• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1557-1561
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• 2012

Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods: Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. Conclusion: These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.43-51
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• 2017

Purpose: This study aimed to analyze G3BP1 and VEZT expression profiles in patients with gastric cancer, and examine the possible relationship between the expressions of each gene and clinicopathological factors. Materials and Methods: Expression of these genes in formalin-fixed paraffin embedded (FFPE) tissues, collected from 40 patients with gastric cancer and 40 healthy controls, was analyzed. Differences in gene expression among patient and normal samples were identified using the GraphPad Prism 5 software. For the analysis of real-time polymerase chain reaction products, GelQuantNET software was used. Results: Our findings demonstrated that both VEZT and G3BP1 mRNA expression levels were downregulated in gastric cancer samples compared with those in the normal controls. No significant relationship was found between the expression of these genes and gender (P-value, 0.4835 vs. 0.6350), but there were significant changes associated with age (P-value, 0.0004 vs. 0.0001) and stage of disease (P-value, 0.0019 vs. 0.0001). In addition, there was a direct relationship between VEZT gene expression and metastasis (P-value, 0.0462), in contrast to G3BP1 that did not demonstrate any significant correlation (P-value, 0.1833). Conclusions: The results suggest that expression profiling of VEZT and G3BP1 can be used for diagnosis of gastric cancer, and specifically, VEZT gene could be considered as a biomarker for the detection of gastric cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6739-6742
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• 2013

Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

• Journal of Life Science
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• v.18 no.10
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• pp.1395-1399
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• 2008

We have recently reported the PRC1 promoter as a promoter candidate to control expression of transcriptionally targeted genes for breast cancer gene therapy. We tested whether the PRC1 promoter could be also applied for the lung cancer gene therapy. In the transient transfection assay with naked plasmids containing the luciferase fused to the PRC1 promoter, the promoter showed little activity in the normal lung cell line, MRC5. However, in the lung cancer A549 cells, PRC1 showed approximately 30-fold activation which was similar to the survivin promoter, the gene whose promoter has been already reportedas a candidate for the gene therapy of lung cancer. In viral systems, the PRC1 promoter showed approximately 75% and 66% of transcriptional activity compared to the CMV promoter in the adeno-associated virus (AAV) and the adenovirus (AV) systems, respectively. However, the PRC1 promoter in either AAV or AV showed approximately 20% activity compared to the CMV promoter in the normal lung cells. In addition, human lung tumor xenograft mice showed that the PRC1 promoter activity was as strong as the CMV activity in vivo. Taken together, these results suggested that PRC1 might be a potential promoter candidate for transcriptionally targeted lung cancer gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3431-3436
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• 2012

Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors.

• Molecules and Cells
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• v.42 no.3
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• pp.237-244
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• 2019

Understanding the mechanisms of cancer drug resistance is a critical challenge in cancer therapy. For many cancer drugs, various resistance mechanisms have been identified such as target alteration, alternative signaling pathways, epithelial-mesenchymal transition, and epigenetic modulation. Resistance may arise via multiple mechanisms even for a single drug, making it necessary to investigate multiple independent models for comprehensive understanding and therapeutic application. In particular, we hypothesize that different resistance processes result in distinct gene expression changes. Here, we present a web-based database, CDRgator (Cancer Drug Resistance navigator) for comparative analysis of gene expression signatures of cancer drug resistance. Resistance signatures were extracted from two different types of datasets. First, resistance signatures were extracted from transcriptomic profiles of cancer cells or patient samples and their resistance-induced counterparts for >30 cancer drugs. Second, drug resistance group signatures were also extracted from two large-scale drug sensitivity datasets representing ~1,000 cancer cell lines. All the datasets are available for download, and are conveniently accessible based on drug class and cancer type, along with analytic features such as clustering analysis, multidimensional scaling, and pathway analysis. CDRgator allows meta-analysis of independent resistance models for more comprehensive understanding of drug-resistance mechanisms that is difficult to accomplish with individual datasets alone (database URL: http://cdrgator.ewha.ac.kr).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1043-1048
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• 2012

The COPS3 gene has stimulating effect on cell proliferation and progression of osteosarcomas and related cells. However, the features of COPS3 and its potential application as a therapeutic target in other cancers has not yet been studied. In this study, therefore, the effect of COPS3 silencing via COPS3 siRNA on lung cancer cell proliferation was examined. Expression levels of COPS3 gene in COPS3 siRNA infected cells and control siRNA infected cells were compared with real time PCR and Western blot analysis. Cell proliferation levels were comprehensively analyzed by MTT, BrdU incorporationy, and colony formation assays. For mechanistic assessment the effects of COPS3 silencing on cell cycle and apoptosis were analyzed using flow cytometry. Results showed that successful silencing of the COPS3 gene at both translational and transcriptional levels significantly reduced the proliferation and colony formation by lung cancer cells (p<0.01). Flow cytometry showed cell cycle arrest in the G0/G1 phase after COPS3 silencing, and more importantly, apoptosis was induced as a result of COPS3 knockdown, which negatively affected cell survival. Therefore, these results provide another piece of important evidence that the COPS3 gene expressed in lung cancer cells may play a critical role in stimulating proliferation. Down-regulation of COPS3 could significantly inhibit lung cancer cell growth, which was most likely mediated via induction of cell cycle arrest in G0/G1 phase and apoptosis.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.433-442
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• 2012

The promise of stem cell therapy for various clinical applications seems getting realistic. An increasing number of researchers, from virtually every discipline of natural sciences, are flocking into this new world. Only ten years ago, gene therapy was the medicine for the 21st century. The possibility was endless. Although the science itself underlying gene therapy was very young, the field was exploding under the optimism that this new medicine would revolutionize both the basic and clinical sciences. For many reasons, the initial target was cancer. Here, we will focus on the results of cancer gene therapy clinical trials using liposome or nonviral gene carrier, hoping that the lesson from here will be a guideline for the new generation of cell-based therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9955-9960
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• 2014

Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. Materials and Methods: A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controls were included in this study. Methylation specific PCR was used to determine the MGMT methylation status in serum samples. Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophageal cancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betel quid and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smoking habit synergistically with MGMT methylation elevated the risk for esophageal cancer development [adjusted OR=5.02, 95% CI=1.35-18.74; p=0.010 for tobacco chewing and Adjusted OR=3.00, 95% CI=1.22-7.36; p=0.014 for tobacco smoking]. Conclusions: Results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by the environmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer in high incidence region of North East India.

• Development and Reproduction
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• v.16 no.3
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• pp.155-168
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• 2012

Therapeutic cancer is a long lasting and turbulent history accompany with the milestones in surgical intervention, chemotherapy and radiotherapy. In the past decade, however, metastatic cancer still obstinately exists challenging the professional scientist. Beside the major forms of cancer treatment, Diphtheria toxin (DT) which is produced by a pathogenic strain of bacterium Corynebacterium diphtheria to shield themselves against the other dangerous organism, have been researched as a potential candidate to overcome the drawback such as non-specific, non-effect to drug resistant cancer cell and side effects when using chemotherapy and radiotherapy. In the context of suicide gene therapy, the DT expression under controlling of tissue-specific promoter will be targeted in cancer cell but defect in normal cell. The molecular mechanism, characteristic of DT-bases therapy and prominent achievements of preclinical and clinical studies for the past decade are summarized and discussed in this review.