• 대한상부위장관⦁헬리코박터학회지
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• 제18권3호
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• pp.168-173
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• 2018

Gastric cancer is still the leading cause of cancer deaths, especially in Asian countries. Recently, many studies have analyzed cell-free nucleic acids (cfNAs) circulating in the blood, for the early diagnosis of cancer and monitoring its progression. Circulating tumor nucleic acids (ctNAs) originate in a tumor and contain tumor-related genetic or epigenetic alterations. This review defines the nomenclatures of each form of cfNAs and describes the characteristics of circulating tumor DNA (ctDNA) and microRNA (miRNA), two major forms of ctNAs studied in gastric cancer research to date. We compare available studies on ctDNA, and explain trends observed in studies of miRNAs in gastric cancers. As these new blood-based biomarkers have attracted increasing attention, we have discussed several important points to be considered before the clinical translation of ctNA detection. We have also discussed the current status of research in this field, and clinical applications of specific ctNAs as tumor markers for gastric cancer diagnosis.

• 한국임상수의학회지
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• 제41권3호
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• pp.143-149
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• 2024

Circulating cell-free DNA (cfDNA) constitutes a fragment of DNA released into the blood through cellular apoptosis or necrosis. In human medicine, cfDNA has been studied as a disease severity biomarker. Recent studies have shown that concentrations of cfDNA in dogs with immune-mediated and tumor-related diseases are increased. Pancreatitis is known to be caused by excessive release of trypsin, which leads to edema, inflammation, necrosis, and apoptosis in the pancreas. Based on the results of research showing an increase of cfDNA due to apoptosis and necrosis of cells, we hypothesized that cfDNA concentration would increase in the presence of pancreatitis. A total of 35 dogs were studied, including 21 with pancreatitis and 14 without any inflammatory diseases (normal group). The results showed that the concentration of cfDNA in dogs with pancreatitis was approximately twice that of normal dogs (median 0.0912 ng/μL. p-value 0.028). This result suggests that cfDNA can serve as a new biomarker for estimating pancreatitis severity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8299-8305
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• 2016

Background: In Egypt, breast cancer is estimated to be the most common cancer among females. It is also a leading cause of cancer-related mortality. Use of circulating cell-free DNA (ccf-DNA) as non-invasive biomarkers is a promising tool for diagnosis and follow-up of breast cancer (BC) patients. Objective: To assess the role of circulating cell free DNA (nuclear and mitochondrial) in diagnosing BC. Materials and Methods: Multiplex real time PCR was used to detect the level of ccf nuclear and mitochondrial DNA in the peripheral blood of 50 breast cancer patients together with 30 patients with benign lesions and 20 healthy controls. Laboratory investigations, histopathological staging and receptor studies were carried out for the cancer group. Receiver operating characteristic curves were used to evaluate the performance of ccf-nDNA and mtDNA. Results: The levels of both nDNA and mtDNA in the cancer group were significantly higher in comparison to the benign and the healthy control group. There was a statistically significant association between nDNA and mtDNA levels and well established prognostic parameters; namely, histological grade, tumour stage, lymph node status andhormonal receptor status. Conclusions: Our data suggests that nuclear and mitochondrial ccf-DNA may be used as non-invasive biomarkers in BC.

• Journal of Digestive Cancer Reports
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• 제8권1호
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• pp.56-60
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• 2020

In recent years, liquid biopsy has received immense attention. Liquid biopsy is a minimally invasive method used for obtaining biological fluids including urine, pleural fluid and, mostly, peripheral blood. Liquid biopsy involves various targets including circulating tumors cells (CTCs), circulating cell-free tumor DNA (ctDNA), and microRNA (miRNA). Colorectal cancer (CRC), like other solid tumors, shed tumor cells into the bloodstream. Analysis of these CTCs, as well as ctDNA is the primary objective of the liquid biopsy. Evaluation of CTC or ctDNA offers information about early tumor release, development of tumor metastasis and also about mechanisms involved in tumor resistance to treatment.

