We previously showed that Na cooperates with the R protein to ind

We previously showed that Na cooperates with the R protein to induce lytic gene expression in latently infected EBV-positive 293 cells, and in some EBV-negative cell lines it can activate the Z promoter in reporter gene assays. Here we show that overexpression of Na alone is sufficient to induce lytic gene NVP-BSK805 cost expression in several different latently infected epithelial cell lines (Hone-Akata,

CNE2-Akata, and AGS-Akata), while knockdown of endogenous Na expression reduces lytic gene expression. Consistent with its ability to interact with tumor necrosis factor receptor-associated factor 2 (TRAF2) in a yeast two-hybrid assay, we demonstrate that Na interacts with TRAF2 in cells. Furthermore, we show that TRAF2 is required for Na induction of lytic gene expression, that Na induces Jun N-terminal protein kinase (JNK) activation Selleck MK-4827 in a TRAF2-dependent manner, and that a JNK inhibitor abolishes the ability of Na to disrupt viral latency. Additionally, we show that Na and the tumor suppressor protein p53 cooperate to induce lytic gene expression in epithelial cells (including the C666-1 nasopharyngeal carcinoma cell line), although Na does not appear to affect p53 function. Together these data suggest that Na plays an important role in regulating the switch

between latent and lytic infection in epithelial cells and that this effect requires both the TRAF2 and p53 cellular proteins.”
“Introduction: Ultrasound (US) contrast agents based on micrbbubbles (MBs) are being investigated as platforms for drug and gene delivery. A methodology for determining the distribution and fate of modified MBs quantitatively in vivo can be achieved by tagging MBs directly with Tc-99m. This creates

the opportunity to employ dual-modality imaging using both US and small animal SPECT along with quantitative ex vivo tissue selleck kinase inhibitor counting to evaluate novel MB constructs.

Methods: A Tc-99m-labeled biotin derivative ((99m)TcL1) was prepared and incubated with streptavidin-coated MBs. The Tc-99m-labeled bubbles were isolated using a streptavidin-coated magnetic-bead purification strategy that did not disrupt the MBs. A small animal scintigraphic/CT imaging study as well as a quantitative biodistribution study was completed using (99m)TcL1 and Tc-99m-labeled bubbles in healthy C57B1-6 mice.

Results: The imaging and biodistribution data showed rapid accumulation and retention of Tc-99m-MBs in the liver (68.2 +/- 6.6 %ID/g at 4 min; 93.3 +/- 3.2 %ID/g at 60 min) and spleen (214.2 +/- 19.7 %ID/g at 4 min; 213.4 +/- 19.7 %1D/g at 60 min). In contrast, (99m)TcL1 accumulated in multiple organs including the small intestine (22.5 +/- 3.6 %ID/g at 4 min; 83.4 +/- 5.9 %ID/g at 60 min) and bladder (184.0 +/- 88.1 %ID/g at 4 min; 24.2 +/- 17.7 %ID/g at 60 min).

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