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.

Cinnamaldehyde is known to have the antitumor effects in vitro and in vivo. In this study, we showed a potent and irreversible cytotoxic activity of the Cinnamaldehyde derivative 2'-benzoyloxycinnamaldehyde (BCA) in human Squamous oral cell carcinoma cell, YD-10B. BCA induced YD-10B cell apoptosis in a dose-responsive manner. BCA-induced apoptosis was associated with corresponding increases in a series of key components in the mitochondria-mediated apoptosis pathways, followed by caspase cleavage and PARP activation. We also observed that BCA induced autophagy through Akt/mTOR pathway in YD-10B cells. BCA treatment increased LC3B-II expression, and induced the formation of autophagosomes and autophagic vacuoles. These experimental findings suggest that BCA is a potent inhibitor of cell proliferation in YD-10B cells and provide new insights about leading to the possible development of a new therapeutic agent.

EGCG has inhibitory effect on a variety of cancers by inducing apoptosis and cell cycle arrest or inhibiting angiogenesis and metastasis. EGCG has been found to induce apoptosis in salivary gland carcinoma cells. But the potential anti-invasive effect of EGCG in salivary gland cancer has not been studied yet. The aim of this study is to evaluate the effect of EGCG on salivary gland adenocarcinoma SGT cell adhesion and migration to Type I collagen treatment. Western blot, adhesion and migration assay were performed to evaluate the impacts of EGCG on the expression of MMP-2/-9 and its upstream signaling molecules after treatment of type I collagen. SGT cell adhesion to type I collagen is significantly suppressed by EGCG. EGCG decreased expression of β1 integrin, phosphorylation of FAK, MMP-2/-9 compared with type I collagen treatment. In addition, EGCG inhibited the migration of SGT cells treated with type I collagen. These results suggest that EGCG could effectively inhibit the invasion and migration of human SGT cells by downregulating the expression of β1 integrin and MMP-2/-9 and phosphorylation of FAK, Akt, and Erk. Adhesion and migration to type I collagen of SGT cells can be influenced through EGCG.

The organotypic raft culture model has been shown to be a useful method for examining the effects of biochemical manipulation on various epithelial cell types, using in vitro conditions that simulate the in vivo environment of the tissue of origin. To investigate this method as a model for photodynamic therapy (PDT), we cultures the oral squamous carcinoma cell line YD-10B on fibroblast-containing collagen gels at the air-liquid interface and assessed the efficacy of PDT using a photosensitiser 5-ALA-hexenyl ester. PDT effect on YD-10B organotypic raft cultures after twenty- four hours was determined. The number of residual cells was significantly reduced in comparison to control at all four different conditions. PCNA immunostaining and TUNEL assay revealed that PDT inhibited cell proliferation and increased apoptosis. These findings suggest that the organotypic raft culture model provides an effective and rapid laboratory method of investigating strategies for PDT on oral precancerous lesions and squamous cell carcinomas

We have previously shown that 5’-nitro-indirubinoxime (5’-NIO) has potent anti-tumor effect in various human cancer cells. But the potential anti-invasive effect of 5’-NIO in salivary gland cancer has not been studied yet. The goal of this study is to evaluate the effect of 5'-NIO on salivary gland adenocarcinoma SGT cell adhesion and migration to Type I collagen treatment. Western blot, adhesion and migration assay were performed to evaluate the impacts of 5’-NIO on the expression of MMP-2/-9 and its upstream signaling molecules after treatment of type І collagen. SGT cell adhesion to type I collagen is significantly suppressed by 5’-NIO. 5’-NIO decreased expression of β1 integrin, phosphorylation of FAK, MMP-2/ -9 compared with type I collagen treatment. In addition, 5’-NIO inhibited the migration of SGT cells treated with type I collagen. These results suggest that 5’-NIO could effectively inhibit the invasion and migration of human SGT cells by downregulating the expression of β1 integrin and MMP-2/-9 and phosphorylation of FAK, Akt, and Erk. Adhesion and migration to type I collagen of SGT cells can be influenced through 5’-NIO..

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

Amino acid transporters play an important role in supplying organic nutrient to cells. The expression profile of L-type amino acid transporter 1 (LAT1) and its subunit 4F2 heavy chain (4F2hc) on different differentiation stages in 4-NQO induced rat tongue carcinogenesis was examined using immunohistochemical analysis. The gradually increasing LAT1 and 4F2hc expression detected during the multistep progressive change shows that the protein may have an important role i n the multistep tongue c arcinogenesis. Conclusively, LAT1 and 4F2 hc c an b e a useful b iomarker f or a better understanding of multistep tongue carcinogenesis, while the specific inhibition o f LAT1 and 4F2 hc would be a new rationale for suppressing tumor cell growth in tongue cancer.

