Use of nude @entity19 xenografts as preclinical drug screens: in vivo activity of established chemotherapeutic agents against @entity320 and XXXX xenografts.

@entity1 @entity43 @entity632 @entity5257 @entity19 @entity5 @entity1138 @entity900 @entity4316 @entity3601 @entity2879 @entity3600 @entity1778 @entity1732 @entity320 @entity5713
To evaluate the utility of nude @entity19 xenografts as preclinical drug screens, the activity of ten established chemotherapeutic agents was evaluated against seven @entity320 and three @entity43 xenografts. Xenografts were established using primary explants from @entity1 who had not received chemotherapy and serially passaged as sc @entity5 in @entity19 . In vivo drug activities for @entity4316 , @entity3600 , @entity5713 , @entity3601 , @entity5257 , @entity900 , @entity1732 , @entity1138 , @entity632 , and @entity2879 were evaluated by 4 weekly ip injections of 10% less than LD10 doses. Plots of relative @entity5 growth versus time were nearly log-linear. Analysis of in vivo activity was performed using percent control growth (treated/control @entity5 volume) and by calculation of a novel growth delay index obtained by fitting growth curves to a quadratic regression model. Both modes of data analysis identified alkylating agents ( @entity3601 , @entity3600 , and @entity1138 ) as the most active drugs against @entity1 @entity320 . @entity3601 , @entity1138 , and @entity900 showed the greatest activity against ovarian xenografts. However, complete @entity5 regressions were noted only with @entity3601 , @entity1138 , and @entity900 against a single @entity43 xenograft. Correlation analysis suggested xenograft @entity5 growth rate was an important determinant of drug response. These results suggest that preclinical, new-drug screening with @entity320 xenografts would identify drugs such as alkylating agents as active, and may not provide an advantage over @entity19 @entity1778 screens. However, screening with ovarian xenografts may more closely reflect clinical drug activity. Criteria for detecting active drugs in such systems are discussed.
