Thus, L9 was more sensitive to TSA than LE, and K9 was more sensitive to MG115 than KE. The differential sensitivities implied that intrinsic properties of the cell lines could have caused reference 4 L9/LE to be more sensitive to TSA than K9/KE, and K9/KE to be more sensitive to MG115 than L9/LE. ELISA was used to measure the induction of p21cip1/waf1 after drug treatments. The increase after TSA treatment was 3. 0 0. 7 fold in K9 cells, 2. 6 1. 0 fold in KE cells, 9. 5 1. 9 fold in L9 cells, and 4. 0 1. 6 fold in LE cells. L9 and LE had more induction of p21cip1/waf1 than K9 and KE, and significantly L9 showed higher induction of p21cip1/waf1 than LE. Similarly, the increase after MG115 treatment was 3. 7 0. 4 fold in K9 cells, 2. 1 0. 5 fold in KE cells, 1. 0 0. 1 fold in L9 cells, and 0. 8 0.

1 fold in LE cells. K9 and KE had more induction of p21cip1/waf1 than L9 and LE, and significantly K9 showed higher induction of p21cip1/waf1than Inhibitors,Modulators,Libraries KE. Thus, consistent with the data on apoptosis, L9 cells had the most significant increase of p21cip1/waf1 under TSA treatment and K9 cells had the most significant increase of p21cip1/waf1 Inhibitors,Modulators,Libraries under MG115 treatment. The effects of TSA and MG115 Inhibitors,Modulators,Libraries on cell growth were measured. Based on 4 repeats, the cell Inhibitors,Modulators,Libraries numbers at 48 hours after TSA treatment were 3. 6 0. 4 for untreated LE, 3. 7 0. 5 for untreated L9, 2. 4 0. 1 for treated LE, and 0. 7 0. 1 for treated L9. Treated L9 cells grew slower than the others. Similarly, the cell numbers at 48 hours after MG115 treatment were 3. 3 0. 1 for untreated KE, 2. 8 0. 1 for untreated K9, 1. 8 0. 1 for treated KE, and 0.

6 0. 1 for treated K9. Treated K9 cells grew slower than the others. Thus, L9 grew slower than LE cells when treated with TSA, whereas K9 grew slower Inhibitors,Modulators,Libraries than KE cells when treated with MG115. Taken together, these data were consistent with the hypothesis that EBER1 suppressed p21cip1/waf1 transcrip tion and conferred resistance to drug induced apoptosis in these model systems. EBV Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis Ninety four HLs, including 68 EBV and 26 EBV cases, were used for the assessment of the clinical significance of p21cip1/waf1 suppression. Immunohistochemical stains were performed for p21cip1/ waf1, active caspase 3 as an apoptotic marker, and Ki67 as a proliferation marker.

The percentages of Reed Sternberg cells that were positive for p21cip1/waf1 pathway signaling were determined, and the median values for the EBV and the EBV groups were listed in Table 2. Compared with the EBV group, the EBV group was slightly more likely to present at a later stage and a higher LDH level. The EBV group expressed significantly less p21 and active caspase 3, in which EBER1 suppresses p21cip1/waf1 transcription indirectly through EGR1, and STAT1. In addition, EBER1 might suppress p21cip1/waf1 through the wild type p53 in KE, but not the mutant type p53 in LE.