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  • 1
    Electronic Resource
    Electronic Resource
    An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy (1999)
    Springer
    Cancer immunology immunotherapy 48 (1999), S. 303-311 
    Details
    ISSN: 1432-0851
    Keywords: Key words Transgenic ; Rat ; EGP-2 ; GA733-2 ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5′ and 3′ distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050579
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  • 2
    Electronic Resource
    Electronic Resource
    Tumor Vascular Endothelium: Barrier or Target in Tumor Directed Drug Delivery and Immunotherapy (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 2-10 
    Details
    ISSN: 1573-904X
    Keywords: tumor vascular endothelium ; targeting ; drug delivery ; immunotherapy ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immuno-modulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and macromolecular drug-carrier conjugates is only sufficient in the blood vessels at the tumor-host interface. Downregulation of the expression of adhesion molecules, required for the facilitation of immune cell recruitment, by the tumor vascular endothelium results in an escape of the tumor from host defence. New therapeutic approaches for the treatment of solid tumors are aimed at the tumor vasculature, either at the endothelial cells themselves or at basement membrane or tumor stroma components. Angiogenesis can be directly blocked with angiogenesis inhibitors, while angiogenesis related factors can serve as tumor vasculature specific epitopes for drug delivery strategies. Some glycoproteins expressed by tumor endothelial cells or present in the basement membrane and tumor stroma are also potential tumor selective targets. Therapeutic modalities that are suitable for site specific delivery are agents that increase tumor accumulation of (targeted) chemo/radiotherapeutics through increasing tumor vascular permeability. The observation that for tumor growth the blood supply is a limiting factor, led to the development of strategies to inhibit angiogenesis or block the tumor blood flow. Manipulation of the expression of endothelial cell adhesion molecules by selectively delivering modulatory agents at or in the tumor vascular endothelial cells may induce (bispecific antibody mediated) host defense activity directed against the tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012038930172
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  • 3
    Electronic Resource
    Electronic Resource
    Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer (1987)
    [s.l.] : Nature Publishing Group
    Nature 330 (1987), S. 578-581 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Analysis of five SCLC cell lines revealed the presence of at least one morphologically normal and one deleted homologue of chromosome 3 per cell line. The shortest region of overlap for the deletion originally reported as 3pl4-3p23 (ref. 6), could be narrowed to 3p21 distal-p22 (Fig. 1). A human ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/330578a0
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    Paper (German National Licenses)
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