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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the antiproliferative effect induced by the natural human tumor necrosis factors alpha and beta (nHuTNF-alpha, -beta) or a combination of these in the clonogenic assay. The antiproliferative effects were evaluated by examining the inhibition of clonogenic growth of RPMI-4788 cells, which had been established from a human colon cancer. TNF-alpha and -beta were natural human types produced by a B cell leukemia line (BALL-1 cells) and were both over 99% pure. The antiproliferative effect in combination of nHuTNF-alpha and -beta was analysed by using the median effect plot and the combination index. The results indicate a synergism between two factors.
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PMID:Synergistic effect of natural human tumor necrosis factors alpha and beta in the clonogenic assay. 322 48

Human myeloid leukemia cells (HL60) and malignant lymphocytes (Namalwa) were grown in protein-free, Fe-supplemented media and used to study growth responses to insulin and insulin-like growth factor 1 (IGF-I). HL60 cells previously grown in serum-free medium containing microgram quantities of insulin showed an 18-fold reduction in cumulative cell production when grown without insulin. However, the same cells showed reduced or absent growth stimulation with 1 to 100 ng/mL insulin or IGF-I for at least four days following insulin deprivation, indicating that culture conditions modified insulin and IGF-I responses. When the same cells were grown in Fe-supplemented, protein-free medium (RPMI-Fe), insulin and IGF-I caused dose-dependent stimulation of HL60 cell growth with half-maximal stimulation at nanogram concentrations. Namalwa cells grown in protein-free medium showed no response to either hormone. Radioligand binding showed the presence of insulin and IGF-I receptors on both HL60 and Namalwa cells grown in RPMI-Fe. HL60 cells grown in fetal bovine serum had higher, and cells grown with microgram quantities of insulin dramatically reduced, insulin binding. Competitive binding studies and cultures with anti-IGF-I receptor antibody showed insulin and IGF-I stimulated growth through their respective specific receptors. Both insulin and IGF-I stimulate growth of some cultured human leukemia cells, but the presence of insulin or IGF-I receptors alone does not predict growth responses. Culture conditions affect both cellular responses and ligand binding by these hormones and must be closely controlled to study growth responses.
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PMID:Effects of insulin and insulin-like growth factor I on growth of human leukemia cells in serum-free and protein-free medium. 329 86

The human leukemia cell line HL-60 consists predominantly of abnormal promyelocytes. When grown in RPMI-1640 and 10% FCS between 5 and 10% of these cells spontaneously differentiate into more mature myeloid cells, becoming smaller in size and developing the ability to generate superoxide. Centrifugal elutriation was used to separate these G0 cells from the bulk of the cycling G1, S and G2M cells. These isolated differentiating cells are shown to be similar in size, DNA content, RNA content and NBT positivity not only to granulocyte induced HL-60 cells but also to human peripheral blood granulocytes. This methodology allows the study of differentiative vs proliferative processes through the quick one-step generation of homogeneous subpopulations of G0, G1, S and G2M cells.
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PMID:Separation of spontaneously differentiating and cell cycle-specific populations of HL-60 cells. 337 66

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
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PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32

The cells of the lymphoblastoid strain, RPMI-6410t (from the blood of a patient suffering an acute myeloblast leukemia), were shown to synthesize constitutively and secrete into the culture medium a growth factor that maintains the reproduction of these cells. The 6410t cells were shown to bind specifically this factor and react to it by proliferation in the conditions of rarefied inoculation. The utilization of a medium conditioned by the 6410t cells provided almost 100% cloning of these cells when using the method of limiting dilutions in 96-well microplates at a density of one cell per well. The cloning of the 6410t cells without the conditioned medium with feeder cells (mouse splenocytes and peritoneal cells) failed. It is suggested that as a result of the second stage of malignant transformation the immortalized cell still requires an exogenous growth factor, unlike was considered earlier, but acquires the ability of producing an endogenous growth factor and, hence, escapes the environmental control.
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PMID:[Autogenous production of growth factor as a mechanism of the cellular multiplication of the lymphoblastoid line RPMI-6410t]. 346 15

Conditioned media from the human myeloid leukemic cell line ML-2 contain a factor that inhibits the entry of normal CFU-GM into S phase of mitotic cycle as measured by the 3H-TdR suicide technique. This factor was detected in conditioned media prepared by incubating 5 X 10(6) ML-2 cells/ml or 1 X 10(6) ML-2 cells/ml in serum-free RPMI for 5 or 24 hours respectively, and was isolated by ultrafiltration through an XM 300 Diaflo membrane followed by chromatography on Sepharose 6 B. Ferritin, prepared from human placenta, had the same inhibitory effect on CFU-GM. Antibodies against human placental ferritin completely inactivated the inhibitory effect of both human placental ferritin and the factor released from ML-2 cells. The inhibitory activity produced by the cell-line ML-2 was considered as LIA (leukemia cell-derived inhibitory activity) earlier found in HL-60 cell line and AML and CML cells.
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PMID:Identification of leukemia cell-derived inhibitory activity (LIA) in conditioned media from human myeloid leukemic cell line ML-2. 348 46

