Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunotoxin (IT) was prepared by conjugating cytotoxin from Chinese Cobra (Naja naja Atra) venom with monoclonal antibody (McAb) Wu71 directed to human T-cells. First, calcium ions were used to suppress the cytolytic reaction while cell antigen was allowed to react with McAb. Then magnesium ions and the chelating agent EGTA were used to abolish the calcium inhibition. With this treatment, the IT showed high cytotoxicity for the leukemic cell line CEM, which was antigen positive (82.4% of the cells were killed at a concentration of 0.5 x 10(-6) mol/L of IT), but very little cytotoxicity for the antigen negative cell line Raji (23.3% cells were killed at the same concentration). Under scanning electron microscopy, it could be seen that the cell membranes of CEM were broken by IT, and the cells had died. The results suggest that the McAb Wu71 plus cytotoxin IT has potential application in leukemia therapy.
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PMID:[Specific killing of human leukemic T-cells by a monoclonal antibody coupled to the cytotoxin from Chinese cobra]. 139 35

The effect of SK&F 96365 (1-(beta-[3-(4-methoxyphenyl)propoxyl]-4- methoxyphenethyl)-1H-imidazole hydrochloride), a recently synthesized inhibitor of receptor-mediated calcium entry, was investigated on human hematopoietic cell lines. We found that treatment of the T-cell leukemia line Jurkat with SK&F 96365 inhibited the Ca2+ influx triggered by antibodies against the CD3/TCR complex, while the inositol trisphosphate-dependent Ca2+ release from intracellular stores remained intact. A 50% inhibition of the Ca2+ influx was obtained with 5 microM SK&F 96365, while higher concentrations of the drug blocked the CD3-dependent Ca2+ influx completely. In addition to its blocking of the Ca2+ influx, treatment with SK&F 96365 was found to accumulate mitotic cells. The drug (5 microM) imposed a total cell cycle arrest in G2/M. The mitosis block could be reversed by removal of the inhibitor from the cultures, while elevation of intracellular or extracellular Ca2+ did not restore cell cycle progression. This suggests that the cell cycle block induced by SK&F 96365 is not directly related to its action as an inhibitor of receptor-mediated calcium entry. Our findings indicate that SK&F 96365, in addition to its ability to inhibit receptor-triggered Ca2+ influx, offers a new method for imposing a reversible mitosis arrest in hematopoietic cell lines.
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PMID:Mitosis-arresting effect of the calcium channel inhibitor SK&F 96365 on human leukemia cells. 139

Cobra venoms cause irreversible destruction of cells cultured in vitro [1,2]. The venom of Naja nigricollis nigricollis possessed the most potent cytotoxic activity towards B16F10 melanoma cells among various examined venoms [2]. The main cytotoxic factor (P4) isolated from this venom showed preferential activity on tumor cell lines and caused lysis at concentrations of 10(-7) M (0.8-1 micrograms/ml) [3]. The present study examined the binding of cytotoxin P4 to melanoma B16F10 and WEHI-3B leukemia cell lines and found that, like cytotoxicity, it depended on concentration, temperature and incubation time. Cytotoxin concentrations that elicited no apparent damage to cells during the first hour of incubation caused lysis after a longer period of incubation, suggesting that a critical number of bound molecules is required in order to cause cell death. Bivalent ions, such as Mg2+, Ca2+ or Sr2+, which decreased binding to the cells also inhibited cytotoxicity. Competition experiments as well as the displacement of 75% of the bound radiolabelled cytotoxin with 'cold' cytotoxin, suggest the presence of specific binding sites for the toxin in the examined tumor cells. The non-specific binding of the cytotoxin P4 to sea urchin ova and sperm cells without affecting their fertility, even at high concentrations of 10(-5) M, indicates that the specific binding to cells is probably a necessary condition for cell lysis.
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PMID:Binding of cytotoxin P4 from Naja nigricollis nigricollis to B16F10 melanoma and WEHI-3B leukemia cells. 141 10

