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

We have used oligonucleotide probes, based on a portion of the p60v-src autophosphorylation sequence, Glu-Asp-Asn-Glu-Tyr-Thr, to identify and characterize a cDNA from the human T-leukemia cell line, JURKAT. The JURKAT cDNA (designated ptk-JURKAT) was homologous to but distinct from the src, yes and fgr oncogenes, which encode protein-tyrosine kinases (ATP:protein phosphotransferase, EC 2.7.1.37). The ptk-JURKAT cDNA hybridized with a 2.2 kb RNA transcript from JURKAT cells and the human T-cell lymphoma line, MOLT-4, but failed to identify any transcript in two human B-cell lymphoma lines or a human erythroid-myeloid leukemia line, K562. Recently the nucleotide sequence has been established for the murine lymphocyte protein tyrosine kinase, p56LSTRA. The ptk-JURKAT cDNA appears to encode the human homolog of p56LSTRA.
 ...
PMID:Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA. 348 86

Biochemical analysis has been used to monitor the induction of differentiation in cultured human T-leukemia cell lines (CCRF-CEM, HPB-ALL, JM and MOLT-4) by the phorbolester 12-0-tetradecanoylphorbol 13-acetate (TPA). The isoenzymes of carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase were separated by isoelectric focusing on horizontal thin-layer polyacrylamide gels and stained by histo-cytochemical methods. TPA inhibited the proliferative activity in all four cell lines and led to aggregation of cells seen as floating clusters. TPA induced an increase in number and staining intensity of isoenzymes of all four enzymes in the cell lines studied. This corresponds to an induced isoenzymatic maturation as the progressive increase in number and staining intensity of the isoenzymes parallels the differentiation along the T-cell pathway. However, regardless of the initial stage of arrested differentiation, the cell lines could be induced only to differentiate to a certain more mature stage, but could not be triggered to differentiate terminally with regard to expression of isoenzyme patterns.
 ...
PMID:T-leukemia cell lines CCRF-CEM, HPB-ALL, JM and MOLT-4: changes in isoenzyme profiles during induction of differentiation. 349 47

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undesirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. We have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell line) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppressing the in vivo growth of the ascitic tumor, we divided 40 nude mice that were injected with Ichikawa cells into four groups. Each group of 10 mice was injected with one of the following mixtures: 40 micrograms of purified control mouse IgG [IgG1(kappa)] (group 1), 40 micrograms of control RA conjugate (group 2), 20 micrograms of purified SN1 antibody [IgG1(kappa)] and 20 micrograms of purified SN2 antibody [IgG1(kappa)] (group 3), or 20 micrograms of SN1-RA and 20 micrograms of SN2-RA (group 4). Mice in groups 1 and 2 formed large ascitic tumors, and died 5.8-7.0 weeks after the transplantation. Group 3 mice also formed large ascitic tumors and died 6.4-7.8 weeks after the transplantation. However, none of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation; these mice were indistinguishable from healthy control nude mice that were not injected with Ichikawa cells. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.
 ...
PMID:Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models. 349 97

The MOLT-16 cell line, which was established from the malignant cells of a patient with T-cell acute lymphoblastic leukemia, is characterized by a translocation involving chromosome 8 (band q24) and chromosome 14 (band q11) [t(8;14)(q24;q11)]. To determine the position of the gene encoding the alpha chain of the T-cell receptor and of the protooncogene MYC (formerly c-myc) in relation to the breakpoint junction and to evaluate their possible role in the pathogenesis of T-cell neoplasia, we applied the techniques of in situ chromosomal hybridization, Southern blot analysis, and molecular cloning to MOLT-16 cells. Our results indicate that the breakpoint on chromosome 14 at band q11 occurs close to a joining sequence of the gene encoding the alpha chain of the T-cell receptor. The constant region and part of the joining region of this gene are translocated to the 3' side of the MYC exons. The breakpoints on chromosomes 8 and 14 are close to, but distinct from, those found in SKW-3, another T-cell leukemia cell line, which has a t(8;14). The identification of a breakpoint to the 3' side of MYC suggests that this recurring translocation is analogous to the variant t(2;8) and t(8;22) translocations observed in the B-cell malignancies.
 ...
PMID:Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3' side of MYC. 352 89

