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  • 25.70.Jj  (2)
  • EXPRESSION  (2)
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  • 1
    Keywords: CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; Germany ; human ; GENE ; HYBRIDIZATION ; TISSUE ; LINES ; PATIENT ; MARKER ; TISSUES ; ANTIGEN ; SKIN ; T cells ; T-CELLS ; CELL-LINES ; DOWN-REGULATION ; SIGNAL ; IN-SITU ; DESIGN ; MUTATION ; CELL-LINE ; LINE ; ABERRATIONS ; HETEROZYGOSITY ; MELANOMA ; REGION ; MUTATIONS ; MONOCLONAL-ANTIBODIES ; MHC CLASS-I ; PHENOTYPE ; IMMUNE ESCAPE ; TUMOR ESCAPE ; in situ hybridization ; MALIGNANT-CELLS ; RE ; LEVEL ; EVENTS ; LOSSES ; CD8(+) T cell ; B2M GENE ; MEDIATED LYSIS ; PROCESSING MACHINERY
    Abstract: Purpose: Total loss of surface presentation of human leukocyte antigen (HLA) class I molecules, protecting tumor cells from the recognition by cytotoxic host CD8(+) T cells, is known to be caused by mutations in the beta 2-microglobulin (beta 2m) gene. We asked whether abnormalities of chromosome 15, harboring the beta 2m gene on 15q21, in addition to beta 2m gene mutations, are causative for the HILA class I-negative phenotype of melanoma cells. Experimental Design: To answer this, we established primary cell lines from the beta 2m-negative metastatic melanoma tissues of four different patients and analyzed them for beta 2m gene mutations and chromosome 15 aberrations, the latter by loss of heterozygosity analysis, fluorescence in situ hybridization (FISH), and multicolor FISH. Results: Mutations at the beta 2m gene level were detected in all cell lines. The loss of heterozygosity analysis of microsatellite markers located on chromosome 15 in three of the four cell lines pointed to an extensive loss of chromosome 15 material. Subsequent molecular cytogenetic analysis revealed the coexistence of apparently normal and rearranged versions of chromosome 15 in three cell lines whereas the fourth cell line solely showed rearranged versions. Two of the four cell lines exhibited a special type of intrachromosomal rearrangement characterized by FISH signals specific for the subtelomeric region of 15q at both ends of the chromosome and one centromeric signal in between. Conclusions: Our data indicate that the complete loss of HLA class I expression in melanoma cells is due to the coincidence of the following mutational events: (a) chromosome 15 instability associated with an extensive loss of genetic material and (b) beta 2m gene mutations
    Type of Publication: Journal article published
    PubMed ID: 16740750
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  • 2
    Keywords: RECEPTOR ; CANCER ; CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; human ; PROTEIN ; MOLECULES ; TUMORS ; LINES ; MICE ; LIGAND ; CUTTING EDGE ; IFN-GAMMA ; MECHANISM ; DENDRITIC CELLS ; mechanisms ; T cells ; T-CELL ; BINDING ; CELL-LINES ; DOWN-REGULATION ; SIGNAL ; HUMANS ; MELANOMA ; DELTA T-CELLS ; NK cells ; NKG2D ; INVOLVEMENT ; CD8(+) ; melanoma cells ; CELL-SURFACE ; cell lines ; INTERFERON-GAMMA ; GENE-MUTATIONS ; CYTOTOXICITY ; STAT1 ; BINDING PROTEIN ; CYTOKINE ; GLIOMA ; therapeutic ; CYTOMEGALOVIRUS UL16 GLYCOPROTEIN ; INTRACELLULAR RETENTION ; natural killer cell ; MHC class I loss ; TUMOR SURVEILLANCE
    Abstract: NKG2D operates as an activating receptor on natural killer (NK) cells and costimulates the effector function of alpha p CD8(+) T cells. Ligands of NKG2D, the MHC class I chain-related (MIC) and UL16 binding protein (ULBP) molecules, are expressed on a variety of human tumors, including melanoma. Recent studies in mice demonstrated that NKG2D mediates tumor immune surveillance, suggesting that antitumor immunity in humans could be enhanced by therapeutic manipulation of NKG2D ligand (NKG2DL) expression. However, signals and mechanisms regulating NKG2DL expression still need to be elucidated. Here, we asked whether the proinflammatory cytokine Interferon-gamma (IFN-gamma) affects NKG2DL expression in melanoma. Cell lines, established from MHC class I-negative and -positive melanoma metastases, predominantly expressed MICA and ULBP2 molecules on their surface. Upon IFN-gamma treatment, expression of MICA, in some cases, also of ULBP2 decreased. Besides melanoma, this observation was made also for glioma cells. Down-regulation of NKG2DL surface expression was dependent on the cytokine dose and the duration of treatment, but was neither due to an intracellular retention of the molecules nor to an increased shedding of ligands from the tumor cell surface. Instead, quantitative RT-PCR revealed a decrease of MICA-specific mRNA levels upon IFN-gamma treatment and siRNA experiments pointed to an involvement of STAT-1 in this process. Importantly, IFN-gamma-treated MHC class I-negative melanoma cells were less susceptible to NKG2D-mediated NK cell cytotoxicity. Our study suggests that IFN-gamma, by down-regulating ligand expression, might facilitate escape of MHC class I-negative melanoma cells from NKG2D-mediated killing by NK cells. (C) 2008 Wiley-Liss. Inc
    Type of Publication: Journal article published
    PubMed ID: 19089914
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  • 3
    ISSN: 1434-601X
    Keywords: 25.70.Jj ; 25.70.Gh ; 25.85.Ge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The20Ne + U reactions are investigated at 290 MeV bombarding energy. The linear momentum transfer and excitation energy are deduced eventwise from the respective measurements of the folding angle between correlated fission fragments and the neutron multiplicity. A simple incomplete fusion picture is shown to essentially account for the data. The sensitivity of the two measurements in order to infer the violence of a collision is discussed in details.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-601X
    Keywords: 25.70.Jj ; 25.85.Ge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Energy spectra and multiplicities of neutrons from the reaction system 838 MeV32S projectiles on197Au have been measured in coincidence with binary fragmentations. Neutron detection was performed simultaneously in a 4π scintillator sphere and by time-of-flight. The linear momentum transfer (LMT) and the excitation energyE CN * are deduced with the folding angle technique. Neutron multiplicities are compared for consistency and discussed as a measure of LMT andE CN * . The saturation ofM 4π (E CN * ) beyondE CN * ≈400 MeV seen for several systems of high fissility (x≧0.8) is attributed to the spreading of the folding angle distribution and the increasing competition of charged particle evaporation.
    Type of Medium: Electronic Resource
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