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  • 1
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Ovarian cancer is the leading cause of death from gynecological malignancy and the fourth leading cause of cancer death among American women, yet little is known about its molecular aetiology. Studies using comparative genomic hybridization (CGH) have revealed several regions of recurrent, ...
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] High-density array comparative genomic hybridization (CGH) showed amplification of chromosome 1q22 centered on the RAB25 small GTPase, which is implicated in apical vesicle trafficking, in approximately half of ovarian and breast cancers. RAB25 mRNA levels were selectively ...
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  • 3
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Signaling pathways invoke interplays between forward signaling and feedback to drive robust cellular response. In this study, we address the dynamics of growth factor signaling through profiling of protein phosphorylation and gene expression, demonstrating the presence of a kinetically defined ...
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  • 4
    ISSN: 1534-4681
    Keywords: Ascites ; Vascular endothelial growth factor ; Angiogenesis ; Colon cancer ; Gastric cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. Results: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. Conclusions: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] To the editor: Data integration in life sciences currently faces a conundrum. On the one hand, the diversity of data is increasing as explosively as its volume. This makes it imperative that some degree of data formatting standardization is agreed upon by the diverse community generating and using ...
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  • 6
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Mitogenic lectins such as phytohaemagglutin (PHA) and con-canavalin A, and non-mitogenic lectins such as wheat germ agglutinin, lead to a rapid rise in [Ca2+]i even when there is no proliferative response9, and this hampers attempts to evaluate the requirement for an increase in [Ca2"^ in the ...
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  • 7
    ISSN: 1573-2592
    Keywords: T-cell ontogeny ; suppressor/helper cells ; thymic hormone ; interleukin 2 (IL2) ; severe combined immunodeficiency disease (SCID)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study of human bone marrow lymphocytes, we analyze a newly recognized population of T suppressor-cell precursors which are found in marrow only and which have the potential to inhibit immunoglobulin (Ig) productionin vitro. Following exposure to interleukin 2 (IL2), suppressor precursors acquire E receptor, T3 determinants, suppressor function, and lectin responsiveness. To distinguish this population within the framework of T-cell ontogeny, it was compared to a previously described population of thymus-dependent helper T-cell precursors which express helper function following exposure to thymus-derived mediators. The two populations are completely distinct and can be separated on density gradients. Suppressor precursors expressed T8 and TAC (IL2-receptor) antigens prior toin vitro induction with IL2. The thymic hormone-dependent cells expressed T4 but not T8 or TAC determinants. In two patients with severe combined immunodeficiency disease (SCID), IL2-responsive precursor cells appeared only late after thymus epithelium transplantation, perhaps best explained by a model in which thymus-dependent differentiation pathways precede, induce, or seed pathways of extrathymic T-cell differentiation. The large pool size of over 1011 suppressor and helper precursor cells present in adult bone marrow suggests that these populations may play an important role in immune homeostasis.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 141 (1989), S. 310-317 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Activation of T-lymphocytes by antigen, mitogenic lectins, or antibodies against the T-cell receptor complex, particularly in the presence of IL1, induces the secretion of the T-cell growth factor IL2. IL2 then has a major role in regulating the duration and magnitude of the immune response. Interaction of antigen, antibodies against the T-cell receptor complex, or mitogenic lectins with T-lymphocytes also induces hydrolysis of membrane phospholipids, leading to the production of diacylglycerol, an activator of the Ca2+- and phospholipid-dependent phosphotransferase, protein kinase C (PKC). Phorbol esters, potent activators of PKC, augment secretion of the T-cell growth factor, interleukin 2 (IL2). Activation of PKC may therefore serve as an important early event in the production and secretion of IL2. We have determined whether IL2 secretion can be induced in the murine cell T-lymphocyte line LBRM 331A5, where PKC is inhibited by staurosporine or sphingosine or in cells where PKC is depleted by prolonged incubation with high concentrations of phorbol esters. In cells in which PKC was either inhibited or depleted, antibodies against the T3 portion of the T-cell receptor complex and the mitogenic lectin phytohemagglutinin (PHA) still triggered IL2 secretion. In addition, the monokine Ill augmented this IL2 secretion irrespective of whether PKC was inhibited or depleted. These data indicate that activation of PKC is not an obligatory step for IL2 secretion in LBRM 331A5 murine T-lymphocytes.
    Additional Material: 1 Ill.
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  • 9
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We studied the effects of recombinant, interferon, 12-O-tetradecanoylphorbol13-acetate (TPA), and phorbol 12,13 dibutyrate (PDB) on surface immunoglobulin expression by Daudi cells. Incubation of cells with recombinant alpha2interferon (IFN-α2) caused a 2.5-fold (60%) decrease in slgM expression as measured by relative fluorescence index (RFI) using a flow cytometer. This decrease in slgM expression was independent of inhibitory effects on proliferation and cell cycle progression. TPA or PDB also caused a threefold (67%) decrease in slgM expression, while enhancing proliferation and cell cycle progression. Coincubation of cells with IFN-α2 or TPA decreased slgM expression by more than fourfold (〉75%), which was greater than the decrease induced by the optimal concentration of either agent alone. Molecular studies demonstrated that the treatment of cells with IFN-α2 or TPA decreased the steady-state levels of mRNA for the heavy chain of IgM (cμ), suggesting that down-regulation of slgM occurred at a pretranslational level. Activation of the cell membrane sodium/proton antiport did not play an integral role in the IFN-α2 or phorbol-ester-induced pathway of slgM down-regulation. Whereas IFN-α2 induced an increase in the activity of 2′,5′-oligoadenylate (2-5A) synthetase, the addition of TPA to IFN-α2 caused a significant decrease in the activity of this enzyme. Although IFN-α2 and TPA exhibited additive effects on slgM expression, they had opposing effects on cell proliferation, cell cycle progression, and induction of 2-5A synthetase activity, suggesting that these agents down-regulate slgM expression through independent pathways.
    Additional Material: 4 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 137 (1988), S. 329-336 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have investigated the induction of competence (IL-2 responsiveness) and progression in human T lymphocyte proliferation triggered by phorbol ester and calcium ionophore. The degree of proliferation induced with the phorbol ester, phorbol 12,13-dibutyrate (PDB) and the calcium ionophore ionomycin was dependent on the duration of exposure to these agents, with more than 6 h required for obtaining maximum proliferation. Following brief exposure to both agents for 30 min, which did not cause significant proliferation, T cells became competent to proliferate in response to exogenous interleukin 2 (IL-2). These competent T cells also progressed to DNA synthesis following incubation with PDB in the absence of ionomycin. Induction of competence to proliferate in response to either PDB or IL-2 was blocked by EGTA, suggesting that transmembrane Ca2+ flux was obligatory at this stage. Since other phorbol esters and synthetic diacylglycerols also stimulated DNA synthesis in competent cells, it is likely that progression was triggered by activation of protein kinase C. Following a brief exposure to PDB and ionomycin, subsequent incubation with PDB induced gene expression and secretion of IL-2 and augmented the expression of IL-2 receptors in the competent cells. Thus, we have demonstrated that Ca2+ mobilization is required for rendering T cells competent to express functional IL-2 receptors, to produce IL-2 in response to subsequent incubation with PDB, and that sustained activation of protein kinase C seems necessary for IL-2 production and subsequent progression of competent T cells to DNA synthesis.
    Additional Material: 4 Ill.
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