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  • 1
    ISSN: 1432-2307
    Keywords: Carcinoembryonic antigen ; Monoclonal antibodies ; Pancreatic tumours ; Immunoreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of CEA and related antigens in formalin-fixed paraffin-embedded tissues of normal pancreas and different pancreatic neoplasms was studied immunocytochemically using three monoclonal antibodies (MAbs) recognizing different epitopes on CEA and related antigens. Additionally, a number of extrapancreatic malignancies were tested. The epitope recognized by MAb 250 (present on CEA and NCA 95) was expressed in all but one pancreatic ductal adenocarcinoma and ampullary carcinoma (42/43). The MAb 431 defined epitope (present only on CEA) was less frequently found (27/43). MAb 374, defining an epitope on CEA, NCA 95 and NCA 55 proved to be nearly as sensitive tive as MAb 250, but also reacted with normal duct epithelium. In contrast, MAb 250 and MAb 431 discriminated clearly between reactive duct lesions and malignant duct changes. Moreover, these MAbs differentiated between pancreatic duct carcinomas and nonduct type carcinomas as well as benign pancreatic tumours. In duct type carcinomas, the strongest staining was observed in well differentiated tumours. No discrimination was possible between pancreatic carcinomas and other adenocarcinomas of the gastrointestinal tract nor between most of the lung carcinomas and some other malignancies, specified below. MAb 250 and MAb 431 failed to react with hepatocellular carcinomas, renal cell carcinomas, carcinoids, sarcomas and melanomas. The findings suggest that paraffin-embedded tissues of pancreatic duct type carcinomas, in contrast to nonduct type tumours and normal ducts, are distinguished by the presence of a CEA and NCA 95 related epitope.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibodies (mAbs) BW 625 and BW 704, of the IgG3 isotype, bound to immunochemically indistinguishable epitopes on ganglioside II3(NeuAc)2-GgOse3-Cer. Despite this fact the mAbs showed a differential binding pattern on human glioma cell lines i.e. immunohistochemical data indicate that the detected epitopes are not identical. Furthermore, either mAb is able to mediate the antibody-dependent cellular cytotoxicity reaction (ADCC) and the human-complement-dependent cytotoxicity reaction (CDC) with epitope-expressing tumor cells. All cryopreserved tissue specimens from gliomas and neuroblastomas were immunohistochemically stained, whereas the other small round cell tumors of childhood, as well as melanomas and small-cell lung carcinomas, were essentially negative. Positive staining of normal cryopreserved tissues was restricted to amyelinic axons, Hassal's bodies and some connective tissue fibers in thymus and the tegumentary epithelium of skin. The high selectivity of mAb BW 704 for gliomas and neuroblastomas, the lack of cross-reactivity with major tissues and the strong ADCC and CDC potential argue for the use of mAb BW 704 in immunotherapy of neuroblastomas and gliomas.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 23 (1986), S. 192-199 
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The therapeutic effect of i. d. injection of tumor cells mixed with Vibrio cholerae neuraminidase (VCN) on tumor progression in dogs with spontaneous mammary tumors was investigated. The i. d. injections were performed in a chessboard-like manner: different numbers (105, 106, 107, and 108) of mitomycin-treated autologous tumor cells (M-TC) were each mixed with different amounts (10, 50, and 100 mU) of VCN. These different mixtures were injected i. d. at different sites in dogs on the day of resection of a part of multiple tumors. In a randomized prospective study in 71 dogs the effect of chessboard vaccination (autologous tumor cells and VCN) on the growth of the residual tumor mass was compared to chessboard-like treatments with mixtures of either autologous erythrocytes and VCN or autologous tumor cells and heat-inactivated VCN. The results show that: chessboard vaccination induced regression (6 of 23) of spontaneous mammary tumors in dogs. No dog died as a result of the tumor within an observation period of 1 year. The therapeutic effect of chessboard vaccination was dependent on the application of tumor cells and enzymatically active VCN. In contrast, control treatment with either heat-inactivated VCN or autologous erythrocytes instead of tumor cells did not induce any regressions. Some animals in both control groups died because of tumor growth (3/21 and 2/27 respectively). The delayed type hypersensitivity (DTH) response of tumor-bearing animals against i. d. applied tumor cells was not significantly enhanced by the admixture of enzymatically active VCN, nor did the DTH response seem to be predictive of a therapeutic effect on the tumor. No difference in the DTH response of dogs to autologous tumor cells mixed with active or inactivated VCN or autologous erythrocytes mixed with active VCN could be found. Thomsen-Friedenreich antigens were serologically detected on canine erythrocytes after treatment with VCN and on untreated cells of mammary tumors from dogs. Exposure of Thomsen-Friedenreich antigens after treatment with VCN was enhanced on canine mammary tumors. As chessboard vaccination proved to be unsuccessful when canine autologous erythrocytes were used instead of autologous tumor cells, it can be concluded that the exposure of Thomsen-Friedenreich antigen plays no decisive role in tumor therapy with tumor cells and VCN. Chessboard vaccination was tolerated without any side effects. Tumor enhancement was never observed. Chessboard vaccination appears to be an effective and safe procedure for tumor therapy using tumor cells and VCN. The mechanism underlying the therapeutic effect of chessboard vaccination is completely unknown.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The murine monoclonal antibody (MAb) BW 494 was characterized in relation to its tissue specificity, the epitope recognized, in vitro and in vivo radiolocalization and its potential to mediate antibody dependent cellular cytotoxicity (ADCC) and complement mediated cytolysis (CMC). The MAb defined carbohydrate epitope located on a 〉200 k daltons glycoprotein was mainly expressed on the majority of well differentiated adenocarcinomas of the pancreas. Furthermore, the epitope is accessible to MAb BW 494 in vivo, allowing an enrichment of radioactive antibody at the tumor site in nude mice. Additionally, MAb BW 494 is able to use human peripheral blood lymphocytes as effector cells for ADCC reactions against appropriate tumor target cells in vitro. In contrast, the antibody does not mediate human or rabbit CMC.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1619-7089
    Keywords: CEA ; Conformational change ; MAb ; Immunoscintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Starting from the phenomenon that the amount of circulating CEA in patients' sera did not significantly influence immunoscintigraphic visualization of CEA expressing tumors, we built up an in vitro model to explain this phenomenon. Blocking experiments in this model system showed that the CEA specific MAbs BW 431/26 and BW 431/31 could not be inhibited in their binding to cell associated CEA, if they were preincubated with a 20 molar excess of serum CEA. In contrast, the CEA-NCA cross reactive MAbs could be inhibited in their binding to tumor associated CEA under identical conditions. These data combined with western blotting analysis of patients' sera and affinity constant determinations argue that conformational changes in serum CEA cause a decreased affinity of the CEA specific MAbs to serum CEA allowing a preferential binding to tumor associated CEA.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: 15-Deoxyspergualin ; pancreatic islets ; graft survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti ⇀ Lewis rats) after pancreatic islet transplantation was tested. A marked prolongation of graft survival could be shown using doses of 1.0, 2.5 and 5.0mg Deoxyspergualin/kg on day 0 until day +9 post transplantation. A maximum of 55.6 days (average) survival time was observed using 2.5mg/kg Deoxyspergualin compared to 5.2±0.6 days without immunosuppression. Using the chemiluminescence reaction of recipient monocytes after islet transplantation, a marked suppression of the monocyte system exceeding the treatment period could be observed. Since, in contrast to cyclosporin, B-cell toxicity could not be shown, the new drug seems to be a hopeful step towards successful allogeneic islet transplantation for treatment of diabetes.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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