We have studied here cytotoxic function of three cloned cell lines--TC12, 48, and 50--derived from circulating lymphocytes that were potentially able to eliminate residual tumor cells in a patient transplanted for treatment of acute lymphocytic leukemia. These cloned cells, which have both phenotypic and functional characteristics of natural killer lymphocytes, were tested in chromium release assays against a panel of 16 uncultured populations of leukemia cells. In addition, their activity was compared with that of cloned and uncloned NK cells from normal individuals. It was found that TC clones induced a much weaker degree of killing against fresh tumor cells compared with conventional NK target cell lines such as K562 or MOLT 4. In addition, there was great heterogeneity in their individual lytic capacity against the various leukemia blasts (TC12, 48, and 50 cells killed in a significant fashion, respectively 7, 1, and 4 of the 16 leukemias), reflecting the functional diversity of normal NK cell populations. Thus, for a fraction of leukemias, there was no correlation between lytic ability of TC cells and that of uncloned lymphokine-activated large granular lymphocytes from normal peripheral blood. Together, these results support the view that direct identification of patients' cytotoxic lymphocytes screened against in vivo relevant tumor cells is necessary to evaluate potentially beneficial immunologic responses in the context of bone marrow transplantation.
 ...
PMID:Characterization of antileukemia cells' cytotoxic effector function. Implications for monitoring natural killer responses following allogeneic bone marrow transplantation. 352 26

Eight human haematopoietic cell lines and four human carcinoma lines were used to compare the activity of a number of cytotoxic drugs including amsacrine, the amsacrine analogue CI-921, methotrexate, nitracrine, doxorubicin, daunorubicin and 5-fluorouracil. Activity was assessed by means of semiautomated microculture growth inhibition assays. Cell density of the non-adherent cell lines was measured using the technique of Mosmann (J Immunol Methods 1983, 65, 55-63), in which the dye thiazolyl blue (MTT) is metabolised to a dark blue formazan product. This technique gives similar results to those obtained by direct cell counting in an electronic cell counter, and when applied to some adherent cell lines gives similar results to those obtained by the methylene blue staining technique previously developed (Anal Biochem 1984, 139, 272-277). Both methylene blue and MTT methods were used to investigate cytotoxicity in conjunction with semi-automated 96-well microculture plate techniques. The results show that the three T-cell leukaemia lines (CCRF-CEM, Jurkat and MOLT-4) are more sensitive to DNA-binding drugs (excluding nitracrine) than are the colon carcinoma lines (HCT-8, HT-29, SW480 and SW620). The more resistant haematopoietic lines are intermediate in drug sensitivity between the T cell leukaemia and carcinoma lines. The DNA binding drugs show remarkably similar patterns of differential activity against the different cell lines.
 ...
PMID:Comparison of in vitro activity of cytotoxic drugs towards human carcinoma and leukaemia cell lines. 375 82

Cytotoxic effects of mannosamine and free fatty acids on human malignant T-lymphoid cell lines derived from patients with T-cell leukemia were investigated. The combination of mannosamine and an unsaturated fatty acid (oleate or linoleate) produced more striking cytotoxic effects on malignant lymphoid cells than on normal human lymphocytes. The amino sugars glucosamine or mannosamine in the combination caused a synergistic cytotoxic effect, while the other carbohydrates (N-acetylmannosamine, N-acetylglucosamine, or mannose) had little effect. On the other hand, the effect of saturated fatty acids (palmitate or stearate) in the same system was nil. An unsaturated fatty acid (oleate) caused an increase in lipid fluidity of the surface membrane in MOLT-4 lymphoid cells, which possess higher lipid fluidity in combination with mannosamine, while saturated fatty acids had no effect on the fluidity properties of the membrane lipids (even in the presence of mannosamine). The relationship between mannosamine and unsaturated fatty acids in cytolysis was discussed.
 ...
PMID:Antitumor activity of D-mannosamine in vitro: cytotoxic effect produced by mannosamine in combination with free fatty acids on human leukemia T-cell lines. 387 90

