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Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF), we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM) induced cell death concomitant with decreases in mitochondrial membrane potential, chromatin condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up-regulated and 548 down-regulated genes, that were differentially expressed by >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4 groups by K-means clustering. Ingenuity® pathway analysis revealed several gene networks from gene clusters. The gene networks Up-I and Up-II included many up-regulated genes that were mainly associated with the biological function of induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos (for Up-I) and Atf4 and Hspa5 (for Up-II). Interestingly, knockdown of Ddit3 and Hspa5 significantly increased and decreased the number of viable cells, respectively. Moreover, several endoplasmic reticulum (ER) stress-related genes including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These findings will provide further insight into the molecular mechanisms of NaF-induced cell death accompanying ER stress in oral epithelial cells.

Hyperthermia (HT) is an important modality in cancer treatment; however, the acquisition of thermal resistance in cancer cells due to the elevation of heat shock proteins (HSPs) makes HT less effective. Accumulating evidence suggests that microRNAs (miRNAs) play an important role in regulating cellular stress sensitivities, such as drug sensitivity and radio-sensitivity, in cancer cells. However, few studies have investigated the involvement of miRNAs in thermal sensitivity. The aim of this study was thus to investigate the contribution of miRNAs to the thermal sensitivity of human oral squamous cell carcinoma (OSCC) cells. When the HSC-2, HSC-3 and HSC-4 OSCC cell lines were treated with HT at 44˚C for 60 min, a significant increase in cell death was observed in HSC-2 and HSC-3 cells but not HSC-4 cells, suggesting that HSC-4 cells were thermally resistant under the present experimental conditions. Moreover, the expression levels of HSPs were most elevated in HSC-4 cells. When the basal expression levels of miRNAs were monitored using two different microarray systems in thermal-sensitive HSC-2 and HSC-3 cells and thermal-resistant HSC-4 cells, five miRNAs that were differentially expressed were identified. Among these miRNAs, the expression level of miR-27a in HSC-4 cells was markedly reducec compared to the expression levels in HSC-2 and HSC-3 cells. Interestingly, treatment of HSC-4 cells with a miR-27a mimic oligonucleotide significantly enhanced HT-induced cell death. Furthermore, the miR-27a mimic oligonucleotide suppressed the elevation of the expression of Hsp90 and Hsp110 in HSC-4 cells, suggesting that these HSPs may be involved in a mechanism of thermal resistance. From these findings, we concluded that in OSCC cells, miR-27a may contribute to thermal sensitivity by modulating the HSP expression.

The silencing of BAG3 seems to enhance the effects of HT, at least in part, by maintaining HT-induced inactivity of NF-κB and the phosphorylation of ERK. These findings indicate that BAG3 may be a potential molecular target for modifying the outcomes of HT in retinoblastoma.

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Additional grid laser photocoagulation for recurrent macular edema in BRVO after IVB maintained mean visual acuity with limited effects on the further recurrence of macular edema.

Baseline VA and IS/OS line grade at 4 weeks may be predictive factors for final VA.