Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differentiation therapy for acute promyelocytic leukemia (APL) using all-trans-retinoic acid (ATRA) has improved the prognosis of the disease. ATRA therapy also causes a newly recognized clinical syndrome, the "retinoic acid syndrome" (RAS), which can be successfully managed with dexamethasone. Because aberrant function of maturing leukemic granulocytes may cause this syndrome, and because dexamethasone is useful clinically, we studied functional properties of maturing HL60 cells cultured in the presence and absence of dexamethasone. HL60 cells were cultured for 4 days with ATRA and studied daily to determine acquisition of mature neutrophil-like properties including phagocytosis, NBT reduction, actin polymerization, chemotaxis and adhesion molecule expression. Undifferentiated HL60 cells could not polymerize actin or reduce NBT, and exhibited only a minimal ability to undergo chemotaxis or ingest latex beads. Following 4 days of maturation with ATRA, the cells would increase F-actin content in response to interleukin-8, ingest latex beads, migrate in a chemotaxis chamber, reduce NBT, and express CD11b. When dexamethasone was added to the cells in culture, there was no major enhancement or suppression of these properties. We also studied the effect of dexamethasone on functional properties of normal neutrophils and found minimal if any effect on their function. Overall, these studies suggest that in vitro, dexamethasone has little effect on the function of leukemic and normal granulocytes. To further investigate the pathophysiology of the retinoic acid syndrome, future studies may need to use endothelial cells, cytokines, or granulocytes obtained from APL patients.
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PMID:The effect of dexamethasone on functional properties of HL60 cells during all-trans retinoic acid induced differentiation. Are there implications for the retinoic acid syndrome? 893 54

Various mechanisms of epithelial cell plasticity in morphogenesis have been studied at the genetic and molecular levels. Several control genes have been identified including genes encoding transcription factors and growth factor receptors. These mechanisms may be reactivated during the progression of carcinomas. One of the mechanisms underlying epithelial plasticity is the epithelial-mesenchymal transition. This process has been extensively studied using the NBT-II bladder carcinoma cell line. Cells of this line undergo a reversible transition following exposure to several growth factors including FGF-1, EGF, TGFalpha and SF/HGF, which activate tyrosine kinase surface receptors. Two separate transduction pathways have been identified. The transient activation of c-Src is involved in cytoskeleton remodeling whereas the Ras pathway controls the transcription of genes such as the transcription factor Slug which is involved in the internalization of desmosomes. These two pathways cooperate to induce the morphological transition, scattering and locomotion of fibroblast-like cells. Growth/scatter factor-producing NBT-II cells are more invasive than cells that do not contain this factor, in orthotopic confrontation assay. In vivo, these cells are very tumorigenic and may confer a more malignant phenotype on parental cells via a community effect. The role of several growth factors and their receptors has been investigated in human bladder carcinomas. A subset of these tumors with poor outcomes produce low levels of FGFR2-IIIb. The synthesis of this receptor de novo in bladder cell lines reduces proliferation in vitro and tumor growth in nude mice. FGFR2-IIIb functions as a tumor suppressor, consistent with the differentiation-inducing capacities of FGF receptors in the suprabasal cells of the skin. FGFR2-IIIb signaling may be involved in the maintenance of E-cadherin, the prototype epithelial adhesion molecule, which is only downregulated in a fraction of tumors with low FGFR2-IIIb synthesis. Human bladder tumors may also activate autocrine loops such as that for EGFR and their ligands, as already demonstrated for murine bladder tumors. Therefore, our results suggest that multifunctional growth factors and their receptors are involved in cell proliferation and epithelial cell plasticity, acting either as positive or negative regulators of tumor progression. The effect on the morphological transition is also clearly relevant to the mechanism governing dissemination and the formation of micrometastatic tumor cells. The extrapolation of these discoveries to human carcinomas should provide markers facilitating the more accurate prediction of the biological behavior of a given tumor and identify clinically and pathologically significant parameters. The identification of critical changes in the growth factor pathways involved in tumor progression will not only provide insight into the genetic and molecular basis of this process, but should also identify targets for new therapies.
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PMID:Epithelial cell plasticity in development and tumor progression. 1050 44

Contact hypersensitivity (CHS) reaction is a classic example of a cell-mediated reaction. As the afferent phase of the reaction includes inflammation, CHS is a suitable model for investigating non-specific immunity. Some aspects of granulocyte activity in the afferent phase of experimentally induced CHS to dinitrochlorobenzene (DNCB) in two genetically different rat strains, AO and DA were examined in this study. A shift in the ratio of granulocytes to lymphocytes in favour of granulocytes and an increase in granulocyte survival were noted in DA rats. Granulocytes from both strains demonstrated increased levels of NBT reduction and an increase in their adhesion to plastic. Decreased granulocyte adhesion in the presence of monoclonal antibodies to beta2 integrins (anti-CD11b/c and anti-CD18) points to the contribution of these molecules to granulocyte adhesiveness during the sensitization phase of CHS. Stimulation of adhesion in the presence of anti-CD11a antibody, points to a differential modulation of adhesion molecule activity during the afferent phase of CHS. Changes in functional activity of granulocytes demonstrated in this study might contribute to the development of CHS in rats.
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PMID:Peripheral blood granulocyte activity following contact sensitization of rats with dinitrochlorobenzene. 1133 11