BACKGROUNDBeta-catenin, a 92 kDa protein that binds to the cytoplasmic tail of E-cadherin, has an essential role in intercellular adhesion and signal transduction. Aberrant expression of beta-catenin has been associated with progression and metastasis of various human cancers. The aim of this study was to elucidate the expression pattern of beta-catenin in primary oral squamous cell carcinoma and examine the correlation between beta-catenin expression and tumor differentiation, histological grade and lymph node status as well as its clinical significances.

METHODSSeventy-six patients with oral squamous cell carcinoma and sixteen metastatic lymph nodes were studied. The beta-catenin expression was determined by immunohistochemical staining. The correlation with clinical, histological data was analyzed statistically.

RESULTSNormal oral epithelium showed strong beta-catenin expression at the cell membrane, but no cytoplasmic or nuclear expression. Different degrees of reduced expression of beta-catenin at the cell membrane were found in 54 cases with squamous cell carcinoma (71%). Cytoplasmic beta-catenin expression was found in 17 tumors (22.4%). Three cases were found with nuclear beta-catenin expression. In sixteen lymph nodes with metastatic squamous cell carcinoma, negative beta-catenin expression at the cell membrane was seen in 13 tumors (81.2%) and weak expression in 3 tumors (18.8%). Statistical analysis showed that there was an inverse correlation between beta-catenin expression and lymph node status and histological grade of tumors.

CONCLUSIONSReduced beta-catenin expression at the cell membrane is clearly associated with lymph node metastasis. A reduced expression of beta-catenin may constitute a hallmark of aggressive biological behavior of squamous cell carcinoma.

Carcinoma, Squamous Cell ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mouth Mucosa ; chemistry ; Mouth Neoplasms ; chemistry ; pathology ; beta Catenin ; analysis

OBJECTIVETo investigate the expression and alteration (including homozygous deletion and mutation) of MTS1 gene in precancerous lesions and squamous cell carcinomas (SCC) of oral mucosa, and to analyse the function of MTS1 gene alteration in oral mucosal carcinogenesis.

METHODSThe expression of p16 protein produced by MTS1 gene was examined with immunohistochemical SP method in 10 normal oral mucosas, 30 precancerous lesions (10 mild, 10 moderate and 10 severe dysplasia respectively) and 45 squamous cell carcinomas (SCCI18, SCCII 19, SCCIII 8). The deletion and mutation of exon1 and exon2 of MTS1 gene were examined with methods of PCR and SSCP in these same samples.

RESULTSAll the precancerous lesions had p16 protein expression and no alteration of MTS1 gene. In SCC, the positive rate of p16 protein was 60.0% with 72.2% in SCCI, 57.9% in SCCII, 37.5% in SCC III, and there were no significant difference among the three groups by chi2 test (P>0.05). Gene homozygous deletion of exon1 and/or exon2 was detected in 10 cases, and gene mutation in 4 cases. The whole rate of gene alteration was 31.1% (14/45). The MTS1 gene alteration rate was 27.8% in SCCI, 31.6% in SCCII, 37.5% in SCC III and there was also no significant difference among the three groups by chi2 test (P>0.05). In SCC with local lymph nodes metastasis, MTS1 alteration rate was 57.1%, while in SCC with no lymph nodes metastasis was 8.3%, and there was significant difference by chi2 test (P<0.05).

CONCLUSIONSMTS1 gene alteration is not an early event in the carcinogenesis of oral mucosa and can not be used as a biology mark to examine oral precancerous lesions. MTS1 gene may play a certain role in the progression of oral squamous cell carcinomas.

Carcinoma, Squamous Cell ; chemistry ; genetics ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Genes, p16 ; Humans ; Lymphatic Metastasis ; Mouth Neoplasms ; chemistry ; genetics ; pathology ; Mutation ; Precancerous Conditions ; genetics

OBJECTIVETo study the expression and significance of apoptosis-related protein p53, Bcl-2, and Bax during the development of oral squamous cell carcinoma (SCC).

