International journal of cancer. Journal international du cancer
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Tissue hypoxia is a common feature in solid tumors. Hypoxia-inducible factor 1 (HIF-1) is a critical transcription factor that regulates the expression of genes encoding factors that influence tumor growth including vascular endothelial growth factor. Previous studies have demonstrated that post-transcriptional modification events are important for regulation of HIF-1alpha protein expression and HIF-1 transcriptional activity. ⋯ On the other hand, NS398 accelerates HIF-1alpha degradation by moderately increasing ubiquitination and remarkably promoting the clearance of ubiquitylated protein, an effect most likely independent of COX-2/PGE2 since exogenous PGE2 fails to reverse it. Finally, NS398 decreases hypoxia-induced shifted form of HIF-1alpha and attenuates HIF-1 activation in greater extent under hypoxic than normoxic conditions. These data not only confirm the inhibitory effect of NS398 on HIF-1alpha and HIF-1 transcriptional activity but also demonstrate that such an effect occurs at multiple levels involving both COX-2 dependent and independent mechanisms.
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Perineal talc use has been suggested as a possible risk factor for ovarian cancer based on its structural similarity to asbestos, a known human carcinogen. A population-based epidemiologic case-control study of epithelial ovarian cancer (EOC) was conducted in 22 counties of Central California that comprise the reporting area for 2 regional cancer registries. Telephone interviews were conducted with 256 cases diagnosed in the years 2000-2001 and 1,122 controls frequency-matched on age and ethnicity. ⋯ Tubal ligation (TL) modified the effect of talc on EOC such that women with TL had an OR of 0.88 (CI = 0.46-1.68) associated with perineal talc use, whereas women with no TL had an OR of 1.54 (CI = 1.10-2.16). Talc use and EOC risk was highest in women with serous invasive tumors (OR = 1.77; CI = 1.12-2.81). This study provides some support for the hypothesis that perineal talc use is associated with an increased risk of EOC.