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We tested whether paclitaxel suppress new blood ves sel formation at one fourth of MTD, a dose similar to those used in the clinic. Healthy mice were inoculated ARQ 197 cell in vivo in vitro on day 0 with tumor free Matrigel containing rmVegf164. Mice were treated on days 1 and 4 with i. p. paclitaxel at 1 4 MTD. Control mice were inoculated with tumor free Matrigel and treated with SU5416 at MTD or PBS plus DMSO on days 1, 3, and 5. Matrigel plugs were analyzed on day 7 for microvascular density. The average microvas cular density at 7 days was 42 microvessels per high power field in control mice treated with PBS DMSO, LD paclitaxel as well as SU5416 at MTD resulted in significant suppression of vascular development, Thus paclitaxel at 1 4 MTD twice per week sup pressed vessel formation in vivo.

Therapeutic AZD1152-HQPA Aurora キナーゼ 阻害剤 efficacy of low dose paclitaxel on ID8 and ID8 Vegf tumors Next, we tested the effects of LD paclitaxel on tumor growth in the ID8 and ID8 Vegf model, Low dose paclitaxel at the above dose and schedule had a sig nificant inhibitory effect on the growth of ID8 tumors, The volume of ID8 tumors treated with paclitaxel was significantly smaller than control ID8 tumors treated with PBS, Low dose paclitaxel had also significant inhibi tory effect on the growth of ID8 Vegf tumors, The volume of ID8 Vegf tumors treated with pacli taxel was significantly smaller, or paclitaxel plus SU5416, Con trol mice were treated with saline plus DMSO.

As previ ously noted, LD paclitaxel delayed the growth of ID8 tumors, while SU5416 had a nonsignificant inhibitory effect on ID8 tumors, The combina tion of paclitaxel and SU5416 resulted in significant sup pression of tumor growth where ID8 tumors treated with LD paclitaxel plus SU5416 were 13 fold purchase AMN-107 smaller than con trol tumors and tumors became undetectable in many animals. Thus, LD paclitaxel was more effica cious than SU5416 against tumors with low Vegf expres sion. Furthermore, combination of SU5416 and paclitaxel was quite efficacious against ovarian carcinoma that expressed low levels of Vegf resulting in substantial tumor regression,microvesselphosphate tumor free MatrigelDMSO in ID8 Vegf tumors treated with PBS, These results show that both ID8 and ID8 Vegf tumors respond to paclitaxel.

To evaluate the interaction between low dose paclitaxel and SU5416 on tumor growth, we treated animals bearing ID8 tumors with LD paclitaxel, SU5416 We used the fitted functional linear models to further characterize the interactions between SU5416 and LD paclitaxel in ID8 tumors, The estimate of the difference between actual effect of combination therapy and the estimated theoretical additive effect of the two drugs on ID8 tumor volumes was approximately zero for all time points, indicating that SU5416 when combined with paclitaxel had an additive effect on ID8 tumors. Effects of LD paclitaxel and SU5416 on microvascular density in ID8 tumors To better understand the interaction of paclitaxel and SU5416, we sought to define the effects of each drug on tumor microvasculature in vivo.