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)

We investigated if deguelin, a naturally occurring rotenoid, was able to inhibit nuclear factor kappa B (NF-kappaB)-binding protein (IkappaBalpha) expression and to induce apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells in vitro. Deguelin-induced cell death in the majority of B-CLL cells and was found to be more toxic toward B-CLL cells than to the normal mononuclear or B-cells, suggesting selectivity towards the malignant cells. Deguelin was found to reduce IkappaBalpha protein expression, and thus interacts with the NFkappaB pathway. The induced apoptosis was characterized by processing of caspase-9 and -3 and poly-(ADP)-ribose-polymerase cleavage. Exposure of B-CLL cells to deguelin resulted in Bcl2-associated protein (Bax) conformational changes and downregulation of the key survival protein myeloid cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. Deguelin retained its ability to induce apoptosis in B-CLL cells in the presence of interleukin-4, a pro-survival cytokine in B-CLL, and when cultured with 50% human serum. These data indicate that deguelin is able to induce apoptosis in B-CLL cells in the presence of pro-survival signals and thus merits further investigation for clinical application either as a single agent or in combination with other anticancer agents.
Leukemia 2007 Aug
PMID:Deguelin inhibits expression of IkappaBalpha protein and induces apoptosis of B-CLL cells in vitro. 1756 18

Virus-like particles (VLPs) represent a promising vaccine against severe acute respiratory syndrome coronavirus (SARS CoV). In this study, recombinant baculovirus vAcS and vAcME were constructed to express the S protein and the M and E proteins of SARS CoV, respectively. Electron microscope analysis demonstrated the formation of VLPs in vAcME and vAcS coinfected insect cells. Mice immunized four times with VLPs developed high antibody titres against SARS CoV. In addition, VLPs elicited cell-mediated immunity as demonstrated by enhanced interferon-gamma and interleukin-4 production. VLPs also conferred protective immunity against the infection of Spike protein pseudotyped murine leukaemia virus. Our findings demonstrate that SARS CoV VLPs are immunogenic and can elicit strong SARS CoV-specific humoral and cellular immune responses in mice. This is the first study describing the immunogenicity of SARS CoV VLPs, providing valuable data for developing a protective vaccine against SARS CoV infection.
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PMID:Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice. 1768 Jul 99

DeltaNp73alpha, the N-terminal truncated form of p73alpha is a candidate tumor antigen because of its selective expression in many human cancers and lack of expression in normal tissues. Therefore, we investigated the effects of dendritic cells infected with adenoviral DeltaNp73alpha (DNp73alpha) on breaking immune tolerance and induction of immunity against DNp73alpha-expressing (A549 lung cancer, K-562 leukemia) and non-expressing (MCF-7 breast cancer) cell lines. Immature dendritic cells generated in the presence of interleukin-4 and granulocyte/macrophage colony-stimulating factor from a human umbilical cord blood were transduced with a recombinant adenoviral (Ad) vector encoding full-length human DNp73alpha cDNA (Ad-DNp73alpha) or a control vector Ad-EGFP, using the centrifugal force method. Induction of DNp73alpha-specific CTL response was evaluated by a cytotoxic assay against the three human tumor cell lines with different DNp73alpha expression levels. The viability and activation status of transduced dendritic cells were assessed by flow cytometry. The dendrocyte/Ad-DNp73alpha-activated cytotoxic T lymphocytes showed significantly higher cytotoxicity against the cell lines A549/DNp73alpha, K-562 that expressed DNp73alpha than the DNp73alpha-null MCF-7 cells. The DCs/Ad-DNp73alpha showed higher survival rates than the DCs/Ad-EGFP or untransduced DCs, presumably due to the inhibition of cell death. These findings, with potential applications for immunotherapy, demonstrate that dendrocytes transduced with Ad-DNp73alpha can induce specific and sustained T cell responses against tumors expressing this variant p53-related gene.
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PMID:In vitro antitumor cytotoxic T lymphocyte response induced by dendritic cells transduced with DeltaNp73alpha recombinant adenovirus. 1791 57

