Positive regulation of HIF-1A expression by EBV oncoprotein LMP1 in nasopharyngeal carcinoma cells.

Latent membrane protein 1 (LMP1) is a pivotal viral oncoprotein that contributes to the carcinogenesis of Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC). We investigated the regulation of hypoxia-inducible factor 1-α (HIF-1α) by LMP1. In NPC cells, we found that LMP1 significantly enhanced the HIF-1α mRNA level, and not only the protein amount as described previously. Mechanistically, the stability of the HIF-1α transcript was remarkably prolonged by LMP1 via reduced expressions of RNA-destabilizing proteins tristetraprolin (TTP) and pumilio RNA-binding family member 2 (PUM2) through C-terminal activation region 1 (CTAR1) and CTAR3 interaction with the ERK1/2 and STAT3 signaling pathways, respectively, in parallel with hindrance of PUM2 binding to the HIF-1α mRNA 3'-untranslated region (3'-UTR). On the other hand, HIF-1A promoter activity was also obviously facilitated by the LMP1 CTAR1-recruited ERK1/2/NF-κB pathway. Intriguingly, in this scenario, augmented HIF-1α further exhibited positive auto-regulation of its own gene transcription. Our results showed the first time that LMP1 directly up-regulates HIF-1A transcription and post-transcription in NPC cells, in addition to providing evidence of an increase in the HIF-1α mRNA level caused by a tumor-associated virus under normoxic conditions.

Simultaneous use of mifepristone and misoprostol for early pregnancy termination.

OBJECTIVE: Simultaneous mifepristone 200mg and vaginal misoprostol 800µg produces a complete abortion rate of approximately 90% at up to 63 days of gestation. The aim of this study was to determine the effectiveness of concurrent administration of mifepristone 200mg and vaginal misoprostol 600µg with respect to early medical abortion. MATERIALS AND METHODS: A total of 254 women with undesired pregnancies of less than 49 days of gestation were enrolled. All women received oral mifepristone 200mg and vaginal misoprostol 600µg concurrently. Follow-up assessment by transvaginal ultrasonography was performed 3 days and 2 weeks after treatment. RESULTS: Efficacy outcome was analyzed for 242 women (95.3%) after excluding 12 individuals lost to follow-up. The complete abortion rate was 92.6%. The mean induction to abortion interval was about 5.8hours. The mean bleeding duration was about 12.6 days. The women indicated that the side effects were tolerable and 90% of them said that their experience was satisfactory. CONCLUSION: Concurrent administration of oral mifepristone 200mg and vaginal misoprostol 600µg is an efficacious regimen for medical abortion of pregnancies up to 49 days of gestation.

High-dose misoprostol as an alternative therapy after failed medical abortion.

OBJECTIVE: The aim of this study was to determine the complete abortion rate for the vaginal administration of high-dose misoprostol after a failed medical abortion. MATERIALS AND METHODS: When their medical abortions failed after the conventional oral administration of mifepristone and misoprostol, participants then received 1,000 microg of misoprostol vaginally. The efficacy and side effects of this treatment were evaluated. RESULTS: Twenty-seven women who failed to abort after the conventional administration of mifepristone and misoprostol were enrolled in this trial. Fourteen days after the vaginal administration of 1,000 microg misoprostol, the overall complete expulsion rate had reached 88.8% (24/27). Most adverse effects were mild to moderate and did not require treatment. CONCLUSION: The vaginal administration of 1,000 microg misoprostol as a salvage therapy after a failed medical abortion appears to be a safe and highly effective alternative to surgical intervention.

Protein expression and intracellular localization of prostate apoptosis response-4 (Par-4) are associated with apoptosis induction in nasopharyngeal carcinoma cell lines.

Prostate apoptosis response-4 (Par-4) is a proapoptotic gene that selectively induces cell death in most cancer cells. In addition to the increased percentage of apoptotic cells, caspase-3 activity, and poly (ADP-ribose) polymerase (PARP) cleavage, we demonstrate that elevated expression of Par-4 and nuclear entry resulted in apoptosis of nasopharyngeal carcinoma (NPC) cell lines either in serum deprivation or by ectopic overexpression of Par-4. Moreover, disassociation from the Par-4/Akt complex was correlated with the induced proapoptotic ability of Par-4. Therefore, our data suggest that the cytoplasmic localization and expression level of endogenous Par-4 in NPC cells are not sufficient to augment apoptosis.