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  • 1
    ISSN: 1432-0843
    Schlagwort(e): Key words Monoclonal antibody ; A33 ; Gastric cancer ; Immunohistochemistry ; Tumor targeting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Murine monoclonal antibody A33 (mA33) was developed by the Memorial Sloan-Kettering Cancer Center and by the New York Branch of the Ludwig Institute for Cancer Research. It is an immunoglobulin (Ig)G2a antibody that detects a protease- and neuraminidase-resistant, periodate-sensitive epitope. Serological analysis of the antigen showed that it is expressed in a few colorectal cancer cell lines and a pancreatic cancer cell line, but is basically not reactive with other types of cell line. Normal fibroblasts and normal kidney cell lines reacted negatively to mA33. Immunohistochemical study of normal tissues identified the large and small intestinal mucosa as the principal site of A33 expression. Tests in tumor samples demonstrated that only tumors of the gastrointestinal tract are consistently A33 positive. A33 is found in 95% of primary and metastatic colorectal cancers, with uniform expression throughout the tumors in most cases. A33 is also detected in 63% of gastric cancers, with uniform expression in 45% of cases. Eighty-three percent of intestinal-type gastric cancers were positive for A33, and about 50% of the diffuse-type and mucinous cancers were mA33 positive. A33 was expressed in 50% of the pancreatic cancers but with marked heterogeneity. Other epithelial cancers, sarcomas, neuroectodermal tumors, and lymphoid neoplasms were generally A33 negative. A33 is the first example of a constitutively expressed, organ-specific epithelial membrane antigen permitting highly specific tumor targeting in patients with gastrointestinal cancer. Encouraged by the success of the biodistribution and imaging characteristic studies performed at Memorial Sloan-Kettering Cancer Center by the New York Branch of the Ludwig Institute in colorectal cancers, a new clinical study of humanized monoclonal antibody huA33 against A33 antigen-positive gastric cancers has been initiated in Japan.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1435-5922
    Schlagwort(e): Key words: ethanol ; asialoglycoprotein receptor ; IL-1β ; IL-6 ; TNF-α
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract: Blood levels of inflammatory-related cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with IL-1β, IL-6, and TNF-α, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%–80% of the number in the untreated cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1β, IL-6, and TNF-α stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients with alcoholic liver disease.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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