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,

Combined epithelial odontogenic tumors are very rare and represent hybrid lesion comprising adenomatoid odontogenic tumor intermixed with calcifying epithelial odontogenic tumor. The authors present 3 cases of combined epithelial odontogenic tumor which contained diagnostic areas for both adenomatoid odontogenic tumor and calcifying epithelial odontogenic tumor. Their behaviour and histogenesis were discussed.

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.

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.

β-catenin is a cytoplasmic protein that participates in the assembly of cell-cell adherens junctions by binding cadherins to the cytoskeleton. In addition, it is a key component of the Wnt signaling pathway. Activation of this pathway triggers the accumulation of β-catenin in the nucleus, where it activates the transcription of target genes. Abnarmal accumulation of β -catenin is characteristic of polyposis coli(APC) or Axin tumor suppressor proteins, which regulates β-catenin degradation, or activating mutations in β-catenin molecule itself. Here we show that overexpression of Sox4 down-regulates wild type β-catenin in HEK 293 cells. The inhibitory effect of Sox4 on wild type β-catenin is apparently mediated by the ubiquitin- proteasoem system and requires an active glycogen synthase kinase 3β(GSK3β). Mutations in the N-terminus of β -catenin(S33Y) which compromise its degradation by the proteasomes or inhibition of GSK3β activity rendered β-catenin resistant to down-regulation by Sox4. In light of recent evidence that Sox4 expression is activated in colon and other tumors with β-catenin dysregulation, our findings suggest that Sox4 is part of a feedback inhibitory pathway for Wnt signaling in normal cells. Moreover, the mutations in APC, Axin or β-catenin in cancer cells appear to render β-catenin resistant to the effects of Sox4 inhibition.

Several tumor animal models have been provided as a tool for developing cancer therapy. Here, we developed rapid, easy-to use, and cost-effective new rat animal model for invasion and metastasis of cancer using genetically k-ras-induced rat kidney cells(RK3E-ras). We observed tumor as early as 3 days after injection of RK3E-ras cells in subcutaneous of Sprague-Dawley rats. Tumor size and volume were increased exponentially for 2 weeks. The tail vein injected rats obtained the lethal infiltration in the lung within 2 weeks. This tumor animal model has great potential for studying cancer processes and short-term screening of variable cancer therapy strategy.

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.

This article desc 1'ibes a pooled analysis 01' Korean indiγ idu a l s with 41 cases 01' metastatic o1'al tumors. The data on this review are based on t he 1'etr ieved published case reports from t he Korean dental and medical li te1'ature between t he years 1983 and 2004, The mean age was 55,2 years and the male to female ratio was 1,9 :1, There were more jaw bone me t astas is than in oral soft tIssues Comparing with the western literatures which report the breast as the most common p rimary s ite, the most common primary s ite was the liver fo llowed by the lung‘ and thyroid, The lung was the most common primary s ite [or t he jawbone metastasis ‘ whereas the liver was for the oral soft tlssues This discrepancy may caused by underestimation or exc lus ion ofthe jawbone in su rveying fo1' the breast tumor metastaslS Anothcr reason is t hat a relat ive ly hi gh incidence rate 이’ hepatocellul ar carcinoma occurs in Ko1'ean, especially in male

Al thou gh calcifi cation is a common finding in inflammatory salivary gland disorders , saliva ry gland tumour ra rely s hows calcifications. A case of clear cell mucoepidermoid carcinoma(MEC) of the hard pa late with extensive intra tumoural calcifïcations vis ible on computed tomog r때hy(CT) scans and histologic sections is described. The calci fï caLion in the sali va ry gland tumour 0 1' the palate recogni zed by a CT scan s hould be considered in the differential diagnosis of a MEC The mechanism of the i ntratumoural calcifi cation in our case is speculated to be a result of a secretory fu nction 0 1' the tumour cells

Amino acids a re required fo1' protein synthesis and energy sources in all living cell s. System L amino acid trans porters neutral amino aci cls i n a Na +' - independent manner. In ma 1ignan t tumors the L-type amino acid t ranspor te r 1(LA1'1), the first isoform 0 1' system L. is highly expressed to suppor t tumo1' cell growth. ln the present study, the expression 0 1' the system L amino acid transporter and BCH cytotoxicity were examined and compa red in both rat gli a l and C6 g lioma cel ls 1'he rat glia l cells expressed the L-type arnino acid t ra nsporter 2(LA1'2). the second isoform 이 system L, with its subu ni t 4F2hc. whereas the LA1'1 was not expressed. 1'he C6 glioma cells expressed LA1'1 with 4F2hc but not LA1'2 1'he [14C]L-leucine uptakes by the glial and C6 glioma cells were inhibi ted by BCH in a co ncent ration-d e pendant man ner wi th the lC50 values of 270.0 :t 13.7 μ M and 73.1 :t 4.5 μ M, respectively. 1'he cell g rowth was inh ibi ted by BCH in the time, concen tration-dependant manner in the gli al and C6 glioma cell s . 1'he rate of cell growth inhi bit ion induced by BCH in the C6 glioma cells was hi gh er than that in the gli al cells 1'hese results s uggesL that the tra ns ports of neutra l amino acids inc1uding several essenti al amino acids into rat g lial and C6 glioma cel ls a re for the most part mediated by LA1'2 and LA1'1, respectively. Therefore‘ the rat glia1 and C6 gJioma cells are excell ent tools for examing the proper ties of LA1'2 and LA1'1, respectively. Moreover, the spec너 i c inh ibi tion 0 1' LATl in cancel cells might be a new rationa le f'or anti -cancer therapy

