To identify robust DDR readouts which could be leveraged to recognize cells wit

4% ARQ 197 905854-02-6 of the cancer sam ples, whereas the remaining 105 samples displayed weak or absent CXCR4 staining. The ETAR and CXCR4 expression levels were closely correlated with each otherin the 48 NPC cases positive for the expression of CXCR4, 46 were also positive for ETAR expression. The correlation between ETAR and CXCR4 and their prognostic value The 5 year OS, progression free survival, locoregional relapse free survival, and DMFS rates in the ETAR positive patients were 56. 6%, 45. 9%, 76. 5%, and 57. 4%, respectively. The corresponding rates in the ETAR negative patients were 75. 0%, 77%, 83. 7%, and 90%, respect ively. With the exception of locoregional failure, all the differences were statistically significant. No cor relation was found between ETAR expression and the gender, age, T stage, N stage, or TNM clinical stage of the patients.<br><br> Next, we analyzed the relationship between the clinical outcome and CXCR4 expression levels. The 5 year OS, PFS, LRRFS, and DMFS rates in the CXCR4 positive patients were 39. 6%, 30. 6%, 69. 1%, and 41. 1%, respectively. the corresponding rates were 71. AZD0530 Bcr-Abl 阻害剤 4%, 64. 9%, 82. 4%, and 76. 9%, respectively, in the CXCR4 negative patients. All the differences were statistically significant. No correlation was found between the CXCR4 expression levels and gender, age, N stage, or TNM clinical stage of the patients. However, CXCR4 expression did show a posi tive correlation with T stage. To adjust for prognostic factors, the following parame ters were included in the multivariate analysis using the Cox proportional hazards modelgender, age, T stage, N stage, clinical stage, ETAR expression, and CXCR4 expression.<br><br> A step wise forward procedure was used for the analyses. By including the ETAR and CXCR4 expression levels sep arately in the Cox model, along with other variables, the multivariate analysis showed that the expression of ETAR was an independent prognostic factor for OS, PFS, and DMFS and that オーダー Alvocidib the ex pression of CXCR4 was an independent significant prognostic factor for OS, PFS, and DMFS. When ETAR and CXCR4 were included to gether in the Cox model, along with other variables, the results showed that CXCR4 expression was an inde pendent prognostic factor for OS and that both ETAR and CXCR4 expression were independent prognostic factors for PFS. For DMFS, N stage, ETAR expression, and CXCR4 expression were independent prognostic factors.<br><br> In contrast, clinical stage was the only independent, significant prognostic factor for LRRFS. ET 1 induces CXCR4 mRNA and protein expression in 6 10B NPC cells We also investigated whether ETAR activation could in crease CXCR4 expression in human NPC cells using real time PCR for CXCR4 mRNA expression and west ern blotting and flow cytometric analysis for CXCR4 protein expression. The results showed that ET 1 in duced CXCR4 mRNA and protein expression in 6 10B cells in a time and concentration dependent manner. siETAR reduces ETAR and CXCR4 protein expression and attenuates ET 1 stimulation of CXCR4 expression in 5 8F cells The knockdown of ETAR protein expression by siETAR reduced the expression of both ETAR and CXCR4 pro teins, and ET 1 could not increase CXCR4 expression after ETAR knockdown in 5 8F cells.