Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma

Khor, Goot Heah,Froemming, Gabrielle Ruth Anisah,Zain, Rosnah Binti,Abraham, Thomas Mannil,Lin, Thong Kwai Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

Background: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. Objectives: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. Materials and Methods: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. Results: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). Conclusions: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.

Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

Khor, Goot Heah,Froemming, Gabrielle Ruth Anisah,Zain, Rosnah Binti,Abraham, Mannil Thomas,Thong, Kwai Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis. Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status. Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

Human Papilloma Virus 18 Detection in Oral Squamous Cell Carcinoma and Potentially Malignant Lesions Using Saliva Samples

Goot-Heah, Khor,Kwai-Lin, Thong,Froemming, Gabriele Ruth Anisah,Abraham, Mannil Thomas,Rosdy, Nik Mohd Mazuan Nik Mohd,Zain, Rosnah Binti Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC.

Effects of Arterial Strain and Stress in the Prediction of Restenosis Risk: Computer Modeling of Stent Trials

Shijia Zhao,Linxia Gu,Stacey R. Froemming 대한의용생체공학회 2012 Biomedical Engineering Letters (BMEL) Vol.2 No.3

Purpose In-stenting restenosis is one of the major complications after stenting. Clinical trials of various stent designs have reported different restenosis rates. However,quantitative correlation between stent features and restenosis statistics is scant. In this work, it is hypothesized that stress concentrations on arterial wall caused artery injury, which initiates restenosis. The goal is to assess the correlation between stent-induced arterial stress and strain and the documented restenosis rates. Methods Six commercially available stents, including balloon-expandable stents and self-expanding stents, were virtually implanted into the arteries through finite element method. The resulted peak Von Mises stress, principal stress,principal logarithm strain, as well as percentage of intimal area with abnormal higher stress were monitored. Results Positive correlation between arterial stress and strain after stent implantations and the documented restenosis rates from the corresponding clinical trials was found regardless of stent types. No statistical significant difference was observed for various stress or strain parameters serving as indicators of artery injury. Conclusions In-stent restenosis are less likely to occur as arterial mechanics are least altered by stent implantations. Optimization of stent designs to minimize the stent-induced arterial stresses and strains can reduce the arterial injury, and thus reduce the occurrence of restenosis. This work improved our understanding of the stent-lesion interactions that regulate arterial mechanics and demonstrated that arterial stress and strain could predict the risk of in-stent restenosis.

Assessment of Shape Memory Alloy Stent Deployment in a Stenosed Artery

Linxia Gu,Shijia Zhao,Stacey R. Froemming 대한의용생체공학회 2011 Biomedical Engineering Letters (BMEL) Vol.1 No.4

Purpose Shape memory alloy (SMA) stents have been used increasingly for the treatment of complex arterial occlusions. There is an immediate need to quantify the mechanical performance of SMA stents to open occluded arteries. Methods The stent crimping and expanding process was assessed through both numerical modeling and in-vitro studies. The implantation of a SMA stent in curved arteries with eccentric stenosis were simulated to evaluate the effect of artery curvature on arterial mechanics. Results The crimping process stored a considerable amount of strain energy in the stent, which were then released through self-expansion until a balance between the stent and stenosed artery was achieved. The deployed SMA stent exhibited a dog-bone shape, where the longitudinal ends of the stent penetrated into the artery causing arterial stress concentrations. However, the maximum arterial stress was observed at the central portion of artery contacting the thin side of the plaque. Furthermore, stent-induced arterial mechanics were more pronounced in the curved artery than the straight artery. The maximum Von Mises stress in the curved artery with a curvature of 0.05 mm-1 was 37% larger than that found in the straight artery. The percentage of the intimal area at higher stress level (> 0.05 MPa) is 5.51% in the curved artery, compared to 1.76% in the straight artery. Conclusions This work provided a fundamental understanding of the behavior of SMA stent and its impact on the vascular wall, and illuminated the possibilities for exploiting their potential to alleviate arterial injury.