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Extracellular matrix antigens in human neuroectodermal tunmors as defined by monoclonal antibodies
180 were also found to contain GFAP. One primitive neuroectodermal tumor was surprisingly positive for GFAP. When formalin fixed, paraffin embedded sections from the same tumors were studied, the results were much inferior. Even following predigestion by trypsin or protease and the use of the amplifying avidin-biotin-techniqueit was often difficult to demonstrate the presence of GFAP in some of the glioblastomas which were positive in the smear and frozen section preparations. The distribution of GFAP positive cells Could vary from all cells positive to evenly distributed single positive cells or areas of positive cells - often in relation to blood vessels. The antigenicity of NFP does not seem to be so sensitive to formalin fixation. However, the best results were obtained following fixation in B5 which was also true for material studied with GFAP-MA. The NFP-MA have not proved to be of such a great value. Their major use has been to demonstrate the disruption of axons in small needle biopsies taken from the edge of gliomas. These antibodies have also demonstrated the presence of neurofilament proteins in a pinealocytoma with neuronal differentiation. All medulloblastomas to-date have been negative for NFP. The NFP-MA, however, have many other uses in neuropathology. Polyclonal cocktails of MA may circumvent the effects of fixatives on the antigen and still permit the use of a well standardized reagent.
15.
Extracellular matrix antigens in human neuroectodermal tumors as defined by monoclonal antibodies - R.D. MeComb and D.D. Bigner (University of Nebraska, Omaha, NE and Duke University, Durham, NC, USA)
Adherent cell monolayers elaborate an extracellular matrix that mediates cell attachment to the underlying plastic or glass substrate. Using mechanically harvested cells, routine monoclonal antibodies (MAs) 2A6 and 81C6 were raised against the medulloblastoma-derived cell line TE-671 and the glioblastoma-derived cell line U251MG, respectively. These antibodies identify glioma-mesenehymal extracellular matrix antigens. The 81C6 was similar, but not identical. By immunocytochemical assay, both antigens were distributed in glioma cell monolayers in a diffuse, amorphous pattern. In frozen tissue sections, 2A6 and 81C6 were associated with neoplastic neuroepithelial cells in 9/10 malignant gliomas and I/4 medulloblastomas. Some tumors exhibited diffuse, amorphous staining. In others there was a fine, granular network between neoplastic cells. The staining was often most intense in the perivascular regions. In two gliomas, the antigens were expressed by only a subpopulation of neoplastic cells. There was strong staining of mesenchymal tissue in each neoplasm, especially in areas of fibroblastic and vascular hyperplasia. The in vivo and in vitro expression of 2A6 and 81C6 differed from that of fibronectin and laminin, and neither MA reacted with purified plasma fibronectin. 2A6 and 81C6 identify gliomamesenchymal extracellular matrix antigens that exhibit novel patterns of expression in malignant neuroepithelial neoplasms. These MAs will be useful in the investigation of cell-matrix interactions in malignant brain tumors.
16.
Monoclonal antibody transport across tumor and systemic tissue - R.G. Blasberg, H. Nakagawa, M.A. Bourdon, D.R. Groothuis, C.S. Patlak, and D.D. Bigner (Betbesda, MD, Durham, NC and Evanston, IL)
The rate of delivery of immunoglobulin to tumor tissue, the rates of associationdissociation with tumor-associated antigen and the rate of plasma clearance are important pharmacokinetic considerations for the successful use of monoclonal antibodies as tumor imaging agents and for therapy. We studied the local distribution kinetics of MAb 81C6 in tumor (human glioma cell line D54MG) growing in the brain and subcutaneous tissue of athymic mice. Paired-label or parallel experiments were performed with a non-specific MAb (45.6). The data for both immunoglobulins (IgG2b) were fitted to a three-compartment model to yield best fit values for intravascular
15.
Extracellular matrix antigens in human neuroectodermal tumors as defined by monoclonal antibodies - R.D. MeComb and D.D. Bigner (University of Nebraska, Omaha, NE and Duke University, Durham, NC, USA)
Adherent cell monolayers elaborate an extracellular matrix that mediates cell attachment to the underlying plastic or glass substrate. Using mechanically harvested cells, routine monoclonal antibodies (MAs) 2A6 and 81C6 were raised against the medulloblastoma-derived cell line TE-671 and the glioblastoma-derived cell line U251MG, respectively. These antibodies identify glioma-mesenehymal extracellular matrix antigens. The 81C6 was similar, but not identical. By immunocytochemical assay, both antigens were distributed in glioma cell monolayers in a diffuse, amorphous pattern. In frozen tissue sections, 2A6 and 81C6 were associated with neoplastic neuroepithelial cells in 9/10 malignant gliomas and I/4 medulloblastomas. Some tumors exhibited diffuse, amorphous staining. In others there was a fine, granular network between neoplastic cells. The staining was often most intense in the perivascular regions. In two gliomas, the antigens were expressed by only a subpopulation of neoplastic cells. There was strong staining of mesenchymal tissue in each neoplasm, especially in areas of fibroblastic and vascular hyperplasia. The in vivo and in vitro expression of 2A6 and 81C6 differed from that of fibronectin and laminin, and neither MA reacted with purified plasma fibronectin. 2A6 and 81C6 identify gliomamesenchymal extracellular matrix antigens that exhibit novel patterns of expression in malignant neuroepithelial neoplasms. These MAs will be useful in the investigation of cell-matrix interactions in malignant brain tumors.
16.
Monoclonal antibody transport across tumor and systemic tissue - R.G. Blasberg, H. Nakagawa, M.A. Bourdon, D.R. Groothuis, C.S. Patlak, and D.D. Bigner (Betbesda, MD, Durham, NC and Evanston, IL)
The rate of delivery of immunoglobulin to tumor tissue, the rates of associationdissociation with tumor-associated antigen and the rate of plasma clearance are important pharmacokinetic considerations for the successful use of monoclonal antibodies as tumor imaging agents and for therapy. We studied the local distribution kinetics of MAb 81C6 in tumor (human glioma cell line D54MG) growing in the brain and subcutaneous tissue of athymic mice. Paired-label or parallel experiments were performed with a non-specific MAb (45.6). The data for both immunoglobulins (IgG2b) were fitted to a three-compartment model to yield best fit values for intravascular