leucyl-leucine-methyl-ester has been researched along with Breast-Neoplasms* in 2 studies
2 other study(ies) available for leucyl-leucine-methyl-ester and Breast-Neoplasms
| Article | Year |
|---|---|
Stefin B deficiency reduces tumor growth via sensitization of tumor cells to oxidative stress in a breast cancer model.
Lysosomal cysteine cathepsins contribute to proteolytic events promoting tumor growth and metastasis. Their enzymatic activity, however, is tightly regulated by endogenous inhibitors. To investigate the role of cathepsin inhibitor stefin B (Stfb) in mammary cancer, Stfb null mice were crossed with transgenic polyoma virus middle T oncogene (PyMT) breast cancer mice. We show that ablation of Stfb resulted in reduced size of mammary tumors but did not affect their rate of metastasis. Importantly, decrease in tumor growth was correlated with an increased incidence of dead cell islands detected in tumors of Stfb-deficient mice. Ex vivo analysis of primary PyMT tumor cells revealed no significant effects of ablation of Stfb expression on proliferation, angiogenesis, migration and spontaneous cell death as compared with control cells. However, upon treatment with the lysosomotropic agent Leu-Leu-OMe, cancer cells lacking Stfb exhibited a significantly higher sensitivity to apoptosis. Moreover, Stfb-ablated tumor cells were significantly more prone to cell death under increased oxidative stress. These results indicate an in vivo role for Stfb in protecting cancer cells by promoting their resistance to oxidative stress and to apoptosis induced through the lysosomal pathway. Topics: Animals; Apoptosis; Breast Neoplasms; Cathepsins; Cell Movement; Cell Proliferation; Cystatin B; Cysteine Proteinase Inhibitors; Dipeptides; Disease Progression; Female; Immunosuppressive Agents; Lysosomes; Mammary Neoplasms, Experimental; Mice; Mice, Knockout; Neoplasm Metastasis; Neovascularization, Pathologic; Oxidative Stress | 2014 |
In vitro primary immunization of B lymphocytes for producing human monoclonal antibodies against tumor-associated antigens.
The selective cytotoxicity of the lysosomotropic leucine methyl ester and its lysosomal condensation product leucyl-leucine methyl ester have been used to investigate their effect on a range of lymphocyte subsets and on the cellular proliferation and secretion by immunoglobulin-secreting B cells from axillary regional draining lymph nodes of breast cancer patients. CD2+, CD3+, and CD8+ lymphocyte subsets were selectively reduced by the leucyl-leucine methyl ester treatment (CD2: 84.2-67.5%; CD3: 76.1-62.3%; and CD8: 8.0-3.4%), but there was no significant reduction in the CD4+ and CD19+ subsets (CD4: 68.2-64.7%; and CD19: 22.6-33.2%). In the presence of mouse splenic macrophages as antigen-presenting cells, rIL-2, IFN-gamma, and pokeweed mitogen-stimulated lymphocyte supernatant, leucyl-leucine methyl ester-treated lymphocytes showed a significant increase in 3H-thymidine incorporation and in the number of immunoglobulin-secreting B cells following coculture with the breast tumor cell line MCF-7. In this study, we have characterized some of the cellular and cytokine factors that are necessary for in vitro immunization of human B lymphocytes. Hopefully, this will enable human MAbs to be produced in vitro against tumor-associated antigens. Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Antigen-Presenting Cells; Antigens, Neoplasm; Axilla; B-Lymphocyte Subsets; Breast Neoplasms; Cell Fusion; Cell Line; Dipeptides; Humans; Interferon-gamma; Interleukin-2; Leucine; Lymph Nodes; Macrophages; Mice; Pokeweed Mitogens; Recombinant Proteins | 1993 |