METHODSThe expression was observed in 10 normal oral epithelia, 48 dysplasia epithelia and 42 SCC by immunohistochemical evaluation.

RESULTSIn normal mucosa, the positive rate of p53, Bcl-2 and Bax were 0%, 20% and 60%. In dysplasia epithelia, the positive rate of p53 is increased (P < 0.05), the positive rate of Bcl-2 and Bax remained no significant change (P > 0.05), but the positive intensity in severe dysplasia was higher than in mild group. In SCC, the positive rate of Bcl-2 increased significantly (compared with dysplasia, P < 0.05), while the expression of Bax was decreased with the increase of SCC histological grade. Further analysis showed the correlation was evident in p53 and Bax in dysplasia, and in p53 and Bcl-2 in SCC.

CONCLUSIONSIn dysplasia, p53 gene mutation results in accumulation of dysplasia cells. In SCC, the cooperation of p53, Bcl-2 and Bax results in the progression of SCC. Apoptosis genes could work either independently or cooperatively.

Apoptosis ; genetics ; Carcinoma, Squamous Cell ; chemistry ; Humans ; Immunohistochemistry ; Mouth Mucosa ; chemistry ; pathology ; Mouth Neoplasms ; chemistry ; Proto-Oncogene Proteins ; analysis ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Tumor Suppressor Protein p53 ; analysis ; bcl-2-Associated X Protein

No abstract available.
Biomarkers, Tumor/analysis ; Biopsy ; Carcinosarcoma/chemistry/*secondary/surgery ; Chemoradiotherapy, Adjuvant ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/*pathology/surgery ; Male ; Middle Aged ; Mouth Floor/chemistry/*pathology/surgery ; Mouth Neoplasms/chemistry/*secondary/surgery ; Pneumonectomy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome

Coxsackievirus A16 belongs to the family Picornaviridae, and is a major agent of hand-foot-and-mouth disease that infects mostly children, and to date no vaccines or antiviral therapies are available. 2A protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4G. Here we present the crystal structure of coxsackievirus A16 2A protease, which interestingly forms hexamers in crystal as well as in solution. This structure shows an open conformation, with its active site accessible, ready for substrate binding and cleavage activity. In conjunction with a previously reported "closed" state structure of human rhinovirus 2, we were able to develop a detailed hypothesis for the conformational conversion triggered by two "switcher" residues Glu88 and Tyr89 located within the bll2-cII loop. Substrate recognition assays revealed that amino acid residues P1', P2 and P4 are essential for substrate specificity, which was verified by our substrate binding model. In addition, we compared the in vitro cleavage efficiency of 2A proteases from coxsackievirus A16 and enterovirus 71 upon the same substrates by fluorescence resonance energy transfer (FRET), and observed higher protease activity of enterovirus 71 compared to that of coxsackievirus A16. In conclusion, our study shows an open conformation of coxsackievirus A16 2A protease and the underlying mechanisms for conformational conversion and substrate specificity. These new insights should facilitate the future rational design of efficient 2A protease inhibitors.
Coxsackievirus Infections ; virology ; Crystallography, X-Ray ; Cysteine Endopeptidases ; chemistry ; genetics ; Fluorescence Resonance Energy Transfer ; Hand, Foot and Mouth Disease ; enzymology ; pathology ; virology ; Humans ; Picornaviridae ; chemistry ; enzymology ; genetics ; Protein Conformation ; Structure-Activity Relationship ; Substrate Specificity ; Viral Proteins ; chemistry ; genetics

OBJECTIVEThe purpose of this study was to screen sialyl Lewis(a) (sLe(a)) in the tumors of patients with oral squamous cell carcinoma (OSCC) and to explore the association of sialyl Lewis(a) expression with local lymph node metastasis.

METHODSSpecimen from 38 patients with primary OSCC were obtained and analyzed by immunohistochemical methods.