A confocal fluorescence microscope with an argon-ion laser (488 nm) and a He-Cd laser (325 nm) was used to study spatial heterogeneity of the calcium signals in rat basophilic leukemia 2H3 cloned cell line (RBL-2H3). After stimulation with antigen (2,4-dinitrophenol-conjugated bovine serum albumin), fluo-3-fluorescence intensities increased in individual RBL-2H3 cells with different lag times. Time-dependent profiles of the fluo-3-fluorescence intensities resembled closely the patterns of the sequential fluorescence-ratio images of fura-2, which were used to measure the intracellular free-calcium concentration ([Ca2+]i) in individual RBL-2H3 cells using a conventional fluorescence microscope. The present results obtained using the confocal fluorescence microscope showed spatial heterogeneities of fluo-3-fluorescence intensities, suggesting the existence of spatial heterogeneity of [Ca2+]i in RBL-2H3 cells. That is, the results showed that calcium signals first occurred transiently at pseudopodia in RBL-2H3 cells, then the signals transferred to the central parts of the cells. In addition, from the fluorescence images of co-loaded Hoechst 33342 (bisbenzimide H 33342, a DNA-specific probe) which were produced by excitation with a He-Cd laser, it was found that the fluorescence images of the nucleus were quite similar to those of the calcium signals mentioned above. This suggested that the receptor-mediated calcium signals were transferred not only to the cytoplasm but also to the nucleus.
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PMID:Cytosolic and intranuclear calcium signals in rat basophilic leukemia cells as revealed by a confocal fluorescence microscope. 142 78

A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2-morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 1 microM completely reversed the resistance to vincristine in vincristine-resistant P388 mouse leukemia cells (P388/VCR), in vitro. PAK-200 at 2 microM inhibited the efflux of [3H]vincristine from P388/VCR and increased the accumulation of [3H]vincristine in P388/VCR to a level similar to that in P388 cells. P-Glycoprotein in membrane vesicles from P388/VCR cells was photolabeled with [3H]azidopine. The labeling was completely inhibited by 10 microM PAK-200. The calcium antagonistic activity of PAK-200 was about 1000 times lower than that of another dihydropyridine analogue, nicardipine. Experiments with P388 and P388/VCR-bearing mice showed that PAK-200 enhanced the effect of vincristine on both leukemia cells in vivo. These results suggest that PAK-200 interacts with P-glycoprotein and reverses drug resistance in P388 mouse leukemia cells in vitro, and that PAK-200 has an ability to potentiate the effect of vincristine on P388 mouse leukemia cells in vivo.
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PMID:Potentiation of the vincristine effect on P388 mouse leukemia cells by a newly synthesized dihydropyridine analogue, PAK-200. 142 98

Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.
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PMID:[Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders]. 143 36

Hypercalcemia with adult T-cell leukemia (ATL) is chiefly caused by an excessive production by tumor cells of parathyroid hormone-related protein (PTHrP). We have previously reported hypercalcemic patients with solid tumors to excrete a large amount of the C-terminal fragments of PTHrP (C-PTHrP) into their urine. To elucidate whether PTHrP production correlates with or predicts the development of hypercalcemia, we studied the urinary excretion of C-PTHrP in 36 ATL patients. The urinary excretion of C-PTHrP was in the normal range (< 0.40 nmol equivalent to PTHrP (109-141)/g creatinine) in HTLV-1-positive carriers (n 3), ATL patients in complete remission (n 2) and chronic type ATL patients (n 2). It was marginally increased in seven patients in partial remission, and gradually increased as the disease progressed. In 20 patients who died without or with hypercalcemia, it was increased to 1.98 +/- 0.69 (n 9) and 7.6 +/- 2.1 nmol/g creatinine (mean +/- SD, n 11, P < 0.01), respectively. Urinary C-PTHrP excretion was significantly correlated with serum calcium and LDH levels as well as with CD25-positive cells in the peripheral blood. In four patients whose urinary excretion had been serially determined, it increased prior to the development of hypercalcemia. The findings suggest the urinary excretion of C-PTHrP to be of use as a predictor of the development of hypercalcemia in ATL patients. In ATL patients whose urinary excretion of C-PTHrP is progressively increasing, the serum calcium concentration should be carefully monitored to prevent hypercalcemic crisis.
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PMID:Urinary excretion of parathyroid hormone-related protein as a predictor of hypercalcemia in patients with adult T-cell leukemia. 146 94

