Search results for "Genetic therapy"
showing 10 items of 121 documents
Gene therapy using IL 12 family members in infection, auto immunity, and cancer.
2009
Interleukin-12 (IL-12) is known for several years to have an essential role in inflammatory responses and innate resistance to infection and cancer. This has been largely attributed to its ability to initiate the differentiation of T-helper-1 (Th1) cells producing interferon-gamma. Recently, two new cytokines, IL-23 and IL-27, with homology to IL-12 were discovered and assigned to the IL-12 family of cytokines. Growing evidence supports a role for IL-23 as key mediator of autoimmune disease regulating the new Th17 subset of CD4+ T cells. IL-27 can have pro- and anti-inflammatory effects, which increase Th1 differentiation, suppress Th2 proliferation, or stimulate cytotoxic T cell activity. …
Allergic contact dermatitis: understanding the immune response and potential for targeted therapy using cytokines.
1997
Allergic contact dermatitis is the most common job-related disease of the western world. The only available treatments are avoidance of contact with the allergen and the use of potent corticosteroids. Recently, the role of cytokines in the pathogenesis of this disease has been studied and, besides defining the key molecules and basic cellular immune responses responsible for disease development, these studies might help to develop new therapeutic strategies to target cytokines and thereby try to alter or abrogate ongoing immune reactions.
The potential of acetaminophen as a prodrug in gene-directed enzyme prodrug therapy.
2000
Acetaminophen is oxidized by human CYP1A2 to the cytotoxic metabolite N-acetylbenzoquinoneimine (NABQI). Incubation of cells transfected with human CYP1A2 (H1A2 MZ cells) with 4-20 mM acetaminophen for 6 hours at 37 degrees C caused extensive cytotoxicity (cell viability10%). In contrast, nontransfected V79 MZ cells were unaffected (viability95%). By mixing H1A2 MZ cells with V79 MZ cells in various proportions and incubating with 4 mM acetaminophen, it was shown that the NABQI released from H1A2 MZ cells also caused cytotoxicity of bystander cells. Thus, in a mixture containing 5% H1A2 MZ cells, exposure to 4 mM acetaminophen for 6 hours resulted in complete cell killing by 24 hours. A sim…
miRNAs and their potential for use against cancer and other diseases
2007
miRNAs are 19–24 nucleotide long noncoding RNAs found in almost all genetically dissected species, including viruses, plants, nematodes, flies, fish, mice and humans. Rapid advances have been made in understanding their physiological functions, while abnormal patterns of miRNA expression have been found in many disease states, most notably human cancer. It is now clear that miRNAs represent a class of genes with a great potential for use in diagnosis, prognosis and therapy. In this review we will focus on the discoveries that elucidate their crucial role in mammalian diseases, particularly in cancer, and propose that miRNA-based gene therapy might become the potential technology of choice …
Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor rnasin.
2001
The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1-2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growth factor. Nevertheless, the administration of the recombinant form of a protein poses several limitations; as a result, we have studied the antitumor effect of RNasin in a murine gene therapy model. RNasin cDNA was subcloned into the pcDNA3 expression vector, and the resulting recombinant plasmid was used to transfect the B16 murine melanoma cell line. An RNasin inverted constr…
Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy
2003
Since neural progenitor cells can engraft stably into brain tumors and differentiate along the neuronal and glial line, we tested the hypothesis that transplanted cytosine deaminase (CD)-expressing ST14A cells (an immortalized neural progenitor cell line) can convert locally 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and produce a regression of glioma tumors. ST14A, retrovirally transduced with the E. coli CD gene, showed a strong bystander effect on glioma cells as assessed by in vitro assay. Intracerebral injection of C6 glioma cells generated a rapidly growing tumoral mass. DiI prelabeled ST14A, coinjected into the rat brain with C6 glioma cells, survived in the tumoral mass up t…
CD83+ human dendritic cells transfected with tumor peptide cDNA by electroporation induce specific T-cell responses: A potential tool for gene immuno…
2000
Dendritic cells (DC) are the most potent immunostimulatory cells, with the capacity to induce primary T-cell responses. Functional autologous DC can be generated from fetal calf serum-free peripheral blood mononuclear cells in the presence of interleukin-4 and granulocyte-macrophage colony-stimulating factor and are stimulated with a defined cytokine cocktail for terminal maturation. We were able to establish a nonviral transfection protocol for these DC by electroporation. Using enhanced green fluorescent protein as a reporter gene, we achieved transfection efficiencies of up to 10%. FACScan analyses revealed a stable phenotype, and the expression of major histocompatibility complex class …
Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of…
2015
Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprote…
MicroRNA-Based Therapeutic Perspectives in Myotonic Dystrophy
2019
Myotonic dystrophy involves two types of chronically debilitating rare neuromuscular diseases: type 1 (DM1) and type 2 (DM2). Both share similarities in molecular cause, clinical signs, and symptoms with DM2 patients usually displaying milder phenotypes. It is well documented that key clinical symptoms in DM are associated with a strong mis-regulation of RNA metabolism observed in patient’s cells. This mis-regulation is triggered by two leading DM-linked events: the sequestration of Muscleblind-like proteins (MBNL) and the mis-regulation of the CUGBP RNA-Binding Protein Elav-Like Family Member 1 (CELF1) that cause significant alterations to their important functions in RNA processing. It ha…
Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 i…
2012
Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) o…