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Chung-Ji Liu

Publications and source records attributed to Chung-Ji Liu.

At least 19 recordsLinked to original sources
PubMed2007

MICA and MICB overexpression in oral squamous cell carcinoma.

BACKGROUND: The concentration of MICA in serum seems be a good candidate marker in cancer. Previous studies from our laboratory have shown that the polymorphic MIC gene may confer a risk for oral squamous cell carcinoma (OSCC). The study investigated the expression levels of MICA and MICB of OSCC patients and cancer cell lines. MATERIAL AND METHODS: We used RT-PCR to analyze the mRNA expression of MICA and MICB in four oral cancer cell lines compared with three normal human oral keratinocyte (NHOK) cell lines and in tissues from 36 patients with OSCC comparing tumor tissue with non-cancerous matched tissue (NCMT). RESULTS: Endogenous MICB mRNA expression in OSCC cell lines was significantly higher than that in NHOK (1.40 +/- 0.27 vs. 0.40 +/- 0.16; P = 0.04). In 20 of 36 sets of tissue from patients with OSCC, MICB mRNA expression was higher in the cancerous tissue than in the NCMT. The mean MICB mRNA expression in OSCC tissues was significantly higher than in NCMT (0.39 +/- 0.08 vs. 0.14 +/- 0.03, P = 0.009, paired t-test). A significantly lower MICA mRNA was found in patients who chewed areca nut compared with those who did not use areca (P = 0.001) and in patients with well-differentiated tumors compared with those with less well-differentiated tumors (P = 0.02). CONCLUSION: MICA and MICB mRNA expression may be increased in OSCC but there appears to be individual variation.

Adult↗
PubMed2006

Ripe areca nut extract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte.

Around 200-600 million Asians chew areca (also called betel), which contains a mixture of areca nut and other ingredients. Epidemiological evidences indicated that areca use is tightly linked to oral carcinogenesis. This study investigated the effects of ripe areca nut extract (ANE) on cultured normal human oral keratinocyte (NHOK). Acute subtoxic ANE treatment inhibited DNA synthesis and induced cell cycle arrest at G1 phase in early passage (< 4th passage) cells. This was accompanied by a slight increase in the sub-G1 cellular fraction. O6-Methylguanine-DNA methyltransferase (MGMT), Hsp27 and p38MAPK was upregulated. p16 and p21 were remarkably upregulated early and declined afterwards. In contrast, the increase of dephosphorylated Rb seemed to be secondary to the episodes of p16 and p21 upregulation. To simulate the chronic areca exposure in vivo, constant ANE treatment in serial NHOK culture was performed. It resulted in a significant decrease in the population doubling, increase in senescence-associated beta-galactosidase (SA-beta-Gal) and decrease in cell proliferation in NHOK of late passages (> or = 4th passage). Induction of senescence-associated phenotypes, G2/M accumulation and genomic instability following long-term ANE treatment were also observed in a low-grade oral carcinoma cell. ANE-treated NHOK also had a higher nuclear factor-kappaB (NF-kappaB) fraction and a lower cytosolic IkappaBalpha level relative to the control in late passages. Moreover, electrophoretic mobility shift assay (EMSA) indicated that ANE treatment shifted the NF-kappaB complex from high mobility position to lower mobility position in late-passaged NHOK. ANE treatment also upregulated IL-6 and cyclooxygenase-2 (COX-2) mRNA expressions in late-passaged NHOK. In summary, our findings suggest that ANE induces the cell cycle arrest at G1/S phase and the occurrence of senescence-associated phenotypes of NHOK. The upregulation of p38MAPK, p16, p21, NF-kappaB, IL-6 and COX-2 are likely to participate in the control of these impacts.

Areca↗
PubMed2006

Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers.

