Biomedical subjects

Shu-Chun Lin

Publications and source records attributed to Shu-Chun Lin.

27 records · Page 2Linked to original sources

PubMed2003

Modulation of KGF-1 gene expression in oral fibroblasts by ripe areca nut extract.

BACKGROUND: Areca chewing is a common habit of Asians, leading to a high propensity for a variety of oral diseases in this population. This research aimed to study the expression level of genes in oral fibroblast cell lines in response to exposure to ripe areca nut extract (rANE). METHODS: Fifteen oral fibroblast cell lines obtained from individuals aged 20-77 years were established. Treatment of a cell line with 40 micro g/ml rANE for 24 h was performed to achieve RNA for cDNA microarray analysis. RESULTS: Among some 320 genes exhibiting detectable expression levels, 14 were up-regulated and 26 were down-regulated more than 2.5-fold. Semi-quantitative RT-PCR analysis suggested that up-regulation of IL-6 expression and down-regulation of PDGFR, APP-1 and KGF-1 expressions in multiple cell lines assayed, were compatible with the results of the microarray analysis. Using quantitative real-time RT-PCR analysis, a remarkable down-regulation of KGF-1 expression in response to 40 microg/ml rANE, ranging 1.5-ninefold as compared to controls, was found in 60% (9/15) of the cell lines. CONCLUSION: This study established a novel toxicogenomic database for rANE. The down-regulation of KGF-1 expression in oral fibroblast cell lines potentially impairs the proliferation of overlying keratinocytes, which could partially explain the frequent epithelial atrophy observed in chronic areca chewers in vivo.

Adult↗

PubMed2003

Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma--evidence for COX-2 induction by areca quid ingredients in oral keratinocytes.

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.

Areca↗

PubMed2003

The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis.

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.

Adult↗

PubMed2003

The increase of voltage-gated potassium channel Kv3.4 mRNA expression in oral squamous cell carcinoma.

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.

4-Aminopyridine↗

PubMed2003

Areca nut extract treatment elicits the fibroblastoid morphological changes, actin re-organization and signaling activation in oral keratinocytes.

BACKGROUND: Areca (named as betel) is an important etiological factor linked with the high prevalence of oral squamous cell carcinoma (OSCC) in South-Asian countries. This in vitro study investigated the cellular changes and signaling activation in oral keratinocytes in response to areca nut extract (ANE) treatment. METHODS: Normal human oral keratinocyte (NHOK) and oral epidermoid carcinoma cell, Meng-1 (OECM-1) OSCC cell line were treated with variable dosages of ripen ANE. The morphological and cytoskeletal changes, as well as the activation of GTPase proteins and signaling kinases, were analyzed. RESULTS: Most NHOK cells in culture were polygonal, with only <5% cells exhibiting fibroblastoid morphology. However, 10 microg/ml ANE elicited fibroblastoid morphological change, genesis of lamellipodia, loss of subcortical actin, and stress-fiber formation in approximately 25% cultivated NHOK cells. Similar morphological changes were observed in nearly all OECM-1 cells following the ANE treatment. The activation of Rac and Rho GTPase, together with the prominent phosphorylation of a stress-activated kinases, particularly JNK1, was identified in treated OECM-1 cells. CONCLUSION: The novel evidences from the study that ANE impairs the actin organization and activates the signals in oral keratinocytes might bestow further insight into the impacts of ANE in oral pathogenesis.

Actins↗

PubMed2002

Multiple molecular alterations of FHIT in betel-associated oral carcinoma.

To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5-9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of the informative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT-PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre-invasive lesions, and 5% of the non-cancerous match tissue. An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. A statistically significant association was found between aberrant transcription of the FHIT gene and an abnormal level of Fhit immunoreactivity. The results indicated that alteration of FHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2002

Regulation of IGFBP-5 expression during tumourigenesis and differentiation of oral keratinocytes.

To identify molecular events involved in the pathogenesis of oral squamous cell carcinoma (OSCC), genes differentially expressed in OSCC and non-cancerous matched tissue (NCMT) samples were analysed using a subtractive hybridization strategy. NCMT-enriching clones that have been linked to suppressor pathway in previous studies were subjected to advanced analyses. Complete absence of insulin-like growth factor binding protein-5 (IGFBP-5) expression at both the mRNA and the protein level was identified in nearly all (5/6) OSCC cell lines with the exception of the SCC25 cell line, which exhibited high IGFBP-5 expression. However, this protein is consistently present in cultured normal human oral keratinocytes (NHOKs). Immunohistochemistry revealed moderate to strong cytoplasmic immunoreactivity of IGFBP-5 in the stratum spinosum and stratum granulosum in the vast majority of NCMT samples. A remarkable reduction in IGFBP-5 immunoreactivity was detected in 56% (26/46) of OSCC samples, compared with the corresponding NCMT (p < 0.0001). Induction of differentiation in both NHOKs and SCC25 up-regulated IGFBP-5 expression. Administration of a green tea compound with anti-cancer properties, (-)-epigallocatechin 3-gallate, at a concentration of 5-20 micro g/ml also up-regulated IGFBP-5 expression in NHOKs in a dose-dependent manner. The findings suggest that IGFBP-5 may be an important factor in the differentiation of oral keratinocytes and that down-regulation of IGFBP-5 may be involved in the neoplastic transformation of oral keratinocytes.

Antineoplastic Agents↗

PubMed2002

Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use.

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.

Adolescent↗

PubMed2002

The retinoic acid receptor-beta (RAR-beta) mRNA expression in the oral squamous cell carcinoma associated with betel quid use.

BACKGROUND: Within the abundant retinoids nuclear receptors, abnormally low expression of the RAR-beta 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-beta expression in OSCC associated with betel quid (BQ) use in our society. METHODS: We examined the cellular expression of RAR-beta 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-beta expression. In 17 paired-samples from buccal mucosa (BM), most NCMT and less than half of OSCC exhibited RAR-beta expression (16/17, 94% vs. 8/17, 47%, P = 0.003). The RAR-beta 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-beta expression and more advanced histopathological grade tumors was observed. This study also suggests that the loss of RAR-beta expression is significant in BM OSCC, which preferentially occurs in BQ users.

Adult↗