Oral squamous carcinoma (OSC) is the most common malignant neoplasm of the oral mucosa. Although the etiology of OSC is not fully understood, accumulated evidences indicate that the activation of proto-oncogenes and the inactivation of tumor suppressor genes underlie the disease development. An OSC cell line, YD-9 was newly established and characterized. However, the mutational analysis of p53 gene was not performed. Thus, in this study, the presence of mutation in the p53 gene was examined by amplification of exon-4 to -8 and subsequent DNA sequencing. Two point mutations were found in exon-4 and -6: A to G, resulting in amino acid change Tyr to Cys in exon-4, and C to G, resulting in amino acid change Gly to Arg in exon-6, respectively. Any mutation was not found in the exon-5, -7 and -8. The presented results would contribute to basic research to understand the biological mechanism of OSC using YD-9 cells.

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

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.

In order to perform the protein analysis using the paraffin sections previous fixed with formalin, we applied the ImmunoMemBlot (IMB) method1) to detect the epitopes of target proteins with specific antibodies. In this study the protein extracts were obtained from the paraffin sections of each representative case of ameloblastoma, adenomatoid odontogenic tumor (AOT), and normal gingiva, and more a protein extract from fresh tissue of ameloblastoma was also compared to evaluate the IMB results used with 24 different antibodies. First of all, in the comparison between the paraffin section extract and fresh tissue extract of ameloblastoma, the latter consistently showed more positive IMB reaction than the former. Meanwhile, the paraffin section extract of ameloblastoma was more comparable with that of normal gingival, disclosing that most of proliferating genes, oncogenes, and apoptosis related genes, i.e., PCNA, CDK4, c-erbB2, CEA, p53, Bax, Bad, FLIP, FAS, Bcl-2, p21, N-ras, MMP-2, MMP-9, caspase-3, -8, -9, were highly expressed in ameloblastoma, but EGFR, HGF, and VEGF were similarly expressed both in the ameloblastoma and in normal human gingiva. On the other hand, the comparison between ameloblastoma and AOT both in the immunohistochemistry and IMB using their paraffin section extracts clearly demonstrated that the ameloblastoma showed more expression of proliferating genes and oncogenes while the AOT showed more expression of apoptosis related genes, i.e., Bax, Bad, FLIP, and caspase-9. Taken together, these data suggest that the IMB can be used for the primary screening of quantitative protein analysis using the paraffin section extract, and that the IMB results could be evaluated in conjunction with the immunohistochemical observation.

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of (30μM)SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration(30μM) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

Adenocarcinoma NOS of salivary glands is characterized by a high rate of local recurrences and metastasis. Long-term survival rate of Adenocarcinoma NOS lis not promising. Thus, different chemotherapeutical approaches had been proposed for this neoplasm, including apoptosis induction by drugs. The current treatment of choice of adenocarcinoma NOS is controversible, and an effective treatment for them is not yet available. Chemotherpeutic agents that can be inhibit or reverse the tumor growth by targeting apoptotic pathways will be new candidates for cancer prevention and therapy. The purpose of this study were to study the effect of Brefeldin A(BFA) as apoptotic inducing agent in SGT cell line from human submandibular adenocarcinoma NOS and apply these results to make a plan of treatment and prognosis of salivary gland tumors involving adenocarcinoma NOS. SGT cells were treated with a 300μM BFA solution in serum-free medium during 18 hours. SGT cells were grown in DMEM with 10% fetal bovine serum served as controls. The growth curve and MTT assay for succinyl dehydrogenase activity were performed. For apoptotic analysis, fragmentation of genomic DNA was confirmed with gel electrophoresis. Transmission electron microscopy was assessed for the effect of BFA on SGT cells phenotype. Apoptotic cell recognition and counting were carried out with Annexin-V, caspase 3 and APo2.7 antibody through flow cytometry. Growth of SGT cell line was abrutply decreased after 1 day of BFA treatment. MTT assay for succinyl dehydrogenase activity of the cells showed about 55% after 300μM BFA treatment. Destruction of cellular organells, numerous vacuolation in the cytoplasm & nucleus, chromatin margination, & fragments of nucleus were seen with TEM after 300μM BFA treatment. DNA fragmentation of SGT cell line was induced by 300μM BFA treatment and confirmed by gel electrophoresis from genomic DNA extraction. Late apoptosis of the cells through flow cytometric analysis of Annexin-V staining as induced by 300μM BFA treatment. Early apoptosis of the cells through flow cytometric analysis of caspase 3 and Apo 2.7 staining was induced by 300μM BFA treatment. It suggested that early and late apoptosis of SGT cell line would be induced by Brefeldin A treatment in vitro study. This work evaluated the efficacy of BFA, a potent apoptosis inducer, on SGT cultured cell line. And BFA as chemotherapeutic agent will be used as the treatment choice for adenocarcinoam NOS, and be need to apply BFA to in vivo study & clinical approach in future.

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.