Areca (betel)-chewing is tightly associated with the high prevalence of oral squamous cell carcinoma (OSCC) in Asians. NFKB1 encodes a 105kDa protein that can be processed to produce p50 subunit of nuclear factor-kappaB protein complex. A insertion (ins)/deletion (del) polymorphism (-94ins/delATTG) in NFKB1 promoter, which may drive the ins allele two-fold increase in NFKB1 transcription relative to del allele, was recently found. This study identified that the odds ratio in OSCC carrying ins allelotype were 1.78 relative to controls (56.7 vs 41.8%) in subjects more than 50 years old. L allelotype of Heme oxygenase-1 (HO-1), accounting for a long (GT)(n) repeat in HO-1 promoter, is associated with the risks of areca-related OSCC. Subjects carried both NFKB1 ins and HO-1 L allelotypes had significant risks for various subsets of OSCC. OSCC with lymph node metastasis or advanced stage had significantly higher frequency of NFKB1 ins and HO-1 L allelotypes. This study suggested that the functional NFKB1promoter polymorphism could be valuable for assessment of cancer risk.

Adult↗
PubMed2006

Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. However, it is unclear what, if any, genomic alterations occur as the disease progresses to invasive and metastatic OSCC. This study used genomewide array-CGH in microdissected specimens to map genetic alterations found in primary OSCC and neck lymph node metastases. We used array-based comparative genomic hybridization (array-CGH) to screen genomewide alterations in eight pairs of microdissected tissue samples from primary and metastatic OSCC. In addition, 25 primary and metastatic OSCC tissue pairs were examined with immunohistochemistry for protein expression of the most frequently altered genes. The highest frequencies of gains were detected in LMYC, REL, TERC, PIK3CA, MYB, MDR1, HRAS, GARP, CCND2, FES, HER2, SIS, and SRY. The highest frequencies of losses were detected in p44S10, TIF1, LPL, MTAP, BMI1, EGR2, and MAP2K5. Genomic alterations in TGFbeta2, cellular retinoid-binding protein 1 gene (CRBP1), PIK3CA, HTR1B, HRAS, ERBB3, and STK6 differed significantly between primary OSCC and their metastatic counterparts. Genomic alterations in PRKCZ, ABL1, and FGF4 were significantly different in patients who died compared with those who survived. Immunohistochemistry confirmed high PIK3CA immunoreactivity in primary and metastatic OSCC. Higher FGF4 immunoreactivity in primary OSCC is associated with a worse prognosis. Loss of CRBP1 immunoreactivity is evident in primary and metastatic OSCC. Our study suggests that precise genomic profiling can be useful in determining gene number changes in OSCC. As our understanding of these changes grow, this profiling may become a practical tool for clinical evaluation.

Adult↗
PubMed2005

Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma.

The A disintergin and metalloprotease (ADAM) superfamilies play important roles in angiogenesis, development, and tumorigenesis. Amyloid precursor protein (APP) is an important protein related to Alzheimer's disease. Recent research shows that ADAM10 alpha-secretase activity can release the secreted form of APP. We have previously demonstrated an increase of APP expression in oral squamous cell carcinoma (OSCC) and related OSCC cell lines. The present study characterizes ADAM10 expression in the neoplastic process of OSCC. RT-PCR analysis revealed a two-fold increase in APP mRNA expression in 50% of OSCC (n=50) relative to corresponding non-malignant matched tissues (NMMT). This increase in mRNA expression occurred at the preneoplastic stage. A significant correlation between mRNA expression of ADAM10 and APP in OSCC was noted. A non-buccal subset of OSCC correlated with an increase of mRNA expression of both ADAM10 and APP. The increase of ADAM10 protein expression in the majority of OSCC tissues and cell lines studies was confirmed by Western blot analysis. Additionally, an increase of ADAM10 immunoreactivity in OSCC relative to NMMT was noted. An antisense oligonucleotide against ADAM10 reduced ADAM10 expression as well as growth in an OSCC cell line. However, this treatment did not reduce the secreted form APP. This study suggests that ADAM10 expression plays a role in the carcinogenesis of OSCC and proliferation of OSCC cells, independent of APP processing.

ADAM Proteins↗
PubMed2005

Copy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewers.

