Words similar to anti-proliferative
Example sentences for: anti-proliferative
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These domains interact with p21, CDK2 and CDK4 [ 22 24 25 36 55 ] . Thus, C/EBPα interactions with at least p21 and CDK4 were not required for the anti-proliferative actions of C/EBPα in GHFT1-5 cells.
These data provide additional evidence that 4-AP exerts neither an anti-proliferative nor a pro-apoptotic influence on serum-supplemented GC cultures, because PCNA expression is a sensitive marker of GC proliferation and apoptosis [ 18 26 27 ] . The lack of 4-AP effect on GC viability is also evident from the flow cytometric analysis; the percentages of cells staining positive for propidium iodide were 8 ± 2% and 7 ± 2% in the presence and absence of drug (n = 4 samples of 10,000 cells/each from 4 GC isolations).
For example, mouse embryonal stem (ES) cells with homozygous deletion of the PTEN gene exhibit increased anchorage-independent growth as compared to normal ES cells [ 12 ] . Similarly, transfer of a wild type PTEN gene into anchorage-independent human glioblastoma cells (which lack functional PTEN), results in their greatly reduced ability to form colonies in soft agar [ 4 5 6 ] . The interpretation of these latter findings, however, is complicated by the strong anti-proliferative effects of PTEN even in monolayer culture, which is consistently observed when the wild type version of this gene is introduced into PTEN-negative tumor cells [ 4 6 7 8 9 10 18 33 ] . Moreover, in human glioma and breast cancer cell lines, the ectopic expression of wild type PTEN leads to anoikis, which is apoptosis initiated by the disruption of cell matrix-interactions [ 23 34 35 36 ] .
We concluded that the anti-proliferative effect of 4-AP may contribute to the decreased progesterone accumulation observed in serum-free but not serum-supplemented GC cultures, then focused additional efforts on understanding other mechanisms responsible for 4-AP inhibition of progesterone production.
Our finding that 24 h exposure to 4-AP decreased the number of viable GC in serum-free but not serum-supplemented primary cultures is consistent with the reported effects of 4-AP and other K +channel antagonists on other cell types [ 8 43 44 ] . It has been shown that the concentrations of K +channel antagonists required to inhibit growth of human bladder tumor cells can be 70 times higher in the presence than the absence of serum [ 43 ] . 4-AP has been shown to inhibit the proliferation of human myelobastic leukemia cells by preventing growth factor activation of mitogen activated protein kinase (MAPK) pathways [ 42 ] . This mechanism may be responsible for the anti-proliferative effect of 4-AP manifest in Table 1. It is likely that MAPK pathways are less robust in GC grown in defined serum-free vs. serum-supplemented media; however, validation of this hypothesis would require additional experiments beyond the scope of the present investigation.
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