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)

A new cytotoxic substance designated as BS-1 was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563. On the basis of spectral data, the structure of BS-1 was determined as bis(2-hydroxyethyl) trisulfide and confirmed by direct comparison with the synthetic compound. BS-1 exhibited potent cytotoxicity against leukemia P388-D1, leukemia P388, mastocytoma P815, lymphoma EL4 and lymphoma MOLT4.
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PMID:Studies on thermophile products. IV. Structural elucidation of cytotoxic substance, BS-1, derived from Bacillus stearothermophilus. 142 83

Calcium-ion uptake by normal and leukemia lymphocytes increased during a 30-min exposure to a 13.6 Hz, sinusoidal magnetic field at 20 microT peak. The time-varying field was horizontal and parallel to a 16.5 microT component of the ambient static magnetic field. The uptake of 45Ca2+ increased 102% in a line of murine, cytotoxic T-lymphocytes (C57B1/6-derived CTLL-1), increased 126% in freshly-isolated spleen lymphocytes (C57B1/6 mice), and increased 75% in a line of lymphoma cells (C57B1/6-derived EL4). In contrast, there was no effect when the same field was applied for 30 min immediately before--as opposed to during--incorporation of calcium ions. When spleen lymphocytes were exposed during incubation with 45Ca2+ to a 60 Hz magnetic field at 20 microT peak, a small but statistically significant increase (37%) in uptake of the labeled ions occurred. These results indicate that weak, alternating magnetic fields might affect calcium-dependent functions of normal and leukemic lymphocytes.
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PMID:Calcium uptake by leukemic and normal T-lymphocytes exposed to low frequency magnetic fields. 185 52

Delayed-type hypersensitivity (DTH) to the chemically induced EL4 and virally induced ARadLV 136 leukemia cells was determined by the radioactive ear test. Prior to the DTH test, mice were prevaccinated with cells treated either with hydrostatic pressure or with the membrane-impermeant crosslinker adenosine dialdehyde or with a combination of these. For both tumor cells, DTH against unmodified cells was markedly potentiated by prevaccination with cells treated with hydrostatic pressure combined with adenosine dialdehyde. In vitro cytotoxicity data indicated that maximal lysis of target cells is induced by vaccination with adenosine-dialdehyde-treated cells, as well as by pressure in combination with adenosine dialdehyde treatment. In addition, increased [3H]thymidine uptake was observed in effector T cells induced by prevaccination with tumor cells modified by adenosine dialdehyde or pressure or both. This novel and innocuous potentiation of an antitumor immune response may have a practical utility in the treatment of human cancer.
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PMID:Potentiation of delayed-type hypersensitivity response to syngeneic tumors in mice prevaccinated with cells modified by hydrostatic pressure and crosslinking. 202 54

We have recently demonstrated that high-dose IL-2 administered for a short period (2.5 days) beginning on the day of bone marrow transplantation mediates a marked protective effect against GVHD in mice, while preserving the ability to achieve alloengraftment (1). This protective effect is augmented by administration of T cell-depleted (TCD) syngeneic marrow, and is dependent upon early administration of IL-2 (1). The graft-vs-tumor effect against the EL4 leukemia/lymphoma is not diminished in animals protected from GVHD by IL-2 (2). In an attempt to determine whether or not IL-2-activated host-type cells might be responsible for GVHD protection, we have now performed adoptive transfer studies. The results failed to provide evidence that treatment of lethally irradiated mice with IL-2 activates protective host-derived or syngeneic marrow-derived cell populations which can be adoptively transferred to lethally irradiated secondary recipients receiving allogeneic GVHD-producing inocula. Likewise, treatment of lethally irradiated mice with a complete 2.5-day course of IL-2 prior to administration of allogeneic inocula did not lead to GVHD protection. These results suggest that either IL-2 directly inhibits the GVH reactivity of allogeneic GVH-reactive cells, or that GVH reactivity is attenuated by IL-2 during the period of interaction of donor- and host-type cells.
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PMID:Mechanism of the anti-GVHD effect of IL-2. I. Protective host-type cell populations are not induced by IL-2 treatment alone. 204 82

C57BL/6 mice with EL4 leukemia cells in ascitic form were intraperitoneally treated with ricin A chain-multivalent antibody immunotoxins. The immunotoxins containing rabbit IgG anti-Thy 1.2 antibodies complemented by protein A of Staphylococcus aureus were able to interact specifically with the target cells and to induce an antitumor effect as revealed by an increase in survival time of the mice. No apparent secondary effects consecutive to a cytotoxic action on the normal Thy 1.2 antigen bearing cells were observed with the immunotoxin doses used.
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PMID:Treatment of murine EL4 leukemia in ascitic form with anti-Thy 1.2 specific immunotoxins. 223 17