Ten human leukemia-lymphoma cell lines were tested for the growth-inhibitory effects of harringtonine (HT). HT was most active against HL-60 acute promyelocytic leukemia cells and least active against DND-41 acute lymphoblastic leukemia cells, with a 70-fold differential activity. Sensitivity of the cell lines is, in decreasing order: HL-60 greater than RPMI-8402 greater than DND-39A congruent to ML-2 congruent to MOLT-3 congruent to KG-1 greater than Daudi congruent to NALL-1 greater than BALM-2 greater than DND-41. The cell lines with rapid cell growth tended to be more sensitive to HT. To further elucidate the selectivity of the differential sensitivity, uptake and release of HT were compared in HL-60 and DND-41 cells. Uptake of [3H]HT into HL-60 and DND-41 cells showed no difference; however, the binding of [3H]HT to cellular components was greater than 16-fold higher in HL-60 cells than DND-41 cells. There were also minor, but significant differences in the inhibition of [3H]leucine incorporation into proteins of these two cell lines in the presence of 1 microgram/ml HT. To test whether the biological effects of HT are related to the concentration of, or exposure time to, HT, KG-1 cells were exposed to HT for different periods of time and the growth-inhibitory effects were compared. Increasing exposure time from 1 h to 3 h resulted in a 100-fold decrease in concentration X exposure time (c X t) at ID50; from 3 h to 6 h, in a 20-fold decrease at ID70; and from 6 h to 24 h, in a 16-fold decrease at ID90. HT was not inactivated by cells up to 24 h. These results indicate that (a) the sensitivity of different cell lines to HT may be related to the degree of HT binding; and (b) the effects of HT are more dependent on exposure time than concentration. Continuous infusion is thus rational for clinical trials of this drug, and the degree of HT binding to leukemic cells may be predictive of clinical response.
 ...
PMID:Biologic and pharmacologic effects of harringtonine on human leukemia-lymphoma cells. 399 83

A human leukemia-associated antigen (LAA) has been identified by immunofluorescence and electrophoretic analyses. LAA was detected on the surfaces of cells from patients with acute lymphocytic leukemia (ALL) as well as on the surfaces of leukemia cells from the established cell lines NALM-1, NALM-16, MOLT-4, CCRF-CEM, and RPMI 8402. The antigen was not detected on BALM-1 or Raji cells (established B-cell lines), bone marrow cells from ALL patients in remission, or on blood lymphocytes from normal donors. This antigen was most frequently associated with common ALL (cALL); however, cells from 2 of 12 patients with T-cell ALL and 1 patient with B-cell ALL also expressed this antigen. Under reduced conditions, the antigen had an approximate molecular mass of 100,000 daltons as determined by sodium dodecyl sulfate--polyacrylamide gel electrophoresis and autoradiographic analysis and appeared to be the same cALL antigen that has recently been described by others. The probability that LAA is a normal differentiation antigen was discussed.
 ...
PMID:Identification of a leukemia-associated antigen of human acute lymphocytic leukemia. 615 21

The antitumor activity of the C-nucleoside, 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), was investigated in four human lymphoid tumor cell lines in culture. Exposure of the cell lines CCRF-CEM (T-cell leukemia), HUT-78 (cutaneous T-cell lymphoma), NALM-1 (B-cell leukemia), and MOLT-4 (T-cell leukemia) for 72 hr to TR resulted in 50% inhibitory concentration of 30, 27, 7, and 6 microM, respectively. Maximum inhibition of DNA and RNA synthesis occurred 6 hr after drug treatment. The 50% inhibitory concentration of TR among the four cell lines varied from 5 to 8 microM for RNA synthesis and from 4 to 8 microM for DNA synthesis. Nucleotide analyses in MOLT-4 cells after 6 hr of drug exposure to 10 and 100 microM TR revealed increased inosine 5'-monophosphate concentrations which were 18- to 20-fold greater than control levels and a parallel reduction of 82 and 100% in guanosine 5'-monophosphate concentrations. Growth inhibition of MOLT-4 cells by 6 hr exposure to TR was almost fully reversible by addition of 50 microM guanosine to the medium for 18 hr. Analyses by high-pressure liquid chromatography revealed two metabolites of TR in all four cell lines, namely, thiazolecarboxamide riboside 5'-monophosphate and thiazolecarboxamide adenine dinucleotide, the latter of which is a potent inhibitor of inosine-5-'-monophosphate dehydrogenase. These results suggest that the antitumor effects of TR in human tumor cell lines may relate to guanine nucleotide depletion.
 ...
PMID:Activity and metabolism of 2-beta-D-ribofuranosylthiazole-4-carboxamide in human lymphoid tumor cells in culture. 618 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>