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      • KCI등재후보
      • KCI등재후보

        A Case of Lynch Syndrome with the Deletion of Multiple Exons of the MLH1 Gene, Detected by Next-Generation Sequencing

        Jinyoung Hong,Hyunki Kim,홍용상,이우창,임석병,변정식,전사일,민원기 대한임상검사정도관리협회 2019 Journal of Laboratory Medicine And Quality Assuran Vol.41 No.4

        A 26-year-old man underwent colonoscopy to investigate weight loss and a lesion suspicious of colorectal cancer was detected. He had a family history of colorectal cancer and hepatocellular carcinoma. The biopsy result of the lesion showed a well-differentiated adenocarcinoma of the sigmoid colon and he underwent curative anterior resection of the colon. A microsatellite instability (MSI) test was performed on the resected tumor tissue specimen and it was found to be MSI-high. A next-generation sequencing (NGS)-based hereditary tumor panel test was performed on his peripheral blood to detect the causative germline variant. Neither a pathogenic variant nor a variant of uncertain significance was found in the single nucleotide variant (SNV) and small indel variant analyses. However, a copy number variation (CNV) detection algorithm identified a variant compatible with the deletion of exon 7 to exon 19 of the MLH1 gene. This finding was confirmed to be a true deletion by multiplex ligation-dependent probe amplification. Therefore, the deletion of exon 7 to exon 19 of the MLH1 gene was regarded as the causative pathogenic genetic variant for his colorectal cancer and familial genetic testing was recommended. Therefore, patients with suspected cancer syndromes, including hereditary colorectal cancer, should be tested for germline mutations including CNVs, SNVs, and indels. NGS is a technique that can simultaneously detect SNVs and CNVs and therefore, it has clinical utility for genetic testing for hereditary diseases.

      • KCI등재

        Toll-like Receptor 4-mediated Apoptotic Cell Death in Primary Isolated Human Cervical Cancers

        Jinyoung Won(원진영),Yunkyung Hong(홍윤경),Sookyoung Park(박수경),Joo-Heon Kim(김주헌),Yonggeun Hong(홍용근) 한국생명과학회 2018 생명과학회지 Vol.28 No.6

        Toll 유사수용체의 TLR4는 세포자연사(apoptosis)와 관련하여 세포의 생존과 증식에 영향을 미치는 것으로 알려져 있다. 본 연구에서는 TLR4의 활성이 부인과 질환 특이적 종양세포의 세포사멸기작에 어떠한 영향을 미치는지 살펴보았다. TLR4의 활성에 의한 세포자연사를 확인하기 위하여 부인암 조직(자궁경부암, 자궁내막암, 난소암)에서 종양세포를 분리하여 초대배양시스템을 구축하였고, lipopolysaccharide (LPS)에 의한 TLR4의 활성유도 과정에서 종양세포의 형태학적 변화를 살펴보았다. 또한, TLR4 매개성 세포사멸 기작을 확인하기 위하여 역전사 중합효소 연쇄반응(RT-PCR)을 통해 유전자 분석을 진행하였다. 연구 결과, 부인암의 초대배양세포에서 세포접촉저지(contact inhibition)현상이 감소되었고, 세포의 배가시간(doubling time)이 단축되어, 종양세포의 성장률 변화를 확인하였다(p<0.05). 자궁근육층(정상조직)의 초대배양세포에서는 민무늬근육 확인 인자인 ITGA5 (an alpha5 integrin marker)의 유전자 발현이 나타났으나, 자궁경부조직의 초대배양세포에서는 발현변화를 확인할 수 없었다. 종양세포의 유전자분석 결과에서 p53과 같은 종양억제인자의 발현이 유의적으로 증가한 반면(p<0.05), 세포사멸 신호기작과 관련하여 TLR4와 Caspase-3의 발현은 감소하였다(Caspase-3, p<0.05). LPS를 처리한 종양세포에서는 LPS 비처리군과 비교 시, TLR4의 발현증가와 함께 Caspase-3의 발현변화가 동반되었다. 이러한 결과들은 TLR4 매개성 apoptosis 유도가 종양세포의 증식억제에 중요한 영향을 미치는 것을 의미하며, TLR4 신호기작을 이용한 종양세포의 새로운 치료적 접근법을 제시할 것으로 기대한다. Toll-like receptor 4 (TLR4) has been implicated in cell proliferation and apoptosis in several types of cancer. In this study, the impact of TLR4 activation on apoptotic cell death in gynecologic cancers induced by lipopolysaccharide (LPS) was investigated. Cervical cancer cell lines were produced from isolated surgical specimens supplied by Paik Hospital. The primary cultures of normal myometrium and gynecologic cancers, including cervical, endometrial, and ovarian cancers, were used to examine the differences in morphological characteristics between normal and cancerous cells. A reverse transcription polymerase chain reaction analysis was used to determine the relative expression levels of TLR4 gene involved in apoptosis-associated signaling in cervical cancer cells. The cancer cell colonies showed a tendency to reach high levels of confluency compared with normal cells. In addition, an enhanced growth rate and loss of contact inhibition were observed in gynecologic cancer cells compared with normal cells (doubling times of 16.6 hr vs. 26 hr, respectively). The expression level of ITGA5, an alpha-5 integrin marker, was upregulated in normal myometrial cells, but this tendency was not exhibited in cervical cancer cells. Furthermore, p53 tumor suppressor gene expression was upregulated, whereas TLR4 and caspase-3 gene expressions were downregulated in cervical cancer cells. Notably, the expression levels of TLR4 and caspase-3 were increased significantly in LPS-treated cancer cells compared with those in non-LPS-treated cells. These results suggest that the TLR4-mediated caspase-dependent apoptotic signaling pathway could be suggested as a therapeutic target for the treatment of gynecologic cancers, including cervical cancers.

