Detection of EBV Infection and Gene Expression in Oral Cancer from Patients in Taiwan by Microarray Analysis

Epstein-Barr virus is known to cause nasopharyngeal carcinoma. Although oral cavity is located close to the nasal pharynx, the pathogenetic role of Epstein-Barr virus (EBV) in oral cancers is unclear. This molecular epidemiology study uses EBV genomic microarray (EBV-chip) to simultaneously detect the prevalent rate and viral gene expression patterns in 57 oral squamous cell carcinoma biopsies (OSCC) collected from patients in Taiwan. The majority of the specimens (82.5%) were EBV-positive that probably expressed coincidently the genes for EBNAs, LMP2A and 2B, and certain structural proteins. Importantly, the genes fabricated at the spots 61 (BBRF1, BBRF2, and BBRF3) and 68 (BDLF4 and BDRF1) on EBV-chip were actively expressed in a significantly greater number of OSCC exhibiting exophytic morphology or ulceration than those tissues with deep invasive lesions (P = .0265 and .0141, resp.). The results may thus provide the lead information for understanding the role of EBV in oral cancer pathogenesis

Outcome of Treatment with Total Main Tumor Resection and Supraomohyoid Neck Dissection in Oral Squamous Cell Carcinoma

Supraomohyoid neck dissection (SOHND) is commonly used to treat oral squa-mous cell carcinoma (OSCC) patients with clinical N0 or selected N1 status. The purpose of this study was to evaluate the clinical outcome of OSCC patients treated with SOHND. Methods: This retrospective study reviewed the clinical outcome of 257 patients (247 men, 10 women) with N0, N1 and N2a OSCC treated with wide excision of the main tumor and SOHND between 1992 and 1999. All patients were followed up for at least 5 years. Survival distributions were analyzed using Kaplan-Meier curves. N status was compared using χ2 and log rank tests. Results: The neck failure rate was 20% for clinically false negative cases, 6.1% for clinically true negative cases, 21.8% for clinically false positive cases, and 40% for clinically true positive cases. The 3- and 5-year overall neck disease-free survival rates were 79.8% and 77.6%, respectively. The 3- and 5-year neck disease-free survival rates were 86.7% and 84.2% for pathologic N0 cases, 56.9% and 56.9% for pathologic N1 cases, and 27.5% and 27.5% for pathologic N2 cases, respectively. Log rank test showed that the p value for difference in survival at 3-5 years was 0.064 for pathologic N0 vs. N1 cases, <0.0001 for pathologic N0 vs. N2 cases, and 0.008 for pathologic N1 vs. N2 cases. Conclusion: This study showed that SOHND is effective for pathologic N0 OSCC, relatively effective for pathologic N1, and less effective for pathologic N2a. These findings also support that when SOHND is used to treat N2a OSCC, postoperative radiotherapy or radical neck dissection may be needed to improve the neck disease-free survival rate

Possible Mechanism of Betel-quid-extract-induced Expression of Matrix Metalloproteinase-2

Betel quid extract (BQE) has been demonstrated to induce matrix metalloproteinase (MMP)-2 expression. This study aimed to establish the possible mechanism involved in this event. Methods: Western blotting, reverse-transcription polymerase chain reaction, and gelatin zymography were used to study the expression level of MMP-2. LY294002, PD98059, U0126, N-acetyl-L-cysteine, SB203580, SP600125, and Bay 11-7082 were used to pretreat OECM-1 cells before BQE treatment and MMP-2 detection. Results: OECM-1 cells were subjected to short-term (10 minutes) or long-term (24 hours) BQE treatment (designated as SBT and LBT, respectively), and we found that both treatments increased MMP-2 protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in a concentration- and time-dependent manner. LBT also increased MMP-2 mRNA level. LBT-induced MMP-2 secretion was not inhibited by PD98059 (up to 50 μM) when ERK was effectively blocked, but was attenuated by LY294002 (0–10 μM) in a concentration-dependent manner. This LBT effect was inhibited strongly by SB203580 (10 μM), SP600125 (10 μM), and Bay 11-7082 (10 μM) and mildly by N-acetyl-L-cysteine (5 mM), but not by U0126 (10 μM). Conclusion: Both SBT and LBT upregulate MMP-2 expression, and LBT-induced MMP-2 expression might be mediated by phosphoinositide 3-kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-?B, and to a lesser extent, by reactive oxygen species, rather than by ERK

YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial–mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer