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However, it was not known whether there was a difference in TRAIL sensitivity between adenoma and carcinoma cells and whether TRAIL receptor expression on the cell surface, rather than intracellular receptor pools, would correlate with sensitivity to TRAIL-induced apoptosis.
The proteins studied could not clearly reveal a difference in TRAIL sensitivity.
We studied whether the protein expression levels of several important proteins involved in apoptosis could explain the difference in TRAIL sensitivity.
The representative site-matched HNSCC cell lines 089 (HPV−) and 090 (HPV+), which demonstrated the highest difference in TRAIL sensitivity, were selected for further analysis.
The killing of H357 cells with activation of MSCFLT cells was higher than A549 cells (as demonstrated previously (Loebinger et al, 2009)) presumably due to a difference in TRAIL sensitivity.
Despite lack of difference in TRAIL receptor or Caspase-8 expression between sensitive and resistance cells, we found that the AZD5582+TRAIL combination effect was strongly correlated with TRAIL sensitivity; we observed no synergistic AZ5582+TRAIL combination effect only in 1 (Cal120) out of 12 cell lines in which TRAIL as a monotherapy reduced cell viability by more than 20%.
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However, there are significant differences in TRAIL sensitivity among human cancer cells.
Differences in TRAIL mean values across study phases were analyzed using analysis of variance (ANOVA) for repeated measures.
This could be either due to species-specific differences in TRAIL expression or due to the small sample size.
Two-sample t-test and one-way ANOVA were used to determine the statistical significance of the differences in TRAIL and its receptors expression levels in OPM and OSCC with various clinicopathologic parameters.
Koornstra et al (2003) also reported overall expression of TRAIL receptors, which have a large cytoplasmic component, to be similar in adenoma and carcinoma cells; therefore, immunohistochemical studies have not revealed a mechanism for the differences in TRAIL sensitivity between the adenoma and carcinoma cells.
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