Chromosomal rearrangements in malignant T-cell disease frequently involve the chromosome bands containing the T-cell receptor genes. The RPMI 8402 cell line, which was established from the leukemia cells of a patient with T-cell acute lymphoblastic leukemia, is characterized by a translocation involving chromosome 14 (band q11) and chromosome 11 (band p15) [t(11;14)(p15;q11)]. By using in situ chromosomal hybridization and Southern blot analysis to examine RPMI 8402 cells, we determined that the break at 14q11 occurs within the variable region sequences of the T-cell receptor alpha-chain gene (TCRA); the break at 11p15 occurs between the HRAS1 gene and the genes for insulin and the insulin-like growth factor 2. These results suggest that the TCRA sequences activate a cellular gene located at 11p15 in malignant T-cell disorders.
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PMID:T-cell receptor alpha-chain gene is split in a human T-cell leukemia cell line with a t(11;14)(p15;q11). 354 Sep 49

The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. The cell lines used in these studies included murine L-1210 leukemia, human RPMI 8226 myeloma, MCF-7 breast cancer and WiDr colon carcinoma. Soft agar colony forming assays showed that BSO was most effective at reducing tumor colony formation when exposed continuously to cells in vitro. Drug concentrations which inhibited colony formation to 50% of control levels ranged from 2.0-6.2 mM (for 1 hour exposures), 2-100 mM for 24 hour exposures and 0.4-1.40 microM (for continuous BSO exposures). Human myeloma cells proved most sensitive to BSO. In vitro cytotoxicity correlated with depletion of intracellular nonprotein sulfhydryls to less than or equal to 10% of control values in both L-1210 and 8226 cells. This was routinely achieved with prolonged exposures to mM BSO concentrations for greater than 24 hours. Normal mice tolerated high BSO doses (up to 5.0 g/kg) without evidence of acute toxicity. BSO was not active against L-1210 leukemia-bearing DBA/2 mice. When tested in vivo against MOPC-315 plasmacytoma-bearing BALB/c mice, BSO was not active at doses up to 4.0 g/kg. In contrast, the bifunctional alkylating agent melphalan (L-PAM) was active against MOPC-315 and this activity was enhanced by a 24 hour pretreatment of mice with 50 mg/kg of L-BSO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells. 358 42

The antitumor activity and mode of action of antitumor agents were assayed by a new method which takes a relatively short time for evaluation. The method was clinically applied to patients with malignant lymphoma or acute leukemia for estimating drug sensitivity. Fresh malignant cells were obtained from patients' bone marrow, lymph nodes, or peripheral blood using Lymphoprep methods in 26 patients with these malignant disorders. Each sample (5 X 10(5) cells/ml) was cultured in the medium with RPMI 1640 supplemented with 10% of FCS and 20% of patients' own sera containing every antitumor agent at predetermined concentrations for 30 minutes. Each sample was again cultured for another 72 hours at 37 degrees C in a 5% CO2 humidified atmosphere after rinsing. Microscopic observation was periodically carried out using a specially devised observation chamber with an inverted immersion microscope for 72 hours. Morphological changes of 200 to 300 cells of each sample were described according to morphological criteria. Of these, irreversible changes in number were considered to be indicative of antitumor activity of the agent tested. More than 50% cellular damage was categorized as effective and more than to 50% reduction of leukemia cells or decrease in size of lymph nodes the same degree in malignant lymphoma were considered to be clinically effective. Forty-four assay runs in 26 patients were done, and on 31 occasions were shown to be coincident. We conclude that this in vitro method is fully applicable for predicting the effectiveness of an agent to be clinically administered regardless of the various controversial problems to be solved.
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PMID:[In vitro predictive activity assay of agents based on dynamic cellular morphological findings--clinical application]. 372 38

The antitumor activity of 1.3.3.5.5-pentaziridino-1-thia-2.4.6-triaza-3.5-diphospho rine-1-oxide (SOAz) was investigated in vitro and in vivo. The results obtained were as follows: SOAz showed marginal cytotoxicity against growth of L1210 cells cultured in vitro. In the cell-cycle traverse of RPMI 8402 cells, SOAz prolonged the duration of the S phase, leading to the eventual accumulation of cells at the G2 phase. At the highest concentration, SOAz stopped the cell cycle progression completely. SOAz was found to have similar activity to carbazilquinone, cyclophosphamide or mitomycin C on P388 leukemia. SOAz showed marked antitumor effect against early-stage L1210 leukemia, and was also effective against advanced-stage L1210 leukemia. The therapeutic efficacy of SOAz depends on the treatment schedule. Single injection and intermittent treatment were superior to daily treatment. Oral administration of SOAz was effective as well as i.p., i.v. and i.m. administration.
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PMID:[Antitumor effect of 1,3,3,5,5-pentaziridino-1-thia-2,4,6-triaza-3,5- diphoshorine-1-oxide]. 378 52


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