• Journal of Preventive Medicine and Public Health
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• 제42권2호
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• pp.89-95
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• 2009

Objectives : To assess the protective effects of wearing protective devices among the residents and volunteers who participated in the cleanup of the Hebei Spirit oil spill. Methods : A total of 288 residents and 724 volunteers were surveyed about symptoms, whether they were wearing protective devices and potential confounding variables. The questionnaires were administered from the second to the sixth week following the accident. Spot urine samples were collected and analyzed for metabolites of 4 volatile organic compounds(VOCs), 2 polycyclic aromatic hydrocarbons(PAHs), and 6 heavy metals. The association between the wearing of protective devices and various symptoms was assessed using a multiple logistic regression adjusted for confounding variables. A multiple generalized linear regression model adjusted for the covariates was used to test for a difference in least-square mean concentration of urinary biomarkers between residents who wore protective devices and those who did not. Results : Thirty nine to 98% of the residents and 62-98% of volunteers wore protective devices. Levels of fatigue and fever were higher among residents not wearing masks than among those who did wear masks(odds ratio 4.5; 95% confidence interval 1.23-19.86). Urinary mercury levels were found to be significantly higher among residents not wearing work clothes or boots(p<0.05). Conclusions : Because the survey was not performed during the initial high-exposure period, no significant difference was found in metabolite levels between people who wore protective devices and those who did not, except for mercury, whose biological half-life is more than 6 weeks.

• 대한영상의학회지
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• 제84권1호
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• pp.185-196
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• 2023

목적 갑상선 유두암 환자에서 림프절 전이를 예측할 수 있는 잠재적인 바이오마커를 개발하기 위해 초음파 영상에 대한 radiomics를 조사하는 것이다. 대상과 방법 2013년 8월부터 2014년 5월까지 431명의 환자가 연구에 포함되었고 통계 소프트웨어를 사용하여 훈련 및 검증 세트로 구분되었다. 총 730개의 radiomics 특징이 자동으로 추출되었다. 훈련 데이터 세트에서 가장 예측 가능한 특징을 선택하기 위해 최소 절대 수축 및 선택 연산자가 사용되었다. 결과 Radiomics 점수는 림프절 전이와 관련이 있었다(p < 0.001). 림프절 전이는 젊은 연령(p = 0.007) 및 더 큰 종양 크기(p = 0.007)와 같은 다른 임상 변수와도 관련이 있었다. 수신자 조작 특성 곡선 하 면적 결과 값은 훈련 세트의 경우 0.687 (95% 신뢰 구간: 0.616-0.759), 검증 세트의 경우 0.650 (95% 신뢰 구간: 0.575-0.726)이었다. 결론 본 연구 결과는 초음파 영상 기반의 radiomics가 papillary thyroid carcinoma 환자에서 경부 림프절 전이를 예측하고 바이오마커로 작용할 가능성을 보여주었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1781-1787
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• 2015

Background: miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer. Materials and Methods: The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT-qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology. Conclusions: Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1441-1446
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• 2014

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC ($P_{SC/ASC}$ =0.000) or AC ($P_{AC}$ =0.000 or $P_{AC}$ =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2037-2042
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• 2013

Background: Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development. Therefore, those proteins may be recognized as potential cancer markers. The aim of this study was to differentiate healthy individuals and lung cancer cases by analyzing their serum protein profiles and evaluate the efficacy of this method in the early diagnosis of lung cancer. Materials and Methods: 170 patients with lung cancer, 53 under high risk of lung cancer, and 47 healthy people were included in our study. Proteomic analysis of the samples was performed with the SELDI-TOF-MS approach. Results: The most discriminatory peak of the high risk group was 8141. When tree classification analysis was performed between lung cancer and the healthy control group, 11547 was determined as the most discriminatory peak, with a sensitivity of 85.5%, a specificity of 89.4%, a positive predictive value (PPV) of 96.7% and a negative predictive value (NPV) of 62.7%. Conclusions: We determined three different protein peaks 11480, 11547 and 11679 were only present in the lung cancer group. The 8141 peak was found in the high-risk group, but not in the lung cancer and control groups. These peaks may prove to be markers of lung cancer which suggests that they may be used in the early diagnosis of lung cancer.

• 수면정신생리
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• 제19권1호
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• pp.11-17
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• 2012

목 적 : 본 연구는 뇌파를 정량분석하는 새로운 방법의 하나인 wavelet 방법을 소개하고 아울러 그것이 임상 수면뇌파 분석에 유용하다는 것을 검증하기 위해 시도되었다. 방 법 : Wavelet 방법을 검증하기 위해 수학적으로 만들어진 인공뇌파들과, 입면주기 임상 뇌파 샘플 하나와 GoNoGo 프레임으로 측정된 ERP 샘플 하나가 사용되었다. Wavelet방법론으로 계산된 time-frequency 파워 스펙트럼과 위상 동조화 정도가 Fourier 및 moving windows 방법으로 계산된 스펙트럼과 coherence 결과들과 비교 분석되었다. 결 과 : Wavelet 방법은 인공뇌파에 인위적으로 포함된 파형의 특징들을 성공적으로 분해해내었다. 임상뇌파 샘플로 한 검증에서도 그 유효성이 확인되었는데, 입면주기 전후로 보이는 스펙트럼의 변화를 유의미하게 확인할 수 있었으며, 표적(target) 및 배경(background) ERP 파형의 특징을 시간-주파수 도표(time-frequency plot)으로 잘 표현하였다. 결 론 : 이러한 결과를 미루어볼 때, wavelet 방법은 임상 뇌파를 정량 분석함에 있어서, Fourier 방법을 효과적으로 대체 혹은 보완함을 알 수 있었다. 특히, 뇌파가 수초에서 수백초의 짧은 시간단위에서 급격한 변화를 보이는 입면주기뇌파와 ERP 분석에 wavelet 방법의 적합성이 크다고 볼 수 있다.

