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  • 1
    Electronic Resource
    Electronic Resource
    Association of GST genotypes with age of onset and lymph node metastasis in oral squamous cell carcinoma (2005)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 34 (2005), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Environment–gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study investigated the association of glutathione S-transferase (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset, and neck lymph node metastasis (LNM) in areca-associated oral squamous cell carcinoma (OSCC).Methods:  A total of 114 OSCC male patients and 100 male controls were recruited. All subjects were areca users and tobacco smokers. DNA was obtained from peripheral blood samples. Genotyping of GSTT1 (non-null/null) and GSTM1 (non-null/null) was determined by polymerase chain reaction (PCR) analysis using specific primers that only amplify non-null alleles.Results:  No association was found between GST genotype and the risk of OSCC based on case–controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03). Those with the GSTM1 null genotype had a higher incidence of neck LNM than those with the GSTM1 non-null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null genotype appeared to have later onset and a higher incidence of neck LNM than those carrying the opposite genotype.Conclusion:  The GST genotypes may be important markers for the age of onset and risk of metastasis in OSCC. The data also suggest that the various GST isoforms may be differentially involved in development or progression of OSCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2005.00345.x
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  • 2
    Electronic Resource
    Electronic Resource
    Frequent microsatellite alterations of chromosome locus 4q13.1 in oral squamous cell carcinomas (2005)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 34 (2005), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Studies have revealed that losses of chromosome 4q24–25 regions are frequent in cancers including head and neck squamous cell carcinoma. Our previous comparative genomic hybridization analysis showed extensive losses of chromosome arm 4q in oral squamous cell carcinoma (OSCC).Methods:  To be more precise in mapping the potential regions of allelic losses and to understand the microsatellite instability (MSI) on 4q involving in oral pathogenesis, we performed allelotypings using eight polymorphic markers. Microsatellite analyses were first performed on 100 randomly selected controls to confirm the high informative rates of markers. Twenty OSCC tissues were microdissected from surgical specimens for microsatellite alterations (MA) analysis.Results:  MA was observed in 95% OSCC cases. The most eminently altered locus was 4q13.1 (75%), followed by 4q22.2 and 4q32.1 (55%). Allelic losses also occurred most frequently on these loci. Thirty-five percent cases had MA spanning 4q13.1 to 4q21.1. MSI occurred in 35% OSCC, at a lesser extent compared with allelic losses. The most common locus for MSI was 4q21.2 (20%). In addition, 4q MSI was significantly associated with the lymph node metastasis of OSCC (P = 0.01). So far, most tumor suppressor genes on 4q have not been specified.Conclusion:  Our results were additive to previous findings and proposed novel scenario of suppressor loci located at 4q13.1–21.1 whose inactivation could be important for progression of OSCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00296.x
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  • 3
    Electronic Resource
    Electronic Resource
    Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas (2004)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 33 (2004), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF), which are highly associated with areca use, are prevalent in most Asian countries. Matrix metalloproteinases (MMPs) are superfamily of metal-dependent proteolytic enzymes, mediating the degradation of extracellular matrix. Insertion/deletion (−1607 2G→1G) polymorphism has been described in the promoter region of the human matrix metalloproteinases-1 (MMP-1) genes, which cause an alteration in the transcriptional activity. This genotype is associated with risks of cancer genesis and metastasis. In this paper, we studied the relationship between such genotype and areca-associated oral diseases.Methods:  Genomic DNA from the blood of OSCC (n = 121), OSF (n = 58) cases and controls (n = 147) were amplified by polymerase chain reaction (PCR)-based genotyping. The OSCC were further grouped into buccal squamous cell carcinoma (BSCC) and non-buccal suqmaous cell carcinoma (NBSCC), in accord with the site of involvement. The significance of the differences was assessed by Fisher's exact test.Results:  The 2G genotype in MMP-1 promoter was observed with a higher frequency in both OSCC (0.69, P = 0.06) and NBSCC (0.76, P = 0.03) cases compared with controls (0.63), with an odds ratio of 2.17 and 4.58, respectively. This genotype was not related to the risk of OSF. No other clinicopathologic parameter was associated with the genotypes in OSCC cases.Conclusion:  The results showed that 2G genotype in MMP-1 promoter was associated with the risk of OSCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00214.x
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  • 4
    Electronic Resource
    Electronic Resource
