Cyclosporine A, immunosuppressive agent, has been applied to treat cancer cells. IHOK(Immortalized human oral keratinocyte)have been accepted as a model system for HPV-linked oral carcinogenesis. It is important to pursue the apoptosisof IHEK culture model by CsA related to the pathogenesis of oral squamous cell carcinoma. But CsA effect on immortalizedhuman oral keratinocyte(IHOK) remains unclear. Transglutaminase 2(TGase 2) which is expressed and activatedin tissue where epithelial cells undergo apoptosis has been used as a marker for apoptotic cells. The purpose ofthis study were to examine the effect of CsA on the proliferation and apoptosis of cultured NHOK by TGase 2expression. After IHOK and HN 12 cell line were treated by 0.1, 1.0 and 10ug/ml Cs A, growth curve, MTT assay forsuccinyl dehydrogenase activity, TGase assay for TGase 2 activity and immunoslot blotting for TGase 2 ptorein expression,and TEM features were done. MTT assay showed about 80% cell viability of HN 12, while about 50% of IHOK at10ug/ml CsA. Growth curve showed normal S curve on control and DMSO, while IHOK was more decreased after 3 daysof higher CsA treatment. Apoptosis index showed about 30% of IHOK and 15% of HN 12, respectively. TGase 2 activityand protein expression of IHOK was the highest at 10ug/ml CsA, while HN 12 was slight higher than control. TEMshowed chromosome fragmentation and margination, and vacuole formation in cytoplasm of IHOK after CsA treatment. Itsuggested that higher cyclosporine A might induce apoptosis of IHOK as Intermediate stage cells correlated with increasedTGase 2 activity and protein expression.

Elevated expression of survivin is strongly associated with tumorigenesis and even in human common cancers. Oralsquamous cell carcinoma (OSCC) is the 7th most frequent cancer in human and responsible for more than 90% of all oralcancer. The purpose of this study is to confirm whether survivin is associated with oral carcinogenesis, expecially has arole in the development of OSCC. For the control group; 3 specimens obtained from normal oral mucosa without any inflammatoryreaction were used a nd for the experimental group, specimens obtained f rom 18 sub jects of OSCC; 6 subjectsfrom Well differentiated type OSCC; 4 subjects from Moderately differentiated type OSCC; 3 subjects from Poorlydifferentiated type OSCC; 3 subjects from Verrucous carcinoma: and 2 subjects from C arcinoma in situ were used.All the specimens were embedded in paraffin, sectioned 5 μm or more in thickness, and stained with hematoxylin-eosin. For immunostain, the specimens were incubated with 1;200 diluted primary antibody (anti-survivin monoclonal,Biocare Inc, USA), followed by the secondary antibody(NovoLink Polymer detection system, Novocastra Lab., UK).The bound antibodies were visualized by addition of diaminobenzidine tetrahydrochloride(DAB) for 30 minutes at roomtemperature. The specimens were counterstained with Mayerʼs Hematoxylin and mounted. Quantitation of immunoreactivitywas performed under the light microscope with the following criteria ; Intensive reaction; +++, Moderate reaction;++, Minimal reaction; +. Using the image analyzer(Korea Optical System), immunoreactivity of tumor cells invarious field was measured and statistically analyzed with SPSS 15.0 Program. The results were as follows: Expression ofsurvivin in OSCC was significantly increased in the nucleus and the cytoplasm of OSCC as compare to those of controlgroup (p<0.05). Expression of survivin in the nucleus and the cytoplasm of the cells in OSCC is correlated with the cellularmalignancy (p<0.05). Expression of survivin in Poorly differentiated type OSCC partly correlated to some extent tocellular malignancy (p<0.05). These results suggest that expression of survivin in OSCC is closely associated with to thedevelopment, and malignancy of the OSCC, b ut it is not enough to be used a s a marker f or the c ellular malignancy.Further studies are needed to relate the expression of survivin to cellular malignancy.

Eukaryotic translation initiation factor 5A (eIF-5A) is essential for proliferation of eukaryotic cells, andwas identifiedas diagnotic marker in cervical intraepithelial neoplasia, cervical and endometrial cancer, but relatively little is knownabout thein vivo and in vitro expression patterns of eIF-5A in oral premalignant and malignant lesions mirror the expressionlevels observed in vitro with cells derived from normal oral mucosa, immortalized oral keratinocytes (IHOK) andprimary and metastatic oral squamous cell carcinoma (OSCC). We used an oral squamous cell carcinoma (OSCC) progressionmodel composed of cell lines and tissue specimens to characterize expression patterns by Western blotting andimmunohistochemistry. eIF-5A and PCNA levels are elevated in IHOKand primary and metastatic OSCC cella as compatredto normal human oral keraitinocytes. eIF5A and PCNA expression was l imited to basal cells of normal oral mucosa.eIF-5A and PCNA expression is increased in dysplastic epithelium spreading to more superficial layers, and its expressionlevels correlated significantly with the degree of dysplasia. Well and moderately differentiated OSCC showedstrong expression of eIF-5A and PCNA. These results suggest that upregulated expression of eIF-5A seems to be an importantepigenetic alteration that accompanies oral carcinogenic progression, and eIF-5A could be used as an biomarkerfor oral premalignat lesion or squamous cell carcinoma.

