Search results for "Cytotoxic"
showing 10 items of 1673 documents
CD8 T-Cell Immunotherapy of Cytomegalovirus Disease in the Murine Model
2010
Publisher Summary Cytomegaloviruses (CMVs) are conditional pathogens that are strictly species specific and are usually well controlled in their respective mammalian hosts by the effector mechanisms of both innate and adaptive immunity. Human CMV (hCMV) is mostly acquired perinatally as well as in early childhood and is transmitted, for instance, through breast milk and saliva. Whilst the immune response in an immunocompetent host prevents an overt CMV disease and rapidly terminates the productive acute infection, viral genome is maintained in most tissues for the life span of the infected host in a state known as viral latency. Latency implies that infectious virions are no longer produced…
T cell receptor Vβ chain restriction and preferred CDR3 motifs of liver-kidney microsomal antigen (LKM-1)-reactive T cells from autoimmune hepatitis …
2001
Aims/Background : The liver-kidney-microsomal antigen (LKM-1) has been recognized as a major CD4 + T cell antigen in autoimmune hepatitis (AIH). The aim of this study was to characterize the antigen recognition sites of the variable T cell receptor β-chain (TCRBV) of T cells specific to LKM-1. Methods: By repeated stimulation of T cells with a recombinant LKM-1 antigen or an LKM-derived peptide followed by limited dilution, we generated T cell clones. Usage of TCRBV was analyzed by RT-PCR and CDR3 antigen recognition sites were sequenced. Results: The 18 LKM-1 specific T cell clones isolated from six AIH patients preferentially expressed the TCR elements BV9, BV5S2+S3, BV6, and BV13S1. Four…
Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B
1991
Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon…
Apoptosis induced by (E)-5-(2-bromovinyl)-2'-deoxyuridine in varicella zoster virus thymidine kinase-expressing cells is driven by activation of c-Ju…
2003
The molecular mode of cell killing by the antiviral drug (E)-5-(2-bromovinyl-2'-deoxyuridine (BVDU) was studied in Chinese hamster ovary (CHO) cells stably transfected with the thymidine kinase gene (tk) of varicella zoster virus (CHO-VZVtk). The colony-forming ability of the cells was reduced to <1% at a concentration of approximately 1 microM BVDU, whereas for nontransfected cells or cells transfected with tk gene of herpes simplex virus type 1 (CHO-HSVtk), a 1000-fold higher dose was required to achieve the same response. BVDU inhibited thymidylate synthase in CHO-VZVtk but not in CHO-HSVtk and control cells. On the other hand, the drug was incorporated into DNA of VZVtk- and HSVtk-expre…
Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell–engrafted NOD/SCID/IL-2Rγcnull mice
2013
Current strategies in cellular immunotherapy of cancer and viral infections include the adoptive transfer of T cell receptor (TCR) and chimeric antigen receptor engineered T cells. When using transient RNA expression systems in clinical studies, multiple infusions with receptor-redirected T cells appear necessary. However, in allogeneic hematopoietic stem-cell transplantation, repeated transfer of donor-derived T cells increases the risk of alloreactive graft-versus-host disease. We investigated naive-derived (T N ), memory-derived (T M ), and Epstein Barr virus-specific (T EBV ) CD8 + T cell subsets for alloreactivity upon redirection with RNA encoding a cytomegalovirus-specific model TCR.…
Epidermal IL-17A leads to bone loss through inhibition of osteoblast differentiation
2012
The AP-1 transcription factor family is a central regulator of skin and bone homeostasis. We have previously shown that specific deletion of JunB/AP-1 in epidermis (JunBmice) results in skin inflammation,myeloproliferative disease, lupus-like disease and osteopenia. While upregulation of serum IL-6 and G-CSF are observed in this model, genetic deletion of these cytokines does not rescue osteopenia in JunB mice. Thus, we carried out a screen for other cytokines that are regulated by the loss of JunB in the epidermis. We have identified IL-17A as a cytokine expressed in JunB epidermis in vivo, and hypothesize that IL-17A leads to osteopenia in JunBmice. To test this,we carried out osteoblast …
Apoptosis and cell growth arrest in A375 human melanoma cells by diorganotin(IV) and triorganotin(IV) complexes of [meso-Tetra(4-sulfonatophenyl)porp…
2011
In previous studies we have demonstrated that two derivatives of meso-Tetra(4-sulfonatophenyl)porphine (TPPS), (Bu2Sn)2TPPS and (Bu3Sn)4TPPS, cause apoptotic death of A375 melanoma cells and, at lower concentrations, arrest of cell proliferation. In the present study, we examined if the manganese metal inside the porphyrin cavity could improve the efficacy of this class of compounds. Thus, [meso- Tetra(4-sulfonatophenyl)porphine]Mn(III)Cl (=MnTPPS) derivatives, namely (Me2Sn)2MnTPPS, (Bu2Sn)2MnTPPS, (Me3Sn)4MnTPPS and (Bu3Sn)4MnTPPS, were tested on the A375 human melanoma cell line. A cytotoxicity assay showed that (Bu2Sn)2MnTPPS and (Bu3Sn)4MnTPPS were highly cytotoxic by inducing apoptosi…
Abstract 3056: Lung tumor spheres as in vitro platform for testing new therapeutic strategies against cancer stem cells
2018
Abstract Background: Treatment resistance is related to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells capable of growing and forming tumor spheres under non-adherent conditions. This study aimed to isolate and characterise CSCs from resected non-small cell lung cancer (NSCLC) patients' tumor-tissue and cell lines like tumor spheres and to use them as an in vitro platform for drug screening. Methods: The study was performed on tumour cells from 8 resected NSCLC patients and 12 NSCLC cell lines grown in monolayer and as spheres. The expression of 60 genes, including CSC-markers, pluripotency inducers, cell cycle regulators and components of the Notch, Wnt and Hedgehog …
Cytotoxicity of the bisphenolic honokiol from Magnolia officinalis against multiple drug-resistant tumor cells as determined by pharmacogenomics and …
2014
A main problem in oncology is the development of drug-resistance. Some plant-derived lignans are established in cancer therapy, e.g. the semisynthetic epipodophyllotoxins etoposide and teniposide. Their activity is, unfortunately, hampered by the ATP-binding cassette (ABC) efflux transporter, P-glycoprotein. Here, we investigated the bisphenolic honokiol derived from Magnolia officinalis. P-glycoprotein-overexpressing CEM/ADR5000 cells were not cross-resistant to honokiol, but MDA-MB-231 BRCP cells transfected with another ABC-transporter, BCRP, revealed 3-fold resistance. Further drug resistance mechanisms analyzed study was the tumor suppressor TP53 and the epidermal growth factor recepto…
Toxic and enzymatic activities of Vibrio vulnificus biotype 2 with respect to host specificity
1996
In this work, the enzymatic activities of selected strains of biotypes 1 and 2 of Vabrio vulnificus were analyzed by using conventional methods and the API ZYM system. The toxic activities of extracellular products (ECPs) were further evaluated by in vitro and in vivo experiments. The ECPs of both biotypes (i) showed high-level hydrolytic activities, (ii) displayed cytotoxicity for fish cell lines, and (iii) were lethal for eels. Exotoxins seem to be proteinaceous since heat treatment of ECP samples destroyed their toxicity. Only biotype 2 strains were virulent for cels, suggesting that host specificity must be related to differences in cell surface properties. Infectivity trials with other…