    Establishment of OC3 oral carcinoma cell line and identification of NF-κB activation responses to areca nut extract (2004)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 33 (2004), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Cell lines derived from oral squamous cell carcinoma (OSCC) exposed to variable etiological factors can bestow advantages in understanding the molecular and cellular alterations pertaining to environmental impacts. Most OSCC cell lines have been established from smoker patients or areca chewing/smoker patients, carrying the genomic alterations in p53.Methods:  A new cell line, oral carcinoma 3 (OC3), was established from an OSCC in a long-term areca (betel) chewer who does not smoke. Cellular and molecular features of OC3 were determined by variable assays.Results:  The cultured monolayer cells were mainly polygonal and had the expression of cytokeratin 14. The chromosomal analysis using comparative genomic hybridization has revealed the gain in chromosomes 1q, 5q, and 8q, the loss in 4q, 6p, and 8p as well as the gain of entire chromosome 20. Loss of heterozygosity and instability in multiple microsatellite markers in chromosome 4q were also noted. OC3 cells bear wild-type p53 coding sequence and have a high level of p53 expression. Its p21 expression was similar to that in normal human oral keratinocyte (NHOK). Interestingly, activation of nuclear factor κB (NF-κB) in OC3 cells following the treatment of areca nut extract was observed.Conclusion:  OC3 cell line could be valuable in understanding the genetic impairments and phenotypic changes associated with areca in oral keratinocyte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00034.x
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  • 5
    Electronic Resource
    Electronic Resource
    The increase of voltage-gated potassium channel Kv3.4 mRNA expression in oral squamous cell carcinoma (2003)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 32 (2003), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Potassium channels have been reported to be involved in the proliferation of many types of cells, including tumor cells. The overexpression of the K+ channel and related channel activity are involved in the neoplastic process.Methods:  We examined the expression of an A-type voltage-gated K+ channel, Kv3.4, in oral squamous cell carcinoma (OSCC) and esophageal squamous cell carcinoma (ESCC) compared with non-cancerous matched tissue (NCMT) using RT-PCR analysis. In addition, administration of an A-type K+ channel blocker, 4-aminopyridine (4-AP), and an antisense oligodeoxynucleotide (ODN) directed specifically against Kv3.4 were performed to identify the involvement of Kv3.4 in the growth of OSCC cells.Results:  A significantly increase in the frequency of Kv3.4 mRNA expression was identified in OSCC (64%) compared to corresponding NCMT (29%) (P = 0.05). The increase of Kv3.4 mRNA expression was also eminent in ESCC. Growth of OSCC cells was significantly inhibited by 4-AP in a dose-dependent manner at different time point of treatment. In OECM-1 OSCC cells, a significant growth inhibition was noted in antisense ODN-treated cells compared to control cells.Conclusion:  We provide novel evidences of the increase of Kv3.4 mRNA expression in OSCC. The abrogation of Kv3.4 inhibits the growth of OSCC cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2003.00197.x
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  • 6
    Electronic Resource
    Electronic Resource
    Cytoplasmic expression of E-cadherin and β-Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas (2005)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 34 (2005), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Inactivation of the adenomatous polyposis coli (APC) gene results in accumulation and translocation of β-Catenin, which are important for malignant development. The aim of the present study is to investigate the possible role of APC/β-Catenin pathway in oral squamous cell carcinomas.Methods:  The DNA from 34 patients was examined for loss of heterozygosity (LOH) at two markers surrounding the APC, and for hypermethylation of the APC promoter by using methylation-specific polymerase chain reaction (MS-PCR). Fifteen of 34 samples were stained immunohistochemically to show the expression of E-cadherin and β-Catenin.Results:  We found that cytoplasmic rather than membrane staining of E-cadherin and β-Catenin was a prominent aberrant tumour-related alteration, and that this expression was mainly present in moderately and poorly differentiated tumours. LOH and hypermethylation of the APC promoter was found in four of 31 and five of 34 carcinoma samples, respectively. Four of five cases presenting LOH/hypermethylation showed cytoplasmic expression of E-cadherin and β-Catenin by immunohistochemical (IHC) staining.Conclusion:  The present results indicate that LOH at the APC locus or hypermethylation of the APC promoter 1a may lead to free β-Catenin accumulation in cytoplasm of oral carcinoma cells and thereby to oral malignant progression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00275.x
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  • 7
    Electronic Resource
    Electronic Resource
    The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis (2003)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 32 (2003), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The increased expression of Cav-1 is seen in various cancers from prostate, esophagus, colon, breast and pancreas yet the information regarding the correlation between the expression of Cav-1 and oral cancer is blind. Thus, the expression profile of caveolin-1 (Cav-1) in oral carcinogenesis and the correlation to the clinicopathologic covariates are examined in this study.Methods:  Immunohistochemistry was used to detect Cav-1 expression in non-cancerous matched tissues (NCMT; n = 12), and tissue from normal oral mucosa (NOM; n = 12), oral pre-cancer lesions (OPL; n= 17), primary oral squamous cell carcinoma (POSCC; n = 47) and metastatic OSCC (MOSCC; n = 8). The Cav-1 expression was correlated to the age, site, areca use, stage, size, nodal involvement, and differentiation stage. Western blot was used to confirm the specificity of antibody and to follow changes in Cav-1 expression.Results:  The Cav-1 immunoreactivity increased significantly from 8% in NOM and 17% in NCMT to 53% in OPL and 79% in POSCC. In addition, lymph node metastasis (LNM) was present in 62% of Cav-1(+) POSCCs, but only in 10% of Cav-1(–) POSCCs. Remarkably, only 38% of MOSCCs had Cav-1 immunoreactivity.Conclusion:  An increased Cav-1 expression is seen in the stepwise carcinogenesis from NOM, NCMT, OPL to POSCC. The decrease in expression from the POSCC to MOSCC indicates the value to explore its biphasic functions in oral carcinogenesis. Whether Cav-1 is an important predictor or prognosis for survival still awaits the extension of clinical follow-up.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2003.00185.x
