Patients with oral squamous cell carcinoma (OSCC) generally have an elevated expression of homeobox C6 (HOXC6) gene. We found that HOXC6 was the significantly upregulated gene in hypopharyngeal squamous cell carcinoma (FaDu) cells using RNA-seq analysis. However, it remains unclear whether HOXC6 plays a role in tumor process mechanism. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in FaDu cells. In this study, Sirt1 was validated to be overexpressed in FaDu cells and associated with HOXC6 expression. Overexpression of HOXC6 promoted the cell colony formation, whereas inhibition of Sirt1 by Sirt1 inhibitor EX527 reduced cell proliferation/colony formation and migration, and induced apoptosis in HOXC6 overexpressed FaDu cells. Interestingly, mechanistic study showed that EX527 mediated Sirt1 suppression led to decreased HOXC6 expression and upregulation of Sirt1 significantly increased the expression of HOXC6. HOXC6 was shown to cooperate with Sirt1 to enhance cell survival. We propose that HOXC6 promotes cell growth/colony formation, and that the HOXC6 may be a progression of hypopharyngeal carcinoma by activating Sirt1 pathways.

Aging is a physiological change that leads to a decline in biological functions from metabolic stress. To investigate the effect of aging on mandibular bone formation, we created SAMP1/Klotho-deficient mice and performed micro-computed tomography (micro-CT) and histology analyses in 4-or 8 week-old SAMP1/kl -/- mice. SAMP1/kl -/- mice exhibited extensive inflammation, tissue calcification, and abnormal mandibular bone development. Using micro-CT analysis, SAMP1/kl -/- mice displayed a loss of incisor roots and irregular dentinal tubule formation, as well as calcification within the pulp root canal. Furthermore, the mandibular ramus showed extensive ground glass appearance in SAMP1/kl -/- mice. In histological analysis, we found calcified skeletal structures and dysplastic bone formation in SAMP1/kl -/- mice. These results provide an understanding of the pathologic alterations of aging-related mandibular bone. SAMP1/kl -/- mice may serve as a novel model for dysosteogenesis in mandibular bone development.

To gain insights into the role of purinergic receptors in human dental pulp cells (hDPCs) differentiation, we characterized the expression and functional activity of P2Y1 receptors and investigated the effects of ADP on the proliferation and differentiation of this pulp stem-like cell population. Our data showed that ADP did not induce cell proliferation to expose the various ADP concentrations for 72 hours, but the proliferative capacity of hDPCs was inhibited at higher ATP concentrations (100 μM). Using RT-PCR analysis, we found that ADP induced several P2Y receptors including P2Y1 as well as odontoblastic differentiation genes, dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) in a dose-dependent manner. The effects of ADP on the expression of DMP-1 and DSPP mRNA were prevented by the P2Y1 antagonist MRS2179. The extracellular matrix calcium deposits were clearly observed in ADP-treated hDPCs by alizarin red S staining. Quantitative measurement of mineralization induced by ADP was significantly inhibited in MRS2179-treated hDPCs. These results may provide new insights into the molecular regulation of the differentiation of hDPCs.

Multidrug resistance (MDR) remains one of the most significant obstacles in various cancer treatment, and this process often involves dysregulation of the number of micro-RNAs. The aim of this study was to explore the role of miR-4708 on the regulation of MDR-1 expression and the regulation of multidrug resistance (MDR) to chemotherapeutic drugs. Luciferase reporter assays demonstrated that miR-4708 directly binds MDR-1 3’-UTR and down-regulated reporter luciferase activity. The mRNA and protein expression levels of MDR1 were significantly decreased following miR-4708 overexpression. Additionally, the accumulation of rhodamine-123 in paclitacel resistant FaDu cells following miR-4708 transfection was significantly increased compared with control, indicating that the efflux capacity was reduced. These results demonstrated that miR-4708 could be involved in the regulation of MDR via targeting MDR-1 and may provide a potential strategy for reversing drug resistance in oral cancer.

