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  • 1
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  The angiogenic mediator vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been studied extensively in neoplastic disease and some inflammatory conditions. Contact hypersensitivity (CHS) is a prototypic Langerhans' cell-dependent, T-helper (Th) 1 cell-mediated inflammatory skin disease that is now also thought to involve angiogenic mediators. The purpose of our study was to examine the role of angiogenesis and VEGF in CHS. We demonstrated that VEGF production is up-regulated in murine skin after challenge with dinitrofluorobenzene. Administration of a monoclonal antibody directed against the VEGFR-2 (DC101) resulted in a 28.8% decrease in CHS response (P 〈 0.001). Examination of the DC101-treated mouse skin 24 h after challenge revealed decreases in dermal inflammatory cellular infiltrates and total vessel area. Furthermore, mRNA and protein of the Th1-type cytokine interferon (IFN)-γ was significantly down-regulated in skin of DC101-treated animals 24 h after challenge. The results of the study demonstrate that VEGFR-2 blockade significantly reduces vascular enlargement and edema formation and effects IFN-γ expression in the skin during challenge in CHS. Our findings suggest that DC101 could function by reducing inflammatory cell migration and hence IFN-γ expression during the CHS response.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 3 (1997), S. 1083-1084 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] RESEARCH ON TUMOR angiogenesis, which began in earnest 25 years ago, is hot news. This was not the case until relatively recently, so why the big change? The answer can be traced to the discovery and molecular characterization of a diverse family of regulators of angiogenesis, both stimulators and ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] A low proliferating fraction in solid tumors limits the effectiveness of cell cycle–dependent chemotherapeutic agents. To understand the molecular basis of such “kinetic” resistance we cultured tumor cells as multicellular spheroids and examined levels of p27 kip1 , a ...
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 259 (1976), S. 226-228 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] MACROPHAGES can have critical roles in repair, inflammation and a large variety of immunological phenomena1'2. The biological roles of these cells often occur subsequent to their 'activation', a subjective term which refers to a greatly heightened state of reactivity1'3. Activation can be induced ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 280 (1979), S. 358-360 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE concept of 'tumour progression', coined some 25 years ago by Leslie Foulds, has stood the test of time. Its importance cannot be overestimated: to understand tumour progression is to understand why cancer is such a frustratingly difficult disease to treat. Simply stated, tumour progression is ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 438 (2005), S. 967-974 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Inhibiting angiogenesis is a promising strategy for treatment of cancer and several other disorders, including age-related macular degeneration. Major progress towards a treatment has been achieved over the past few years, and the first antiangiogenic agents have been recently approved for use in ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 390 (1997), S. 335-336 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The relentless growth of tumours depends on a good blood supply, and thus on subverting host mechanisms for making blood vessels. Attack on that process provides a promising route for treating cancer, but one that may take some years to reach clinical fruition. Dozens of drugs are used ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0851
    Keywords: Human melanoma cells ; Recombinant interferons ; Growth suppression ; Differentiation ; Antigenic phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of interferon as a single therapeutic regimen in cancer patients with various neoplasias has had only limited efficacy in ameliorating the negative clinical course of their disease. In the present study, we have evaluated the effect of recombinant human fibroblast (IFNβ) and immune (IFNγ) interferon, alone and in combination, on growth, differentiation and the expression of class I and II histocompatibility locus antigens (HLA) and melanoma-associated antigens on the human melanoma cell line H0-1. The effect of combinations of interferons on the antigenic profile of human melanoma cells displaying different organ colonization and spontaneous metastatic potential in athymic nude mice was also determined. H0-1 cells were more sensitive to the antiproliferative activity of IFNβ than to IFNγ and the combination of interferons resulted in a potentiation of growth suppression. The antiproliferative effect of both interferons was greater in later-passage than in earlier-passage H0-1 cells, possibly reflecting alterations in the evolving tumor cell population as a result of long-term in vitro propagation and/or the selective outgrowth of cells with an increased growth rate. The enhanced growth suppression observed in H0-1 cells treated with the combination of IFNβ plus IFNγ was not associated with a significant increase in the level of melanin, a marker of melanoma differentiation, above that observed with either interferon used alone. IFNβ and IFNγ differentially modulated the expression of class I and II HLA and melanoma-associated antigens in H0-1 cells and a series of melanoma cells with different organ colonization and metastatic potential, including MeWo, MeM 50-10, MeM 50-17, 3S5 and 70W. No consistent potentiation or antagonism in the expression of any specific antigen was observed in any of the melanoma cell lines exposed to the combination of interferons. The present study demonstrates that the combination of IFNβ plus IFNγ can potentiate growth suppression in H0-1 human melanoma cells and that this effect is not associated with an increase in differentiation or a potentiation in antigenic modulation. In addition, no direct correlation between the expression of any specific antigen or its modulation by IFNβ or IFNγ, alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7233
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A novel model of tumor progression in metastatic cancer is described which grew out of attempts to derive stable non-metastatic variants from a highly metastatic mouse tumor called MDAY-D2. The variants were obtained by selection of so-called lectin-resistant (LecR) membrane mutants using toxic concentrations of wheat germ agglutinin (WGA) as the selective agent, after mutagenesis. Cloned WGAR variants almost all appeared to be highly tumorigenic and metastatic, but displayed altered growth properties which were highly suggestive of major cellular phenotypic alterations occurring prior to metastasis. This were confirmed with the discovery that spontaneous visceral metastases always consisted of WGA-sensitive (WGAS) ‘revertant’ tumor cells. Such revertants also arose at the site of the subcutaneous inoculation and, with time, comprised an increasing proportion of the tumor cells at that location. The WGAS/high metastatic phenotype was stable in vitro or in vivo, implying the WGAR→WGAS shift had an underlying genetic basis. Thus, it appeared that the WGAR tumor cells could not metastasize, because of either an intrinsic cellular defect or a host imposed barrier, but that this block could be circumvented through a genetic change in the WGAR tumor cells which was accompanied by reversion of the WGAR phenotype. Non-tumorigenic (tum-) WGAR variants were also obtained, but in these cases the mutagenesis treatment itself appeared responsible for development of the tum- phenotype. The reduced tumorigenicity had an underlying immunological basis, a finding which could be exploited to immunotherapeutically treat established visceral metastases of poorly immunogenic tumors. Throughout these studies, emphasis was placed on the considerable potential of using tumor cell populations having various stable drug-resistant genetic markers to monitor aspects of tumorigenesis, tumor progression, and metastasis.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 17 (1998), S. 261-261 
    ISSN: 1573-7233
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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