Tumor cells culture systems

New drugs suspected of having anticancer activity are tested in standard animal models in which tumors are transplanted from one generation of animals, generally mice, to the next and are thus perpetuated in vivo. In vitro tumor cell culture systems are commonly used to determine if a new drug has cytotoxic or growth-inhibiting activity. However, the in vivo test is considered to be a better predictor of activity in humans. 

BS DeSilva, TL Hendrickson, EM Topp. Development of a cell culture system to study antibody convection in tumors. J Pharm Sci 86 858-864, 1997. 

Adherent tumor cell cultures can be used in vitro and in vivo to characterize tumor growth, metastasis, regulation of the immune system, and gene expression. The standardization of the cell suspension for injection is a process critical to generate reproducible metastasis. 

Ansamycin antibiotics are probably the most complex organic compounds produced by the genus Streptomyces. In addition to the antibacterial, they also exhibit antiviral effects. Ansamitocin P-3 shows a potent cytotoxicity against the human solid tumor cell lines A-549 and HT-29. The compound exhibits a significant activity against P-388 lymphocytic leukemia in mice and both 9PS (murine lymphocytic leukemia) and 9KB (human nasopharyngeal carcinoma) in cell culture systems. [38]. 

A variefy of chemical agents are known to act as tumor promoters in various systems. However, much of our knowledge of the cellular and molecular mechanisms of tumor promotion has come from studies using the phorbol ester tumor promoters in the mouse skin model and in various cell culture systems. 

Nanocapsules covered with phospholipids can be functionalized by attaching or inserting substances with particular properties, like monoclonal antibodies which can be used for targeting. Monoclonal antibodies produced in mammalian cell culture systems are becoming increasingly important as auxiliaries for the treatment of human diseases. Antibodies [65] attached to a phospholipid layer that cover radioactive nanocapsules can be transported by blood to a specific cell for binding to a tumor marker. Functionalization can also be used for self-assembly to obtain organized two- and three- dimensional stmctures [66]. 

The tumor promoters as a class exhibit mitogenic activity and as already discussed, the ability of retinoids to oppose or to enhance that effect depends on the particular cell culture system employed and on experimental design. Kaneko... 

In the course of our synthetic efforts, we discovered a new, unnatural conformational isomer of the VBL piperidine ring (see Chapter 2, this volume, for details). This compound is inactive with the microtubule system in vitro and is poorly cytotoxic to cultured tumor cells (Fig. 5b). Therefore, the functional determinism of the C-20 position of VBL-like molecules mediates reactions, as yet unknown, that are dependent on the binary alkaloid structure and on the natural stereochemical configuration at C-16 and C-14 as well as on the conformation of the cleavamine moiety. 

Rotating culture vessels such as simulated microgravity systems are primarily used to study 3-D tumor growth and differentiation. However, mixed cell populations combined with matrix proteins can be used to generate a complex microenvironment in which cell-cell interactions and invasion can be measured (95). A similar system has also been described for the coculture of endothelial cells, myofibroblasts, and tumor cell clusters embedded in Matrigel . Differential labeling of the cell populations enables their invasion and the effects of inhibitors to be measured (96). 

Topotecan has radiation-sensitizing properties demonstrated in log- and plateau-phase cell cultures (23,36) and in murine fibrosarcomas (37,38). Trials have begun in patients with nonsmall-cell lung cancer (NSCLC) and in those with central nervous system (CNS) tumors. 

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