• BMB Reports
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• v.42 no.8
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• pp.535-539
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• 2009

Voltage-gated $K^+$ (Kv) channels are widely expressed in the plasma membranes of numerous cells such as epithelial cells. Recently, it has been demonstrated that Kv channels are associated with the proliferation of several types of cancer cells. Specifically, Kv1.3 seems to be involved in cancer cell proliferation and apoptosis. In the present study, we examined the expression of Kv1.3 in immortalized and tumorigenic human mammary epithelial cells. We also evaluated the expression level of Kv1.3 in each stage of breast cancer using mRNA isolated from breast cancer patients. In addition, treatment with tetraethylammonium, a Kv channel blocker, suppressed tumorigenic human mammary epithelial cell proliferation. Therefore, Kv1.3 may serve as a novel molecular target for breast cancer therapy while its stage-specific expression pattern may provide a potential diagnostic marker for breast cancer development.

• Molecules and Cells
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• v.41 no.12
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• pp.993-999
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• 2018

One of the most interesting findings from genome-wide expression analysis is that a considerable amount of noncoding RNA (ncRNA) is present in the cell. Recent studies have identified diverse biological functions of ncRNAs, which are expressed in a much wider array of forms than proteins. Certain ncRNAs associated with diseases, in particular, have attracted research attention as novel therapeutic targets and diagnostic markers. BC200 RNA, a 200-nucleotide ncRNA originally identified as a neuron-specific transcript, is abnormally over-expressed in several types of cancer tissue. A number of recent studies have suggested mechanisms by which abnormal expression of BC200 RNA contributes to the development of cancer. In this article, we first provide a brief review of a recent progress in identifying functions of BC200 RNA in cancer cells, and then offer examples of other ncRNAs as new therapeutic targets and diagnostic markers for human cancer. Finally, we discuss future directions of studies on BC200 RNA for new cancer treatments.

• Natural Product Sciences
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• v.28 no.2
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4049-4057
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• 2016

Background: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. Objective: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Materials and Methods: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. Results: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (p<0.05, OR 20, 95% CI 1.9-211.8; p<0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. Conclusions: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.249-254
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• 2016

Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb-B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC.

• Journal of KIISE:Computer Systems and Theory
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• v.35 no.8
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• pp.372-377
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• 2008

Multiclass cancer classification has been actively investigated based on gene expression profiles, where it determines the type of cancer by analyzing the large amount of gene expression data collected by the DNA microarray technology. Since gene expression data include many genes not related to a target cancer, it is required to select informative genes in order to obtain highly accurate classification. Conventional rank-based gene selection methods often use ideal marker genes basically devised for binary classification, so it is difficult to directly apply them to multiclass classification. In this paper, we propose a novel method for multiclass gene selection, which does not use ideal marker genes but directly analyzes the distribution of gene expression. It measures the class-discriminability by discretizing gene expression levels into several regions and analyzing the frequency of training samples for each region, and then classifies samples by using the naive Bayes classifier. We have demonstrated the usefulness of the proposed method for various representative benchmark datasets of multiclass cancer classification.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1685-1688
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• 2014

Background: CEA and CA 15.3 serum tumor markers are currently used in clinical practice for monitoring therapy. The aim of this study was to evaluate serum level of these markers among healthy females and invasive breast carcinoma (IBC) patients and to determine any relationships with clinicopathological factors. Materials and Methods: 60 Iranian females were enrolled in this study, 30 healthy and 30 diagnosed with breast cancer who had not received any preoperative chemotherapy or hormone therapy. Enzyme linked immunosorbent assays were used for the quantitative determination of the cancer associated antigens, CEA and MUC1 (CA15-3). Results: The serological levels of CEA and CA15-3 ($5.0033{\pm}0.49{\mu}g/L$ and $178.1667{\pm}15.11$ U/ml) in the breast cancer patients were significantly higher (p=0.00) than the serum levels of normal controls ($1.1237{\pm}0.11{\mu}g/L$ and $21.13{\pm}3.058$ U/ml). Regarding the CEA marker, a significant correlation with grade of tumor was shown. Furthermore, there was a low correlation between CA15-3 and CEA marker with correlation coefficient r=0.08. Conclusions: Collectively, markedly high levels of CEA and CA15-3 were found in our patients, pointing to their use as additional tools after clinical diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3319-3323
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• 2012

Objective: The results from the published studies on the association between prohibitin 3' untranslated region C > T gene polymorphism and cancer risk are conflicting. This meta-analysis was performed to evaluate the relationship with cancer susceptibility overall, and to explore whether the T allele or TT genotype could become a predictive marker for cancer risk. Methods: Association studies were identified from the databases of PubMed, Embase, and Cochrane Library as of March 1, 2012, and eligible investigations were synthesized using the meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Six investigations were identified for the analysis of association between the prohibitin 3' untranslated region C > T gene polymorphism and cancer risk, covering of 1,461 patients with cancer and 1,197 controls. There was a positive association between the T allele and cancer susceptibility (OR=1.20, 95% CI: 1.03-1.39, P=0.02), and CC homozygous might play a protective role (OR=0.80, 95% CI: 0.68-6.11, P=0.95). In the sub-group analysis, prohibitin 3' untranslated region C > T gene polymorphism and cancer risk appeared associated with the risk of breast cancer, but not ovarian cancer. Conclusions: Our results indicate that T allele is a significant genetic molecular marker to predict cancer susceptibility and CC genotype is protective, especially for breast cancer. However, more investigations are required to further clarify the association of the prohibitin 3' untranslated region C > T gene polymorphism with cancer susceptibility.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6605-6611
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• 2013

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.18-26
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• 2009

Purpose: Recently, the role of serum tumor marker has been studied for an important issue on diagnosing and treating tumors in the head and neck region because tests using tumor markers need relatively simple procedures and are acceptable to patients, compared with other test methods. Tumor marker tests were performed on patients with squamous cell carcinoma, which were known to have the highest prevalence among tumors in the head and neck region. Association between each tumor marker, and diagnosis and prognosis of tumors was assessed. Materials and methods: Tumor marker tests were carried out on 31 patients who visited Oral and Maxillofacial Surgery Department in Dankook University Dental Hospital between January 2003 and August 2008 and who were diagnosed as primary oral squamous cell carcinoma through out histopathologic diagnosis. Blood sample from these patients was performed to measure tumor markers using nuclear medicine diagnostic equipment. Measured entries were as follows: PSA(prostate-specific antibody), SCCAg( Squamous Cell Carcinoma Related Antigen), CA 19-9(Cancer Antigen 19-9), Ferritin, $\alpha$- FP(Alpha-Fetoprotein), Cyfra 21-1, CA125 (Cancer Antigen 125) and p53. Results: Analyses on each tumor marker indicated that squamous cell carcinoma in the head and neck region had statistically significant correlation with p53, SCC-Ag(TA-4), Cyfra 21-1 and Ferritin. p53 demonstrated the highest sensitivity. Especially, 4 cases among 18 cases which Ferritin was measured exhibited metastasis. In all those 4 cases, Ferritin values were higher than the standards (15 - 332ng/ml). Therefore, Ferritin is considered to have a close relation with metastasis of squamous cell carcinoma. Conclusion: This study shows that tumor marker tests are more useful in evaluating progression and prognosis of tumors rather than in diagnosing them. Particularly, serum Ferritin is considered to be beneficial in assessing metastasis of squamous cell carcinoma in the head and neck region and in developing treatment plans based on the assessment.