PURPOSE: @entity687 ( @entity687 ) is a pleiotropic chemokine with both chemoattractant and angiogenic properties. In addition to its cytotoxic effects on @entity43 cells, @entity1311 can transcriptionally activate genes such as @entity687 that may play a role in tumorigenesis. Utilizing @entity687 as a prototypic marker of @entity5 -derived modulators of growth, we undertook a systematic study of @entity1311 and 11 structurally modified @entity1311 analogs to identify the region of the @entity3907 skeleton responsible for @entity687 gene induction. METHODS: The @entity1 @entity43 cell line OVCA-420 was exposed to @entity1311 or @entity1311 analogs. @entity687 gene induction was assessed by Northern blot analysis after 6 h and @entity137 after 72 h. RESULTS: Changes in the southern hemisphere ( @entity6746 to C-4) of the @entity3907 skeleton had greater effects on @entity687 induction than changes in the northern hemisphere ( @entity36381 to C-11). Some of the @entity1311 analogs modified at positions @entity6746 and/or @entity3627 with increased hydrophobicity induced @entity687 expression more than threefold over that induced by @entity1311 or taxotere and more than 20-fold over control cells. Cells that failed to induce @entity687 gene expression in response to @entity1311 were only marginally responsive to the analogs unless first primed with @entity1356 . Modifications to the northern hemisphere did not alter @entity1311 's effect on @entity687 expression in @entity1 cells, but did influence @entity310 expression in @entity19 macrophage cells, suggesting species and/or gene specificity. We found a direct correlation between @entity687 induction and @entity137 , in that analogs that dramatically upregulated @entity687 expression proved to be the most cytotoxic, inhibiting cell survival by > 90%. CONCLUSION: Taken together our results demonstrate that changes in the southern hemisphere of the @entity3907 skeleton influence both the gene induction and cytotoxic potential of @entity1311 in @entity1 @entity43 cells.

Identification of the structural region of @entity1311 that may be responsible for cytokine gene induction and XXXX in @entity1 @entity43 cells.

@entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancer'] @entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity6746 :: ('3183', 'Gene') :: ['C-1'] @entity1356 :: ('3553', 'Gene') :: ['IL-1beta'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity310 :: ('7124', 'Gene') :: ['TNFalpha'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['taxol'] @entity3907 :: ('MESH:C080625', 'Chemical') :: ['taxane'] @entity3627 :: ('717', 'Gene') :: ['C-2'] @entity36381 :: ('730', 'Gene') :: ['C-7'] @entity687 :: ('3576', 'Gene') :: ['Interleukin-8', 'IL-8']
@entity137 :: (MESH:D064420,Disease) :: ['cytotoxicity']