Renal osteodystrophy is the complex disease of the skeleton that occurs in patients with chronic renal failure. A29-year-old female with chronic renal failure and a h istory of hemodialysis during 10 years showed localized jaw enlargementin the anterior mandible. She also revealed increased serum PTH level, osteosclerosis in her skull base andfacial bone, chronic pain in the both knee joint, and gastrointestinal disorder which are symptoms of renalosteodystrophy. The patient was diagnosed hyperparathyroidism associated with chronic renal failure. Parathyroidectomywas performed, however, serum PTH level increased again after the parathyroidectomy, the affected area of the mandiblewas enlarged as the serum PTH level increased. The enlarged area seemed like as peripheral lesion clinically. We reporteda case of localized jaw enlargement as oral manifestation in renal osteodystrophy

Calcifying epithelial odontogenic tumor(CEOT) is a rare benign, though occasional locally invasive, odontogenic tumor.It was first described by Pindborg in 1955. they occur as intraosseous(94%) and extraosseous variants. Although theprognosis of CEOT was regarded as ameloblastoma in the past, contemporary accumulating data suggest that CEOT havebetter prognosis than ameloblastoma. But decisive evidences are lacked. Although CEOT is a rare odontogenic tumor, thehistopathologic features have so much diversity. Especially interesting aspects are the being of amyloid and Langerhans'cells. Author classify 6 cases of CEOT to scanty, small, and lage as produced amount of amyloid and then perform immunohistochemicalstudy about pancytokertin, cytokeratin8/18, vimentin, CD1a, and VEGF(vascular endothelial growthfactor) for verifying the differentiation state of tumor cells and the comparative infiltrative potential withameloblastoma. Author obtain several conclusion and presumptive facts through this study and previous researchs. Tumorcells of CEOT exhibited different differentiating features as amount of amyloid, presumably tumor cells of CEOT withscanty amount of amyloid represent enamel epithelium-like cells of presecretory stage in amelogenesis, tumor cells ofCEOT with small amount of amyloid represent ameloblast-like cells of secretory stage in amelogenesis, and tumor cellsof CEOT with large amount of amyloid represent reduced enamel epithelium-like cells after enamel formation.Epithelial-Mesenchymal transition phenomenon developed in tumor cells of CEOT with small amount of amyloid.Inflammatory reaction was not related with being Langerhansʼ cells. Author tentatively concluded that CEOT withLangerhans cells exhibited a tendency of non-calcification, scanty amyloid formation and frequently occurring at themaxillary anterior region through the previous studies and this study. Infiltrative growth potential of CEOT was lowerthan ameloblastoma regarding only VEGF expression.

Artemisia scoparia (A. scoparia), perennial herb is indigenous to Korea and has been traditionally used in liverdamage. We investigated the effect of the essential oil obtained from A. scoparia on apoptosis of KB cells.Cytotoxicity and cellular DNA content were analyzed by MTT assay and flow cytometry, agarose gel electrophoresis,and Hoechst 33258 staining. The caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins were estimatedby Western blotting method. We found that the essential oil induced the apoptosis of the KB cells by concentrationsof 0.4 to 0.2 mg/ml which was verified by DNA fragmentation, apoptotic bodies, and the sub-G0/G1ratio. The essential oil also transient caspase-9 and caspase-3 activity and cleavage of PARP in KB cells for 24 h.The essential oil-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation ofBcl-2. In conclusion, we demonstrated that the essential oil of A. scoparia induces apoptosis in KB cells.

Tumor cells under hypoxic conditions are often found due to the rapid outgrowth of their vascular supply, and,in orderto survive hypoxia, these cells induce numerous signaling factors. Erk is an important kinase in cell survival, andits activity is regulated by Raf kinases through numerous growth factor receptors. The authors investigated Erk activationand Raf/Erk signaling using the hypoxia-mimetic agent, cobalt chloride (CoCl2), in oral squamous cell carcinoma(OSCC) cells. CoCl2 increases Erk phosphorylation in both a dose- and time-dependent manner. In addition, blocking theactivation of epidermal growth factor receptor (EGFR) using PD168393 abolished Erk activation in response to CoCl2,suggesting that Erk phosphorylation by CoCl2 is dependent on EGFR.

Irritation fibroma(IF) is the most common tumor-like lesion. IF is characterized by over-production of collagen and,thus, resembles scar tissue. TGF-β1, MMP and TIMP play an essential role in remodeling extracellular matrix duringscar formation. This study investigates the pathogenesis of IF with respect to the coordinated expression of factors involvedin wound healing. Proliferative activity and expression of TGF-β1, MMP-1 and TIMP-1 were observed using immunohistochemistryin 88 cases of IF and 9 cases of normal oral mucosa(NOM). Proliferative activity and expression ofTGF-β1 and TIMP-1 were increased in IF compared to NOM. MMP-1 expression was not significantly increased in IF. Wepropose that IF is caused by increased expression of TGF-β1 and an imbalance in expression of MMP-1 and TIMP-1.

