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

INTRODUCTIONOral changes observed during pregnancy have been studied for many years, but their magnitude and frequency have not been stressed upon. This study was undertaken to assess the prevalence of oral lesions during different trimesters of pregnancy and their correlation with salivary pH change.

METHODSThe gingival, simplified oral hygiene, community periodontal and decayed-missing-filled teeth indices were used to assess a total of 120 pregnant women (40 in each trimester group) and 40 nonpregnant women (control group). Salivary pH was measured using a digital pH meter. Presence of any oral lesions was determined via oral examination.

RESULTSScores for all indices increased while salivary pH decreased from the control group to the first trimester group, through to the third. Oral lesions were seen in 44.2% of pregnant women. Lesions were seen in 27.5%, 52.5% and 52.5% of women in the first, second and third trimesters, respectively. The percentage of pregnant women with one oral lesion was highest in the second trimester (47.5%), whereas the third trimester had the highest prevalence (17.5%) of two concurrent oral lesions. The incidence of fissured tongue was highest in the first trimester group, and that of gingival enlargement was highest in the third trimester group. In the second trimester group, there was an almost equal incidence of fissured tongue and gingival/mucosal enlargement.

CONCLUSIONMost changes in oral tissues during pregnancy can be avoided with good oral hygiene. Salivary pH could be used to assess the prevalence of oral lesions in the different trimesters of pregnancy.

Adolescent ; Adult ; Dental Caries ; complications ; diagnosis ; Female ; Gingiva ; pathology ; Humans ; Hydrogen-Ion Concentration ; Mouth Diseases ; complications ; diagnosis ; Oral Hygiene ; Pregnancy ; Pregnancy Complications ; Pregnancy Trimesters ; Prevalence ; Saliva ; chemistry ; Tongue ; pathology ; Young Adult

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

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

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

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

AIMTo study the antitumor effect of an immunoconjugate composed of pingyangmycin (PYM) and anti-type IV collagenase monoclonal antibody (mAb) 3G11.

METHODS3G11-PLG-PYM immunoconjugate was prepared by linking 2-iminothiolane (2-IT) modified mAb to PYM via N-succinimidyl-3-(2-pyridyldithiol) -propionate (SPDP) derived poly-alpha-L-glutamic acid (PLG) backbone as the intermediate drug carrier. Characterization of the conjugate was performed by SDS-PAGE and spectrophotometry. Immunoreactivity of the conjugate against type IV collagenase was determined by ELISA. The cytotoxicity of the conjugate to hepatoma 22 (H22) and KB cells was examined by MTT assay. Antitumor effect of the conjugate in vivo was evaluated in mice bearing subcutaneously implanted H22 tumor, the candidate drugs were administered intravenously by "q2d x 6" regimen.

RESULTSThe molecular weight of the conjugate was approximately 170 kD. The molecular ratio of 3G11-PLG-PYM was 1 : 2. 4 : 10. The conjugate retained part of the immunoreactivity of mAb 3G11 against the antigen. The cytotoxicity of the conjugate to H22 and KB cells was moderate comparing with free PYM. In vivo however, free PYM inhibited the growth of H22 by 60.6% on day 22 at the dose of 10 mg x kg(-1), while the equivalent dose of 3G11-PLG-PYM conjugate reached 90.8%. The median survival time of the mice treated with the conjugate was prolonged by 71.7% as compared with that of the untreated group, whereas that of free PYM prolonged only 10.9%. 3G11-PLG-PYM conjugate was notably more effective than free PYM in tumor suppression and life span prolongation.

CONCLUSION3G11-PLG-PYM displayed more marked antitumor efficacy than free PYM in vivo and might be a novel candidate for cancer treatment.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antibodies, Monoclonal ; Bleomycin ; analogs & derivatives ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Collagen Type IV ; immunology ; Female ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; Liver Neoplasms, Experimental ; pathology ; Mice ; Molecular Weight ; Mouth Neoplasms ; pathology ; Neoplasm Transplantation

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

AIMTo determine the effects of azide methyl anthraquinone derivative (AMAD) on growth inhibition and inducing apoptosis of multidrug resistant (MDR) KBv200 cells and parental drug-sensitive KB cells.

METHODSCytotoxicity was determined by tetrazolium (MTF) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (deltapsi(m)) in cells were labeled with DCFH-DA and DiOC6 and tested by flow cytometry. Annexin V stain and DNA ladder were used to examine the apoptosis of KB and KBv200 cells induced by AMAD.

RESULTSAMAD was shown to inhibit the growth of KB and KBv200 cells significantly in a concentration-dependent manner, with mean IC50 of 0.36 and 0.45 micromol x L(-1), respectively. The generation of ROS increased obviously after the cells were treated with AMAD for 12 h, up to the peak in 24 h, meanwhile the levels of deltapsi(m) were time-dependently decreased. DNA fragmentation appeared on the agarose gel. Annexin V stain showed AMAD induced apoptosis of KB and KBv200 cells also in a concentration-dependent manner.

CONCLUSIONAMAD showed inhibitory effect on both MDR KBv200 cells and parental drug-sensitive KB cells. The mechanism of action was associated with the increase of the cellular ROS level and the decrease of the mitochondrial membrane potential induced by AMAD, which result in cell apoptosis.

Anthraquinones ; administration & dosage ; chemistry ; pharmacology ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; KB Cells ; Mitochondria ; physiology ; Molecular Structure ; Mouth Floor ; Mouth Neoplasms ; pathology ; Reactive Oxygen Species ; metabolism ; Vincristine ; pharmacology

OBJECTIVETo study the mechanism of anti-tumor activity of Acanthopanax gracilistylus extract (Age).

METHODSThe tumor cells proliferation was detected by using (3H)-TdR incorporation method, and the effects of Age on cell cycle of tumor cells, retinoblastoma (Rb) protein and cyclin-dependent kinases (Cdk) were analyzed by flow cytometry and Western blotting assay, respectively.

RESULTSIt was indicated by cytoactivity test in vitro that Age only had effect in inhibiting the proliferation of tumor cells, it couldn't lead to death of cells. Under action of Age, the proliferation of tumor cells was halted at G0/G1 stage of cell cycle, and showed no direct cytotoxic effect by Age. Age could induce lowering of the expression of Rb, Cdk2 and Cdk4, cause halt of tumor cell proliferation.

CONCLUSIONThe tumor inhibitory effect of Age is realized by way of regulating the activity of cell cycle controlling enzymes to suspend the proliferation of tumor cells.

Adenocarcinoma ; pathology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase 2 ; biosynthesis ; Cyclin-Dependent Kinase 4 ; biosynthesis ; Drugs, Chinese Herbal ; pharmacology ; Eleutherococcus ; chemistry ; Humans ; Leukemia, T-Cell ; pathology ; Mouth Neoplasms ; pathology ; Retinoblastoma Protein ; biosynthesis ; Stomach Neoplasms ; pathology ; Tumor Cells, Cultured