The dentigerous cyst(DC) and giant cell granuloma(GCG) in the jaws are well known entities that have been extensively reviewed. However, a search of the literature failed to reveal simulataneous occurrence of these two lesions. We describe a case of DC displaying foci of GCG-like lesion of a 11-year-old Korean girl. The lesion exhibited the characteristic histologic features of DC, which included a lining epithelium with underlying fibromyxoid stroma. The most intersting aspect of this lesion, however, was the presence of a prominant histologic component that resembled GCG. The most probable diagnosis was GCG-like lesion in association with a DC.

Odontogenic ghost cell tumor (OGCT) is considered as a neoplastic counterpart of the calcifying odontogenic cyst (COC). β-catenin mutations have been described in COC suggesting a critical role in its histogenesis. In this study, we report a patient with OGCT contains a missense mutation on codon 3 (ACT -> TCT). Immunohistochemistry showed nuclear, cytoplasmic, and membranous accumulation of β-catenin in the tumor cells. TUNEL assay showed positive signals in nucleated cells adjacent to the ghost cells. Our data suggest that β-catenin plays an important role in the tumorigenesis of OGCT. OGCT may developed by improper differentiation process coordinated by WNT signaling pathway. Further studies are needed to determine a genotypic/phenotypic characteristics of ghost cell containing odontogenic lesions.

Cyclooxygenase- 2 (COX-2) is an inducible enzyme that is not found in normal conditions,. but is induced by a varie ty of pathophysiologic conditions of tissues by growth factors. inflammatory stimuli. oncogenes and tumor promoters, COX-2 is upregulated in a number of epithelial cancers. including in oral premalignant and malignant lesions, The mode of action of COX-2 in carcinogenesis may include mutiple mechanisms that may be acting at different stages of malignant disease, In this study. the expression of COX- 2 protein was assessed quantitatively 없d qualitatively by immunohistochemistry during DMBA-induced hamster buccal pouch carcinogenesis, The immunoreactivity for COX-2 protein increased as the tissue passed from hyperplasia to dysplasia and SCC, The highest mean expression was SCC at 14 week, The differences between COX-2 expression in the normal and that the dysplastic and carcinomatous lesions was statistically significant, In addition. the mean values of COX -2 expression in the stromal cells increased gradually during malignant progression, The results suggest that increased COX-2 expression may be associated with the chemically induced carcinogenic progression of hamster buccal pouch model, The gradual increasing COX-2 expression de tected during the progressive manner toward more malignant lesions shows that the COX-2 protein can have an important role in both the early and the later stages of multistep oral carcinogenesis

Florid cemento-osseous dyspl잃ia with concommitant traumatic bone cyst is uncommon condition. We report a case of florid cemento 。，sseous dysplasia involving four quadrants of the jaws and associated with large cystic lesion of the mandible misdiagnosed as a multiple odontogenic keratocysts in a 37-year-old Korean woman. Histological examination revealed unencapsulated fibroblastic proliferation with formation of bone and cementum, showing different developmental stages, and cys디c lesions resembling a traumatic bone cyst.

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.

The myotubularin (MTM) family constitutes one of the most highly conserved protein-tyrosine phosphatase subfamilies in eukaryotes. MTM1, the archetypal member of this family, is mutated in X-l띠ked myotubular myopathy, whereas mutations in the MTM related (MTMR)2 gene cause the type 4B Charcot-Marie-Tooth disease, a severe hereditary motor and sensory neuropathy. In this study, we investigated the role of pleckstrin homology (PH) domain of MTMR2. We demonstrate here that the PH domain of MTMR2 directly interacts with phosphatidylinositol (PtdIns)(3)P, PtdIns(5)P, and to a Iesser extent Pt，이 ns(4)P. Furthermore, MTMR2-PH domain is required for targe띠g Mη00 to the 다πoplasmic compartment. Mutation in the PH domain abolished its phospholipid binding ability and MTMR2 subcel1ular localization. These results su잃.est that the PH domain regulates MTMR2 1αalization and function through its interaction with phosphoinosi디des and give us the clue to understand the pathogenic effect of PH domain

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.

A case was reponed in which an odontogenic cyst that appeared to be a dentigerous cyst associated with an impacted mandibular third molar was found histologically to demonstrate characteIistics of glanclu lar odontogenic cyst with para- and orthokeratinization. 까1ese histologic cliversities were interpreted as a reflection of the pluripotentiality of the epithelial remnants of the mandibular thircl molars or clentigerous cyst epithelium. It was conceivable that it would have the capacity of inclucing the fonnation of cysts with both squamous and glandular epithelium.