• 대한상부위장관⦁헬리코박터학회지
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• 제18권3호
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• pp.150-156
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• 2018

Precision medicine stands for 4Ps - precise, preventive, participatory, and personal; in which "precision" is important because the current modern medicine starts from "trial and error," and "one does not fit all". Current targeted therapies for cancer have changed treatment approaches and led the precision medicine; however, clinical use of liquid biopsy, using blood or other liquid specimens to characterize circulating tumor cells (CTC) or tumor genes instead of biopsies of tumor tissues, still awaits availability of more information regarding non-invasive cancer detection and characterization, prediction of treatment response, monitoring the disease course and relapse possibilities, identification of mechanisms of drug resistance, and newer pathogenesis. In this review, we will introduce the basic concept of CTC, circulating cell free DNA, and exosomes and their possible application for gastric cancer relevant with Helicobacter pylori infection.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.939-944
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• 2016

Background: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. Objectives: To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Materials and Methods: Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ALU 115bp. Results: Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (p<0.001). ROC curves for differentiating CRC patients from normal controls and benign groups had areas under curves of 0.90 and 0.85 respectively. Conclusions: The DNA integrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.

• 대한상부위장관⦁헬리코박터학회지
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• 제18권3호
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• pp.157-161
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• 2018

Liquid biopsy, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA, and exosomes, offers a less invasive, new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to personalized treatment. Recent advances in microfluidics and molecular analysis technologies have resulted in greatly improved CTC enumeration and detection. In this article, we review commercially available technologies used to isolate CTCs from peripheral blood, including immunoaffinity and label-free, physical property-based isolation methods. Although enormous technological progress has been made, especially within the last decade, only a few CTC detection methods have been approved for routine clinical use. Here, we provide an overview of the current CTC isolation methods and examples of their potential application for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to cancer therapy. Furthermore, the challenges that remain to be addressed before such tools are implemented for routine use in clinical settings are discussed.

• Journal of Genetic Medicine
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• 제8권1호
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• pp.1-16
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• 2011

현재 사용되고 있는 침습적 산전진단법(양수천자, 융모막샘플링)은 1-2%의 태아 손실이 초래되어, 비침습적 산전진단법이 산전진단의 궁극적인 목표로 대두되어 왔다. 1997년 Dr. Lo에 의해서 임신부 혈장 내에 세포 유리 태아 DNA (cffDNA)의 존재가 발견된 후 비침습적 산전진단의 새로운 가능성이 열렸으며, 과거 10년간 이에 대한 연구의 많은 진전을 보여주고 있다. 최근에 cffDNA를 이용한 Hemophilia A와 듀센형 근이영양증 등 반성 유전병(X-linked disorders) 진단에 필수적인 산전태아의 성 판정과 RhD-음성 임신부에서 태아의 RhD유전자 핵형 분석 등이 이미 외국에서 임상적으로 적용되고 있으나, 한국에서는 아직 실용화되지 않고 있다. CffDNA의 임상 사용에는 여전히 많은 제약점이 있으며, 이는 임신부 혈장 내 cffDNA 양에 비해 많은 양의 모태 DNA가 존재하고, 종래에 사용되었던 특이적인 Y염색체 유전자(Y-specific gene)는 남아 태아 임신 시에만 적용된다는 것에 기인한 다. 따라서 모든 태아에 적용할 수 있는 태아 성과 무관한 마커(sex-independent universal fetal marker as internal positive controls)가 요구되며, 이를 이용하여 정확한 태아 DNA를 검출할 수 있다. 본 연구진은 국내 처음으로 임신부 혈장 내에 cffDNA를 이용하여 SRY 유전자, RhD-exon 7, 태아 성과 무관한 DNA마커(universal fetal DNA marker)로써 RASSF1A 유전자를 실시간 중합효소연쇄반응(RT- PCR)을 사용하여 뛰어난 결과를 얻었다. 이는 한국에서 처음으로 성공적으로 시도된 것이다. 연구결과에서 산전 태아 성 판별과 산후 태아의 성이 100% 일치하였으며, 임신 주기별 SRY 수치는 임신이 진행할수록 증가함을 확인할 수 있었다. 따라서 이러한 방법은 혈우병 A, 듀센형 근이영양증, 선천성 부신증식증과 연골 무형성증의 진단과 치료 상담에 이용할 수 있으며 50%에서 침습적인 방법을 줄일 수가 있다. 또한, RhD-음성 임신부 대상으로 태아의 성 판정과 RhD 태아 유전자형을 분석한 결과 RhD-음성 태아를 정확히 검출함으로써 앞으로 기존 양수천자 등 침습적 검사를 대체할 수 있을 것이다. 특히 이는 치료가 필요 없는 RhD-음성 태아에서 RhD-면역글로불린의 예방적 치료를 사전에 막을 수 있어, 임신부 건강을 보호하고 의료 비용을 줄일 수 있는 큰 장점을 가진다. 한국에서 최초로 시도된 임신부 혈장 내 cffDNA를 이용한 본 연구의 성공은 비침습적 산전진단 임상 적용의 새 길을 제시하였다. 따라서 이를 각 유전질환의 산전진단에 유용하게 활용하는 것은 태아와 임신부의 건강 증진과 의료비용 절약 등 개인과 국가에 많은 기여를 할 것으로 사료된다.

