Microarray identifies cyclo-oxygenase-2-dependent modulation of insulin-like growth factor binding protein-3 in non-small cell lung cancer cells.
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Adenocarcinoma↗
Biomedical subjects
S Dubinett
Publications and source records attributed to S Dubinett.
Tolerance and determinant hierarchy.
The overall T cell response to a multideterminant antigen consists of the sum of responses to a limited number of different determinants on the protein. Antigen-presenting cells (APCs) are crucial in delimiting the determinants on the protein to which a response will be mounted. This influence is apparent at two levels. First, the determinants that are generated and displayed by APCs in the thymus are pivotal in shaping the T cell repertoire that will be available for responding to antigen determinants in the periphery. Second, antigen processing affects the selection of determinants that become displayed by the various peripheral APC populations that are involved in inducing and promoting a T cell response. We have studied the effect of the display hierarchy on tolerance induction to individual determinants in transgenic mice expressing different serum levels of hen egg lysozyme. We have also analysed aspects of the processing machinery that contribute to shaping the hierarchy of determinant display on MHC class II molecules: proteolysis and reduction of disulfide bonds.
Amino Acids, Diamino↗
Mononuclear cells and cytokines stimulate gastrin release from canine antral cells in primary culture.
Patients with Helicobacter pylori-associated gastritis have an increased release of gastrin. The mechanisms by which H. pylori affects the endocrine cells are unclear. We have used primary cultures containing canine antral G cells to examine the effects of human blood mononuclear cells, purified monocytes and lymphocytes, recombinant cytokines, and NH4Cl on gastrin release. Mononuclear cells and purified monocytes in direct contact with G cells stimulated gastrin release dose dependently. Separating mononuclear cells from G cells by Transwell filters with 0.4-micron pore size still produced a significant increase of gastrin release. Three human recombinant cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, but not interleukin-6 and interleukin-1 beta, each produced dose-dependent increases of gastrin stimulation. NH4Cl did not stimulate gastrin release. We conclude that mononuclear cells and purified monocytes prepared from human blood, as well as several cytokines, stimulate gastrin release from antral G cells. These factors may play an important role in the pathogenesis of H. pylori-associated hypergastrinemia.
Animals↗
Treatment of patients with advanced cancer using tumor-infiltrating lymphocytes and interleukin 2.
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Humans↗
Tumor-derived interleukin-2-dependent lymphocytes in adoptive immunotherapy of lung cancer.
A trial of adoptive immunotherapy was performed in which long-term cultured, interleukin-2 (IL2)-dependent T-lymphocytes were administered to patients with metastatic adenocarcinoma of the lung. Lymphocytes were isolated from explants of cancer tissues that were cultured in medium with recombinant IL-2. These T-cells expressed surface markers of activation, and killed a broad panel of tumor targets. Intravenously injected 111indium-labeled T-cell blasts distributed primarily to lungs, liver, and spleen. Despite a paucity of infused lymphocytes detected by external imaging at sites of tumor, five of seven patients showed reduction of their cancers. However, in no case was greater than 50% reduction of total tumor burden achieved. Evidence of increased delayed cutaneous hypersensitivity to protein antigens was observed in three patients following therapy. We conclude that long-term cultured tumor-derived T-cells can be transferred safely into humans and that these cells may be capable of enhancing immune responses and mediating tumor reduction in vivo.
Adenocarcinoma↗
A comparison of gene transfer methods in human dendritic cells.
Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for the initiation of antigen-specific T-cell activation. DCs may be highly enriched from peripheral blood-adherent leukocytes by short-term (7-day) culture in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. Various methods of gene transfer were studied, including DNA/liposome complexes, electroporation, CaPO4 precipitation, and recombinant adenovirus (AdV) vectors. Low levels of expression were obtained with the physical methods tested. In contrast, AdV vectors expressing luciferase, beta-galactosidase, IL-2, and IL-7 all readily transduced human DCs. Increasing levels of gene expression were observed over a range of multiplicity of infection (MOI) of 10:1 to 10,000:1, with transduction efficiencies exceeding 95% at higher MOI. Although levels of maximal gene expression in DCs were significantly lower than those obtained using human tumor cell lines, IL-2 and IL-7 production of up to 5 x 10(2) ng/10(6) DC were achieved. These results suggest that AdV vectors are a promising vehicle for genetically engineering human DCs.
Dendritic Cells↗