Two Additional Remarkable Issues Involving ABT-199

Flow cytometric analysis confirmed that CD27 was not expressed on SNK6, SNT8, SNK1, KAI3, YT and NK92, but it was detected in PBMC, Jurkat, MOLT4, PEER and Raji (Fig?2B). CD27 http://www.selleckchem.com/products/ABT-263.html is cleaved from membrane-bound CD27, resulting in the formation of a soluble form of CD27. Recently, it is reported that soluble CD27 conjugates CD70 expressed on the cell surface and then induces IgG production from antigen-primed B-cells (Dang et?al, 2011), suggesting that CD70 operates as a receptor to induce a signal transduction pathway in these cells, as previously shown in some B-cell lines (Lens et?al, 1999). In the present study, in order to investigate whether CD70 acts as a growth factor by binding to soluble CD27 in NNKTL cell lines, we performed MTS assays on NNKTL cell lines under culture conditions with exogenous soluble CD27. As shown in Fig?3A, exogenous soluble CD27 enhanced cell growth in a dose-dependent manner in NNKTL cell lines (SNK6, SNK1) and Raji cells. The exogenous soluble CD27-dependent cell growth showed a statistically significant level at a dose of 1?��g/ml of soluble CD27 (P? http://www.selleckchem.com/products/abt-199.html growth of NNKTL cell lines (SNK6, SNK1), but the soluble CD27-dependent cell growth was inhibited by anti-CD27 neutralizing antibodies in a dose-dependent manner and it was completely inhibited by the concentration of 10?��g/ml of the antibody. However, exogenous soluble CD27 as well as anti-CD27 neutralizing antibodies did not affect cell growth of the CD70-negative cell line NK92. Next, we performed double immunohistological staining for expressions of CD70 and CD56 on the biopsy samples from 21 patients with NNKTL, to confirm whether CD70 is expressed on the lymphoma cells in the patients' tissues. CD70 expression of CD56-positive lymphoma cells was detected in the tissues from 7 (33%) of 21 patients. Representative immunohistological http://www.selleck.cn/products/CP-690550.html feature is shown in Fig?4A: A certain number of atypical large lymphoma cells co-expressed with CD70 and CD56 (arrow) are seen together with some small sized CD56-positive lymphoma cells without CD70 expression (white arrow head) and CD70-positive small lymphocytes (black arrow head) in the lymphoma tissue. We also performed ELISA for measurement of soluble CD27 in sera from eight patients with NNKTL patients and seven healthy individuals, to confirm whether soluble CD27 was present in patients' sera. As shown in Fig?4B, the serum level of soluble CD27 in NNKTL patients was significantly higher than that of healthy individuals (median: 25�C75 percentile?=?3930: 3352�C4894?U/ml vs. 2966: 1768�C3351?U/ml; P?=?0��018).