| Â | Â | Â | +ASM | + Anti-MDM2 AS |
|---|
Day | Â | No Oligo [1] (% T:C) | [2] (% T:C) | Ratio (%) ([2]/[1]) | [3] (% T:C) | Ratio (%) ([3])/[1]) |
|---|
3 | Oligo alone | 100 | 99 | 99 | 51 | 51 |
| Â | HCPT | 74 | 103 | 138 | 37 | 49 |
| Â | 5-FU | 50 | 51 | 102 | 47 | 94 |
6 | Oligo alone | 100 | 105 | 105 | 44 | 44 |
| Â | HCPT | 41 | 55 | 134 | 24 | 58 |
| Â | 5-FU | 40 | 67 | 167 | 38 | 96 |
9 | Oligo alone | 100 | 70 | 70 | 30 | 30 |
| Â | HCPT | 30 | 32 | 107 | 15 | 50 |
| Â | 5-FU | 33 | 51 | 156 | 35 | 108 |
12 | Oligo alone | 100 | 82 | 82 | 34 | 34 |
| Â | HCPT | 44 | 37 | 85 | 15 | 34 |
| Â | 5-FU | 40 | 39 | 99 | 29 | 73 |
15 | Oligo alone | 100 | 79 | 79 | 45 | 45 |
| Â | HCPT | 49 | 37 | 75 | 16 | 32 |
| Â | 5-FU | 41 | 39 | 95 | 22 | 53 |
18 | Oligo alone | 100 | 73 | 73 | 37 | 37 |
| Â | HCPT | 51 | 32 | 63 | 12 | 24 |
| Â | 5-FU | 45 | 33 | 72 | 11 | 24 |
- The ratio ([2])/[1] or [3]/[1]) can be used to illustrate the potential additive or synergistic effects when the oligos were given in combination with cytotoxic agents. When the ratio for combination therapy is less thatn 100% (compared to cytotoxic agents alone), an effect of antisense oligo is indicated. If the ratio for combination therapy is the same as that of oligo treatment alone, an additive effect is indicated. If the ratio for combination therapy is significantly less than that of oligo treatment alone, a synergistic effect is indicated. For example, at the end of the experiment (day 18), the ratio for 5-FU + AS/5-FU is 24% (10.9%/45%) and less than 100%, indicating an effect of oligo AS, and, in addition, this ratio is less than the ratio for oligo AS alone (37%; AS/Saline), indicating a synergistic effect between 5-FU and Oligo AS. The ratio for 5-FU + ASM/5-FU is 72% (33%/45%) and less than 100%, indicating an effect of oligo ASM; however, this ratio is almost the same as the ratio for oligo ASM alone (73%), indicating no synergistic effect, but an additive effect, between 5-FU and Oligo ASM. In conclusion, additive or synergistic effects between HCPT and Oligo AS were found throughout the treatment period. Additive or synergistic effects between 5-FU and Oligo AS were found only on days 15 and 18. No additive or synergistic effects between Oligo ASM and HCPT or 5-FU were found, except for HCPT + ASM on days 15 and 18 and 5-FU + ASM on day 18. An additive effect between HCPT and ASM was found on these days.