Primary localized amyloidosis of the palate is a rare condition. We present a case of localized amyloidosis of the palate of a 49-year-old Korean female who suffered from asymptomatic nodular swelling. Microscopic examination revealed extensive deposition of pale eosinophilic amorphous material throught the lamina propria and within the walls of small blood vessels. A diagnosis of localized amyloidosis was made after the biopsy revealed characteristic staining on Congo red, and an extensive workup for systemic involvement was negative. Localized amyloidosis should be considered in the differential diagnosis of palatal nodular lesions

Recently, new antibacteri al strategy has been demanded because of the incr eased occurrence 0 1' drug-resistant bact ena Accordingly , phot odynarnic therapy has been attempted for clinical appli cation against drug-resistant bact eri a, Antimi crobial photodyna rni c t herapy combines a nontoxic photosensiti zer with harmJ ess vi sible light to generate singlet oxygen and free radicals that kill lni croor ganism. In thi s study , we investigated bactericida l effect of photodynarnic ther apy by using phot osensiti zer chl orin e6 to pathogenic bacteria including a gram- positive Stapbylococuus a ureus and gram- negative strains including Pseudomonas aeruginosa, EscbeJicbia coù; and SaJmoneJla en terica sero v，없' 7γpbimurium， To exa때 n e antimicrobial ef fec t 0 1' photodynamic t herapy, we measured inhibition zone‘ colony forrning units (CFU) , and in situ viability of bacteri al cell s after illumination with an energy density (Diode pumped laser driver LD203이 01 20J/cm2 in the presence 0 1' lOuM chlorin e6, We found the incr ease 0 1' inhibition zone on agar plat es‘ the reduction 0 1' colony forming unit , and the rapid decrease 0 1' viable cell number 0 1' all bacterial species exarnined while those 0 1' control bacteria treated so ley wi th ei t her light 0 1' photosensiti zer were unchanged. The susceptibility of 8. aureush and P. aeru - ginosa was much higher t han that 01' the other strains These resu lts show tha t photodynamic t hera py using photosensi ti zer chlorin e6 is very effective to inhibit bacterial s urviva l, suggesti ng t hat t his system can be clin ically appli cable as an alternative antibacterial strategy to treat mul t iple drug-resistant bacteria

Photodynamic therapy (PDT) is a clinically approved and ra pidly developing cancer treatment regimen, It is a minimally invasive procedure that requires the administration of a photosens iti zer foll owed by the illumination of the tumor with Iigh t of an appropriate wavelength, In the presence of molecular oxygen, cytotoxic intermedi a ries a re produced‘ thus damaging cellular structures containing the photosensitizer , In the present study. we exa mined the effectiveness of newly d evelped chlorin e6- induced PDT on malignant animal tumor model of 3prague-Da wley (3D) ra t Three-week-old male 3D rats we re inocula ted s ,c, on the right f1 ank with our previously esta blished k- ras-trans formed RK3E cell line (RK3E- ras. tota l, 5xl07 cell s) , The experiments were carried out 1 week after inoculation of tumor cell s , by which time the tumors had r eached about 0,7 mm to 1.0 cm in diameter, L3-chlorin e6 (L8 Pharm Co" Gwa ngju, Korea) was admin istrated intravenous ly by the tail vein of 3D rat at a dosage of 10 mg/kg after inhalation a nesthesia of ether, Twenty- four hours a fter L8-chlorin e6 ad ministration, PDT was pe rfol‘med using a laser diode (Geumgwang Co ‘ Ltd‘’ Daejeon, Korea) a t a light dose of 100 J /cm2 and wavelength of 664 nm, A..nimals were monitered daily and tumor volume was measured by calipel The tumor t reated with PDT using Ce6 had significant reduction in tumor s ize examined by gross tumor volume , softex x- ray image, molecular imaging a nalysis, respectively, PCNA immunostaining and TUNEL assay revealed that the treat ed tu mor caused signifi cant inlübition of tumor formati on with decreased tumor cell proliferation a nd increased a poptosis , Our dat a showed Ce6-induced PDT effecti vely arrested the tumor growth by inhibi t ing cell proliferation a nd inducing a poptosis , These findings provide the potential value of Ce6- induced PDT as an a lternative candidate for a nt i- tumor therapy, Furthel bi ochemical and cellular studies will reveal the precise molecul ar mecha ni sm of cell death induced by PDT