53 years old female showed repeated ulceration of labial gingival mucosa at upper and lower anterior teeth, which wasa partly desquamated and erythematous lesion. The lesion was slightly extended into vestibule and buccal mucosa in oralcavity, but the similar lesion was not found in other organs by medical inspection. The incisional biopsy including theborder of the ulcerated mucosa and normal mucosa showed a severely inflamed mucosa, of which epithelium was graduallydetached from the underlying conective tissue, so that it was diagnosed as a mucous membrane pemphigoid (MMP)pathologically. The epithelium was thinned, almost lost its rete pegs, and the basement membrane was completely distortedby the epithelial detachement. The inflammatory cell infiltration was mainly composed of small round cells andplasma cells. Immunohistochemistry was performed to know the expression of pathogenetic proteins using antisera ofIgk, E-cadherin, laminin a5, elafin, and eIF5A. The basement membrane at the epithelial detachment was condenselypositive for Igk, and the involved epithelium became atrophic but showed consistently positive reaction of matrix proteinsand protein translation factor, i.e., E-cadherin, laminin a5, elafin, and eIF5A similar to the adjacent normal mucosacontinuous to the MMP lesion. The Igk was also diffusely deposited on the basement membrane of nearby normalmucosa. Many plasma cells infiltrated around the lesion were strongly positive for Igk in their cytoplasms. Therefore, wesuggest that the MMP be characterized by the deposition of Igk on the basement membrane of the detached epitheliumin the absence of no other pathognomic changes of molecular events.

Zygomycosis and aspergillosis are representative filamentous fungal infections in the sinonasal region. However, theircombined form seldom occurs. This report describes one case of zygomycosis and aspergillosis occurring in a patient thatdid not have diabetes or any other immunocompromising conditions. The patient presented with a history of intermittentswelling and pus discharge from the gingiva of the right maxillary posterior teeth. The radiographs demonstrated a periapicalradiolucency around the right maxillary first molar, together with mild haziness and mucosal thickening of theright maxillary sinus. U nder t he c linical impression o f odontogenic sinusitis, a Caldwell-Luc operation was performed.However, the final diagnosis based on microscopic examination was combined zygomycosis and aspergillosis. Previousstudies of zygomycosis occurring alone describe a very aggressive clinical course, including necrosis of tissue,cranialnerve involvement and death. Our patient did not show any of these symptoms, and recovered after surgical debridementonly. It can be concluded from the present case that the prognosis of fungal infections depends on the immune status ofthe host, rather than behavior of the fungi.

Renal osteodystrophy is the complex disease of the skeleton that occurs in patients with chronic renal failure. A29-year-old female with chronic renal failure and a h istory of hemodialysis during 10 years showed localized jaw enlargementin the anterior mandible. She also revealed increased serum PTH level, osteosclerosis in her skull base andfacial bone, chronic pain in the both knee joint, and gastrointestinal disorder which are symptoms of renalosteodystrophy. The patient was diagnosed hyperparathyroidism associated with chronic renal failure. Parathyroidectomywas performed, however, serum PTH level increased again after the parathyroidectomy, the affected area of the mandiblewas enlarged as the serum PTH level increased. The enlarged area seemed like as peripheral lesion clinically. We reporteda case of localized jaw enlargement as oral manifestation in renal osteodystrophy.

Department of Dental Hygiene, Namseoul University1), Department of Oral Pathology, Yonsei UniversityCollege of Dentistry2), Oral Cancer Research Institute, Yonsei University College of Dentistry3), Departmentof Oral and Maxillofacial Surgery, Oral Science Research Center, Yonsei University College of Dentistry4)Epithelial-mesenchymal transition (EMT) can play an important role in carcinogenesis of oral squamous cell carcinoma(OSCC). EMT is characterized by morphological and phenotypical change of epithelial cells into mesenchymal cells, andtranscriptional repressor of E-cadherin, Snail is critical for EMT. In order to investigate the role of Snail and E-cadherinin OSCC, we analyzed the immunohistochemical pattern of Snail and E-cadherin in 18 OSCCs. The expression ofSnail in the OSCC was increased whereas the expression of E-cadherin in the OSCC was decreased in comparison withthose of normal oral mucosa, showing reverse correlation. Especially, the fibroblasts near the islands of OSCC showedthe positivity of Snail, suggesting the reactive fibroblasts to the EMT of epithelial tumor cells. In metastatic squamouscell carcinoma in cervical lymph node, the positivity of Snail of tumor cells was higher than that of primary OSCC. Weconcluded that the increased Snail expression and the decreased E-cadherin expression were involved in the progression,invasion and metastasis of OSCC.