• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3819-3823
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• 2013

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. The outcome of HCC depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory. Talins were firstly identified as cytoplasmic protein partners of integrins but Talin-1 appears to play a crucial role in cancer formation and progression. Our study was conducted to assess the diagnostic value of serum Talin-1 (TLN1) compared to the most feasible traditional biomarker alpha-fetoprotein (AFP) for the diagnosis of HCC. Methods: TLN1 was detected using enzyme linked immunosorbent assay (ELISA) in serum samples from 120 Egyptian subjects including 40 with HCC, 40 with liver cirrhosis (LC) and 40 healthy controls (HC). Results: ROC curve analysis was used to create a predictive model for TLN1 relative to AFP in HCC diagnosis. Serum levels of TLN1 in hepatocellular carcinoma patients were significantly higher compared to the other groups (p<0.0001). The diagnostic accuracy of TLN1 was higher than that of AFP regarding sensitivity, specificity, positive predictive value and negative predictive value in diagnosis of HCC. Conclusions: The present study showed for the first time that Talin-1 (TLN1) is a potential diagnostic marker for HCC, with a higher sensitivity and specificity compared to the traditional biomarker AFP.

• Journal of Yeungnam Medical Science
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• 제2권1호
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• pp.167-174
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• 1985

1985년 5월부터 1985년 11월까지 영남대학병원 내과에 입원한 간질환 환자 255예를 대상으로 간질환에 동반된 피부 증상을 관찰하여 다음과 같은 결론을 얻었다. 1. 255예중 161예 (63%)에서 피부증상을 동반하였다. 2. 피부증상은 황달 및 소양증 (43.1%), 혈관의 변화 (39.6%), 알레르기성 변화 (10.6%), 조갑변화 (5.1%), 호르몬에 의한 변화 (4.3%), 색소변화 (3.5%), 기타 (2.4%)의 순으로 많았다. 3. 피부증상을 상기 7개 군으로 분류할때 간경화증에서 가장 않은 피부 증상을 동안 하였고 (1.6군), 만성 활동성 간염(0.7군)과 급성 바이러스성 간염 (0.8군)에서 적었다. 4. 알레르기성 변화는 주로 급성 바이러스성 간염(AVH) 환자에 서 나타났고, serum sickness-like prodrome의 증상은 3예였다. 5. 혈관의 변화, 조갑의 변화, 호르몬에 의한 변화, 색소 변화 등은 주로 만성 간질환에서 관찰 되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7211-7217
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• 2015

Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/${\Delta}G$ and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC.

• Investigative Magnetic Resonance Imaging
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• 제22권1호
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• pp.1-9
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• 2018

Purpose: This study was designed to optimize the flip angle (FA) and scan timing of the hepatobiliary phase (HBP) using the 3D T1-weighted, gradient-echo (GRE) imaging with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique on gadoxetic acid-enhanced 3T liver MR imaging. Materials and Methods: Sixty-two patients who underwent gadoxetic acid-enhanced 3T liver MR imaging were included in this study. Four 3D T1-weighted GRE imaging studies using the CAIPIRINHA technique and FAs of $9^{\circ}$ and $13^{\circ}$ were acquired during HBP at 15 and 20 min after intravenous injection of gadoxetic acid. Two abdominal radiologists, who were blinded to the FA and the timing of image acquisition, assessed the sharpness of liver edge, hepatic vessel clarity, lesion conspicuity, artifact severity, and overall image quality using a five-point scale. Quantitative analysis was performed by another radiologist to estimate the relative liver enhancement (RLE) and the signal-to-noise ratio (SNR). Statistical analyses were performed using the Wilcoxon signed rank test and one-way analysis of variance. Results: The scores of the HBP with an FA of $13^{\circ}$ during the same delayed time were significantly higher than those of the HBP with an FA of $9^{\circ}$ in all the assessment items (P < 0.01). In terms of the delay time, images at the same FA obtained with a 20-min-HBP showed better quality than those obtained with a 15-min-HBP. There was no significant difference in qualitative scores between the 20-min-HBP and the 15-min-HBP images in the non-liver cirrhosis (LC) group except for the hepatic vessel clarity score with $9^{\circ}$ FA. In the quantitative analysis, a statistically significant difference was found in the degree of RLE in the four HBP images (P = 0.012). However, in the subgroup analysis, no significant difference in RLE was found in the four HBP images in either the LC or the non-LC groups. The SNR did not differ significantly in the four HBP images. In the subgroup analysis, 20-min-HBP imaging with a $13^{\circ}$ FA showed the highest SNR value in the LC-group, whereas 15-min-HBP imaging with a $13^{\circ}$ FA showed the best value of SNR in the non-LC group. Conclusion: The use of a moderately high FA improves the image quality and lesion conspicuity on 3D, T1-weighted GRE imaging using the CAIPIRINHA technique on gadoxetic acid, 3T liver MR imaging. In patients with normal liver function, the 15-min-HBP with a $13^{\circ}$ FA represents a feasible option without a significant decrease in image quality.