System L amino acid transporter is a major route for providing living cells with neutral amino acids including several essential amino acids. To elucidate the expression pattern of L-type amino acid transporter 1 (LAT1) in the bone formation process, the expressions of LAT1 and its subunit 4F2 heavy chain (4F2hc) were investigated in the healing process after the implantation of bone graft materials in the calvarial osseous defected rats. Circular calvarial defects (1 cm in diameter) were made midparietally. The rats were divided into 4 groups of 1 control group and 3 experimental groups. In the control group, the defect was only covered with soft tissue flap. In the experimental groups, they were filled with human particulate dentin (particulate dentin group), with plaster of Paris (plaster of Paris group) and with the mixture of human particulate dentin and plaster of Paris with ratio of 2 : 1 by weight (mixture group). The rats were sacrificed at the 1, 2, 4 and 8 weeks after operation and the RT-PCR analysis and immunohistochemical analysis were performed. In the RT-PCR analysis, the mRNAs of LAT1 and 4F2hc were strongly detected in all 4 groups. In the immunohistochemical analysis, at 1 week after operation, the LAT1 protein and its subunit 4F2hc protein were mainly expressed in the osteoblasts, osteocytes and interstitial tissues of the around the defect and inner part of newly forming bone in all 4 groups. The expressions of LAT1 and 4F2hc proteins were decreased at 2 and 4 weeks after operation. The LAT1 and 4F2hc proteins were scarcely expressed at 8 weeks after operation in all 4 groups. These results suggest that the LAT1 and its subunit 4F2hc highly expressed at the early stage of new bone formation and may have an important role in providing cells with neutral amino acids including several essential amino acids at that stage.

A novel indirubin analog, 5'-nitro-indirubinoxime inhibits cell proliferation and induces apoptosis against various human cancer cells. In this study, we performed the microarray analysis to identify genes differentially expressed in the KB oral squamous carcinoma cells after treated with 5'-nitro-indirubinoxime. Among the 10,800 genes analyzed, 1,701 genes (15.8%) showed statistically different expression level in the 5'-nitro-indirubinoxime treated cells with respect to untreated control cells. Among those, 263 genes (15.5%) were down-regulated and 220 genes (12.9%) were up-regulated more than 2-fold. Functionally related gene clusters include genes associated with signal transduction (18.1%), especially genes related with apoptosis (3.5%) and cell cycle regulation (5.8%). Our application of microarray analysis on 5'-nitro-indirubinoxime treated oral cancer cells allows the identification of candidate genes for providing novel insights into the indirubin mediated antitumor activity.

Amino acid transporters play an important role in supplying organic nutrient to cells. The expression of L-type arnino acid transporter 1 (LATl) and its subunit 4F2 heavy chain (4F2hc) was evaluated to deterrnine the alterations to these transporters in oral norrnal mucosa (ONM) , oral precancerous lesion (OPL) and oral squamous cell carcinoma (OSCC). Sections from formalin-ftxed, paraffm-embedded S따nples of ONM, OPL or OSCC were exarnined using immunohistochernical staining to detect LATl and 4F2hc proteins. 까le LATl and 4F강lC expression increased progressively from ONM to hypeφ，Iastic and to dysplastic lesions and OSCC. In partiαlar， LATl rnay be a more S야dftc indicator of tumor prog~않sion than 4F2hc. 까le gradually increasing LA Tl and 4F2hc expression detected during the multistep progressive change shows that the protein rnay have an important role in the early stages of multistep oral carcinogenesis. In addition, the specific inhibition of LA Tl and 4F2hc rnight be a new rationale to suppress oral cancer progression.

Nitric oxide (NO) plays a key role in the processes of inflammation and carcinogenesis. Three isoforms of NO 야mthase have been identified: endothelial 띠띠c oxide 와nth앓e (NOS), neuronal NOS, and inducible NOS (이OS). The purpose of this study was to investigate the characteristics of iNOS expression in 7, 12-dimethylbenz[alanthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Sixty three outbred young (6-week-old) male Syrian golden hamsters were randomly divided into three groups: DMBA treated group (n=57) and non-treated (n=3), and mineral-oil treated group (n=3). No iNOS activity could be detected in the untreated or mineral oil-treated pouches. 80th cytoplasmic and nuclear stainings were observed in the DMBA-treated pouch kera띠lCX까es. There were iNOS expression 외so in the strorna1 cells. The mean values of iNOS expression in the epithelium increased gradually from control to dysplastic lesions and more to invasive squ따nous cell carcinoma. πle clifference between iNOS expr'않sion in the normal and that the dysplastic and carcinomatous lesions is statistically significant. The mean values of iNOS expression in the stroma increased gradually from control to dysplastic lesions and more to invasive squamous cell carcinoma. The difference between iNOS expression in the normal and that the carcinomatous lesions is statistica11y si맑， ificant. In conclusion, this study has demonstrated that iNOS is expressed in DMBA-induced hamster pouch carcinomas. πlis finding suggests that iNOS expression may be associated with the development of chemically induced oral carcmomas.