Tunisian olive oils have been traditionally used as a medicinal food for chronic inflammation. To investigate the antiallergic effect of virgin olive oil samples from five principal olive varieties grown in various regions of Tunisia, we used the type I allergy reaction model using rat basophilic leukemia (RBL-2H3) cells and different dilutions of olive oil samples to determine beta-hexosaminidase release inhibition at two different response stages. Results showed that the Sayali olive oil significantly inhibited beta-hexosaminidase release by the IgE antibody-sensitized, BSA antigen-stimulated RBL-2H3 cells at the antibody-antigen binding stage. The result of our experiment shows that the anti-allergic effect of olive oil at this binding stage may be dependent on their flavone content. The Zarrazi olive oil significantly inhibited beta-hexosaminidase release at the antigen-receptor binding stage. Moreover, we investigated the effect of olive oil samples on histamine release and production of cytokines by activated human basophilic (KU812) cells. Different dilutions of Sayali olive oil dose-dependently inhibited the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4), and different dilutions of Zarrazi olive oil dose-dependently inhibited histamine release and IL-4 production by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA)-stimulated KU812 cells.
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PMID:Inhibitory effect of various Tunisian olive oils on chemical mediator release and cytokine production by basophilic cells. 1817 46

The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-alpha, interleukin-4, tumor necrosis factor-alpha (TNF-alpha), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-alpha with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-alpha enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-alpha in combination with DMSO on HL-60 differentiation, but the inhibition NF-kappaB pathway did not. These results suggest that TNF-alpha synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway.
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PMID:Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway. 1825 85

Cancer immunotherapy using heat shock protein (HSP) derived from autologous tumor requires cluster of differentiation (CD)4(+) as well as CD8(+) T-cells for the prolongation of patient survival, suggesting that a humoral immune response through CD4(+) T-cells is important in addition to cellular immunity. However, the role of humoral responses in HSP-based autologous tumor immunotherapy remains unclear. In the present study, we investigated whether leukemia-specific antibodies and antibody-mediated cytotoxicity against autologous leukemia cells have a crucial role in a mouse A20 leukemia model by immunizing A20-derived HSP70. Immunization with A20-derived HSP70 induced the production of anti-A20-antibodies and the antibodies recognized HSP70-binding peptides derived from A20. One of those was a major histocompatibility complex (MHC) class-I binding peptide, which has been clarified as the target peptide of CD8+ cytotoxic T-cells (CTL) against A20. The anti-A20-antibodies produced by immunization with A20-derived HSP70 induced complement-dependent cytotoxicity (CDC) against A20 in vitro. In addition, immunization with A20-derived HSP70 increased intracellular interleukin-4 (IL4)-production of CD4(+) T-cells, confirming the activation of type-2 helper T-cells. Taken together, immunization with leukemia-cell-derived HSP70 induces antibodies against leukemia-cell-specific peptides and might play a crucial role in the eradication of leukemia cells by CDC in mice. These findings will enable future establishment of a novel therapeutic strategy using antileukemia antibodies in HSP-based autologous tumor immunotherapy.
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PMID:Induction of leukemia-specific antibodies by immunotherapy with leukemia-cell-derived heat shock protein 70. 1845 62

Treatment of acute myeloid leukaemia (AML) cells with differentiation agents leads not only to the acquisition of normal phenotypes but also contributes to the understanding of special immuno-haematology issues. For instance, induction of HLA-DR antigens on human promyelocytic leukaemia HL-60 cells by interleukin-4 (IL-4) is of pivotal importance in immunology not only because class II expression is prerequisite to antigen recognition and response but also because IL-4 participates in a plethora of inflammatory or non-inflammatory reactions. At the same time, the same observation coupled with an increase in Mac-1, mature monocyte marker, is revealing ways to haematologists for converting malignant cases to normal situations. Based on previous reports that HLA-DR induction by IL-4 in the HL-60 system is mediated via the G-protein system (p21(ras)), this study was undertaken in order to define the intermediate signalling steps followed by this agent from the moment it is added to cultures to the differentiated cellular form obtained. It is proposed that IL-4 increases p21(ras) which in turn suppresses the HL-60 cells' p34(cdc2) constitutive expression. This inhibition appears to be responsible for the subsequently.observed cessation ofgrowth. Concomitant to decreased cellular proliferation, HI-DR antigen expression increases, a finding that matches the initially mentioned induction of p21(ras) since its inhibition abolishes HI-DR upregulation.
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PMID:Analysis of Signals Leading to Differentiation of Immature HL-60 after Administration of IL-4. 1847 89