The thymic leukemia cell line EL4 has been shown to produce the lymphokine Interleukin-2 (IL-2) following stimulation with phorbol ester (PMA). We investigated intracellular enzyme pathways triggered by phorbol stimulation using an EL4 cell line which responds to PMA with IL-2 synthesis (EL4r) and one which does not produce IL-2 following stimulation (EL4nr). By comparing these two cell lines we hoped to establish which enzyme activities were associated with IL-2 synthesis. The enzyme pathways studied included calcium/phospholipid dependent protein kinase (C-kinase) activity, the induction of polyamine synthesis, RNA, DNA and protein synthesis and finally IL-2 production. Our results indicate that both EL4 cell lines have a receptor for PMA, which can activate the C-kinase enzyme. Further, in both cell lines PMA activates the nuclear synthesis of polyamines as demonstrated by ornithine decarboxylase induction. Both RNA and protein synthesis measured by 3H-uridine and 3H-leucine uptake respectively appear comparable between EL4r and EL4nr. The only difference in cellular responsiveness between EL4r and EL4nr was in the 3H-thymidine uptake, and IL-2 production. IL-2 production or lack of production was established by 3H-uridine and 3H-thymidine incorporation as well as viable cell count using the IL-2 dependent cell line CTLL-2. We, therefore, conclude that EL4r and EL4nr cells show similar intracellular responses to phorbol ester except for 3H-thymidine uptake and detectable IL-2 production. Our results suggest that failure of PMA-stimulated EL4nr cells to produce IL-2 is either due to inability of this cell line to synthesize IL-2 or the production of defective IL-2. It is not due to failure of PMA to activate C-kinase or the subsequent nuclear events.
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PMID:The activation of calcium/phospholipid dependent protein kinase and the association with interleukin-2 production. 242 45

We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, alpha-difluoromethylornithine (DFMO), on growth of the Roser acute T-cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood-borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour-cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti-tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.
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PMID:Influence of cyclosporin A and alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on two rodent T-cell cancers in vivo. 251 49

4-amino-4-methyl-2-pentyne-1-al (AMPAL), a new irreversible inhibitor of aldehyde dehydrogenase (ALDH) has been assayed for its in vitro and in vivo antitumor activity. In vitro, AMPAL inhibits the proliferation and the ALDH activity of L1210 and RBL5 cell lines. In vivo, AMPAL significantly increases the mean survival time of mice i.p. grafted with leukemia (L1210, P815, MBL2, EL4, RBL5 cell lines) or carcinoma cells (Krebs cell line), without haematopoetic toxicity. No carcinostatic effect was observed against the P388 leukemia and the 3LL Lewis lung carcinoma. A possible relationship between the ALDH isoenzyme activity of the tumor and its sensitivity to AMPAL is discussed in the light of previous reports concerning the role of aldehydes in cell growth control.
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PMID:In vivo antitumor activity of 4-amino 4-methyl 2-pentyne 1-al, an inhibitor of aldehyde dehydrogenase. 251 73

A monoclonal anti-I-Jk antibody JK10-23 was capable of precipitating the putative I-Jk molecule from NP-40 lysates of 125I-surface labelled mouse T cell clones with either helper or suppressor functions. The I-J molecule detected by specific immunoprecipitation and subsequent one- or two-dimensional gel analysis was a Mr 84-90 K dimer composed of 42-46 K glycopeptide subunits having isoelectric point pH 5.3 to 6.4. A monomeric form of I-J also existed in some of the T cell clones. The I-J subunit was a glycosylated polypeptide with a 41 K backbone having at least two glycosylation sites. I-J was distinguishable from other known dimeric T cell surface molecules with comparable molecular size, that is, T cell receptor alpha beta heterodimer, A1 and YE molecules expressed on a T cell leukemia EL4, and mouse CD28. The I-Jk molecule was precipitable from T cell clones with I-Ak and I-Ek restriction specificities including a clone derived from an H-2b----H-2bxkF1 radiation bone marrow chimera. None of the H-2b-restricted T cell clones from H-2b and its F1 showed the I-Jk immunoreactivity. T cell clones having either I-Ab or I-Ek restriction specificities derived from intra-H-2 recombinant mouse B10.A(5R) were positive for the I-Jk, while an I-Ab-restricted T cell clone from B10.A(3R) was negative in the I-Jk immunoprecipitation. The results indicate that I-J is a novel dimeric surface molecule, most likely to be a homodimer, expressed on T cells according to the major histocompatibility complex.
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PMID:Biochemical identification of I-J as a novel dimeric surface molecule on mouse helper and suppressor T cell clones. 253 59

Two immunotoxins, the ricin A chain-multivalent hybrid antibody (750 kDa) and the complex A chain-staphylococcal protein A-rabbit IgG antibody (370 kDa), were prepared. A simple method was elaborated to test the immunotoxins' efficiency in selectively killing target cells in tumor-bearing mice. The target cell (murine EL4 leukemia) was coated with a xenogenic molecule by a method conserving its ability to proliferate and kill the inoculated animals. When the challenged animals were treated with these immunotoxins, which were specific for the antigenic molecule coating the tumor cells, survival time was lengthened compared with that of untreated animals, corresponding to a proportion of over 90% cells killed. This demonstrates the efficiency of the immunotoxins and the validity of the method elaborated.
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PMID:Experimental model for testing the efficiency of immunotoxins administered in vivo: evaluation of two ricin A-chain--multivalent antibody immunotoxins. 278 2


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