• Design & Manufacturing
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• 제17권1호
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• pp.20-26
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• 2023

Lab-on-a-disc is a circular disc shape of cartridge that can be used for blood-based liquid biopsy to diagnose an early stage of cancer. Currently, liquid biopsies are regarded as a time-consuming process, and require sophisticated skills to precisely separate cell-free DNA (cfDNA) and circulating tumor cells (CTCs) floating in the bloodstream for accurate diagnosis. However, by applying the lab-on-a-disc to liquid biopsy, the entire process can be operated automatically. To do so, the lab-on-a-disc should be designed to prevent blood leakage during the centrifugation, transport, and dilution of blood inside the lab-on-a-disc in the process of liquid biopsy. In this study, the main components of lab-on-a-disc for liquid biopsy are fabricated by injection molding for mass production, and ultrasonic welding is employed to ensure the bonding strength between the components. To guarantee accurate ultrasonic welding, the flatness of the components is optimized numerically by using the response surface methodology with four main injection molding processing parameters, including the mold & resin temperatures, the injection speed, and the packing pressure. The 27 times finite element analyses using Moldflow® reveal that the injection time and the packing pressure are the critical factors affecting the flatness of the components with an optimal set of values for all four processing parameters. To further improve the flatness of the lab-on-a-disc components for stable mass production, a quarter-disc shape of lab-on-a-disc with a radius of 75 mm is used instead of a full circular shape of the disc, and this significantly decreases the standard deviation of flatness to 30% due to the reduced overall length of the injection molded components by one-half. Moreover, it is also beneficial to use a quarter disc shape to manage the deviation of flatness under 3 sigma limits.

• 대한임상검사과학회지
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• 제51권1호
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• pp.26-33
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• 2019

최근 반려동물 시장의 급격한 성장으로 인해 동물용 질병 진단키트의 개발이 이루어지고 있다. 이에 동물 분자진단 개발을 위한 바이오마커의 도입으로 효용성을 재평가하고 있다. 좋은 바이오 마커는 정확하고 신뢰할 수 있어야 하고, 정상 상태와 질병 상태를 구별하고, 다른 질병을 구별해야 한다. 최근 보고된 유전마커나 세포유리 DNA, 순환종양세포, granzyme, 피부종양에 관한 종양마커의 개발이 활발히 이루어지고 있으며, 기타로는 브루셀라증, programmed death receptor-1, symmetric dimethylarginine, periostin, cysteinyl leukotrien이 활발히 도입되고 있다. 따라서 바이오마커는 위험 예측에 사용되거나 질병 진행의 스크리닝, 진단 및 모니터링에 사용된다. 관련 바이오 마커에 대한 가장 중요한 기준은 질병 특이성이며 많은 잠재적 바이오 마커가 실험실 및 시험 연구에서 출현했지만, 독립적인 실험이나 대규모 임상 연구에서 검증이 부족하다. 후보 바이오 마커는 질병과 연관성을 평가하고, 조기 발견, 질병 진행에 대한 바이오 마커의 유효성을 검증하여서 인간 및 동물에게 접목하게 된다. 향후 잘 구조화 된 바이오마커 기반 연구의 효용성을 재평가하고 동물 질병 진단에 도입되는 추세에 맞춰 현장검사에서 활용될 수 있는 키트의 개발에 대한 연구가 요구돼야 할 것으로 사료된다.