The viabliity of tumor cells and enlargement of a tumor mass requires the support and growth of a vascular system and capillary network. It has been suggested that vascular occulsion and inhibition of capillary growth in a tumor mass can prevent tumor growth. Complete regression of experimental tumors has been demonstrated through either physical interruption of blood flow, or by inhibition of capillary growth by angiogensisinhibitors. The antitumor effects of these procedures do not depend on direct killing of tumor cells. Recent work suggest that antitumor agents, including hyperthermia, radiation, and some drugs can have direct cytotoxic effect on endothelial cells, with secondary destruction of capillary functions. These antitumor agents can also indirectly impair proliferation and migration, both essential for capillary growth, by interfering with the stimulatory effect of endothelial growth factors. Once an endothelial cell has been damaged, it releases chemotactic molecules, attracting phagocytes which cause further endothelial cell injury due to their release of toxic oxygen radicals and proteases. We plan to evaluate the above mentioned processes experimentally, using cultured capillary endothelial cells. Cytotoxicity will be monitored according to cell replication and colony development, and nonlethal damage will be evaluated by measurements of cell retraction, detachment, migration, and expression of C3b and Fc receptors.
| Lin, P S; Ho, K C; Sung, S J et al. (1992) Effect of tumour necrosis factor, heat, and radiation on the viability and microfilament organization in cultured endothelial cells. Int J Hyperthermia 8:667-77 |
| Ho, K C; Lin, P S (1991) Response of erythrocytes to heat in the presence of D2O, glycerol, and anisotonic saline. Radiat Res 125:20-7 |
| Lin, P S; Quamo, S; Ho, K C et al. (1991) Hyperthermia enhances the cytotoxic effects of reactive oxygen species to Chinese hamster cells and bovine endothelial cells in vitro. Radiat Res 126:43-51 |