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  • 8
    Electronic Resource
    Electronic Resource
    Tumor necrosis factor-α promoter polymorphism is associated with susceptibility to oral squamous cell carcinoma (2005)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of oral pathology & medicine 34 (2005), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Oral squamous cell carcinoma (OSCC) is one of the leading cancers in most Asian countries. Alterations of immune function have been detected in OSCC patients. The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) is a central mediator of the immune response involved in a wide range of immuno-inflammatory and infectious diseases. Polymorphism of the TNF-α gene has been intensively studied as a potential determinant of susceptibility to numerous cancers.Methods:  We genotyped 192 patients with OSCC and 146 healthy case controls by using polymerase chain reaction-double restriction fragment length polymorphism with amplification-created restriction sites to assess allelic determinants at the TNF-α polymorphic sites −308 and −238 in the promoter region. Genotype frequencies were evaluated with Fisher's test.Results:  The −308 TNFG (tumor necrosis factor G) allele genotype was higher in patients with OSCC (91.2% vs. 82.2%; P = 0.02) and TNFG/A was lower (8.3% vs. 11.8%; P = 0.02); the −238 TNFG/A allele genotype was lower in patient with OSCC (2.1% vs. 6.9%; P = 0.02).Conclusion:  This is the first report that the TNF-α polymorphism is associated with the risk for OSCC in Taiwan.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2005.00359.x
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  • 9
    Electronic Resource
    Electronic Resource
    The molecular markers for prognostic evaluation of areca-associated buccal squamous cell carcinoma (2004)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 33 (2004), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Buccal squamous cell carcinoma (BSCC) is the most frequently occurring oral cancer in Asians due to the popularity of areca use in this area. The aim of the present study was to evaluate the survival of areca-associated BSCC associated with multiple molecular markers.Methods:  Using immunohistochemistry, we evaluated the survival of a cohort of 55 patients with BSCC being followed long term, as correlated to the expression of variable markers.Results:  We found that p53, p21, Rb, cyclin D1 (CCD1), MDM2, and γ-catenin were positive in 81, 60, 70, 31, 88, and 44% of patients, respectively. Subjects with −ve immunoreactivity for CCD1, and +ve immunoreactivity for MDM2 and γ-catenin had significantly better survival than subjects with the opposite immunoreactive pattern. Kaplan–Meier survival curves confirmed this association.Conclusion:  The data indicate that expression of CCD1, MDM2, and γ-catenin might serve as potential prognostic markers for BSCC in areca-using patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00092.x
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  • 10
    Electronic Resource
    Electronic Resource
    Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis (2004)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 33 (2004), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Matrix metalloproteinase-2 (MMP-2) can degrade extracellular matrix and basement membrane, and play an important role in the development and progression of multiple carcinomas, including oral squamous cell carcinoma (OSCC). A −1306C→T polymorphism in the MMP-2 promoter disrupts Sp1-binding site, and results in reduction of transcriptional activity. This study aimed to assess the association of such genotype with the risk of OSCC and oral submucous fibrosis (OSF), which is a precancerous condition that exhibits excessive collagen production and etiologically links to areca use.Methods:  Genomic DNA from the blood samples of 121 OSCC cases, 58 OSF cases and 147 controls were amplified by polymerase chain reaction (PCR) and subjected to denaturing high-performance liquid chromatography (dHPLC) analysis for genotyping. The OSCC were further classified into buccal squamous cell carcinoma (BSCC) and non-buccal squamous cell carcinoma (NBSCC), according to the site of involvement. Fisher's exact test and unconditional logistic regression models were used for statistical analysis.Results:  Subjects carrying CC genotype had nearly twofold increased risk for developing OSCC when comparing with CT or TT genotype. Subjects carrying CC genotype had more apparent risk (greater than fourfold) for developing NBSCC. However, no increase in risk for lymph node metastasis or advanced stage was identified in OSCC cases carrying such genotype. Preliminarily data suggest no significant association between subjects carrying CC genotype and the development of BSCC or OSF.Conclusion:  This is the first paper demonstrating that functional genotype of MMP-2 promoter is a risk factor for oral carcinogenesis, particularly for the subsets occurring on non-buccal site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00231.x
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