Hypercalcaemia occurs in up to 80% of patients with adult T-cell leukaemia-lymphoma (ATLL) associated with human T-cell leukaemia virus-1 infection. Elevated serum levels of 1,25-dihydroxycholecalciferol, implicated in the pathogenesis of hypercalcaemia in lymphoma, and of parathyroid hormone-related protein (PTHrP), which is associated with hypercalcaemia of several solid malignancies, were demonstrated in a patient with ATLL hypercalcaemia. Treatment with bisphosphonates reduced the serum calcium but had no significant effect on the serum PTHrP levels. This case supports recent in vitro evidence for enhanced PTHrP expression in ATLL tumour cells and suggests that more than one tumour cell product may be involved in the pathogenesis of ATLL hypercalcaemia.
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PMID:Elevated serum parathyroid hormone related protein and 1,25-dihydroxycholecalciferol in hypercalcaemia associated with adult T-cell leukaemia-lymphoma. 148 May 40

Protein kinase C (PKC) isoforms are key mediators in hormone, growth factor, and neurotransmitter triggered pathways of cell activation (Nishizuka: Science 233:305-312, 1986; Nature 334:661-665, 1988). Stimulation of kinase activity by diacylglycerol and calcium often leads to translocation of PKC from the cytosol to a particulate fraction (Kraft and Anderson: Nature 301:621-623, 1983). The beta isoform of PKC is translocated and degraded much more rapidly than the alpha isoform in phorbolester-stimulated rat basophilic leukemia (RBL) cells (Huang et al.: J. Biol. Chem. 264:4238-4243, 1989). We report here immunofluorescence evidence that the distributions of PKC alpha and beta are strikingly different in antigen-activated RBL cells. PKC beta associates with perinuclear filaments and filaments that extend from the perinuclear area to the cell periphery whereas PKC alpha concentrates in regions of the cell periphery. This distribution of PKC beta is distinctly different from that of actin filaments and microtubules as determined by phalloidin staining and by anti-tubulin antibody labeling. In contrast, the staining patterns obtained with antibodies to PKC beta and to the intermediate filament protein vimentin are almost identical, indicating that PKC beta associates with vimentin filaments. These bundles of 100 A filaments may provide docking sites for interactions of PKC beta with its substrates and thus confer specificity to the actions of this isoform.
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PMID:Association of the beta isoform of protein kinase C with vimentin filaments. 151 48

In order to clarify the cellular tropism of human T-cell leukemia virus type I (HTLV-I) and the effects of HTLV-I infection on T-cell functions, we investigated the infectiousness of HTLV-I on T cells bearing T-cell receptor (TCR) gamma delta and functional alterations of the HTLV-I-infected TCR-gamma delta + T cells. CD3+ CD4-CD8-TCR-gamma delta + T-cell clones which possessed cytotoxicity were co-cultured with a HTLV-I-producing T-cell line. After several weeks, integration of HTLV-I proviral DNA in TCR-gamma delta + T cells was detected by Southern blot analysis. During the continuous culture of HTLV-I-infected TCR-gamma delta + T-cell clones, 2 distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR-gamma delta complex. Early after HTLV-I infection, TCR-gamma delta + T cells lost their spontaneous cytotoxicity, but this was restored by the addition of lectin. At this time, no differences were observed in the expression of various surface molecules between HTLV-I-infected and uninfected parent cells, except for increased expression of CD25 on HTLV-I-infected cells. At about 30 weeks after HTLV-I infection, the cytotoxicity of HTLV-I-infected cells was almost completely lost, even in the presence of lectin, and expression of the CD3-TCR-gamma delta complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3-TCR-gamma delta complexes, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti-CD3 and anti-TCR monoclonal antibodies (MAbs) was also observed. Our present findings thus show that HTLV-I can infect TCR-gamma delta + T cells, and that consequently their functions are profoundly affected through 2 distinct phases.
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PMID:Human T-cell leukemia virus type I(HTLV-I) infection of T cells bearing T-cell receptor gamma delta: effects of HTLV-I infection on cytotoxicity. 153 Dec 9


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