Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used the MTT colorimetric assay to determine the sensitivity to ethacrynic acid of lymphocytes from normal donors and of peripheral blood cells from leukaemia patients. Whereas normal lymphocytes and cells from acute or chronic myeloid leukaemia showed similar sensitivities (median inhibitory dose, ID50 = 20-22 microM), lymphocytes from chronic lymphocytic leukaemia patients were much more sensitive (ID50 = 6 microM). This result was found irrespective of the assay duration.
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PMID:Selective toxicity of ethacrynic acid towards lymphocytes of chronic lymphocytic leukemia in vitro. 162 94

Utility of drug response modulators to increase therapeutic:toxic ratio of anticancer drugs in the treatment of refractory malignancies is becoming desirable. In this study, we have attempted to potentiate the tumor cell killing ability of Adriamycin (ADR) against chronic myeloid leukemia cells (CML), in the presence of vitamin K3. Cell growth was evaluated by the MTT assay and the 3H-thymidine incorporation inhibition assay. A highly significant (p less than 0.001) inhibition of cell survival and 3H-thymidine incorporation was effected in CML cells exposed to the combination of ADR and vitamin K3. When the CML cells were treated with ADR and vitamin K3 simultaneously, a greater fragmentation of the intact DNA was revealed as observed by the enhanced formation of DNA single strand breaks. Results demonstrate the therapeutic significance of employing vitamin K3 as an adjuvant in CML chemotherapy with ADR.
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PMID:Single and combination treatment with vitamin K3 and adriamycin: in vitro effects on cell survival and DNA damage in human chronic myeloid leukemia cells. 177 Dec 99

The four kinds of plant polysaccharides, i.e., pachyman polysaccharides (PPS), Acanthopanax senticosus polysaccharides (ASPS), polysaccharides of tremella fuciformis (TF) and lentinan, have obviously inhibitory action against the animal tumor growth and have been applied to the treatment of cancer. The mechanism was that they could enhance the body immune function, but whether the tumor cells were killed is not clear. In this paper, the effects of the four plant polysaccharides on cell proliferation in mice sarcoma (ascitic type) S180 and human chronic myelogenous leukemia K562 cells were studied with MTT chromometry. Tt was found That TF and lentinan had no effect on both cell line, but PPS and ASPS could obviously inhibit the proliferation of them, the IC50 of PPS was 1.5mg/ml in both cell line, that of ASPS was 0.38 mg/ml (S180 cells) and 0.28mg/ml (K562 cells) respectively. This result indicated that the PPS and ASPS were able to kill the tumor cell directly. To investigate the mechanism of antitumor action of PPS and ASPS, the sialic acid (SA), phospholipid (PI) and cholesterol (Ch) contents of S180 cell membrane were examined after the PPS or ASPS application for 24 hours. No significant changes were observed for the Ch and Ch/Pl ratio, the amount of SA increased and that of PI lowered respectively (P < 0.05). The results suggested that the antitumor action of PPS and ASPS not only related to the action of enhancing the body immune function but also related to the changes of cell membrane.
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PMID:[Effects of plant polysaccharides on cell proliferation and cell membrane contents of sialic acid, phospholipid and cholesterol in S 180 and K 562 cells]. 784 57

The antileukemic activities of the lysosomotropic compounds, such as phenylalanine methyl ester (PME), have received little attention. In this study, a 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate the antileukemic activity of PME. Leukemic specimens from untreated patients that contained greater than or equal to 75% blasts were used. Leukemic cells were treated with PME at 37 degrees C and 22 degrees C in concentrations ranging from 0.5 to 50 mM. Normal blood mononuclear cells served as controls. At both 37 degrees C and 22 degrees C, the recovery of normal peripheral blood cells was approximately 28% following incubation with 50 mM PME. At 37 degrees C, 50 mM PME caused greater than one log reduction of leukemic cells in 13/16 acute myelogenous leukemia (AML), 7/9 acute lymphocytic leukemia (ALL), and 8/8 in blast crisis of chronic myelogenous leukemia (CML-BC) specimens. PME had less activity at 22 degrees C than at 37 degrees C. PME was compared with 100 micrograms/ml 4-hydroperoxycyclophosphamide (4HC). In contrast to PME, 4HC was associated with a greater than one log reduction of leukemic cells in only 1/13 AML, 1/3 ALL and 0/6 CML-BC specimens. 4HC activity exceeded PME activity in only one case each of ALL and prolymphocytic leukemia (PLL). In a case of CD34+ B cell ALL, synergy of PME and 4HC was demonstrated. These studies indicate 1) PME has antileukemic activity and 2) 4HC has less antileukemic activity than PME.
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PMID:Antileukemic activity of phenylalanine methyl ester (PME): a lysosomotropic peptide methyl ester. 819 62

