• Journal of Yeungnam Medical Science
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• v.37 no.2
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• pp.73-78
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• 2020

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5055-5060
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• 2013

Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6843-6848
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• 2014

Background: Diffusion-weighted magnetic resonance imaging (DWI) is reported to be useful for detecting malignant lesions. The purpose of this study is to clarify characteristics of imaging, detection rate and sensitivity of DWI for recurrence or metastasis of lung cancer. Methods: A total of 36 lung cancer patients with recurrence or metastasis were enrolled in this study. While 16 patients underwent magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), 17 underwent MRI and CT, and 3 underwent MRI and PET-CT. Results: Each recurrence or metastasis showed decreased diffusion, which was easily recognized in DWI. The detection rate for recurrence or metastasis was 100% (36/36) in DWI, 89% (17/19) in PET-CT and 82% (27/33) in CT. Detection rate of DWI was significantly higher than that of CT (p=0.0244) but not significantly higher than that of PET-CT (p=0.22). When the optimal cutoff value of the apparent diffusion coefficient value was set as $1.70{\times}10^{-3}mm^2/sec$, the sensitivity of DWI for diagnosing recurrence or metastasis of lung cancer was 95.6%. Conclusions: DWI is useful for detection of recurrence and metastasis of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2689-2692
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• 2014

Purpose: To investigate the risk factors for appendiceal metastasis of epithelial ovarian cancer and compare findings with the previous studies. Materials and Methods: One hundred and thirty-four patients with epithelial ovarian cancer were assessed in this study. All of them had undergone a surgical procedure including appendectomy. Of these, 21 (15.7%) patients who had appendiceal metastasis were analyzed as the case group and the patients with no metastasis were the controls, compared according to stage, grade, histology of tumor, preoperative Ca125 levels, presence of ascites, peritoneal cytology, diameter and site of tumor considered as risk factors. Results: We found statistically significant differences between the groups in terms of stage, grade, right-sided tumor location, presence of ascites, diameter of tumor${\geq}10cm$ and positive peritoneal cytology (p<0.05). In the logistic regression model, stage, grade, presence of ascites, right-sided location and diameter of tumor were independent risk factors. ROC curve analysis showed that stage, grade and diameter of the tumor were discriminative factors for appendiceal metastasis. Conclusions: In epithelial ovarian cancer, stage, grade, presence of ascites, right-sided location and large tumor size have importance for estimation of risk of appendiceal metastasis. As we compare our findings with previous studies, there is no definite recommendation for the risk factors of appendiceal metastasis in epithelial ovarian cancer and more studies are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3183-3186
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• 2013

Purpose: The 7th edition of the American Joint Committee on Cancer Staging Manual for esophageal cancer (EC) categorizes N stage according to the number of metastatic lymph nodes (LNs), irrespective of the site. The aim of this study was to determine the prognostic value of subcarinal LN metastasis in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis of 507 consecutive patients with ESCC was conducted. Potential clinicopathological factors that could influence subcarinal LN metastasis were statistically analyzed. Univariate and multivariate analyses were also performed to evaluate the prognostic parameters for survival. Results: The frequency of subcarinal LN metastasis was 22.9% (116/507). Logistic regression analysis showed that tumor length (>3cm vs ${\leq}3cm$; P=0.027), tumor location (lower vs upper/middle; P=0.009), vessel involvement (Yes vs No; P=0.001) and depth of invasion (T3-4a vs T1-2; P=0.012) were associated with 2.085-, 1.810-, 2.535- and 2.201- fold increases, respectively, for risk of subcarinal LN metastasis. Multivariate analyses showed that differentiation (poor vs well/moderate; P=0.001), subcarinal LN metastasis (yes vs no; P=0.033), depth of invasion (T3-4a vs T1-2; P=0.014) and N staging (N1-3 vs N0; P=0.001) were independent prognostic factors. In addition, patients with subcarinal LN metastasis had a significantly lower 5-year cumulative survival rate than those without (26.7% vs 60.9%; P<0.001). Conclusions: Subcarinal LN metastasis is a predictive factor for long-term survival in patients with ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3289-3292
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• 2013

Introduction: The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. Materials and Methods: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. Results: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was $69.2{\pm}7.3$ years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among thowse with a low PSA level less than 20ng/ml, and less than 10ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml)+1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=$2.718^x/1+2.718^x$. Conclusion: Newly diagnosed prostate cancer patients with a PSA level of 10ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

• International journal of thyroidology
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• v.11 no.2
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• pp.117-122
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• 2018

Metastases to regional cervical lymph nodes occur frequently in patients with thyroid cancer. The appropriate management of regional lymph node is important to achieve good disease control and to classify risk stratification for adjuvant radioactive iodine. However, there are some occasions that neck dissection is difficult and embarrassing in thyroid cancer. Especially, extensive or unusual nodal metastases bring challenges and makes neck dissection more difficult. Carotid artery management is one of the most difficult procedure in neck dissection. The management of patients who have persistent or recurrent cervical metastasis involving the carotid artery has been controversial and treatment dilemma to the surgeon. Metastasis of well differentiated thyroid cancer to the retropharyngeal lymph nodes is rare but occasionally encountered. The complete surgical excision is usually recommended for retropharyngeal lymph node metastasis of well differentiated thyroid cancer. An extensive mediastinal dissection in advanced differentiated thyroid carcinoma is occasionally required. This paper will review recent reports of management of advanced nodal metastasis of thyroid cancer and share the author's personal experience.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10513-10524
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• 2015

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2003.10a
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• pp.139-146
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• 2003

암의 조기 발견 및 예후 예측을 위하여 마이크로어레이 데이터를 이용할 수 있다. 하지만 이를 분석하기 위해서는 40${\mu}g$ 이상의 RNA 샘플이 필요한데, 실제 임상 시료를 사용하는 경우 요구되는 충분한 양을 얻기가 어려운 단점이 있다. 따라서 소량의 RNA 샘플을 채취한 후 PCR 증폭 과정을 통하여 요구되는 양의 샘플을 얻을 수 있는 RNA 증폭 방법이 시도되고 있고, 이를 마이크로어레이 실험에 이용하기 위해서는 증폭 전후의 유사성이 보장되어야 한다. 본 논문에서는 증폭 RNA와 전체 RNA의 유사성을 비교하기 위한 새로운 방법으로 엔트로피 기반의 방법을 제시한다. 아울러 다양한 조건에 따라서 엔트로피값을 측정하여 세포주와 조직에서 엔트로피 값이 어떻게 사용될 수 있는지 체계적인 분석을 하였다.