      • KCI등재

        Establishment of External Quality Assessment Material Preparation Method for Next-Generation Sequencing-Based Liquid Biopsy Scheme

        Jinyoung Hong,Joonsang Yu,Hyunjung Gu,Juhee Lee,Woochang Lee,Sail Chun,Won-Ki Min 대한임상검사정도관리협회 2022 Journal of Laboratory Medicine And Quality Assuran Vol.44 No.3

        Background: Next-generation sequencing (NGS)-based liquid biopsy testing using peripheral blood is a minimally invasive technique that can identify the characteristics of tumor-derived circulating tumor DNA (ctDNA) in cellfree DNA (cfDNA). External quality assessment (EQA) should be implemented to ensure the reliability of NGS-based liquid biopsy tests. This study aims to establish a method for producing EQA materials for NGS-based liquid biopsy tests. Methods: Eight cell lines harboring clinically important somatic mutations were selected for further analysis. Genomic DNA from the cell lines was extracted and fragmented using an ultrasonicator (Covaris Inc., USA). Two EQA materials were produced by spiking fragmented DNA into fresh frozen plasma and frozen at –70℃. The manufactured EQA materials were evaluated using a cfDNA gene panel (Dxome, Korea) using NextSeq Dx (Illumina, USA). Results: After sonication, the average sizes of the fragmented DNA were 203 and 201 bp, respectively. The results of the cell-free NGS panel showed a combination of different variants between the two EQA materials, and clinically important somatic mutations were detected as intended. Conclusions: In this study, a method for manufacturing materials for an NGS-based liquid biopsy test EQA scheme is presented. EQA materials with conditions similar to ctDNA clinical specimens can be produced at a relatively low cost using cell line-derived DNA and an ultrasonicator. The distribution of adequate EQA materials can improve the reliability of NGS-based liquid biopsy tests.

      • KCI등재

        Intuitive Modification of the Friedewald Formula for Calculation of LDL-Cholesterol

        Hong Jinyoung,Gu Hyunjung,Lee Juhee,Lee Woochang,Chun Sail,Han Ki Hoon,Min Won-Ki 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.1

        Background: High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C. Methods: Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol − HDL-cholesterol − (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared. Results: In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101–200, 201–300, and >300 mg/dL, respectively. In the validation set, the coefficient of determination (R2) between measured and calculated LDL-C was higher for LDL-CM than for LDL-CF (R2=0.9330 vs. 0.9206). The agreement according to the National Cholesterol Education Program Adult Treatment Panel III classification of LDL-C was 86.36%, 86.08%, 86.82%, and 86.15% for LDL-CM, LDL-CF, LDL-CMa, and LDL-CS, respectively. Conclusions: We proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.

      • KCI등재

        Development of a Method for Manufacturing External Quality Assessment Material for Genetic Testing of Solid Tumors Using Mutant and Wild-Type Cell Lines

        Jinyoung Hong,Ji Hyun Kim,Seungman Park,Sang Gon Lee,이우창,전사일,민원기 대한임상검사정도관리협회 2021 Journal of Laboratory Medicine And Quality Assuran Vol.43 No.1

        Background: DNA extracted from mutant cell lines is frequently used as an external quality assessment (EQA) material for genetic testing of solid tumors because it is easy to obtain. However, the proportion of mutations in cell lines is different from that in actual tumor samples. In this study, mixtures of mutant DNA and wild-type DNA mimicking patient samples were analyzed to optimize the amount of mutant DNA in EQA specimens. Methods: Four cell lines harboring the selected mutation were cultured, and genomic DNA was extracted from cultured cells. Wild-type cell line DNA was prepared in the same manner. Diluted samples were prepared by mixing each mutant cell line DNA and wild-type cell line DNA at different ratios. Sanger sequencing of target variants was performed. For reliability, sequencing was repeated three times and read by two readers. The cutoff was based on the lowest proportion of mutant DNA that was determined to be positive in all three experiments. Results: The cutoffs of mutant cell line DNA ratios were 10%, 5%, 25%, and 25% for KRAS G12C, EGFR exon 19 deletion, EGFR T790M, and BRAF V600E, respectively. For the cell lines harboring EGFR T790M and BRAF V600E, the mutant fraction was not 100%. Conclusions: When manufacturing EQA material for solid tumor genetic testing, consistent results can be obtained if the mutant proportion is 10% or more. In addition, the mutant allele frequency of the cell line should be checked in advance to guarantee that EQA materials contain enough mutant DNA.