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the BCR-ABL hybrid gene. Two types of hybrid BCR-ABL mRNA have been found, B2A2 and B3A2. As the BCR-ABL rearrangement is specific to leukemic cells, selective inhibition of leukemic cell growth by BCR-ABL antisense oligonucleotides (ASO) has been reported in vitro for CML patients and cell lines. However, controversial results have been obtained from preclinical studies using anti-BCR-ABL ASO, as nonspecific inhibition of leukemic cell growth was evidenced in some cases. B3 exon secondary structure was deduced from its sequence and found to be a loop. According to this predictive structure of exon B3, a 56-mer antisense oligonucleotide targeting the polypurine bases from the B2A2 junction was devised which would inhibit proliferation (MTT assay) of B3A2 junction cell lines (K562 and a murine cell line Ba/F3 transfected with the B3A2 junctional sequence). This ASO had a hairpin-like secondary structure and was found to be much more resistant to the action of nucleases than control 18-mer standard oligonucleotides. Hybridization to its target mRNA occurs via formation of a triplex structure. A concentration of 5 microM of specific 56-mer B2A2 ASO was necessary to demonstrate 50% optical density (OD) reduction for K562 cell line and Ba/F3 transformed by B3A2 cDNA. Sense and non-sense 56-mer sequence or 18-mer linear ASO showed no effect for these concentrations. Western blot showed a partial inhibition of P210 protein; expression of P145abl remains unchanged. The 56-mer ASO also inhibited the proliferation of B2A2 junction cell line BV173 at the same concentration and showed no effect on the HL60 cell line used as control.
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PMID:Inhibition of chronic myelogenous leukemia cells harboring a BCR-ABL B3A2 junction by antisense oligonucleotides targeted at the B2A2 junction. 854 54

Alpha-interferon (alpha-IFN) and gamma-interferon (gamma-IFN) are highly effective biologic agents in the treatment of chronic myelogenous leukemia (CML). 4-hydroperoxycyclophosphamide (4-HC) is the most commonly used chemotherapeutic drug when purging bone marrow contaminated with malignant cells. To investigate the efficacy of alpha-IFN, gamma-IFN and 4-HC as purging agents in CML patients, K562 cells, a human CML cell line, were treated in vitro with these drugs singly or in combination. The cytotoxic effect was evaluated by MTT assay. Data were analyzed for synergism by the median effect principle of Chou and Talalay. Using Southern blot analysis, the effect of purging on the suppression of bcr gene rearrangement was also evaluated. Alpha-IFN, gamma-IFN and 4-HC all showed good concentration-dependent cytotoxic effect. Median cytotoxic doses of alpha-IFN gamma-IFN and 4-HC were 0.03 microM 0.20 microM and 1.97 microM respectively, and molar ratios of median doses of alpha-IFN to 4-HC, gamma-IFN to 4-HC and alpha-IFN to gamma-IFN were 1:80, 1:10 and 1:8, respectively. The combination treatment of alpha-IFN and 4-HC, and gamma-IFN and 4-HC showed significant synergistic cytotoxic activities, but combination of alpha-IFN and gamma-IFN was antagonistic. Status of bcr gene rearrangements in K562 cells was not changed after the treatments. Our results appear to provide an efficient method for removing CML cells from the bone marrow of CML patients.
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PMID:Efficacy of in vitro treatment of chronic myelogenous leukemia cell line, K562 cells, using 4-hydroperoxycyclophosphamide, alpha-interferon and gamma-interferon. 870 67

The effect of heparin as a reversing agent of multidrug resistance (MDR) was tested on normal mononuclear cells from 24 healthy volunteers and leukaemic cells from 12 acute myeloid leukaemia, five chronic myeloid leukaemia, five acute lymphoid leukaemia and three chronic lymphoid leukaemia patients. Two cell lines were used as controls, the human erythroleukaemia K562 and its vincristine-resistant derivative K562-Lucena 1. Heparin was not cytotoxic by itself as determined using a MTT assay and cell counts. MDR modulation was assessed by Rhodamine 123 extrusion using flow-cytometry. Modulation of the resistant cell line was produced by the classical reversing agent verapamil and also by heparin, the same being observed in normal and leukaemic cells and being independent of the type of leukaemia. Our work suggests that heparin may be considered a potential MDR modulator.
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PMID:Heparin reverses Rhodamine 123 extrusion by multidrug resistant cells. 882 53