Oral squamous cell carcinoma (OSCC) is a worldwide disease. In South Asians, the high prevalence of OSCC is tightly linked to areca chewing. The prognosis for OSCC remains dismal and improvement in early diagnosis may benefit the survival of patients with this disease. Chromosome region 3q26-27 has been shown to carry several oncogenes. By quantitative PCR (Q-PCR), the gene copy numbers of TERC, PI3KCA, ZASC1, and TP63 from microdissected OSCCs have been determined. Copy number amplifications of PI3KCA and ZASC1, a newly identified zinc finger transcription factor, were identified in 30 (65%) and 32 (70%) of 46 primary OSCCs, respectively. Co-amplification of PI3KCA and ZASC1 in 50% of primary OSCCs suggests that they are critical targets of the 3q26.3 amplicon. OSCCs carrying higher levels of PI3KCA and/or ZASC1 copy number amplification were associated with a significantly higher propensity for lymph node metastasis. ZASC1 mRNA expression in OSCC was also associated with lymph node metastasis. In addition, copy number amplification of at least one 3q26-27 oncogene was detected in brush samples from 10 of 22 (45%) patients with oral leukoplakia and 5 of 20 (25%) oral mucosa samples from areca chewers without a visible lesion. These data indicate frequent copy number amplification and overexpression of ZASC1 in OSCC. The findings also suggest the potential use of Q-PCR analysis and brush collection of samples to dissect OSCC risk.

Adult↗
PubMed2005

Cytoplasmic expression of E-cadherin and beta-Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas.

BACKGROUND: Inactivation of the adenomatous polyposis coli (APC) gene results in accumulation and translocation of beta-Catenin, which are important for malignant development. The aim of the present study is to investigate the possible role of APC/beta-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 beta-Catenin. RESULTS: We found that cytoplasmic rather than membrane staining of E-cadherin and beta-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 beta-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 beta-Catenin accumulation in cytoplasm of oral carcinoma cells and thereby to oral malignant progression.

Cadherins↗
PubMed2005

Frequent microsatellite alterations of chromosome locus 4q13.1 in oral squamous cell carcinomas.

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.

Adult↗
PubMed2005

Association of GST genotypes with age of onset and lymph node metastasis in oral squamous cell carcinoma.

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.

Adult↗
PubMed2005

Tumor necrosis factor-alpha promoter polymorphism is associated with susceptibility to oral squamous cell carcinoma.

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-alpha (TNF-alpha) is a central mediator of the immune response involved in a wide range of immuno-inflammatory and infectious diseases. Polymorphism of the TNF-alpha 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-alpha 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-alpha polymorphism is associated with the risk for OSCC in Taiwan.

Adenine↗
PubMed2004

Increased expression of amyloid precursor protein in oral squamous cell carcinoma.

In our previous study, we identified amyloid precursor protein (APP) in an oral squamous cell carcinoma (OSCC)-enriching subtractive hybridization library. Our present study attempts to define the significance of APP expression in the genesis of OSCC. RT-PCR analysis showed increase in APP mRNA expression for more than 2-fold in 76% of OSCC (n = 55) relative to corresponding non-cancerous matched tissues (NCMT). The majority of esophageal SCCs also had increase in APP mRNA expression. OSCC patients exhibiting increase in APP mRNA expression had significantly lower survival rate compared to patients exhibiting the opposite status. Western blotting analysis identified APP751 and APP770 as the major APP isoforms in oral keratinocytes. A high correlation between mRNA and protein expressions of APP was noted in OSCC/NCMT pairs. Immunohistochemistry further showed a remarkable increase of APP in OSCC tissue relative to NCMT. Treatment with an antisense oligonucleotide against APP reduced cellular and secreted APP as well as growth in an OSCC cell line. Our study provides novel clues that APP expression is involved in the proliferation and carcinogenesis of OSCC. Correlated with such pathogenesis was the survival of its victims. The degree of APP expression could serve as an invaluable marker for oral carcinogenesis.

Adult↗
PubMed2004

Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma.

Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also examined DNA from these tumors for loss of heterozygosity (LOH) at markers surrounding the ABO locus at chromosome 9q34, for loss of specific ABO alleles, and for hypermethylation of the ABO promoters. Loss of A or B antigen expression was found in 21 of 25 tumors (84%) and was a consistent feature of tumors lacking expression of A/B glycosyltransferases. LOH at 9q34 was found in 7 of 27 cases (26%), and one case showed microsatellite instability. Among 20 AO/BO cases, 3 showed loss of the A/B allele and 3 showed loss of the O allele. Analysis of the proximal ABO promoter by methylation-specific PCR and melting curve analysis showed hypermethylation in 10 of 30 tumors (33.3%), which was associated with loss of A/B antigen expression. ABO promoter hypermethylation was also found in hyperplastic or dysplastic tissues adjacent to the tumors, suggesting that it is an early event in tumorigenesis. Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas.

ABO Blood-Group System↗
PubMed2004

Association of CTLA-4 gene polymorphism with oral submucous fibrosis in Taiwan.

BACKGROUND: Oral submucous fibrosis (OSF) is an insidious, pre-cancerous, chronic disease that may affect the entire oral cavity and sometimes extend to the pharynx. It has been reported to be associated with immune function. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; CD (cluster of differentiation) 152) is a negative regulator of T-lymphocyte activation. Particular genotypes of the locus encoding the CTLA-4 glycoprotein have been associated with susceptibility to various autoimmune diseases. This study was designed to investigate the role of CTLA-4 polymorphism in susceptibility to OSF. METHODS: We genotyped 62 patients with OSF and 147 healthy controls for allelic determinants at the exon 1 +49 polymorphism site by restriction fragment length polymorphism. Genotype and phenotype frequencies were evaluated with Chi-squared test. RESULTS: The G allele at position +49 of exon 1 was significantly associated with OSF. The frequency of A/A homozygotes was higher in controls than in patients (17.0% vs. 3.2%; chi(2) = 7.65, P = 0.02); the G phenotype was more frequent in patients than in controls (96.8% vs. 83.0%; chi(2) = 9.31, P = 0.002). Compared with controls, the G allele genotype and phenotype frequencies were increased in patients with OSF. CONCLUSION: This is the first report that the CTLA-4 +49 G allele confers an increased risk of OSF in Taiwan.

Adenine↗
PubMed2004

Establishment of OC3 oral carcinoma cell line and identification of NF-kappa B activation responses to areca nut extract.

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 kappa B (NF-kappa B) 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.

Areca↗
PubMed2004

Polymorphism of the MICA gene and risk for oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF), an insidious, pre-cancerous, chronic disease that may affect the entire oral cavity and sometimes extend to the pharynx has been reported to be associated with immune function. The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is expressed by keratinocytes and other epithelial cells, and its encoded protein interacts with gamma/delta T-cells localized in the submucosa. The MICA gene has a triplet repeat (GCT) polymorphism in the transmembrane domain resulting in five distinct allelic patterns. METHODS: We analyzed MICA polymorphism in 80 OSF patients and 351 randomly selected unrelated controls by using the ABI Prism 377-18 DNA sequencer (Applied Biosystems) to analyze the sample DNA PCR products. The number of microsatellite repeats was estimated with Genescan 672 software (Applied Biosystems) with a standard size marker of GS-350 TAMRA. RESULTS: The phenotype frequency of allele A6 of MICA in subjects with OSF was significantly higher than that in controls (OR = 3.48; 95% CI = 1.8-6.71; P = 0.0002), as was the frequency of the allele (OR = 2.65; 95% CI = 1.44-4.86; P = 0.001). CONCLUSION: The results suggest that allele A6 in MICA might confer a risk for OSF.

Adult↗
PubMed2004

The molecular markers for prognostic evaluation of areca-associated buccal squamous cell carcinoma.

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 gamma-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 gamma-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 gamma-catenin might serve as potential prognostic markers for BSCC in areca-using patients.

Adult↗
PubMed2004

Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas.

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.

Adult↗