Traumatic eosinophilic granuloma(TEG) of the oral mucosa is considered to be a reactive benign condition. Histology revealed diffuse mixed infiltration of eosinophil and atypical mononuclear cells. We have described an additional case of TEG simulating oral malignany where immunohistochemistry revealed the presence of CD30+ large atypical cells. The CD30+ lymphoproliferative disorder(LPD) of oral mucosa, although rare, has also been described. In this case, there was scattered distribution of CD30+ cells. After the incisional biopsy, the remainder of oral lesion got disappeared progressively and there is no sign of recurrence. We believe that this case could be a reactive rather than neoplastic process, and it has been suggested that a subset of TEG could be included within the spectrum of CD30+ LPDs. Therefore, oral surgeon and pathologists’ awareness of this condition will reduce the likelihood of misdiagnosis and inappropriate aggressive treatment for this benign, self-limiting lesion.

Traumatic eosinoph ilic gra nul oma(TEG) of the oral mucosa is considered to be a reactive benign lesion, which commonly ma nifests as an ulcer with eleva ted and indurated borders Clinically. this lesion simulates a maligna nt tumor Hi s to logy shows a diffut;e‘ dense. polymorphic. and eosinophil-rich cellular infiltrate. which extends deeply into the un derl ying soft ti ss ues‘ A major constituent of infïltrates is a population of mitotically active, large. atypical monol1 uclear cell s . Immunohi stologic eval uation of the large atypical cells has suggested a myofibroblastic 0 1' histi ocyti c origi 1γ However ‘ recent reports have shown that these cells are positive for CD30 antigen. We have descr ibed a case of ora l mucosal lesions with featu res of TEG that had a CD68 posite atypical cells. The large cells showed s trong pos itive for CD68‘ but negative for CD30. The sma ll Iymphocy tic cells exprerssed CD3. This case was interpreted as an atypical histiocytic g ran uloma .

A case of a distinctive variety of basalαd squamous cell carcinoma (B8CC) of the floor of mouth is described Histologic evaluation of the tumor showed lobules and aggregates of medium-sized basaloid cells with distinctive periph eral palisading and focal areas of comedo- necrosis. This appearance together with microcystic spaces simulated that of an adenoid cystic carcinoma. Accompanying epithelial dysplasia of the overlying mucosa was found. Immunohistochemistry of the tumor revealed diffuse strong expression for cytokeratin AE1/3, focally positive for Epithelial Membrane Antigen in the inner cells of tubular structures However, CEA, 8-100, smooth muscle actin, and vimentin were negative. The histologic differential diagnosis considered were adenoid cystic carcinoma and adenosquamous cell carcinoma Immunohistochemistry and awareness of this unusual pattern of B8CC will facilitate the correct diagnosis being reached.

Osteoblastoma is a benign bone forming neoplasm most commonly occurring in the vertebrae, long bones, but the jaw involvement is very rare events. When localized close to the periapical region or laterally to the roots of the t eeth, the lesion is easily confused with inflammatory periapical pathosis. In this article, we report our experience with a case of osteoblastoma located in the periapical region that was initially misdiagnosed as an inflammatory periapical pathosis, which led to unnecessary dental treatment and a delayed diagnosis. This case demonstrates the importance of proper diagnosis and treatment planning when one is dealing with radiolucent lesions in the periapical area Therefore, this case stresses the importance of biopsy of periapical lesions that do not respond to endodontic treatment or are otherwise S USpl CIOUS.

Oral fo cal mucinosis(OFM) is a tumor-Iike mass which is considered to be the oral counterpart of cutaneous focal mucinos is 01' a cutaneous myxoid cyst. Although all OFM havebeen reported to appear in the oral soft tissues, we describe a case of OFM with alveo lar bone involvement and review of thc prcvious reports. Histology revealed a localized area of myxomatous connective tissue surrounded by dense fibrous tlssue 8tromal mucins (alcian blue pH 2.5) and met achromasia( toluidine bl Lle pH 3) were obserγed in the tissue sectlOns Neither periodic acid-8chiff reaction nor retic Ll lin fiber nor 8-100 protein was observed. It is unclear whether the primary soft tissue lesion exte11ded into the cent1'al le Si011 or primari ly the lesion arose in the alveolar b011e 01' periodontal ligament.

