2000 had little influence on the efficacy of cobalt hti 286 the most direct demonstration of this was provided by treatment of xenografts derived from hct116 cells in which the p53 gene was purposefully disrupted by gene targeting bunz et al 1998 the results were very similar to those shown in fig3 a and b for parental hct116 cells with 38 of the mice cured of their p53 u2212 u2212 tumors cobalt vinorelbine vinorelbine is a clinically approved drug that like hti 286 inhibits microtubule synthesis and thereby disrupts microtubules two tumor xenograft models one hct116 relatively sensitive to cobalt hti 286 and one ht29 relatively resistant to cobalt hti 286 were chosen to evaluate cobalt vinorelbine cobalt vinorelbine also induced hemorrhagic necrosis though this necrosis was less pronounced than that obtained with cobalt hti 286 compare fig1 b with fig1 a as with cobalt hti 286 hct116 responded much better to cobalt vinorelbine than did ht29 fig5 cobalt docetaxel and cobalt mac 321 as noted above a very different type of response was observed with c novyi nt when used in combination with microtubule stabilizing drugs exemplified by docetaxel and mac 321 in particular there was a much slower response and no hemorrhagic necrosis following cobalt with these agents fig2 additionally the tumors generally underwent a more pronounced regression with docetaxel or mac 321 alone than with hti 286 or vinorelbine alone nevertheless the addition of c novyi nt spores substantially improved the durations of the remissions achieved with these agents all mice bearing hct116 xenografts treated with cobalt docetaxel were cured unlike the case with docetaxel alone fig6 a b the responses of mice bearing hucc t1 were also encouraging fig6 c d like the case with cobalt hti 286 ht29 did not.