The aim of the study was to assess the predictive value of MTT in vitro assay for evaluation of tumour cell resistance/sensitivity to cytotoxic drugs. We analyzed 105 samples of malignant cells of different origin. The study included patients with a diagnosis of acute and chronic lymphatic leukaemia, acute and chronic myeloid leukaemia, non-Hodgkin lymphoma, carcinoma of the lung, stomach and liver, rhabdomyosarcoma and breast carcinoma. The results demonstrate outstanding chemosensitivity in the majority of childhood acute lymphoblastic leukaemias, medium chemosensitivity of adult haematopoietic malignant diseases and chemoresistance of solid tumour cells. Our preliminary data suggest a good correlation between in vitro MTT assay and clinical curability of individual malignant diseases.
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PMID:Decreased in vitro chemosensitivity of tumour cells in patients suffering from malignant diseases with poor prognosis. 886 13

The synthesis, DNA binding and biological evaluation of two benzoic acid mustard derivatives of imidazole-containing analogues of distamycin in which the C-terminus is modified to contain a terminal carboxamide are described. The apparent DNA binding constants of compounds 5 and 6 were determined using an ethidium displacement assay, and the results showed that they do not have the AT sequence selectivity of distamycin and they show an acceptance for GC base pairs. Based on their pronounced binding to T4 DNA the data suggest that they bind to the minor groove of DNA. The cytotoxicities of compounds 5 and 6 in human chronic myeloid leukemia cells were determined using a MTT assay, and their IC50 values were 27 and 16 microM, respectively, and higher than the corresponding non-terminal carboxamide-containing analogues 3 and 4. Both compounds were however markedly more active than the non-targeted mustard BAM [N,N-bis (-2-chloroethyl)-4-aminobenzoic acid]. In the NCI panel of cell lines 5 gave a distinctly different pattern of tumor selectivity from 6. While these compounds were shown to alkylate DNA using a CD alkylation assay (35 +/- 10% for 5 and 85 +/- 10% for 6), they produced interstrand crosslinks poorly, even at 100 microM drug concentrations. Based on preliminary data from a polymerase stop assay compounds 3-6 gave different patterns of sequence selection monoalkylation which may contribute to their differing biological activities.
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PMID:Design, synthesis and biological evaluation of benzoic acid mustard derivatives of imidazole-containing and C-terminal carboxamide analogues of distamycin. 904 Sep 92

The anti-leukemic activity of a series of alkylphosphocholines (APCs) was studied against a panel of human leukemic cell lines (HL-60, K-562, Reh, MOLT-4, Jurkat, Ramos and Raji). Cytotoxic efficacy was measured by the MTT cell survival assay. All cell lines were found to be sensitive, except the multipotential CML-derived K-562 cell line. Flow cytometry of HL-60 cells showed a significant decrease of cells in S phase and the formation of a sub-G fraction. DNA fragmentation typical for programmed cell death was detected by DNA gel electrophoresis in these cells but not in any of the other leukemic lines. At concentrations below the cytotoxic range, mitogenic effects were seen in HL-60 cells after 14-hr exposure. Colony formation by K-562 cells revealed an augmented clonogenicity after exposure to APC with a short alkyl chain. In contrast, cells of lymphoid origin did not undergo DNA fragmentation or show mitogenic stimulation after exposure to APC. Normal bone marrow cells were also investigated for mitogenic and genotoxic effects. No decrease was found in the number of hematopoietic progenitors in long-term bone marrow cell cultures after exposure to APC. On the contrary, a significant increase was found after short exposure. Dodecylphosphocholine, hexadecylphosphocholine (HPC) and (octadecyl-[2-(N-methylpiperidino)-ethyl]phosphate exhibited a mild clastogenicity at equimolar high doses on murine bone marrow cells in vivo, which is unusual for the majority of classical DNA-interacting anti-cancer drugs. In conclusion, APCs are agents with a broad spectrum of in vitro anti-leukemic effects, which lack hematological toxicity.
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PMID:Alkylphosphocholines: Effects on human leukemic cell lines and normal bone marrow cells. 968 13


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