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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 25 (2000), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Thus far, the use of classical anti-cancer treatment modalities had only rarely a beneficial impact on the prognosis of patients with metastatic melanoma. We as physicians have therefore the obligation as well as the chance to develop and test new therapeutic strategies. Our growing knowledge about the genetic basis of melanoma provides one platform to fulfil this task. Another one comes from our increasing understanding of the molecular and cellular mechanisms involved in the induction/modulation of immune responses, as well as the progress made in the field of identification of melanoma antigens, and allows for the development of a new generation of vaccines. The aim of this article is to discuss several of these new concepts towards the use of immune and gene therapy of melanoma.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predominant expression of the CD44 variant isoform v10 on CD3 CD4/CD8 co-expressing tumor-infiltrating lymphocytes (TIL). We further analyzed the role of CD44v10 in adhesion of lymphocytes to human melanoma cells. In contrast to CD44– lymphatic cells, CD44v10+ lymphatic cells strongly bound to cultured human melanoma cells and to frozen tissue samples of melanomas. Antibody blocking studies revealed a hyaluronan-, integrin-, and selectin-independent pathway of adhesion. Furthermore, CD44v10+ lymphatic cells exhibited significantly higher invasiveness in three-dimensional collagen matrices as compared with CD44H+ and CD44-negative lymphocytes. These results indicate that expression of CD44v10 on TIL may mediate adhesion to melanoma cells and result in gain of novel invasive properties.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The urokinase-type plasminogen activator (uPA) is secreted into the urine at high concentrations and both the uPA protein and mRNA are present in human renal tissue. Normal kidney tissue also expresses the receptor for uPA. Neither the precise sites of uPA mRNA expression, nor the distribution of the uPA-receptor antigen, have been elucidated in the human kidney. In the present study, the sites of uPA mRNA expression were identified by in situ hybridization, and the cellular localization of both uPA and uPA-receptor was determined by immunohistochemical analysis. High-level uPA mRNA expression was restricted to epithelial cells of the convoluted proximal tubules and the thick ascending limb of Henle's loop (the straight part of the distal tubule). However, uPA immunoreactivity was not confined to sites of uPA mRNA expression, but was present in all segments of the tubular epithelium. Tubular epithelial cells also exhibited a consistent immunoreactivity with uPA-receptor antibody, indicative of a co-localization of the uPA antigen and its receptor in the uriniferous epithelium. We propose that the uPA antigen expression in nephron segments lacking demonstrable endogenous uPA synthesis may be the result of a uPA-receptor-mediated uptake of uPA.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Key words Melanoma ; Pmel17/gpl00 ; Immunotherapy ; Phenotyping ; Expression analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pmel17/gp100-encoded tumor-associated antigens are recognized by cytotoxic T lymphocytes in melanoma patients and may represent attractive target antigens for immuno- and gene-therapeutic strategies. An important prerequisite for identifcation and monitoring of melanoma pateints that could potentially benefit from Pmel17/gpl00-based immuno- and gene-therapies is the detailed knowledge of Pmel17/gpl00 expression in vivo. Immunophenotyping is considerably hampered by the different immunoreactivities of Pmel17/gpl00-reactive antibodies. Therefore, we analyzed an extended series of different primary normal and malignant human tumor specimens for Pmel17/gpl00 expression at the mRNA level. Transcripts were detectable in all malignant melanoma tissue specimens representing all stages of tumor progression, with significant levels even in early and amelanotic melanoma lesions. In contrast, normal melanocytes exhibited significantly less Pmel17/gpl00 mRNA in vivo, as determined by comparative in situ hybridization. Tissue specimens from the retina and substantia nigra also contained Pmel17/gpl00 mRNA, whereas other normal and malignant human tissues were negative. As determined by comparative in situ hybridisation and HMB-45 immunostaining, even tumor tissue lacking Pmel17/gpl00 immunoreactivity contained Pmel17/gp100 transcripts. Our results indicate a melanocytic-cell-lineage-restricted expression of Pmel17/gpl00 with significant transcript levels in all stages of melanoma progression, including early and amelanotic melanoma lesions, and a significantly differential expression between melanoma cells and normal melanocytes in vivo. Owing to its higher sensitivity, phenotyping of individual tumor specimens by mRNA expression analysis seems to be more valuable than phenotyping by immunostaining.
    Type of Medium: Electronic Resource
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