BACKGROUND: Several studies have shown that @entity842 (NO)-releasing agents can kill @entity5 cells. Unfortunately, currently available NO delivery molecules do not target @entity5 cells preferentially. To exploit the overexpression of @entity413 transport proteins and the high level of @entity413 transport characteristics of @entity5 cells, @entity413 was conjugated to @entity16475 ( @entity68634 ) and evaluated for @entity137 in @entity1 @entity43 cells. METHODS: The @entity137 of @entity68634 and SNAP was assessed by clonogenic cell survival assays performed in @entity68635 ( @entity900 sensitive) and A2780cP ( @entity900 -resistant) @entity43 cells in vitro. Immunoblotting and immunohistochemistry were used to assess the expression of @entity1365 @entity12015 transport protein in the cell lines as well as in paraffin blocks from 28 surgical specimens of @entity43 . Apoptosis was assessed by an end-labeling assay. RESULTS: The @entity43 cell lines consistently were more sensitive to @entity68634 than SNAP alone. The median effective doses (MEDs) for @entity68634 and SNAP in the A2780s cell line were 0.0042 microM and 20.4 microM, respectively. Therefore, @entity68634 was nearly 5000-fold more potent than the NO-donating moiety (SNAP) alone. In the A2780cP cells, the MED for @entity68634 (0.38 microM) was 250-fold lower than that for SNAP alone (100 microM). Immunoblotting and immunohistochemistry studies showed overexpression of @entity1365 in the cell lines and in 23 of 28 @entity43 specimens. CONCLUSIONS: The novel glyco-NO conjugate @entity68634 exhibits a much greater @entity137 than the parent NO donor without the hexose moiety. These agents have the potential to target @entity5 cells preferentially, that overexpress @entity1365 . This transporter is expressed highly in @entity43 .

Antitumor activity of a novel glyco- XXXX conjugate in @entity43 .

@entity68634 :: ('MESH:C528975', 'Chemical') :: ['2-gluSNAP', '2-GluSNAP'] @entity1 :: ('9606', 'Species') :: ['human'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian carcinoma', 'epithelial ovarian carcinoma'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity16475 :: ('MESH:D026423', 'Chemical') :: ['S-nitroso-N-acetyl-penicillamine'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity68635 :: ('p|SUB|A|2780|S', 'ProteinMutation') :: ['A2780S'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity12015 :: ('CHEBI:18133', 'Chemical') :: ['hexose'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity1365 :: ('6513', 'Gene') :: ['Glut-1'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity842 :: (MESH:D009569,Chemical) :: ['nitric oxide']
