• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5303-5306
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• 2012

Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. Methods: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR-restriction fragment-length polymorphism (PCR-RFLP). Results: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57). Conclusion: Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.

• The Journal of the Korea Contents Association
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• v.12 no.5
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• pp.1-9
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• 2012

The popularity of digital music and smart phones led to develope noise-robust real-time audio fingerprinting system in various ways. In particular, The Multiple Hashing(MLH) of fingerprint algorithms is robust to noise and has an elaborate structure. In this paper, we propose a filter engine based on MLH to achieve better performance. In this approach, we compose a energy-intensive filter to improve the accuracy of Q/R from music database and a statistic filter to remove continuity and redundancy. The energy-intensive filter uses the Discrite Cosine Transform(DCT)'s feature gathering energy to low-order bits and the statistic filters use the correlation between searched fingerprint's information. Experimental results show that the superiority of proposed algorithm consists of the energy and statistical filtering in noise environment. It is found that the proposed filter engine achieves more robust to noise than Philips Robust Hash(PRH), and a more compact way than MLH.

• Bulletin of the Korean Chemical Society
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• v.30 no.9
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• pp.1956-1962
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• 2009

The binding abilities of two multidentate tripodal amine catechol ligands, cis,cis-1,3,5-tris[(2,3-dihydroxybenzylamino) aminomethyl]cyclohexane (TMACHCAT, $L^1)\;and\;N^1,N^3,N^5$-tris(2-(2,3-dihydroxybenzylamino) ethyl)cyclohexane-1,3,5-tricarboxamide (CYCOENCAT, $L^2$) with Ga(III) and In(III) have been investigated by potentiometric and spectrophotometric methods in an aqueous medium of 0.1 M KCl at 25 ${\pm}\;1\;{^{\circ}C}.$ The ligands $L^1\;and\;L^2$ formed various monomeric species $MLH_3,\;MLH_2$, MLH and ML (M = $Ga^{+3}\;and\;In^{+3}$) and showed potential to form strong encapsulated tris(catechol) type complexes. The coordination modes, binding ability and selectivity of the ligands towards Ga(III) and In(III) have been discussed with the help of experimental evidences, and supported with molecular modeling calculations.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.227-236
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• 2006

Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

• 대한예방의학회:학술대회논문집
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• 2001.10a
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• pp.314-315
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• 2001

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.264-274
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• 2023

Purpose: In this study, polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in patients with gastric cancer (GC). Materials and Methods: In 5,676 GC cases, PCR-based MSI testing using five microsatellites (BAT-26, BAT-25, D5S346, D2S123, and D17S250) and IHC for MLH1 were performed. Reevaluation of MSI testing/MLH1 IHC and additional IHC for MSH2, MSH6, and PMS2 were performed in discordant/indeterminate cases. Results: Of the 5,676 cases, microsatellite stable (MSS)/MSI-low and intact MLH1 were observed in 5,082 cases (89.5%), whereas MSI-high (MSI-H) and loss of MLH1 expression were observed in 502 cases (8.8%). We re-evaluated the remaining 92 cases (1.6%) with a discordant/indeterminate status. Re-evaluation showed 1) 37 concordant cases (0.7%) (18 and 19 cases of MSI-H/MMR-deficient (dMMR) and MSS/MMR-proficient (pMMR), respectively), 2) 6 discordant cases (0.1%) (3 cases each of MSI-H/pMMR and MSS/dMMR), 3) 14 MSI indeterminate cases (0.2%) (1 case of dMMR and 13 cases of pMMR), and 4) 35 IHC indeterminate cases (0.6%) (22 and 13 cases of MSI-H and MSS, respectively). Finally, MSI-H or dMMR was observed in 549 cases (9.7%), of which 47 (0.8%) were additionally confirmed as MSI-H or dMMR by reevaluation. Sensitivity was 99.3% for MSI testing and 95.4% for MMR IHC. Conclusions: Considering the low incidence of MSI-H or dMMR, discordant/indeterminate results were occasionally identified in GCs, in which case complementary testing is required. These findings could help improve the accuracy of MSI/MMR testing in daily practice.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.181-186
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• 2012

The aim of this study was to evaluate the methylation status of three important cancer related genes viz. p16, E-cadherin and hMLH1 promoters and to associate the findings with specific dietary habits in Kashmiris, a culturally distinct population in India, with gastric cancer. The study subjects were divided into three age groups viz. 0-30yrs ($1^{st}$), 31-60yrs ($2^{nd}$) and 61-90yrs ($3^{rd}$). A highly significant association between the intake of local hot salted tea in $2^{nd}$ (p=0.001) and $3^{rd}$ (p=0.009) age groups was observed with the promoter hypermethylation of E cadherin. Again a highly significant association between the aberrant methylation of hMLH1 (p=0.000) and p16 (p=0.000) promoters and the intake of local hot salted tea was observed in the $2^{nd}$ age group of gastric cancer patients. The intake of sun-dried food was also significantly associated with the promoter hypermethylation of E cadherin (p=0.003) and p16 (p=0.015) genes in $3^{rd}$ age group. The results of the present study suggest a close association between the aberrant methylation of p16, E-cadherin and hMLH1 promoters and the intake of local hot salted tea and sun-dried foods in Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2587-2592
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• 2016

Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ${\leq}45$ years) with controls (>45 years). Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features. Results: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls. Conclusions: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3767-3771
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• 2015

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. Materials and Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. Results: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.