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

We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.
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PMID:Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts. 310 70

The induction of procoagulant activity (PCA) by human recombinant tumor necrosis factor (rTNF) was studied in human monoblastic leukemia cell line U937 and human peripheral blood monocytes. Using a one-step recalcificating clotting assay, PCA in cell lysates or whole cell preparations was measured by comparison to a rabbit brain thromboplastin standard. There was a dose- and time-dependent increase in PCA when U937 cells were cultured with rTNF. The effect of rTNF was not enhanced by recombinant human interferon-gamma (rIFN gamma). Cycloheximide inhibited the expression of PCA by U937 cells, showing that protein synthesis was necessary to mediate the effects of rTNF. Whole cell preparations demonstrated that greater than 80% of the PCA was expressed on the surface of the cells. The PCA functioned as a tissue factor-like substance, since it required coagulation factor VII and factor X. rTNF also increased PCA in human monocytes in a dose- and time-dependent manner. This effect was abrogated by boiling the rTNF for ten minutes, and was not inhibited by adding polymyxin-B to the cultures, making it unlikely that endotoxin accounted for the observed effects. These results suggest that TNF-induced expression of tissue factor by mononuclear phagocytes may modulate immunologic, inflammatory, and hemostatic processes.
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PMID:Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. 313 64

We have identified a leukemia-differentiating activity (LDA) in medium conditioned by the LD-1 melanoma, a G-CSF secreting human tumor line. Partially-purified LDA induces HL-60 cells to produce superoxide, become phagocytic, and to develop macrophage-like morphology and surface markers. The LDA markedly suppresses clonal growth in agar of HL-60 cells, and cells of the human myeloid leukemia lines PBL 985 and K562, but does not suppress clonal growth of the B-lymphoblast lines Raji and Daudi. The molecular weight of this material is approx. 40,000 daltons. It can be separated from the bulk of the colony stimulating activity on phenyl sepharose chromatography. The LDA is not neutralized by antibodies to G-CSF, GM-CSF, IFN alpha, IFN gamma, TNF, urokinase, and tissue plasminogen activator, and is not inhibited by preincubation with aprotinin. The LDA in conditioned medium may be different from previously described differentiating factors, and may represent an additional class of human growth regulators.
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PMID:Leukemia-differentiating activity expressed by the human melanoma cell line LD-1. 316 98

The murine IL-3-dependent mast cell line, PT18-A17, and the rat basophilic leukemia cell line, RBL-2H3, were found to mediate natural cytotoxic (NC) activity via the release of a soluble factor which specifically lysed NC-sensitive WEHI-164 but not NK-sensitive YAC-1 tumor cells. The release of this NC cell-specific cytotoxic factor was enhanced by triggering of both types of cells via IgE receptor bridging. This factor had activity on TNF-sensitive but not TNF-resistant cell lines and could be neutralized by two independently produced polyclonal anti-mouse TNF antisera. It was not neutralized by antibodies against mouse IFN-alpha/beta or IFN-gamma. Moreover, it was not neutralized by a monoclonal or a polyclonal anti-human TNF, demonstrating that the rodent TNF differed antigenically from human TNF. These results indicate that the cytotoxic factor released from a murine IL-3-dependent mast cell line and from a rat basophilic leukemia cell line is immunologically and functionally related to murine TNF.
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PMID:Natural cytotoxic cell-specific cytotoxic factor produced by IL-3-dependent basophilic/mast cells. Relationship to TNF. 326 77

In this article, the clinical effects of rH-TNF on various cancer patients and the mechanism of self-induction of defense against rH-TNF cytotoxicity in tumor cells and the counter measures against this are reviewed. 1) Clinical effects of rH-TNF Intratumoral administration of rH-TNF was performed in 7 patients and clinical efficacy (PR + MR) was observed in 3/7 (42.9%). Also a reduction of leukemia cells in peripheral blood was observed in all 4 leukemia patients following intravenous (i.v.) administration of rH-TNF. Furthermore, in 2 multiple myeloma patients, the myeloma protein and plasma cells in bone marrow were reduced by i.v. administration of rH-TNF. 2) Self-induction of defense against rH-TNF cytotoxicity Investigation of the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed that their synthesis in tumor cells was increased at 12 h and peaked at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells, upon addition of Act D or CHI increased the cytotoxic effect of TNF, thus suggesting that the elevated RNA and protein synthesis is related not to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubation of HEL cells with TNF in the presence of either inhibitor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor cells. 3) Combination therapy of rH-TNF with various anticancer drugs. A synergistic increase in the cytotoxic effects of rH-TNF and anti-cancer drugs was demonstrated in vitro The cytotoxicity of rH-TNF against L-M cells in combination with MMC, ADM, Ara-C, ACD, DM, CDDP, VCR and 5-FU was 4 to 347 times as high as that of rH-TNF alone. These results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.
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PMID:[Anti-tumor effect of human recombinant TNF]. 329 72

