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..

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.

T:raumat ic eosinophili c granuloma(TEG) of the oral mucosa is considered to be a reactive benign lesion. which commonly manifests as an ulcer with elevated and indurated borders Clinically, this lesion simulates a malignant tumor. Histology shows a diffuse. dense, polyrnorphic, and eosinophil - rich cellular infiltra te. which extends deeply into the underlying soft t issues. A major constituent of infil trates is a population of mitotically active‘ la rge‘ atypi cal mononuclear cells. Immunohistologic evaluation of the large atypical cells has suggested a myofibroblastic 01' his tiocytic ol'igin. However, recent reports have shown that these cells are positive 1'01' CD30 antigen and it has been s llggested tha t a subset of TEG cOllld be included within the spectrum of CD30+ lymphoprolifer ative disorders. We have described 2 patients who had oral mllcosal lesions with features of TEG. ln patient 1. the lesiona l cells expressed CD3 .. CD43, LCA. Interestingly, the large cells were strongly CD30 positive. bl1t nega tive for CD68, CD45Ro‘ CD56, CD20. This case was interpreted as a CD30+ Iymphoproliferative disorder. In pa tient 2‘ t he la rge cell s showed strong posit ive for CD68, hut negative for CD30 The small lymphocytic cells ex prerssed CD3 This case was interpreted as an atypical histiocytic granuloma. Therefore, TEGs inclllde atypical histiocytic granllloma a long with the CD30+ lymphoid lesions. These findings suggested that TEG w0111d be a hete rogenous category of oral mucosal di sorders

Heat shock p1'otein (Hsp) 40 acts as a co-cha perone of Hsp70 by fac ilitating the ATPase activity of Hsp70 as well as promoting the protein fo lding and rena turation by Hsp70. In the present study. Hsp40 gene was fu sed with a gene f’ragment encoding the HJV-l TAT protein transduction domain(YGRKKRRQRRR) in a bacterial exp1' ession vector pTAT-HA to produce the TAT-fused Hsp40(TAT- Hsp40). Purified TAT-Hsp40 was effectively t 1'ansduced into the HEK 293 cells in a time- and dose-dependent manne1' To examine the effec t of TAT- Hsp40 upon oxidalive stress, HEK293 cells were exposed to H2Û2. Oxidative stress induced the ra pid increase of proteasome activity foll owed by celJ death in HEK 293 cells However ‘ HEK 293 cells t 1'ansduced by TAT- Hsp40 showed r esistance against oxidative st 1'ess induced cytot oxicity, TAT- Hsp40 transduced cell s showed dec1'eased p1'oteasome activity and inhibi ted Hs p70 degradation. These results suggest that Hs p40 rnight protect cell death f rom oxida tive st1'ess by p1'ese1'ving the cellula1' level of Hs p70.

Wnt genes encode a large fami ly of secreted cysteine-rich signaling mol ecules involved in cell growth‘ differentiation and tumorigenesis, Wnt5a, a non-transforming member of the Wnt fa mily behaves as a putative onco 一 gene in many cancers including melanomas, The aim of our study was to determine Wnt5a ex pression pattern in pnmalγ oral mucosal melanomas(Ol\αÆ) and correlate it with tumor thlckness Archival ti ssues from 18 OMM cases were subjected to immunohistochemical detection of Wnt5a by the streptavidin-biotin method , These were categorized into tumors of (4 mm(thin and intermediate thickness lesions) and )4 mm(t hi ck lesions) t hickness, Most OMM cases(17/18; 94, 4%) stained positive for Wnt5a, though heterogeneously, Seven t hi ck(7/11: 64%) and one in termediate thickness(1/7‘ 14%) ol\α‘ demonstrated strongly positive Wnt5a staining(P(O, 05), The only Wnt5a-neg ative case was a thi ck OMM without local recurrence after treatment Strong Wnt5a express ion at tumor adva ncing sites suggests a role in local tumor spread, Identification of pleomorphi c epitheli oid and spindle cells as mel anoma cell populations with the most pronounced Wnt5a staining suggests that Wnt5a overexpression inJ] uences cellular phenotype, These results taken together suggest that Wnt5a is up- regulated in OMM a nd may play a role in tumor progression, Wnt5a activity is most frequently detected in advanced OMM suggesting its function in tumor progression, Expression level of Wnt5a in OMM correlated with tumor grade and t hickness

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.

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.