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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
    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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  • 4
    Electronic Resource
    Electronic Resource
    Alterations of p16/MTS1 gene in oral squamous cell carcinomas from Taiwanese (2000)
    Copenhagen : Munksgaard International Publishers
    Journal of oral pathology & medicine 29 (2000), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: To determine the alterations of the p16/MTS1 gene in oral squamous cell carcinoma (OSCC), we examined in Taiwanese patients the mutation, deletion and methylation of p16/MTS1 in primary OSCCs associated mostly with betel quid (BQ)/tobacco use. Among 110 tumors undergoing mutational analyses, seven (6%) showed mutations in exon 2 or the intron 1/exon 2 splice site. All but one mutation disrupted the encoded proteins. Base transitions represented the vast majority (6/7) of the mutations identified in BQ/tobacco consuming subjects. It was noted that 15/56 (27%) tumors examined by restriction fragment methylation analysis revealed a significant level of methylation in different loci of exon 1 as compared with the respective non-cancerous tissue. Mutation of p16/MTS1 was exclusively identified in carcinomas of buccal mucosa, whereas methylation of the p16/MTS1 promoter region occurred preferentially in carcinomas of the tongue (54%) rather than at other sites (22%). Homozygous deletion was not found in 56 paired samples examined, nor was hemizygous deletion indicated in 12 informative cases. The results indicated aberrant methylation and mutation as the molecular abnormality of p16/MTS1 in the OSCC from Taiwanese.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2000.290403.x
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  • 5
    Electronic Resource
    Electronic Resource
    The involvement of Kv3.4 voltage-gated potassium channel in the growth of an oral squamous cell carcinoma cell line (2004)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of oral pathology & medicine 33 (2004), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  In our previous study, an A-type voltage-gated K+ channel, Kv3.4, was found more frequently expressed in oral squamous cell carcinoma (OSCC) when compared with non-cancerous matched oral tissue. An OSCC cell line, OECM-1, was found to have moderate level of Kv3.4 expression.Methods:  To further elucidate the roles of Kv3.4 for the involvement of neoplastic process, we amplified Kv3.4 coding sequence by reverse transcriptase polymerase chain reaction (RT-PCR), constructed an expression vector carrying this sequence and then stably transfected into OECM-1 OSCC cells.Results:  We demonstrated the integration and constitutive expression of Kv3.4 in the cell. A unique A-type current elicited by such expression in OECM-1 cells was defined by patch clamp analysis. This current pattern can be reversibly blocked by an A-type K+ channel blocker 2 mM 4-aminopyridine (4-AP). The acquisition of Kv3.4 activity in OECM-1 cells bestowed growth advantage. However, in 3T3 cell, transfected Kv3.4 caused only limited increase of growth without forming transformation foci.Conclusion:  The present study established a stable keratinocyte system carrying functional Kv3.4 and increase of growth, by which the anti-Kv3.4 modalities for potential OSCC control can be further investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0714.2004.00236.x
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  • 6
    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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  • 7
    Electronic Resource
    Electronic Resource
    Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use (2002)
    Oxford, UK : Munksgaard International Publishers
    Journal of oral pathology & medicine 31 (2002), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:   The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3′-untranslated region (3′-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases.Methods:   We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3′-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping.Results:   The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P 〈 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P 〈 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3′-UTR.Conclusion:   The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2002.00158.x
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  • 8
    Electronic Resource
    Electronic Resource
    Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma – evidence for COX-2 induction by areca quid ingredients in oral keratinocytes (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:  Elevated expression of cyclooxygenase (COX)-2 has been demonstrated in several human cancers. Whether COX-2 is up-regulated in areca quid (AQ) related oral squamous cell carcinoma (OSCC) is unknown and the potential of AQ ingredients to induce COX-2 expression has not been studied.Methods:  COX-2 expression was analyzed by immunohistochemistry and RT-PCR in oral tissues. The COX-2 mRNA and protein induction potential of AQ ingredients were analyzed by real-time RT-PCR and Western blotting in normal human oral keratinocyte (NHOK).Results:  COX-2 protein expression was significantly higher (P 〈 0.01) in OSCC (n = 27) as compared to their adjacent non-cancerous matched tissue (NCMT). COX-2 protein was nearly undetectable in control normal oral mucosa. The level of COX-2 mRNA was markedly elevated in 63% (12/19) of OSCC compared to NCMT. Hydroxychavicol induced COX-2 mRNA and protein expression in NHOK.Conclusions:  COX-2 protein as well as mRNA expression were significantly enhanced in OSCC as compared to NCMT. Hydroxychavicol, a unique ingredient in AQ, induced COX-2 expression in NHOK, which highlighted early involvement of COX-2 in AQ-associated oral oncogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2003.00182.x
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  • 9
    Electronic Resource
    Electronic Resource
    Cyclin D1 genotype in areca-associated 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:  Oral squamous cell carcinoma (OSCC) is the most common malignancy in areca-chewing regions, accounting for up to 50% of malignant tumors in some South Asian countries. Amplification and/or over-expression of cyclin D1 (CCND1) is a frequent event in human malignancies, including OSCC. CCND1 G870A polymorphism (codon 242) gives rise to two isoforms of the protein. The objective of the present study was to evaluate if the risk, onset, and prognosis of areca-associated OSCC is related to CCND1 genotypes.Methods:  We analyzed the CCND1 genotype in 70 OSCC cases and 93 control Taiwanese using single-strand conformation polymorphism techniques.Results:  Statistical analysis showed that CCND1 genotype had no impact on the risk, onset, or survival of areca-associated OSCC. However, buccal squamous cell carcinoma (BSCC) appeared to be less frequently associated with AA genotype than non-BSCC (P = 0.02). In addition, amplification of CCND1 was significantly more prevalent in OSCC cases (22%) than in control subjects (2%, P 〈 0.01).Conclusion:  This study demonstrates that the CCND1 genotype may confer different risks for BSCC and non-BSCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2003.00131.x
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  • 10
    Electronic Resource
    Electronic Resource
    The retinoic acid receptor-β (RAR-β) mRNA expression in the oral squamous cell carcinoma associated with betel quid use (2002)
    Oxford, UK : Blackwell Science, Ltd
    Journal of oral pathology & medicine 31 (2002), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Within the abundant retinoids nuclear receptors, abnormally low expression of the RAR-β has been shown to contribute to neoplastic progression in oral epithelium in western countries. Distinctly different risk factors contributing to oral squamous cell carcinoma (OSCC) in epidemiologically different societies denote the value of exploring the role of RAR-β expression in OSCC associated with betel quid (BQ) use in our society.Methods:  We examined the cellular expression of RAR-β using in situ hybridization (ISH) analysis on 38 pairs of surgical specimens of primary OSCC and non-cancerous matched tissues (NCMT) to correlate with their clinico-pathological features including age, sites of tumor, habit of BQ use, stage, size of primary tumor, lymph node metastasis, differentiation.Results:  Of all cases analyzed, BQ users were significantly younger than non-BQ users (51.2 ± 2.1 vs. 60.2 ± 2.6, P= 0.01). 52% OSCC of BQ users (13/25) and 23% OSCC of non-BQ users (3/13) exhibited the absence of RAR-β expression. In 17 paired-samples from buccal mucosa (BM), most NCMT and less than half of OSCC exhibited RAR-β expression (16/17, 94% vs. 8/17, 47%, P= 0.003). The RAR-β expression was seen in the vast majority of the well-differentiated OSCC and in less than half of the moderately differentiated OSCC only (15/20, 75% vs. 7/18, 39%, P= 0.03).Conclusion:  A correlation between the loss of RAR-β expression and more advanced histopathological grade tumors was observed. This study also suggests that the loss of RAR-β expression is significant in BM OSCC, which preferentially occurs in BQ users.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2002.310405.x
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