The involvement of adult T-cell leukemia (ATL) cells in organs such as the skin and lymph nodes is observed in about 50% of cases of ATL. Epstein-Barr virus (EBV) infection has often been observed in the clinical course of ATL. In this study, we established two B-cell lines from peripheral blood of patients with ATL. EBV DNA, proviral DNA for HTLV-1 and Tax mRNA were detected in both lines. As part of the characterization of these cells, an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) or ICAM-3 (ICAM-3) (CD50), lymphocyte function-1 (LFA-1) (CD11a/CD18), and Mac-1 (CD11b/CD18) was observed. To investigate the role of the interaction of these viruses, we transfected EBV and/or HTLV-1 into a healthy donor's lymphocytes, an EBV-infected B cell line, Raji, and a HTLV-1 negative T-cell line, Jurkat. Enhanced expression of adhesion molecules was also observed in double transfectants (EBV and HTLV-1). In the clinical course of ATL, LMP-1, EBNA-2, CD50 and CD54 were detected in lymph nodes and skin specimens by immunohistochemical staining. Furthermore, high levels of interleukin-4 (IL-4) were detected in these cell lines and transfectants. The results indicated that coinfection with HTLV-1 and EBV may induce aggressive organ involvement through the enhanced expression of adhesion molecules via IL-4 signaling. A new mechanism of ATL involvement is discussed.
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PMID:Influence of Epstein-Barr virus infection in adult T-cell leukemia. 1870 73

Human T lymphotropic virus-type 1 (HTLV-1) is the causal agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T cell leukaemia/lymphoma and infective dermatitis associated with HTLV-1 (IDH). Over-production of proinflammatory cytokines and an increase in HTLV-1 proviral load are features of HAM/TSP, but the immunological basis of IDH has not been established. In addition to severe cutaneous manifestations, the importance of IDH relies on the observation that up to 30% of children with IDH develop HAM/TSP in childhood and adolescence. In this study we determined the immune response in patients with IDH measuring interleukin (IL)-4, IL-5, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha levels as well as the HTLV-1 proviral load. Additionally, regulatory cytokines and anti-cytokines were added to cultures to evaluate the ability of these molecules to down-modulate TNF-alpha and IFN-gamma synthesis. HTLV-1 carriers and patients with HAM/TSP served as controls. TNF-alpha and IFN-gamma levels were higher in IDH than in HTLV-1 carriers. There was no difference in IFN-gamma and TNF-alpha concentrations in IDH and HAM/TSP patients. There was a tendency for higher IL-4 mRNA expression and immunoglobulin E (IgE) levels in IDH than in HTLV-1 carriers, but the difference did not reach statistical significance. The HTLV-1 proviral load was significantly higher in IDH patients than in HTLV-1 carriers. IDH is characterized by an exaggerated Th1 immune response and high HTLV-1 proviral load. The similarities between the immunological response in patients with IDH and HAM/TSP and the high proviral load observed in IDH provide support that IDH is a risk factor for development of HAM/TSP.
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PMID:Infective dermatitis has similar immunological features to human T lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis. 1943 98

The aim of this study was to investigate the activation ability of CpG oligodeoxynucleotide (CpG ODN) 2216 on the peripheral blood mononuclear cells (PBMNCs) from leukemia patients in remission and the killing effect of activated PBMNCs on K562 cells. PBMNCs obtained from leukemia patients in remission were incubated with CpG ODN 2216. In control group, PBMNCs were incubated with normal saline (NS). The concentrations of cytokines (IFN-gamma, interleukin-12, interleukin-4, interleukin-10) in culture supernatant of PBMNCs from leukemia patients in remission were analyzed by using ELISA kits. The percentages of Th1, Tc1, Th2, Tc2 cells and killed K562 cells were detected by flow cytometry. The results showed that as compared with control group, CpG ODN 2216 induced higher concentrations production of IFN-gamma, IL-12 in supernatant (p < 0.01). There were no differences in IL-4, IL-10 in supernatant as compared with control group (p > 0.05). The percentages of Th1 and Tc1 cells increased significantly after culture with CpG ODN 2216 as compared with control group (p < 0.05). There was no difference between the percentages of Th2 and Tc2 cells in stimulated group and control group. The killing effect of PBMNCs on K562 cells was significantly different between the stimulated group and control group (p < 0.05). It is concluded that CpG ODNs 2216 can induce strong Th1-like immune activation, with the secretion of type-I cytokine and activation of strong CD8(+) T-cell responses. PBMNCs activated by CpG ODNs can more strongly kill k562 cells in vitro.
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PMID:[Activation ability of CpG ODNs 2216 on PBMNCs from leukemia patients in remission and killing effect of activated PBMNCs on K562 cells]. 1969 20


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