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

lndil‘ ubin is the active ingredient of Danggui Longhui Wan‘ a mixture of herbal medici l1e t hat is used to treat chronic myelocytic leukemia in tradi t ional Chinese medicine‘ He re, we show that new indirubin deri vatives 5' -ni tro-indirubinoxime, 5' -f1 uoro-indiru binoxime and 5’ -tri rnethylacetamino-i nd i 1'1.1 bi noxi me‘ have potent a n ti- proliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells with lC50 con centration ranging from 1-25 μ M, When the RK3E-ras cells were treated with indirubin derivatives for 24 h, the activity of caspase-3 and caspasc-7 was induccd followed by apoptosis , 011 the other hand, the activity of SAPK/JNK was inhi bited over the same period , lndirubin deri vatives a lso s howed strong ant i-tumor activity in rat s이 id and oral tumor models The inhibition of tlUl10r g:rowth was observed in animals beaJ‘ing RK3E-ras-induced turnor given subcutaneous dose of 100 mg/kg every other day for 10 days, Histologically, μeatment of indirubin derivatives caused significant inhibition of tumor formation associated wi th increased apoptosis and decreased proliferation of tumor cell s , These findings provide the potential value of indirubin derivatives as a novel candi date fOl 없l tJ -cancer agents ,

Ameloblastoma and adenomatoid odontogenic tumor showed quite different tumorigenesis and prognosis , Besides theil‘ growth potential and histological features , there must be an essential diffcJ'cncc in gene expJ'ession profile between ameloblatoma and adenomatoid odontogenic tumor , The gene expression profiles we1'e compared by im munohi stochemi stry and immunoblot methods using different monoclonal and monospecific antibodies against on cogenes, growth factors, signaling molecules‘ matrix proteins, enzymes, Based on the immunohi stochemical find ings previously J'epo1'ted in the literature we found some di stinguishing feature of gene expressions 1'0 1' the tu mOl'igenesis between ameloblastoma and adenomatoid odontogenic tumors , The hi s togeneti c and mol eculal' mechani sms of both tumors wiII be discussed

The adenomatoid odontogenic tumor(AOT) is a benign tumor of odontogenic epithelium characterized by slow but progressive growth and rare recurrence. Tumor growth may cause displacement of teeth rather than root resorption. The AOT appears in 3 clinicotopographic variants such as follicular, extrafollicular, and peripheral. The follicular AOT mimics a dentigerous or follicular cyst and the extrafollicular cyst does a residual cyst, globulo-maxillary cyst and lateral periodontal cyst. Although over 750 cases of AOT were reported in the literature, clinicopathologic parameters of AOT in Koreans has not been investigated. 22 cases of AOT were retrieved from the files of the department of Oral Pathology, Seoul National University Dental Hospital and their clinicopathologic findings were reviewed. The central type accounts for 95%, 72% of which are follicular. The follicular and extrafollicular varients together are more commonly found in the maxilla than in the mandible with a ratio of 4.5:1. Age distribution showed that 59% of AOTs were diagnosed in the second decade of life, and mean age was 18.5 years. The female to male ratio was 3.4:1. All variants of AOT showed identical histologic features.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear factor-kB(NF-kB) determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce NF-kB and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

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.

In odontogenic osteolytic lesions, the mechanism involved in inflammation 때d osteolysis is still under debate. We investigated the role 。OL-l ~ -1 ß, -4, -6, -8, TNF- a in the expansion of the odontogenic cysts, by using 50 cases of excised odontogenic cysts. The degrees of inflammation were graded into 2 groups and immunohistochernical stainings were performed, The cytoplasrnic reaction in squamous epithelial cells, stromal cells and infIitrating inflammatory cells was examined. The relationship between the expressions of IL-1 q -1 ß, -4, -6, -8, π-JF- aand the degree of inflammation and the correlation among them were analyzed. 까1e 비Stilαγtic expressions of IL-l ~ IL-l ß and TNF-awere 66.6%, 66.6% and 4O.00Al respeαively and the epithelial exp~않sions of IL-4, -6, -8 were 32.00Al, 38.00Al and 24.00Al respeαively. IL-4, -6 and 용 were positively stained in plasma cells in 38.00Al, endothelial cells in 40.00/0 and neutrophils in 24. 00Al respectively. The expresssion rate of IL-4 in plasma cells and IL-8 in epithelium and neutrophils were inα얹sed in ca않s with marked inflammation. 까1e exp!1않sion rate of IL-1 ßin 피해ocytes and IL-4 in plasma cells were positively correlated with the expæssion of TNF-1 ain histiocytes. π1e expression rate of anti-inflammatory cytokine IL-4 in the epithelium were correlated with the expression of IL-6 in the epithelium and endothelial cells. A1though statistically insi.맑표ìcant， the expression rate of IL-6 were decreased in cases with marked inflammation and nega디vely correlated with IL-8, the proinflammatory cytokine, and the expressions of IL-4 and IL-6 in the epithelium can be considered as inhibiting the inflammatory reaction. These results suggest that the expressions of IL-4 and IL-6 suppress and IL-8 stimulates the inflammatory reaction in Odontogenic Cysts.