Indirubin is the ac ti ve ingredi ent of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for t he t reatment of chronic myelocytic leukemia Here, we report that novel indirubin ,- 11‘ ivative‘ 5’ - nitro-indirubinoxime (5’ NIO) , has potent anti- proliferative activity on va rious human cancel‘ cells and oncogenic RK3E- ras rat kidney cells with ha lf- inhibi tory concentrati ons (1C50) ra nging from 1- 12 M, Treatment with indirubin derivative induced the activation 01' caspase 7 rollowed by apoptos is in RK3E- ras cells. lndirubin derivative showed strong anti-tumor activity in rat solid and oral tUll10r models , Direct inj ection of indirubin deri vative every other day for 10 days induced signifi cant inhi bition of tumor growth in Sprague-Dawley rats bearing RK3E- ras-induced tumors Histologically. t reatment with indiru bin de ri vative caused s ignifi cant inhi bit ion of tumor formation with increased apoptosis and decreased tumor cell prolife ration, These f indings provide the potent ial va lue of indirubin deri vative a s a novel candidate for ant i-tumor agents

Indirubin is the active ingredient 0 1' a traditional Chinese herbal medicine, Danggui Longhui Wan, used for the t reatment of chronic myelocytic leu kelma The author reports that novel indirubin derivative, 5'-nitro-indirubinox ime (5'-NIO) , has potent a nti -proliferative activity on human o1'al cancer cells , Treatment of KB cells with 5’ NIO s howed a s t rong cell growth inhibit ion during indicated time point , A typical apoptosis pattern was obtained with DNA fragmenta tion and i mmunofl uorescence analysis of annelxn-v-f!ous Western blot data revealed that p53 and p21CIP1/Waf- l level increased strongJy upon 5'-NIO treatment , The a uthor next tested whether 5'-NIO could activate apoptos is related proteins s uch as caspase-3/-7/-9, [n cells exposed to 5‘-NIO, activation of caspase-3 and -7 was observed, Interesti ngly‘ caspase-9 and cytochrome c cou ld s li ghtly activate in response to 5’-NIO. These results indicate that 5’-NIO strongly induces oral cancer cells apoptosis via a Mi tochondria-mediated cas pase cascade pathway, These observations together s uggest that 5’ NTO may have a possible therapeutic potentia[ to oral cancer

Cherubi sm is a ra re autosoma l dominant inherited condi tion caused by mutations in the c-Abl-binding protein SH3BP2. 1t is characteri zecl by mul t iple cystic giant cell lesions of the jaw appearing in early childhood with stabi li zation and rcmi ssion after pubcr ty, In thc present study, genomic DNA was purified f rom a blood sample obtained from the patient a ncl pa rents a ncl used f'or di rect sequence analysis of the SH3BP2 gene, 1n addit ion, a sample of the lesion was used f0 1" hi stologic ancl immunoh is toche mical purposes, Histology revealed a proliferation of spindle s haped fibroblas t ic cells and irregu la ry dis persed multinucleated giant cell s , The multinucleated giant cells proved posit ive for CD68 and TRAP, Ge nomic DNA sequencing f'ou ncl a missense mutation Pro418Arg in exon 9 of the SH3BP2 gene of the patient and the mother, Theref'ore, the mul t inucleated giant cells are basically osteoclastic in nature, Additionally, as the PI'o418Arg mutation had been repol' ted as caus ing cherubism, it represents a mutational hotspot,

Hereditary dentin defects consist of dentin dysplasia(DD) and dentinogenesis imperfecta(DI). The DI associated with osteogenesis imperfecta has been classified as DI type I, whereas isolated inherited defects have been categorized as DI types II and III. However, whether DI type III should be considered a distinct phenotype or a variation of DI type II is debatable. Recent genetic findings have focused attention on the role of the dentin sialophosphoprotein(DSPP) gene in the etiology of inherited defects of tooth dentin. We have identified a novel mutation(c.727G → A, p.D243N) at the 243th codon of exon 4 of the DSPP gene in a Korean patient with DI type III. The radiographic and histologic features of the patient revealed the classic phenotype of shell teeth. These findings suggest that DI type II and III are not separate diseases but rather the phenotypic variation of a single disease.

Polo-Like Kinase(PLK) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Recent reports have shown a critical role for PLK during tumorigenesis. To explore whether PLK plays a general role as a tumor marker of oral squamous cell carcinomas, we examined the expression of PLK mRNA and protein in oral squamous cell carcinoma cells and immortalized normal oral keratinocytes(INOK). We also investigated that PLK mRNA was expressed in specimens from 4NQO-induced SD rat tongue carcinomas using in situ RT-PCR methods. Immunocytochemically, most of the PLK was highly expressed in the nucleus of carcinoma cells, but not INOK. RT-PCR revealed PLK1 mRNA was detected in the FaDu and Hep2 cancer cells, but no detected in the INOK. In situ RT-PCR revealed PLK1 mRNA expression increased sequentially from hyperplasia to dysplasia, and squamous cell carcinoma during the malignant progression. PLK1 expression could reflect the degree of malignancy and proliferation in oral squamous cell carcinomas. Thus, in addition to being of diagnostic value, modulation of PLK1 activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value.