Cancer Research and Taurolidine
that reacts with bacterial mobile membrane components to prevent adhesion to epithelial mobile surfaces. Reflecting the key role of adhesion in the growth and development of human solid tumors, studies were initiated to examine the antiproliferative activity of this agent in picked human and murine tumour cell lines. A 3-day exposure to Taurolidine inhibited the expansion of all of the cell lines examined with IC50s ranging from 9. 6–34. 2 μm. Studies to identify the mechanism liable for this effect were conducted in NIH-3T3 murine fibroblasts and the PA-1 and SKOV-3 human ovarian tumor cells. These kinds of studies revealed that a 48-h exposure to taurolidine had little effect on mobile cycle distribution in PA-1 and SKOV-3 cells but significantly increased the appearance of DNA debris in the sub-G0/G1 region, an effect regular with an induction of apoptosis. Inside contrast, in NIH-3T3 tissue, taurolidine exposure did not increase DNA debris in the sub-G0/G1 region. Added studies assessed phosphotidylserine externalization following a 24-h exposure to taurolidine using annexin-V holding as a cell surface marker. These studies revealed that taurolidine increased the percentage of annexin-V-positive tissues by 4-fold and 3-fold in PA-1 and SKOV-3 cells, respectively. In NIH-3T3 cells, taurolidine exposure a bit increased (∼5%) annexin-V holding. Parallel studies revealed that contact with taurolidine also lead in poly(ADP-ribose) polymerase boobs in both ovarian tumour cell lines although not in NIH-3T3 cells. Finally, murine-based studies were conducted to determine the antineoplastic activity of three consecutive daily i. p. bolus injections of taurolidine at dosages ranging from 5-mg injection/mouse to 30-mg injection/mouse. The particular 20-mg injection dose produced ∼10% mortality and was discovered as the maximally tolerated dose in this model. Administration of this regimen to nude mice bearing i. p. human ovarian tumor xenografts significantly inhibited both tumor formation and growth. These findings are discussed in light of these clinical implications.
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