize WT1, a tumor antigen that is overexpressed on 70% of the AMLs. Aims: In this study we have evaluated the functionality and specificity of the generated WT1-directed T-cells both in vitro and in vivo. The ultimate goal is to use these cells in patients, as this form of immunotherapy is promising and could be an option for cure in patients who are not eligible for stem cell transplantation. In contrast to the more widely used immunotherapy using TCR-transduced peripheral T-cells, our therapy is expected to be more effective and carry less risk of autoreactivity. Methods: CD34+ cells isolated from cord blood and mobilized peripheral blood mononuclear cells were cultured on OP9-DL1 in the presence of the cytokines IL-7, Flt3-L and SCF, for 2 weeks, until T-cell commitment. Subsequently, they were transduced with a WT1-TCR (H. Stauss) or a CMV-TCR (M. Heemskerk), and again co-cultured until CD4+CD8+ double positive cells were abundantly present (generally after another 2-3 weeks). At that point, the agonist peptide WT1 or CMV resp was added to the culture together with IL-7, and 5 days later cells were harvested and expanded (polyclonally or using agonist peptide), in the presence of IL-2, or IL-7+IL-15. T-cells were evaluated using a 51Chromium release assay, for cytotoxicity against WT1 and HLA-A2 positive and negative targets. Also, upon activation, production of IFN-g was evaluated using ELISA. Immunodeficient 6-8 weeks old NSG mice were irradiated (200 cGy), and 24 hours later injected intravenously with either a luciferase-positive, WT1, HLA-A2 transduced K562 cell line (R. Stripecke), or luciferase-transduced, HLA-A2+, WT1+ primary AML cells (expanded on MS-5 in the presence of cytokines) in the current experiments, and 24 hours later, with 5x106 or 107WT1-TCR T-cells or CMV-TCR T-cells (negative control). Mice were evaluated using the IVIS bioluminescence assay. Results: We observed that a nice mix of WT1-TCR CD8+ and CD4+ T-cells (50%/50%) was generated with cells expanded after harvest from the coculture using the combination of the agonist peptide, IL-7 and IL-15. Using 51Cr release assay and ELISA, we could show that upon activation, the T-cells showed specific cytokine production and efficient killing of tumor cells. We observed that the luciferase+, WT1, HLA-A2 transduced K562 cell line homed to ovaria and brain (female mice) or liver, testes and brain (male mice) when injected intravenously, and these are largely sanctuary sites, not reached by the T-cells, therefore resulting in low efficiency. When this cell line was injected subcutaneously in the hind flank, mice showed significant swelling of the resp limb and needed to be euthanized for ethical reasons before full evaluation was possible. Currently, experiments are ongoing evaluating the efficacy of the WT1 T-cells against luciferase transduced primary AML cells (after long term expansion culture on MS-5), as these cells are expected to home to the bone marrow and blood of the mice, and therefore reflect more the physiological situation, and can be more easily reached by the T-cells. Results of these experiments will be presented at ASH. Summary/Conclusion: We have shown that, using the OP9-DL1 model, we were able to generate large numbers of high-avidity tumor-specific naïve and resting T-cells, after a process similar to thymic positive selection. After expansion (polyclonal or antigen specific -in the presence of the agonist peptide-) and activation, these cells show specificity and functionality in vitro and are currently evaluated in an in vivo immunodeficient mouse model. Disclosures No relevant conflicts of interest to declare.

scholarly journals SOX6 Downregulation Induces γ-Globin in Human β-Thalassemia Major Erythroid Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Jing Li ◽  
Yongrong Lai ◽  
Jun Luo ◽  
Lin Luo ◽  
Rongrong Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Sickle Cell ◽  
K562 Cell ◽  
Mononuclear Cells ◽  
Genetic Modifier ◽  
Fetal Hemoglobin ◽  
Thalassemia Major ◽  
Normal Donor ◽  
K562 Cell Line

Background. Fetal hemoglobin (HbF; α2γ2) is a potent genetic modifier of the severity of β-thalassemia and sickle cell anemia. Differences in the levels of HbF that persist into adulthood affect the severity of sickle cell disease and the β-thalassemia syndromes. Sry type HMG box (SOX6) is a potent silencer of HbF. Here, we reactivated γ-globin expression by downregulating SOX6 to alleviate anemia in the β-thalassemia patients. Methods. SOX6 was downregulated by lentiviral RNAi (RNA interference) in K562 cell line and an in vitro culture model of human erythropoiesis in which erythroblasts are derived from the normal donor mononuclear cells (MNC) or β-thalassemia major MNC. The expression of γ-globin was analyzed by qPCR (quantitative real-time PCR) and WB (western blot). Results. Our data showed that downregulation of SOX6 induces γ-globin production in K562 cell line and human erythrocytes from normal donors and β-thalassemia major donors, without altering erythroid maturation. Conclusions. This is the first report on γ-globin induction by downregulation of SOX6 in human erythroblasts derived from β-thalassemia major.

Suppressor Substance Produced by the K562 Cell Line In Vitro

1984 ◽  
Vol 132 (1) ◽  
pp. 196-197
Author(s):  
J.M. Korzelius ◽  
P.M. Bealmear ◽  
O.A. Holtermann
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
K562 Cell Line

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Ebru Zeytün ◽  
Mehlika D. Altıntop ◽  
Belgin Sever ◽  
Ahmet Özdemir ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
In Silico ◽  
K562 Cell ◽  
Kinase Inhibitors ◽  
K562 Cell Line ◽  
Cytotoxic Effects ◽  
Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

Optimization of differentiation condition for K562 cell line and rat erythroleukemia cell line

2018 ◽  
Vol 295 ◽  
pp. S251
Author(s):  
M. Otani ◽  
K. Iwashita ◽  
T. Utsumi ◽  
S. Kawamura
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
K562 Cell Line ◽  
Erythroleukemia Cell

Tyrosine Kinase Inhibitor STI571 (Imatinib) Cooperates with Wild-Type p53 on K562 Cell Line to Enhance Its Proapoptotic Effects

2005 ◽  
Vol 114 (3) ◽  
pp. 150-154 ◽  
Author(s):  
Gianluca Brusa ◽  
Manuela Mancini ◽  
Fabio Campanini ◽  
Alberto Calabrò ◽  
Elisa Zuffa ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Line ◽  
K562 Cell ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
K562 Cell Line ◽  
Wild Type P53

scholarly journals Modification by Heme Oxygenase Inhibitor, Tin Protoporphyrin, of Cellular Differentiation of Human Myeloid Leukemia K562 Cell Line.

1999 ◽  
Vol 22 (4) ◽  
pp. 439-440 ◽  
Author(s):  
Yukiko KOISO ◽  
Yasuyuki FUJIMOTO ◽  
Daisuke MATSUMURA ◽  
Osamu NAKAJIMA ◽  
Yuichi HASHIMOTO
Keyword(s):  
Cell Line ◽  
Heme Oxygenase ◽  
K562 Cell ◽  
Myeloid Leukemia ◽  
Cellular Differentiation ◽  
K562 Cell Line ◽  
Tin Protoporphyrin ◽  
Leukemia K562 Cell
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