Myeloma cells, functions

Alt, F.W., Enea, V., Bothwell, A.L.M., Baltimore, D. (1980a). Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain. Cell 21, 1-12. 

Bortezomib. Bortezomib (Velcade) inhibits pro-teasome activity in mammalian cells.11 Mammalian proteasome is responsible for degrading certain cellular proteins affecting cell function and division. By prolonging the activity of these proteins, bortezomib brings about complex changes in cell function that lead to cell dysfunction and death. Certain types of cancer, such as multiple myeloma, are more sensitive to impaired proteasome regulation, hence the use of this drug in these cancers. 

Because each B-cell clone produces antibody to a single epitope on an antigen, an opportunity exists for producing chemically and functionally homogeneous antibody in substantial quantity. However, the short B-cell lifetime that is determined by normal apoptosis initially made this impractical. However, the discovery by Kohler and Milstein that B cells could be fused with immortal myeloma cells to create hybridomas that can be maintained almost indef-... 

Keen, M.J. and Hale, C., The use of serum-free medium for the production of functionally active humanized monoclonal antibody from NSO mouse myeloma cells engineered using glutamine synthetase as a selectable marker, Cytotechnology, 18, 207, 1995. 

Figure 8. Critical ac field strength, Ecrit, for electroporation of myeloma cells as a functions of ac frequency. Data were obtained in media of different resistivities 52,600 1 cm (O) 7050 2 cm (%) 2380 1 cm ( ). The curves drawn through these data points were obtained by calculation (O) or optimization ( and ) according to the Schwan equation. (Reproduced with permission from reference 12. Copyright 1990.)...

Bortezomib is the hrst therapeutic proteasome inhibitor. It inhibits the activity of the 26S-proteasoom protein complex which regulates protein expression and function and thus plays a role for cell homeostasis. It is used for the treatment of relapsed mulh-ple myeloma. Following intravenous administrahon bortezomib is mainly metabolised with an elimina-hon halflife of 5-15 h. It is frequently associated with somehmes irreversable neuropathy. Myelosuppression may be dose limiting. 

Physiologically, these plasma changes are included here since they reflect impaired numbers or function of B-lymphocytes. Two broad categories are recognizable. First, such immunodeficiency states may exist on congenital basis and often do so with concurrent defects in the T cells (Fig. 1). Alternatively, severe reductions in immunoglobulin levels often develop in the course of chronic lymphocytic leukaemia and myeloma. Not dissimilar impairment of immune competence is found with nephrotic syndrome, protein-losing enteropathy or even malnutrition, and in these instances is equally profound. 

Becker L et al. (2005) Preprotein translocase of the outer mitochondrial membrane reconstituted Tom40 forms a characteristic TOM pore. J Mol Biol 353 1011-1020 Blobel G, Dobberstein (1975a) Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol 67 835-851 Blobel G, Dobberstein (1975b) Transfer to proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J Cell Biol 67 852-862... 

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