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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Treosulfan is a water-soluble odorless, white crystalline powder that slowly decomposes by hydrolysis within three hours at pH 7.5 and 25°C in water. In vitro studies have shown that conversion to the epoxide is required for the alkylation and interstrand cross-linking of plasmid DNA, and it is assumed that this process also occurs in vivo. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells growing in vitro, cross-links form, slowly reaching a peak after approximately 24 hours. However, incubation of K562 cells with preformed epoxides such as L-diepoxybutane itself provides faster and more efficient DNA cross-linking, thus supporting the proposed prodrug conversion step.
Immunodeficiency Diseases
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
NK cell defects manifest as recurrent herpes infection or as hemophagocytic lymphocytosis (HLH) or X linked lymphoproliferative syndrome. Testing involves immunophenotyping for CD16/CD56/57 cells and assaying for cytotoxicity against labeled K562 cells as the target. Patients with XLP1 have absent CD3+Vα24+Vβ11+ staining. Intracellular flow cytometry is used to evaluate expression of SAP (SLAM associated protein) XIAP (X-linked inhibitor of apoptosis), the proteins defective in XLP1 and XLP 2 respectively (Marsh et al. 2009).
Extracorporeal Purging of Bone Marrow Grafts by Dye-Sensitized Photoirradiation
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
For lack of simple and accurate physical calibration methods, photopheresis equipment, reagents, and procedures have to be calibrated with an indicator cell line. We calibrate our instrument and reagents by processing 999 ml of K562 leukemia cells at a density of 106 cells per milliliter in the apparatus, removing small (5 to 10 ml) aliquots after each cycle, and determining the surviving fraction of cells by in vitro clonal assay. Trypan blue exclusion tests are not suitable for this task because they greatly underestimate the cytotoxic effects of MC 540-sensitized photoirradiation.64 Recent evidence indicates that different strains of K562 cells may differ considerably with regard to their susceptibility to MC 540-sensitized photoinactivation. This suggests that K562 cells may not be the best choice as a reference cell line. Similar problems have not been encountered with different strains of L1210 cells, and it is probably advisable to check the validity of K562 data with L1210 cells. If processed at dose levels I, II, and III, linear extrapolations of the survival curves for L1210 cells should indicate approximately 10, 12.5, and 15 log, respectively.
Dual inhibition of STAT3 and STAT5 may overcome imatinib resistance in chronic myeloid leukemia
Published in Hematology, 2023
Lingling Yin, Jiawen Xu, Wenjian Wu, Mingshan Niu, Zhenyu Li, Feng Zhu, Kailin Xu
To further elaborate the effect of SH-4-54 on gene expression profile of CML cells, we next conducted next-generation sequence (NGS) to analyze possible SH-4-54 induced alterations in the mRNA transcriptome of CML cell. To this end, K562 and K562R cells were either treated with DMSO (control) or exposed to 20 μM SH-4-54 for 24 h prior to the collection of total RNA. A total of 467 genes were upregulated and 1811 genes were downregulated in the K562 cell line. Similarly, the expression levels of 271 genes were increased, whereas 1290 genes were decreased in K562R cell line (Figure 5(A–B)). The altered genes are complex and involve multiple signaling pathways, including the JAK-STAT pathway. As shown in Figure 5(C), STAT3 and STAT5 were significantly reduced in the K562 and K562R cell lines, which further confirmed that SH-4-54 regulated the JAK-STAT signaling pathway of CML cells from the gene level.
Downregulation of Smad4 expression confers chemoresistance against imatinib mesylate to chronic myeloid leukemia K562 cells
Published in Hematology, 2022
Jiangzhao Zhang, Min Zhang, Yan Liang, Min Liu, Zhiping Huang
CML K562 cells were obtained from KeyGEN (Nanjing, China) and cultivated in RPMI 1640 medium supplemented with 10% heat-inactivated FBS and 1% penicillin–streptomycin in a humidified atmosphere containing 5% CO2 at 37°C. Stable K562R cells were obtained through stepwise treatment of parental K562 cells with increasing drug concentrations (from 0.1 to 1 μM) for 6 months. IM (1 μM) was added to the complete medium of K562R cell clones to maintain selection pressure. Moreover, K562R cells exhibited resistance to other chemotherapeutic agents. K562R cells (>90% viability, Supplementary Figure S1) were rinsed via washing and low speed centrifugation to remove IM before subsequent experiments. K562R clonal sublines retained their drug resistance phenotype even after long-term storage in liquid N2.
Epifriedelanol enhances adriamycin-induced cytotoxicity towards K562/ADM cells by down regulating of P-gp and MRP2
Published in Xenobiotica, 2022
Yuhua Li, Zhengzheng Liao, Xiaohua Wei, Xiong Xiao, Jinfang Hu
K562/ADM cells derived from the parental drug-sensitive K562 cells by stepwise selection with Adr were obtained from the Department of Pharmacology, Institute of Hematology of Chinese Academy of Medical Science (Tianjin, China). The human chronic myeloid leukaemia cell line K562 cells were kindly provided by the Cancer Center, Sun Yat-sen University. To maintain the drug resistance phenotype, K562/ADM was cultured in the presence of 1 μg/ml Adr in a complete RPMI-1640 medium supplemented with heat-inactivated 10% foetal bovine serum (Gibco) and antibiotics (100 units/ml penicillin and 100 μg/ml streptomycin). Cells were maintained at 37 °C in a humidified atmosphere of 5% CO2 and cultured for 2 weeks in drug-free medium prior to their use in the experiments.