@entity1 @entity43 from A2780 cells were grown as xenografts in immunodeficient @entity19 , treated with a single i.p. dose of melphalan and @entity5 cells were removed and placed into tissue culture. The cells from the treated @entity5 exhibited an approximately 2-fold resistance to melphalan in vitro compared to cells taken from untreated @entity5 . This degree of resistance was similar to that of cells from @entity5 formed from @entity3601 -resistant A2780-ME cells. The cells from the treated @entity5 were also resistant to @entity900 but not to @entity632 . They contained approximately 2-fold higher levels of @entity2041 than cells from the untreated @entity5 . Exposure of the cells to @entity3016 (a specific inhibitor of @entity2041 biosynthesis) eliminated the difference in @entity2041 levels as well as the difference in sensitivity to melphalan. When @entity5 -bearing animals were treated with @entity3016 in addition to melphalan the resulting @entity5 cells were not resistant to the drug. Resistance could also be demonstrated in the @entity5 themselves in vivo: the growth of previously untreated @entity5 was severely inhibited by a high dose of melphalan (11.7 mg/kg) administered i.p. to the animals, whereas the growth of @entity5 which had received prior treatment with melphalan was unaffected by the subsequent high dose. The rapid development of drug-resistant @entity5 cells after a single drug treatment in vivo makes this an excellent system for the investigation of the mechanisms by which resistance develops as well as for use in the screening for agents which can prevent it.

Rapid development of drug resistance in XXXX @entity43 xenografts after a single treatment with melphalan in Vivo.

@entity1 :: ('9606', 'Species') :: ['Human'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian tumors'] @entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity3601 :: ('MESH:D008558', 'Chemical') :: ['melphalan'] @entity3016 :: ('MESH:D019328', 'Chemical') :: ['buthionine sulfoximine']
@entity1 :: (9606,Species) :: ['human']
