@entity38450 ( XXXX ) improves the activity of @entity2903 and radiation for orthotopic @entity11 .

@entity1 @entity11349 @entity38450 @entity137 @entity5 @entity19 @entity11 @entity2903 @entity8498 @entity463
@entity11 are highly lethal @entity5 resistant to current therapies. The standard treatment modality for these @entity5 , surgical resection followed by radiation therapy and concurrent @entity2903 , has demonstrated activity, but development of resistance and disease progression is common. Although oncogenic Ras mutations are uncommon in @entity11 , Ras has been found to be constitutively activated through the action of upstream signaling pathways, suggesting that farnesyltransferase inhibitors may show activity against these @entity5 . We now report the in vitro and orthotopic in vivo results of combination therapy using radiation, @entity2903 and @entity38450 ( @entity38450 ), an oral @entity11349 transferase inhibitor, in a @entity19 model of @entity463 . We examined the viability, proliferation, farnesylation of @entity8498 , and activation of downstream signaling of combination-treated U87 cells in vitro. @entity38450 alone or in combination with radiation and @entity2903 had limited @entity5 cell @entity137 in vitro although it did demonstrate significant inhibition in @entity5 cell proliferation. In vivo, @entity38450 alone had a modest ability to inhibit orthotopic U87 @entity5 , radiation and @entity2903 demonstrated better inhibition, while significant anti- @entity5 activity was found with concurrent @entity38450 , radiation, and @entity2903 , with the majority of animals demonstrating a decrease in @entity5 volume. The use of @entity5 neurospheres derived from freshly resected adult @entity1 @entity463 tissue was relatively resistant to both @entity2903 and radiation therapy. @entity38450 had a significant inhibitory activity against these neurospheres and could potentate the activity of @entity2903 and radiation. These data support the continued research of high grade @entity11 treatment combinations of @entity11349 transferase inhibitors, @entity2903 , and radiation therapy.