      • KCI등재

        미국 배심제도에서의 배심원 평의 비공개 원칙과 그 한계 - 국민참여재판 배심원 평결의 기속력과 관련하여 -

        홍진영(Jinyoung Hong) 한국법학원 2019 저스티스 Vol.- No.174

        국민의 형사재판 참여에 관한 법률 제12조 제2항에서는 배심원은 법령을 준수하고 독립하여 성실히 직무를 수행하여야 한다고 규정하고 있고, 제3항에서는 배심원은 재판의 공정을 해하는 행위를 하여서는 아니 된다고 규정하고 있다. 배심원은 일시적으로만 공무를 담당하는 주체이지만, 그 공무를 담당하는 동안에는 배심원 직무의 공정성, 불가매수성이 침해되지 않는 방식으로 성실하게 직무를 수행하여야 하고, 사안에 관한 공정하고 합리적인 결론에 이를 수 있도록 최선의 노력을 하여야 한다. 국가 기능의 일부를 맡아 수행하는 공적 주체에 대하여는 판단을 받는 당사자의 불복의 기회가 보장되어야할 뿐 아니라, 적정한 수준의 비판과 견제, 감시가 이루어질 수 있는 제도적 장치가 갖추어져야만 그 공적 주체가 공정하고 성실하게 임무를 수행할 것임이 합리적으로 기대될 수 있으며, 여기에서는 배심원도 예외라고 하기 어렵다. 그러나 현행 국민참여재판법에서는 평의 비공개의 원칙을 매우 엄격하게 관철하고 있는 동시에 배심에게 평결의 이유를 제시할 것을 요구하지 않고 있어 배심의 평결에 대한 당사자의 불복과 국민의 비판의 기회가 봉쇄되고 있으며, 그 결과 배심원의 책임성 수준을 매우 낮게 설정하고 있는 미국의 경우보다도 더 평결에 대한 비판과 견제, 감시가 어려운 상황이다. 본고에서는 향후 국민참여재판 평결에 대하여 제한적 범위에서라도 기속력을 부여하는 방향으로 나아가고자 한다면 이 점에 관한 정비가 필요함을 주장하고자 하였다. Article 12(2) of Act on Citizen Participation in Criminal Trials stipulates that every juror shall abide by Acts and subordinate statutes and perform his/her duties independently and sincerely. In addition, Article 12(3) stresses that no juror shall commit any act of undermining the fairness of a trial. Even though jurors take public office temporarily, they shall fulfill their duty sincerely to ensure fairness and impartiality of verdict. In jurors’ decision-making process, juror accountability can be achieved when there are mechanisms for appeal from the parties as well as check and criticism from the public. However, the fact that Act on Citizen Participation in Criminal Trials does not require reasoning of the verdict from jury impairs juror accountability, compounded with the principle of ensuring secrecy of jury deliberation. This article analyzed relevant laws and precedents of the non-impeachment rule in the United States from a comparative perspective, to show that the Korean system maintains a lower level of juror accountability, by almost not allowing exceptions to jury deliberation secrecy. Finally, this article concludes that lawmakers should consider amending this rigid secrecy rule if they intend to give the jury’s verdict binding effect, as widely discussed recently.

      • 비직교 다중 접속 시스템의 보안 공평성을 고려한 딥러닝 기반 보안 빔형성 설계

        이진영(Jinyoung Lee),윤상석(Sangseok Yun),하정석(Jeongseok Ha) 한국통신학회 2021 한국통신학회 학술대회논문집 Vol.2021 No.2

        본 논문에서는 보안 공평성을 고려하여 비직교 다중 접속을 위한 보안 빔형성 설계에 관해 연구한다. 비직교 다중 접속 시스템에서의 보안 빔형성 방식을 찾는 문제는 수학적, 수치적으로 다루기가 힘들고 보안 공평성까지 고려한다면 문제는 더욱 풀기 어렵다. 따라서 본 논문에서는 딥러닝을 활용하여 비직교 다중 접속에 적합한 보안 빔형성 설계방식을 제안하고, 제안한 방식이 보안 공평성을 유지하면서 기존의 직교 다중 접속 방식에 비해 높은 보안 전송률을 얻을 수 있음을 보여준다.

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