RESULTSThe expression of sLe(a) protein, but not E-selectin, of OSCCs significantly correlated to the local lymph node metastasis. sLe(a) was expressed in 79% (15/19) of the metastatic cases compared with 21% (4/19) of the non-metastasis ones, indicated the association of sLe(a) expression with the local lymph involvement.

CONCLUSIONHigh expression of sLe(a) in OSCC may be related to the metastasis of cervical lymph nodes and it seems useful in predicting poor prognosis in OSCC.

Adult ; Aged ; Antigens, Tumor-Associated, Carbohydrate ; analysis ; Biomarkers, Tumor ; analysis ; Carcinoma, Squamous Cell ; chemistry ; genetics ; pathology ; secondary ; E-Selectin ; analysis ; genetics ; Female ; Gangliosides ; analysis ; genetics ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mouth Neoplasms ; chemistry ; genetics ; pathology

Sporadic sclerotic fibroma (SF) and solitary fibrous tumor (SFT) arising in the oral cavity are very rare. In this report, we describe two cases of oral pathology, one involving SF and the other involving SFT. Both cases presented with well- circumscribed, firm nodules with similar gross findings. However, the histologic findings of the SF and SFT showed rather distinct features. The SF was composed of hyalinized sclerotic collagen bundles arranged in a whorled pattern, whereas the SFT was formed by spindles cells arranged in hypo- and hypercellular areas. The immunohistochemical findings were similar in both cases; there was positivity for vimentin, CD34, and CD99, but bcl-2 positivity was only seen in the SFT. Although their histopathologies are similar, SF and SFT should be considered in the differential diagnosis of soft tissue tumors in the oral cavity.
Adult ; Antigens, CD/analysis ; Antigens, CD34/analysis ; Cell Adhesion Molecules/analysis ; Diagnosis, Differential ; Female ; Fibroma/*diagnosis/metabolism ; Humans ; Immunohistochemistry ; Mouth/chemistry/*pathology ; Mouth Neoplasms/*diagnosis/metabolism ; Neoplasms, Fibrous Tissue/*diagnosis/metabolism ; Proto-Oncogene Proteins c-bcl-2/analysis ; Vimentin/analysis

Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.
Antineoplastic Agents ; chemistry ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; drug therapy ; enzymology ; pathology ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Fibroblasts ; drug effects ; enzymology ; Growth Inhibitors ; chemistry ; therapeutic use ; Humans ; Mouth Neoplasms ; drug therapy ; enzymology ; pathology ; Phytotherapy ; Plant Extracts ; chemistry ; therapeutic use ; Signal Transduction ; drug effects ; Tumor Suppressor Protein p53 ; drug effects ; Ulmaceae ; chemistry

OBJECTIVETo detect the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), p16 protein in lip cancers and oral squamous cell carcinoma (OSCC) as well as their clinicopathological significance.

METHODSImmunohistochemisty for expression VEGF, EGFR, P16 were carried out in 69 cases of lip cancers and OSCC.

RESULTSExpression of VEGF, EGFR, p16 protein in OSCC and lip cancers was respectively 71.01%, 46.37%, 28.98% and there were no significance between their positive expressions (P > 0.05) as well as in different sites of them (P > 0.05). Expression of VEGF was respectively 71.01% in cancers and 10.00% in non-tumor tissues, there was statistic significance among those (P < 0.05).

CONCLUSIONSThe results show that there is no correlation to the expression of VEGF, EGFR and P16 protein in OSCC and lip cancers. It is suggests that the expression of VEGF might become one of the useful markers for OSCC.

Adult ; Aged ; Carcinoma, Squamous Cell ; chemistry ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; analysis ; Lip Neoplasms ; chemistry ; pathology ; Lymphokines ; analysis ; Male ; Middle Aged ; Mouth Neoplasms ; chemistry ; pathology ; Receptor, Epidermal Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cyclin D1 ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mouth Mucosa ; chemistry ; metabolism ; pathology ; Mouth Neoplasms ; metabolism ; pathology ; Prognosis