• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2781-2785
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• 2016

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

• Tuberculosis and Respiratory Diseases
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• 제82권2호
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• pp.126-132
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• 2019

Background: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. Methods: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in ${\beta}$ value above 0.1 for three consecutive years. Results: We found three significant CpG sites with differentially methylated ${\beta}$ values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated ${\beta}$ values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). Conclusion: This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

• 한국환경성돌연변이발암원학회지
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• 제23권2호
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• pp.56-62
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• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2185-2193
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• 2016

Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

• Tuberculosis and Respiratory Diseases
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• 제66권6호
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• pp.444-450
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• 2009

연구배경: 폐암은 진단 당시에 완치할 수 있는 확률이 적어 예후가 불량한 종양으로 알려져 있어, 폐암 진행을 예측할 수 있는 암 표지자(tumor marker)의 발굴이 필요한 실정이다. 그러나 폐암에서 아직까지 특이적인 항원이 없고 현재까지 알려진 많은 종양관련 항원들의 민감도가 떨어지기 때문에 보편화되지 못하고 있다. 본 연구에서는 원발성 폐암 환자에서 혈장 G-CSF를 측정하고 암의 진행 및 예후와 관련이 있는지 알아보고자 하였다. 방 법: 원발성 폐암으로 진단된 100명 환자와 건강 검진에서 이상 소견이 없는 127명 정상인을 대상으로 하였다. 결 과: 정상인에서 혈장 G-CSF 농도는 12.2$\pm$3.6 pg/mL (mean$\pm$SD), 폐암환자에서는 46.0$\pm$38.0 pg/mL였다(p<0.001). 비소세포폐암에서 G-CSF 농도는 유의하게 소세포폐암보다 높았으며(p<0.05), 비소세포 폐암중 대세포 폐암이 가장 높았고, 편평세포암, 선암, 세기관지폐포암 순이었다. G-CSF 농도는 국소형보다는 진행형 비소 세포폐암에서 증가하는 경향을 보였다. 또한 타 장기로의 전이가 있을 때 유의하게 증가하였으며(p<0.05), 다발성 전이에서는 뇌, 부신, 골 전이 순으로 혈청 G-CSF 농도가 증가하는 경향이었다. 결 론: 혈장 G-CSF 농도는 폐암이 진행한 경우, 특히 타 장기로의 전이가 있을 때 유의하게 증가하였다. 그러므로 진행형 폐암의 추적관찰에 이용할 수 있으리라 사료된다.

• Bulletin of the Korean Chemical Society
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• 제34권9호
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• pp.2635-2639
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• 2013

The rapid and accurate identification of biological agents is a critical step in the case of bio-terror and biological warfare attacks. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been widely used for the identification of microorganisms. In this study, we describe a method for the rapid and accurate discrimination of Bacillus anthracis spores using MALDI-TOF MS. Our direct in-situ analysis of MALDI-TOF MS does not involve subsequent high-resolution mass analyses and sample preparation steps. This method allowed the detection of species-specific biomarkers from each Bacillus spores. Especially, B. anthracis spores had specific biomarker peaks at 2503, 3089, 3376, 6684, 6698, 6753, and 6840 m/z. Cluster and PCA analyses of the mass spectra of Bacillus spores revealed distinctively separated clusters and within-groups similarity. Therefore, we believe that this method is effective in the real-time identification of biological warfare agents such as B. anthracis as well as other microorganisms in the field.

• Journal of Gastric Cancer
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• 제17권1호
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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.

• Journal of Plant Biotechnology
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• 제39권1호
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• pp.81-92
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• 2012

단백질체학에서 이차원 전기영동 (2-DGE)은 고해상도 단백질 분리가 가능한 중요 기술 중 하나이다. 본 논문에서는 2-DGE 이미지 분석 일치도를 향상시킴으로써 작물 단백질 검출과 정량분석이 가능하도록 하는 전반적인 주요 장비, 시약 등을 자세히 기술한 프로토콜을 제시하고 있다. 이 프로토콜은 식물의 발달, 생물학적, 비생물학적 스트레스 반응 등과 관련된 작물 단백질 바이오마커를 개발하기 위한 목적에서 2-DGE를 처음 시도하는 연구자들에게 유용할 것으로 기대한다.

• 한국어정보학회:학술대회논문집
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• 한국어정보학회 2016년도 제28회 한글및한국어정보처리학술대회
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• pp.317-320
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• 2016

기계학습 기반의 자연어처리 모듈에서 중요한 단계 중 하나는 모듈의 입력으로 단어를 표현하는 것이다. 벡터의 사이즈가 크고, 단어 간의 유사성의 개념이 존재하지 않는 One-hot 형태와 대조적으로 유사성을 표현하기 위해서 단어를 벡터로 표현하는 단어 표현 (word representation/embedding) 생성 작업은 자연어 처리 작업의 기계학습 모델의 성능을 개선하고, 몇몇 자연어 처리 분야의 모델에서 성능 향상을 보여 주어 많은 관심을 받고 있다. 본 논문에서는 Word2Vec, CCA, 그리고 GloVe를 사용하여 106,552개의 PubMed의 바이오메디컬 논문의 요약으로 구축된 말뭉치 카테고리의 각 단어 표현 모델의 카테고리 분류 능력을 확인한다. 세부적으로 나눈 카테고리에는 질병의 이름, 질병 증상, 그리고 난소암 마커가 있다. 분류 능력을 확인하기 위해 t-SNE를 이용하여 2차원으로 단어 표현 결과를 맵핑하여 가시화 한다. 2차원으로 맵핑된 결과 값을 코사인 유사도를 사용하여 질병과 바이오 마커간의 유사도를 구한다. 이 유사도 결과 값 상위 20쌍의 결과를 가지고 실제 연구가 되고 있는지 구글 스콜라를 통해 관련 논문을 검색하여 확인하고, 검색 결과를 점수화 한다. 실험 결과 상위 20쌍 중에서 85%의 쌍이 실제적으로 질병과 바이오 마커 간의 관계를 파악하는 방향으로 진행 되고 있으나, 나머지 15%의 쌍에 대해서는 실질적인 연구가 잘 되고 있지 않은 것으로 파악되었다.

• Mass Spectrometry Letters
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• 제6권4호
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• pp.116-119
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• 2015

Globotriaosylsphingosine (lyso-Gb3) is considered as one of the biological marker for Fabry disease. To date, a reliable biomarker that reflects disease severity and progression has not been discovered to guide the management of Fabry disease. A new method included a simple protein precipitation with acetonitrile in 100 μL of plasma following analyte separation on an Phenomenex Kintex- C18 column using a gradient elution (0.1% formic acid in 5-90% acetonitrile). Total run time was within 12 min including sample preparation and MS/MS analysis. The limit of detection and limit of quantitation were 1 ng/mL and 2 ng/mL, respectively. The calibration curve was linear over the concentration range of 2.0-200.0 ng/mL (r² = 0.9999). Inter-day accuracy and precision at 7 level were 93.4-100.7% with RSD of 0.55-5.97%. Absolute recovery was 97.6-98.6%. The method was applied to human and mice plasma, proved the suitability for quantification of lyso-Gb3 for screening, diagnosis and therapeutic monitoring of Fabry disease patients.