Cytotoxic activity of recombinant human TNF (rHu-TNF) on various human cell lines was examined in vitro. rHu-TNF exerted a cytostatic effect on various types of human tumor cells such as carcinoma, sarcoma, leukemia, melanoma and other types. When the cytocidal effect was examined on the tumor cells which were cytostatically susceptible to rHu-TNF, the cytocidal effect of rHu-TNF was also noticed on many of these tumor cells. However, some tumor cells were affected cytostatically only. Human diploid cells were not affected cytostatically or cytocidally by rHu-TNF. WI-38 VA13 cells which are an SV-40-transformed derivative of WI-38 diploid cells, were affected both cytostatically and cytocidally by rHu-TNF. These results suggest that rHu-TNF exerts cytostatic and cytocidal effects against a broad spectrum of human tumor cells, and its cytotoxic activity is tumor-specific.
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PMID:Recombinant human tumor necrosis factor--I. Cytotoxic activity in vitro. 352 33

The effects of recombinant human tumor necrosis factor (rH-TNF) on the colony growth of human leukemia progenitor cells (L-CFU), granulocyte-macrophage progenitor cells (CFU-GM), and erythroid progenitor cells (BFU-E) were studied. L-CFU was assayed with leukemia cells obtained from patients with acute myelogenous leukemia. CFU-GM and BFU-E were assayed with bone marrow cells obtained from hematologically normal donors and patients with acute leukemia or non-Hodgkin's lymphoma in complete remission. A dose-dependent growth inhibition of L-CFU as well as CFU-GM and BFU-E was observed by rH-TNF at concentrations of 1 to 100 U/mL. The inhibitory effect on L-CFU was significantly greater than that on CFU-GM. No correlation was observed between the inhibitory effect on L-CFU and the number of colonies formed in the cultures without rH-TNF. Preincubation of the progenitor cells in culture medium containing 20% fetal calf serum with up to 1,000 U/mL of rH-TNF for 24 hours did not result in the inhibition of colony growth of L-CFU or CFU-GM. The inhibitory effect of rH-TNF was neutralized by an anti-rH-TNF murine monoclonal antibody.
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PMID:Effect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cells. 380 62

A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.
Leukemia 1995 Oct
PMID:Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice. 747 25

Binding of circulating cells to endothelium is mediated by recognition between endothelial adhesion molecules and their counter-receptors. The beta 2 integrins are a group of adhesion molecules, mainly expressed on leukocytes, that mediate intercellular binding by recognizing their counterparts on endothelial cells, among others ICAM-1. In this study we have studied the regulation of this interaction in myelomonocytic cells treated with genistein, a tyrosine kinase inhibitor with several other biological functions. We show that genistein upregulates the surface expression of the beta 2-integrins in the monoblastic THP-1 and to a lesser extent in the promyelocytic HL-60 leukemia cell lines. This upregulation leads to an increase in the adherence of THP-1 cells to ICAM-1. Genistein also modulates the expression of ICAM-1 on endothelial cells by potentiating the upregulating effect of TNF and IFN-gamma. Genistein may thus enhance intercellular binding by affecting both the endothelium and the circulating cells.
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PMID:Genistein enhances the ICAM-mediated adhesion by inducing the expression of ICAM-1 and its counter-receptors. 752 Nov 64

The human MONO-MAC-6 cell line expresses the monocyte-associated differentiation markers CD14 and monocyte-specific esterase (MSE) and can be stimulated by lipopolysaccharide (LPS) to produce high mRNA levels of monocyte-related cytokines. This similarity to human peripheral blood monocytes (PBMo) renders this cell line a promising model for studies of monocyte activation and differentiation. Interleukin-4 (IL-4) is known to act antagonistically to LPS during the activation process of PBMo, inhibiting the production of cytokines. Therefore, this study was designed to compare the effects of IL-4 and LPS on the expression of monocytic markers and tumor necrosis factor alpha (TNF alpha) mRNA on PBMo and the MONO-MAC-6 cell line. IL-4 inhibited the LPS-induced expression of TNF alpha mRNA in PBMo and downregulated the LPS receptor CD14 but it had no influence on MONO-MAC-6 cells regarding these parameters. However, upregulation of CD14 and MSE mRNA expression in the cell line by a 2-day incubation with LPS were inhibited by IL-4. This response to IL-4 after long-term treatment with LPS was seemingly contradictory to the missing reduction of TNF alpha mRNA expression after short-term incubation with LPS. Obviously long-term treatment with LPS made the cells responsive to IL-4. The increase in responsiveness was not due to IL-4 receptor (IL-4R) upregulation, as LPS did not influence the constitutive expression of the IL-4R.
Leukemia 1994 Sep
PMID:IL-4 inhibits the LPS-induced expression of CD14 and monocyte-specific esterase mRNA in MONO-MAC-6 cells. 752 93


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