• Clinical and Experimental Reproductive Medicine
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• 제47권3호
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• pp.194-206
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• 2020

Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1137-1144
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• 2012

Introduction: Recent studies have shown that circulating tumor cells (CTCs) play potential roles as diagnostic and prognostic biomarkers with various cancer types. The aim of this study was to comprehensively and quantitatively summarize the evidence for the use of CTCs to predict the survival outcome of lung cancer patients. Materials and Methods: Relevant literature was identified using Medline and EMBASE. Patients' clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CTC positive rates at different time points (before, during and after treatment) were extracted. A meta-analysis was performed to clarify the prognostic role of CTCs and the correlation between the CTC appearance and clinical characteristics. Results: A total of 12 articles containing survival outcomes and clinical characteristics and 15 articles containing only clinical characteristics were included for the global meta-analysis. The hazard ratio (HR) for OS predicted by pro-treatment CTCs was 2.61 [1.82, 3.74], while the HR for PFS was 2.37 [1.41, 3.99]. The HR for OS predicted by post-treatment CTCs was 4.19 [2.92, 6.00], while the HR for PFS was 4.97 [3.05, 8.11]. Subgroup analyses were conducted according to histological classification and detection method. Odds ratio (OR) showed the appearance of pro-treatment CTCs correlated with the lymph node status, distant metastasis, and TNM staging, while post-treatment CTCs correlated with TNM staging only. Conclusion: Detection of CTCs in the peripheral blood indicates a poor prognosis in patients with lung cancer.

• 생태와환경
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• 제53권2호
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• pp.165-172
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• 2020

중금속은 다양한 경로를 통해 환경 중 배출되어 서식 생물에 노출되며 체내 다양한 생리학적 불균형을 유도한다. 본 연구에서는 수서생물지표종으로 이용되는 깔따구(Chironomus riparius)를 이용하여 야외 중금속(Al, Aluminum; Cr, Chromium; Cu, copper; Mn, Manganese; Zn, Zinc) 농도 노출에 따른 다양한 분자발현 반응과 상관성을 분석하였다. 생물 체내 분자 반응을 관찰하기 위해 heat shock protein 40, 70, 90 (HSP40, 70, 90), cytochrome 450(CYP450), Glutathione S-transferase (GST) and Serine-type endopeptidase (SP)를 이용하였다. 그 결과, 스트레스 분자마커로 이용되는 HSPs 유전자들은 중금속 노출된 개체들에서 대조군보다 높은 경향을 보였으며 Cu 노출 시 가장 높은 발현을 나타냈다. 해독에 관여하는 CYP450과 GST 유전자 발현 결과, Cr과 Cu에서는 다른 노출군에 비해 높은 발현 경향을 나타냈다. SP 유전자 발현 결과 Al을 제외한 모든 노출군이 대조군과 유사한 발현 패턴을 보였다. 이와 같은 연구 결과는 실내에서 환경 중 존재하는 실제 농도를 반영한 독성실험을 통해 노출물질과 농도에 따라 특이적으로 발현하는 분자마커 패턴을 보고하였다. 또한, 수생태계로 유입되는 중금속이 하천에 서식하는 생물에 주는 유해 영향에 대한 정보와 분자 지표 유전자들의 현장 적용 가능성을 보여준다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.307-314
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• 2015

Background: Bladder cancer is among the five most common malignancies worldwide. Altered expression of suppressor of cytokine signaling -3 (SOCS-3) has been implicated in various types of human cancers; however, its role in bladder cancer is not well established. Aim: The present study was undertaken to investigate the mRNA expression of SOCS-3 in normal and cancerous bladder tissue and to explore its correlation with urinary levels of some proinflammatory cytokines, cytokeratin-18 (CK -18) and with tumor histopathological grading, in order to evaluate their role as potential diagnostic markers. Materials and Methods: SOCS3 mRNA expression levels were evaluated using quantitative real time PCR. Urinary levels of interleukins 6 and 8 were estimated by enzyme linked immunosorbent assay (ELISA). Cytokeratin-18 expression was analyzed by immuunohistochemistry then validated by ELISA. Results: SOC3 m RNA expression levels were significantly lower in high grade urothelial carcinoma ($0.36{\pm}0.12$) compared to low grade carcinoma ($1.22{\pm}0.38$) and controls ($4.08{\pm}0.88$), (p<0.001). However, in high grade urothelial carcinoma the urinary levels of IL-6, IL-8, total CK-18($221.33{\pm}22.84pg/ml$, $325.2{\pm}53.6pg/ml$, $466.7{\pm}57.40U/L$ respectively) were significantly higher than their levels in low grade carcinoma ($58.6{\pm}18.6pg/ml$, $58.3{\pm}50.2pg/ml$, $185.5{\pm}60.3U/L$ respectively) and controls ($50.9{\pm}23.0pg/ml$, $7.12{\pm}2.74pg/ml$, $106.7{\pm}47.3U/L$ respectively), (p<0.001). Conclusions: Advanced grade of urothelial bladder carcinoma is significantly associated with lowered mRNA expression of SOC3 as well as elevated urinary levels of proinflammatory cytokines and CK-18. Furthermore, our results suggested that urinary IL-8, IL-6 and CK-18 may benefit as noninvasive biomarkers for early detection as well as histopathological subtyping of urothelial carcinoma.