Activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma.

Unlabelled: THE AIM of this study was to determine the activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma.

Patients And Methods: The study was conducted on 52 women operated for a unilateral breast tumor, divided into two groups, according to the number of metastases and tumor size. Cathepsin D activity was determined using the method of Anson, while alpha(1)-antitrypsin activity was determined according to the Eriksson method.

[Changes in arylsulphatase activity in blood serum in patients with breast cancer before and after treatment].

We evaluated arylsulphatase activity in 52 women with breast cancer. In women with breast cancer this enzyme activity is 2,5-fold higher than in healthy women. After operation and chemiotherapy arylsulphatase activity decreased to normal values.

[Significance of cathepsin B and D in physiologic and pathologic processes].

The lysosomal proteases play an important role in the cells nourishment, immunogenesis, development of the arteriosclerosis perturbations in blood vessel cells and in the pathogenesis of degeneration diseases, cancer diseases and in the great number of others. For the many cancer disease durations, an increased activity of the lysosomal enzymes both in blood serum and in tumor tissues was revealed. Over the past few years a particular attention have been paid to the fact that the high activity of some lysosomal enzymes i.

Mitochondrial diseases.

Prevalence of mitochondrial diseases equals 1:10,000 of life-born infants. Mutations of mitochondrial DNA are their most frequent cause. The study presents short description of some of these diseases.

In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid immunoconjugates which bind to three distinct epitopes of carcinoembryonic antigen.

A panel of four murine monoclonal antibodies apparently directed against three distinct epitopes of carcinoembryonic antigen (CEA) was conjugated via oxidized carbohydrate groups to 4-desacetylvinblastine-3-carboxyhydrazide. The resulting antibody-vinca conjugates were evaluated for antitumor activity against 2-9-day-established LS174T human colorectal carcinoma xenografts. The antibodies (immunoglobulin G, IgG) employed in this study were 11.

In vivo antitumor activity of a monoclonal antibody-Vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes.

It is widely believed that antigen heterogeneity and noninternalization of antigen-antibody complexes will severely limit the antitumor activity of monoclonal antibody-drug conjugates. The B72.3 monoclonal antibody binds to a tumor-associated antigen which is heterogeneously expressed in human carcinomas (J.

In vivo selection of human tumor cells resistant to monoclonal antibody-Vinca alkaloid immunoconjugates.

UCLA-P3 human lung adenocarcinoma cells were grown in nude mice and given repetitive treatments of a monoclonal antibody-Vinca alkaloid immunoconjugate. Although this therapy resulted in a greater than 4-fold reduction in mean tumor mass of the established tumors, some animals experienced a reinitiation of tumor growth after cessation of conjugate treatment. Two such animals were treated again with high doses of monoclonal antibody-Vinca but one of the tumors was no longer regressed by the drug conjugate.

Selective cloning of hybridoma cells for enhanced immunoglobulin production using flow cytometric cell sorting and automated laser nephelometry.

Techniques for selective cloning of murine hybridoma cells by flow cytometric cell sorting and use of automated laser nephelometry to determine the resultant clones' immunoglobulin secretion levels are described. Using a commercially available attachment to a fluorescence-activated cell sorter, individual hybridoma cells were successfully distributed into microtiter wells in an automated manner based on their forward angle light scatter properties and their reaction to fluorescein-conjugated anti-mouse-IgG. The techniques were used to estimate successfully the frequency of immunoglobulin-secreting cells in established cultures.

In vivo efficacy of monoclonal antibody-drug conjugates of three different subisotypes which bind the human tumor-associated antigen defined by the KS1/4 monoclonal antibody.

A panel of three hybridomas has been isolated each of which secretes a single species of monoclonal antibody (MoAb) directed against the KS1/4 tumor-associated antigen originally described by Varki et al. (Cancer Res 44: 681, 1984). These MoAbs were designated L1-(IgG2b), L2-(IgG1), and L4-(IgG2a)KS.

Development of a dual label fluorescence technique that can be utilized to elucidate the mechanism of action of monoclonal antibody-drug conjugates.

A method is described that allows the simultaneous visualization and relative assessment of both the antibody and drug components of monoclonal antibody-drug conjugates at the target cell membrane. The antibody is detected by a fluorescein-conjugated anti-mouse immunoglobulin serum while the drug is visualized by rhodamine avidin or phycoerythrin-streptavidin binding to a biotinylated anti-Vinca alkaloid monoclonal antibody. This technique was effective in demonstrating the cell surface localization of a monoclonal antibody-Vinca alkaloid conjugate to human lung adenocarcinoma cells grown in vitro and was also used to demonstrate targeting of the conjugate in vivo to the membranes of these same tumor cells grown as a nude mouse xenograft.