• Genomics & Informatics
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• 제8권1호
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• pp.9-18
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• 2010

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

• Journal of Hospice and Palliative Care
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• 제20권3호
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• pp.177-187
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• 2017

목적: 2017년 8월부터 말기 암 이외에도 후천성 면역결핍 증후군, 만성 폐쇄성 폐질환, 간경화 환자들에게도 호스피스 완화의료가 적용될 예정이다. 이에 본 연구에서는 비암성 질환 전문가들을 대상으로 세 가지 질환에서의 호스피스 완화의료의 목표, 내용 및 적용 방법에 대한 심층 면담을 통해, 호스피스 완화의료에 대한 생각, 인식, 태도에 대해 살펴보아, 국내 실정에 맞는 비암성 호스피스 완화의료 진료 모델 마련에 기여하고자 하였다. 방법: 본 연구는 반구조적 심층 면담조사를 통한 질적 연구이다. 암환자의 호스피스 완화의료를 담당하는 네 명의 임상 의사가 85편의 문헌 검색을 통해 핵심 질문을 선정하여 총 11명의 비암성 질환 전문가들에게 면담을 하고 질적 연구 방법에 따라 분석되었다. 결과: 전문가들은 비암성 질환의 말기환자를 정의하기 어렵다고 하였고, 호스피스 완화의료의 목표와 내용은 암환자들을 대상으로 한 것과 다르지 않다고 하였지만, 통증보다는 다른 신체 증상과 정서적 문제에 중점을 두어야 한다고 하였다. 또한, 말기라고 진단할 수 있는 시점에 호스피스 완화의료를 적용해야 한다고 하였다. 질환 별로 특수한 점들(AIDS 환자들의 항바이러스제 사용, COPD 환자들의 호흡곤란, LC 환자들의 간이식)과 의료진들에 대한 교육의 필요성에 대해 언급하였다. 호스피스 완화의료 적용 시 환자들이 자신을 포기한다는 느낌을 받을 수 있다고 하였고 정부의 재정 지원 문제에 대해서도 언급하였다. 결론: 비암성 질환에 대한 호스피스 완화의료 도입의 문제점을 최소화하기 위해서는 심도 있는 논의를 통해 비암성 질환의 말기환자에 대한 정의를 마련해야 할 필요가 있다. 또한, 비암성 말기환자들을 돌보는 의료진과 현재 말기 암환자의 호스피스 완화의료를 담당하고 있는 인력의 협력이 필요하다.

• Investigative Magnetic Resonance Imaging
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• 제12권2호
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• pp.115-122
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• 2008

목적: SPIO-enhanced MRI상에서 얻은 radiological non-invasive hepatic fibrosis index (RNHFI)와 AST/혈소판 비(AST to platelet ratio index, APRI)간의 상관관계를 알아보고자 하였다. 대상 및 방법: 5년동안 SPIO-enhanced MRI를 시행받은 환자들을 대상으로 하였다. 환자들을 간경변 집단과 비(非)간경변 집단으로 분류했다. PACS를 이용, 각 환자의 SPIO-enhanced MRI에서 RNHFI (간실질 신호강도 표준편차의 평균(SD), 잡음교정 변이계수(CV))를 산출했고, 각 환자의 실험실 검사 결과를 이용, APRI를 산출했다. Student's t-test를 이용하여 두 집단간의 RNHFI와 APRI의 차이를 비교했다. 각 집단에서, RNHFI와 APRI간의 이변량 상관분석을 시행했다. 결과: 간경변 집단에서, SD, CV의 평균은 각각 $10.3{\pm}3.7$, $0.19{\pm}0.08$였다. 비간경변 집단에서, SD, CV의 평균은 각각 $6.5{\pm}1.6$, $0.08{\pm}0.05$였다. 두 집단의 평균 APRI는 각각 $2.04{\pm}1.7$, $0.32{\pm}0.32$였다. RNHFI와 APRI는 두 집단 사이에서 의미 있는 차이를 보였다 (p<0.05). 간경변 집단에서, SD와 APRI는 양의 상관관계를 보였다 (r=0.5, p<0.001). 결론: SD값이 간섬유화의 간단하고 유용한 예측 인자가 될 수 있을 것으로 기대된다.

• BMB Reports
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• 제42권12호
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• pp.834-839
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• 2009

DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, $P^{corr}$ = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, $P^{corr}$ = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, might affect HBV clearance.

• Genomics & Informatics
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• 제7권4호
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• pp.195-202
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• 2009

BIRC5 (Survivin) belongs to the inhibitor of apoptosis gene family. The BIRC5 protein inhibits caspases and consequently blocks apoptosis. Thus, BIRC5 contributes to the progression of cancer allowing for continued cell proliferation and survival. In this study, we identified eight sequence variants of BIRC5 through direct DNA sequencing. Among the eight single nucleotide polymorphisms (SNPs), six common variants with frequencies higher than 0.05 were selected for larger-scale genotyping (n=1,066). Results of the study did not show any association between the promoter region polymorphisms and the clearance of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence. This is in line with a previous study in which polymorphisms in the promoter region does not influence the function of BIRC5. Initially, we were able to detect a signal with the ＋9194A>G, which disappeared after multiple corrections but led to a change in amino acid. Similarly, we were also able to detect an association signal between two haplotypes (haplotype-2 and haplotype-5) on the onset age of HCC and/or HCC occurrence, but the signals also disappeared after multiple corrections. As a result, we concluded that there was no association between BIRC5 polymorphisms and the clearance HBV infection and/or HCC occurrence. However, our results might useful to future studies.

• Genomics & Informatics
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• 제7권4호
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• pp.187-194
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• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.