In an 18-month carcinogenicity study, Pim1 transgenic mice were exposed to pulsed 900 MHz (pulse width: 0.577 ms; pulse repetition rate: 217 Hz) radiofrequency (RF) radiation at a whole-body specific absorption rate (SAR) of 0.5, 1.4 or 4.0 W/kg [uncertainty (k = 2): 2.6 dB; lifetime variation (k = 1): 1.2 dB]. A total of 500 mice, 50 per sex per group, were exposed, sham-exposed or used as cage controls. The experiment was an extension of a previously published study in female Pim1 transgenic mice conducted by Repacholi et al. (Radiat. Res. 147, 631-640, 1997) that reported a significant increase in lymphomas after exposure to the same 900 MHz RF signal. Animals were exposed for 1 h/day, 7 days/week in plastic tubes similar to those used in inhalation studies to obtain well-defined uniform exposure. The study was conducted blind. The highest exposure level (4 W/kg) used in this study resulted in organ-averaged SARs that are above the peak spatial SAR limits allowed by the ICNIRP (International Commission on Non-ionizing Radiation Protection) standard for environmental exposures. The whole-body average was about three times greater than the highest average SAR reported in the earlier study by Repacholi et al. The results of this study do not suggest any effect of 217 Hz-pulsed RF-radiation exposure (pulse width: 0.577 ms) on the incidence of tumors at any site, and thus the findings of Repacholi et al. were not confirmed. Overall, the study shows no effect of RF radiation under the conditions used on the incidence of any neoplastic or non-neoplastic lesion, and thus the study does not provide evidence that RF radiation possesses carcinogenic potential.

Endocan (or called Esm-1) has been shown to have tumorigenic activities and its expression is associated with poor prognosis in various cancers. Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein and has been shown to play an important role in the pathogenesis of EBV-associated nasopharyngeal carcinoma (NPC). To further understand the role of LMP1 in the pathogenesis of NPC, microarray analysis of LMP1-regulated genes in epithelial cells was performed. We found that endocan was one of the major cellular genes upregulated by LMP1. This induction of endocan by LMP1 was confirmed in several epithelial cell lines including an NPC cell line. Upregulation of endocan by LMP1 was found to be mediated through the CTAR1 and CTAR2 domains of LMP1 and through the LMP1-activated NF-κB, MEK-ERK and JNK signaling pathways. To study whether endocan was expressed in NPC and whether endocan expression was associated with LMP1 expression in NPC, the expression of endocan and LMP1 in tumor tissues from 42 NPC patients was evaluated by immunohistochemistry. Expression of endocan was found in 52% of NPC specimens. Significant correlation between LMP1 and endocan expression was observed (p<0.0001). Moreover, NPC patients with endocan expression were found to have a shorter survival than NPC patients without endocan expression (p=0.0104, log-rank test). Univariate and Multivariate analyses revealed that endocan was a potential prognostic factor for NPC. Finally, we demonstrated that endocan could stimulate the migration and invasion ability of endothelial cells and this activity of endocan was dependent on the glycan moiety and the phenylalanine-rich region of endocan. Together, these studies not only identify a new molecular marker that may predict the survival of NPC patients but also provide a new insight to the pathogenesis of NPC.

Summary Mixed chimerism has been shown to lead to prolonged major histocompatibility complex (MHC) disparate allograft survival and immune‐specific tolerance; however, traditional conditioning regimes often involve myeloablation, which may pose a significant safety risk. In this study we examined the use of donor C57BL/6 (H‐2b) immature dendritic cells (imDCs) to tolerize the BALB/c (H‐2d) recipient to bone marrow transplantation (BMT), allowing the induction of mixed chimerism without immunosuppression or myeloablation. We showed that successful mismatched bone marrow engraftment can be achieved using imDCs given up to 3 days prior to BMT and that mixed chimerism can be established and detected in excess of 100 days post‐BMT without evidence of graft‐versus‐host disease. Furthermore, we showed that imDCs can suppress lymphocyte proliferation in response to mismatched MHC stimulation, leading to increased expression of interleukin (IL)‐4 and IL‐10 and decreased expression of IL‐2 and interferon‐γ (IFN‐γ). The induction of stable chimeras through pre‐conditioning of mice with donor imDCs followed by BMT led to tolerance, allowing the long‐term survival (> 110 days) of mismatched cardiac allografts and the prolonged survival of mismatched skin allografts without the need for immunosuppression or myeloablation. Transplantation with third‐party C3H allografts were rapidly rejected in this model, suggesting that immune‐specific tolerance was achieved. The induction of immune‐specific tolerance without the need for immunosuppression or myeloablation represents a significant advance in transplant immunology and may provide clinicians with a plausible alternative in combating organ rejection following transplantation.